bluuebunny/crossref_metadata_2025 huggingface dataset:
Real-world changes in the clinical management of resected stage III melanoma at high risk of local recurrence in the era of modern systemic therapies.
Authors: Kibel Seth , Kuehne Nathan , Ribeiro Mauricio , Pimentel Muniz Thiago , Wong Philip , Spreafico Anna , Hogg David , Saibil Sam , Sun Alexander , Mak David Y. , Gray Diana , Butler Marcus O.
Published: June 2022

e21575

Background: Adjuvant systemic therapies (ST) for patients with resected stage III melanoma have improved relapse-free survival; however, the role of adjuvant radiotherapy (RT), previously the mainstay adjuvant treatment, is undefined in the modern ST era. Real-world data detailing clinical practice changes and its impact on outcomes are needed to help inform the choice of adjuvant therapy for patients with resected stage III melanoma. Methods: In this single-center retrospective study, patients from Princess Margaret Cancer Centre with resected stage III cutaneous melanoma treated between 2010 and 2019 and fitting the 2016 Cancer Care Ontario guidelines for adjuvant RT were included. Demographic, pathological, and clinical data were abstracted from electronic medical records. PFS was defined as the time from lymph node dissection to local-regional recurrence in the treated nodal basin or distant recurrence. OS was defined as time from lymph node dissection to death by any cause. The Log-rank method was applied to assess survival endpoints. A p-value < 0.05 was considered statistically significant. Results: From 4,959 records reviewed, 109 patients were identified. Median age at time of surgical resection was 59.4 years (23.6-89.8), and 74 (68%) were male. Type of adjuvant therapy and number of local-regional recurrences (LR) are expressed in the table. The median follow-up among those alive at last follow-up was 54.2 months (range 1.9-122). The proportion of patients receiving adjuvant RT was higher between 2010 and 2014 than it was between 2015 and 2019 (59% to 26%), whilst the proportion of those receiving adjuvant ST progressively grew (3% to 50%). LR > 90 days following lymph node dissection as the first site of relapse or synchronously with progression to metastatic disease was rare in patients treated with either adjuvant RT (6.8%) or adjuvant ST (14.3%, chi-square p = 0.33). Median progression free survival was 12.3 months in patients treated with adjuvant RT and 43.8 months in patients treated with adjuvant ST (p = 0.007). Overall survival was not significantly different (p = 0.08). Conclusions: The advent of ST has changed our institution’s clinical practice with ST replacing RT as the primary adjuvant treatment modality. Our data suggests that in the current adjuvant treatment landscape, omission of RT does not seem to increase rates of local-regional recurrences, and patients with resected stage III melanoma can be safely spared from adjuvant RT without detrimental effect on survival.[Table: see text]
The association of Ki67 level and adjuvant treatment options in mucosal melanoma.
Authors: Wei Xiaoting , Tang Lirui , Li Caili , Bai Xue , Mao Lili , Chi Zhihong , Cui Chuanliang , Lian Bin , Tang Bixia , Du Yu , Wang Xuan , Sheng Xinan , Yan Xieqiao , Li Siming , Zhou Li , Kong Yan , Dai Jie , Guo Jun , Si Lu
Published: June 2022

e21582

Background: Both chemotherapy and high-dose IFN-α2b (HDI) are effective treatment options in adjuvant setting for patients with resectable mucosal melanoma (MM). However, it is still unknown whether Ki67 level affects the selection of chemotherapy and HDI. Methods: Data from resected MM patients diagnosed as MM in Peking Cancer Hospital, were retrospectively collected and analyzed. Key inclusion criteria were: (1) diagnosed as resectable MM, with the date between Jan. 1, 2010, and Dec. 31, 2018; (2) Ki67 was identified by immunohistochemical staining; (3) received TMZ-based adjuvant chemotherapy or HDI. All patients were divided into two subgroups according to the Ki67 level proposed by previous publications: low (< 30%), high (> = 30%). Relapse-free survival (RFS) and melanoma-specific survival (MSS) were compared across different subgroups by log-rank tests. Multivariate Cox proportional hazards models were used to calculate hazard ratios (HRs), controlling for age, sex, primary site, lymphatic metastasis, LDH level, and gene mutational status (BRAF, c-KIT and NRAS). Results: In total, 1106 MM patients were screened and 175 met the inclusion criteria for analysis. 100 and 75 patients received temozolomide (TMZ)-based adjuvant chemotherapy and HDI therapy, respectively. Patients who received adjuvant chemotherapy had a superior RFS (21.0 vs. 9.6 months, HR = 0.47, P = 0.002) as compared to those with HDI, but no significant difference for MSS (45.9 vs. 37.6 months, HR = 0.63, P = 0.396). Longer RFS and MSS were observed in the ki67-low subgroup (HRs were 0.51, 95%CI 0.34-0.76 and 0.41, 95%CI 0.24-0.68 for RFS and MSS, respectively). For patients with low Ki67 (< 30%), two regimens showed no statistically different RFS (33.9 vs. 22.7 months, HR = 0.76, P = 0.329) and MSS (114.5 vs. 61.4 months, HR = 1.23, P = 0.967). However, for those with high Ki67, TMZ-based chemotherapy achieved an extended RFS compared with HDI (18.0 vs. 6.7 months, HR = 0.36, P < 0.001) and a trend toward improvement for MSS (41.4 vs. 25.1 months, HR = 0.47, P = 0.067). Conclusions: Ki67 level is an independent negative prognostic factor and impacts the selection of adjuvant treatment options for MM patients. Chemotherapy should be considered as the preference for patients with Ki67 > = 30%.
Optic pathway gliomas in children: Demographic, clinical characteristics, and results of an adapted protocol.
Authors: Kebudi Rejin , Yıldırım Ulku Miray , Iribas Ayca , Tuncer Samuray
Published: June 2022

e22016

Background: Optic pathway gliomas (OPG) constitute 1-5% of childhood brain tumors. The presence of neurofibromatosis type 1 (NF-1) is generally associated with more indolent disease. The aim of this study is to evaluate patients with optic pathway gliomas diagnosed/treated/ followed in a single center over 32 years. Methods: The medical files of 85 patients with OPG diagnosed/treated between 1990-2021 in the Istanbul University, Oncology Institute were retrospectively assessed for demographic, clinical characteristics, treatment and outcome. Results: The median age of the 85 patients (42 male, 43 female) was 60 (1-216) months, 53 (62.4%) had NF-1. Seven had diencephalic syndrome (8.2%). According to Dodge classification, 23 (27.1%) had Dodge 1, 30 (35.3%) Dodge 2 and 32 (37.6%) Dodge 3 disease. Median follow up time was 10.5 years (1-31 years). Twenty (23.5%) patients had stable disease and were followed without treatment, 14 patients underwent surgery (5 gross total tumor resection, 2 subtotal resection, 3 ventriculoperitoneal shunt operation, 4 excision/biopsy). 7 patients recieved radiotherapy (RT), none had NF1. 56 patients received chemotherapy (CT) due to severe/progressive clinical symptoms (such as diencephalic syndrome, visual impairment, nystagmus) or radiologic progressive disease. Chemotherapy consisted of an adapted SIOP-LGG regimen: vincristine (VCR) 1.5 mg/m²/dose and carboplatinum 550 mg/m²/dose every 21 days for three courses with weekly VCR, followed by VCR and carboplatinum every 28 days for a total of 12 cycles (3 cycles induction, 9 cycles consolidation). Vinblastin or cisplatinum with etoposide were used for second line or further treatment in progressive disease. One of the seven patients who had diencephalic syndrome and two of the 3 patients with leptomeningeal metastasis died. Ocular findings were recorded in 47 patients: vision was stable in 30 (63.8%), improved in 15 (31.9%), detoriated in 2 (4.3%). Radiology (MRI) revealed stable disease/regression of tumor in 41 patients, and complete regression of spinal metastasis in 1 patient. Endocrinologic follow-up was done and 13(15.2%) recieved hormonal treatment. Ten year overall survival(S) in all patients, in patients with NF1 and without NF1 were 96.5%, 96.1% and 95%, respectively; 10 year event free survival (EFS) in all patients, in patients with NF1 and without NF1 were 80.6%, 90.5% and 60% (p:0.001) respectively. Conclusions: OPG may remain indolent for many years after diagnosis, especially in patients with NF 1. However, these tumors develop progressive characteristics and can cause visual disturbances, endocrine dysfunction, blindness and even death among some of the patients. In young children who are symptomatic/have progressive disease, chemotherapy with an adapted regimen consisting of vincristine and carboplatinum seems to be effective and provides a relatively good quality of life.
Pediatric Cancer Registry in Turkey 2009-2021 (TPOG & TPHD).
Authors: Kutluk M. Tezer , Yeşilipek Akif
Published: June 2022

e22020

Background: The pediatric cancers is in the global agenda to improve the survival rates which is still low in LMICs although it is more than 80% in HICs. More than 300.000 pediatric cancer cases annually are expected in children and adolescents aged 0-14 globally. Registry is the first step of an efficient cancer control. Here, we present the most updated results of the pediatric cancer registry fromTurkey. Methods: Turkish Pediatric Oncology Group and Turkish Pediatric Hematology Association has established the pediatric cancer registry in 2002. The childhood cancer cases registered between 2009-2021 was included in this analysis. International Childhood Cancer Classification System was used for the classification. Essential demographic findings, ICD-O-3 morphology and topography codes were recorded for each case. Results: During the 13 years from 2009 to 2021, 24080 cases were registered. For all cases, median age was 6.7 year (0-19; M/F 13461/10609, 4 hermaphrodite, 6 unknown). Age distribution was 0-4 yrs, 40.8%; 5-9 yrs, 23.8%; 10-14 yrs, 23.3%; 15-19 yrs, 12.1%) The distribution of the tumor types were [number of cases, percentage of total, median age yrs, M/F]: Leukemia (5819, 24.2%, 5.5, 3366/2453); Lymphoma & other RES tumors (4446, 18.5%, 9.8, 2956/1487, 1 hermaphrodite & 2 unknown); CNS [brain & spinal] (3730, 15.5%, 6.8, 2061/1668, 1 unkown); Symphatetic system (1965, 8.2%, 2.3, 1010/955); Retinoblastoma (675, 2.8%, 1.4, 375/300); Renal (1160, 4.8%, 3.1, 557/601, 1 hermaphrodite & 1 unknown); Liver (409, 1.7%, 2.2, 234/175); Malignant bone (1584, 6.6%, 12.6, 864/720); Soft tissue sarcomas (1726, 7.2%, 7.7, 983/743); Germ cell (1593, 6.6%, 9.6, 588/1001, 2 hermaphrodite, 2 unknown); Carcinoma & other malignant epithelial (804, 3.3%, 13.5, 381/423); Other/non-specific malignant (169, 0.7%, 7.9, 86/83). Five year survival rate was found as 72.3%. Conclusions: The registry shows that the survival rates for children and adolescents have been improved to 72% which reflects the status of the pediatric cancer care in Turkey. The data from this work became a valuable source for all stakeholders in national and international level working on improvement the pediatric cancer control.
Symptom profiles and health care utilization in long-term survivors of Survivors of Childhood Childhood Cancer Survivor (CCSS) study.
Authors: Webster Rachel Tillery , Liu Wei , McGrady Meghan Eileen , Alberts Nicole M. , Brinkman Tara M. , Ness Kirsten K. , Fuemmeler Bernard , Kunin-Batson Alicia , Srivastava Deokumar , Huang I-Chan , Armstrong Gregory T. , Howell Rebecca M. , Green Daniel M. , Yasui Yutaka , Krull Kevin R.
Published: June 2022

e22024

Background: Physical and psychological symptoms co-occur among survivors of childhood cancer, and subgroups with high symptom burden may be at increased risk for problematic healthcare utilization (HCU). Methods: Childhood Cancer Survivor Study participants (N = 17,231; Mean [SD] age = 27.4 [5.98]; 79% non-Hispanic White; 48% female) self-reported sensory, motor, cardiac, respiratory, pain, gastrointestinal, fatigue, memory, depression, and anxiety symptoms at baseline evaluation and latent class analysis identified symptom profiles. Chronic health conditions (CHCs) at baseline (graded per CTCAE 1-2 [mild or moderate; reference] vs 3-4 [severe-life threatening or disabling). HCU (no health care, general care, oncology-focused, long-term follow-up, emergency room visit) for the past 2 years was assessed 6.3 median years after baseline. Logistic regressions examined associations between class membership and follow-up HCU, adjusted for sex, age, health insurance and CHCs. Results: Five symptom classes were identified: 1) Global symptoms (global; 7.7%); 2) emotional distress and pain (distress-pain; 13.3%); 3) neurologic and pain (neuro-pain; 10.6%); 4) cardiopulmonary and pain (cardio-pain; 5.3%); 5) non-elevated symptoms (norm; 63.1%). Bone tumor survivors had higher risk of falling into global, neuro-pain and cardio-pain groups (p’s < .001), and CNS tumor survivors had higher risk of falling into global and neuro-pain group (all p < .001) compared to leukemia survivors. Radiation, Grade 3-4 CHCs, female sex, and older age increased risk of global, distress-pain, neuro-pain and cardio-pain membership compared to norm (all p’s < .001). Oncology-focused care was more common in cardio-pain and global symptom groups, while long-term follow-up care was more common in neuro-pain and global groups (Table). All elevated symptoms groups were more likely to have emergency room visits compared to norm group. Conclusions: Adjusting for insurance, CHCs and older age, elevated symptoms are associated with future emergency room use. Pain is prevalent in all high symptom groups, and suggests an important intervention target.[Table: see text]
Effect of anticancer therapy on mortality and COVID-19 severity in cancer patients with COVID-19.
Authors: Myint Phyo Thazin , Thet Aye
Published: June 2022

e22510

Background: Cancer patients are more susceptible to severe complications and high mortality from Coronavirus disease 2019 (COVID-19). There is no solid evidence of whether anti-cancer therapy plays a significant role in increasing COVID-19 severity or mortality in cancer patients. Also, there is no definitive US guideline on how to justify anti-cancer treatment in cancer patients with COVID-19. Therefore, we conducted a systematic review and meta-analysis of the effect of anti-cancer therapy in cancer patients infected with COVID-19. Methods: A systematic search of Pubmed and Cochrane databases was conducted and two reviewers screened the articles independently. Previously published review articles were also evaluated to include the studies not identified in the Pubmed and Cochrane. Any clinical study of adults was included if it contains data on mortality or COVID-19 severity in cancer patients, both treated and untreated within 3 months before COVID diagnosis. Pooled odds ratio (OR) and 95% confidence intervals (CI) were calculated by employing the random-effects model, Mantel-Hazel method. Review Manager (RevMan) Version 5.4, The Cochrane Collaboration 2020 was used. Results: Out of 1690 studies identified from the databases and 8 studies from previous review articles, 22 studies (4777 patients) were included for analysis of the effect on mortality, and 12 studies (1898 patients) were included for the effect on COVID-19 severity. There were no significant differences in mortality between patients receiving anticancer treatment and those not (OR 1.17, 95% CI: [0.92-1.49], I2 = 56%, p = 0.21). There were no significant differences in mortality between patients receiving chemotherapy and those not receiving anticancer treatment but there was a trend towards higher mortality in patients receiving chemotherapy. (OR 1.43, 95% CI: [0.96-2.15], I2 = 68%, p = 0.08). There were no significant differences in COVID-19 severity between patients receiving anticancer treatment (OR 1.43, 95% CI: [0.96-2.15],, I2 = 10%, p = 0.27) and those not and between patients receiving chemotherapy and those not receiving anticancer treatment (OR 1.17, 95% CI: [0.83-1.65], I2 = 10%,p = 0.36). Conclusions: The results of our study were similar to previous meta-analyses despite more clearly defining anti-cancer treatment recency (anti-cancer treatment within 3 months before COVID diagnosis). There was low heterogeneity among studies for COVID-19 severity but high heterogeneity among studies for mortality. Most of the studies we analyzed were conducted in the 2020 and pre-vaccine era. Novel COVID-19 treatments and vaccination will likely affect outcomes in cancer patients with or without anti-cancer treatment. We need updated research and more detailed guidelines on anti-cancer therapy in COVID-19 infections.
The prevalence of HPV infection in Chinese solid tumor patients.
Authors: Yang Cheng , Wang Yizhou , Liu Ming , Huang Tanxiao , Liao Wenting , Li Yingmei , Mu Tianhao , Chen Shifu
Published: June 2022

e22519

Background: Human papillomavirus (HPV) is a family of small double-stranded DNA viruses. It is associated with a series of cancer types, such as cervical, oropharyngeal, anal, vulvar, vaginal, and penile cancers. In the world, nearly 70% of HPV-related cancer cases are HPV types 16 and 18. In this study, we investigated HPV infection prevalence among a cohort of Chinese solid tumor patients. Methods: The study enrolled thousands of Chinese patients with different types of cancers. We finally collected 4,606 tumor tissue DNA (ttDNA), 7,296 plasma cell-free DNA (cfDNA), and 7,509 peripheral blood mononuclear cell genomic DNA (gDNA) samples, respectively. Using a targeted capture technique that covering the whole reference genome of HPV16 and HPV18 and the next generation sequencing (NGS) technology, we calculated the percentage of HPV16 and HPV 18 reads in all sequencing reads for each sample. Finally, we explored the prevalence of HPV infection in each cancer type. Results: Based on different types of DNA samples, the HPV infection rate was 38.75%, 28.62%, and 10.43% in ttDNA, cfDNA, and gDNA samples, respectively. Besides, the magnitudes of the mean percentage of HPV reads in all the sequencing reads in ttDNA, cfDNA and gDNA samples were 10-5, 10-6 and 10-8, respectively, while in the HPV infection positive the percentages of ttDNA, cfDNA, and gDNA samples increased to 10-4, 10-5, and 10-7, respectively. The prevalence of HPV infection rate in different cancer types was shown in table. Conclusions: ttDNA and cfDNA are better material for HPV infective detection compared with gDNA, and NGS is capable of HPV detection.[Table: see text]
Ovarian cancer mortality: implications of income-inequality and availability of medical doctors in Brazil.
Authors: Maselli-Schoueri Jean Henri , Werneck De Carvalho Luis Eduardo , Paiva Laercio da Silva , de Almeida Roediger Manuela , de Abreu Luiz Carlos , Fonseca Fernando Luiz Affonso , Sette Claudia Vaz De Melo , Adami Fernando
Published: June 2022

e22520

Background: Ovarian cancer mortality varies by region and age group in Brazil. However, it is still unknown if socioeconomic inequalities may affect its outcome even if indirectly as it happens for other gynecologic neoplasms in the country. Methods: Ecological study conducted with secondary data from 2016-2018 to examine the relationship between income-inequality and the amount of doctors per inhabitant on ovarian cancer mortality in Brazil. All data were gathered from Brazil’s public health system. Mortality was analyzed by sex and age, which was standardized according to the World Health Organization’s population. Income-Inequality was measured using the Gini index, obtained from the United Nations Development Programme. The number of doctors was obtained from the Unified Health System and was also calculated as the rate per 100,000 inhabitants. Linear regression was performed using stepwise selection/backward elimination. Results: Despite income inequality as measured by the Gini index not having any statistically significant relationship with ovarian cancer mortality rates, we found that the amount of doctors per inhabitant was positively associated with ovarian cancer mortality rates (β 0.037, IC95% 0.028;0.045), whereas the amount of clinical oncologists (β-0.426, IC95% -0.805; -0.047) and higher income (β -0.004, IC95% -0.005; -0.003) were all negatively associated with those rates (p < 0.05), meaning that the higher those variables, the lower the mortality. Conclusions: Ovarian cancer mortality differs among federative units in Brazil. Higher mortality is associated with a greater amount of doctors per inhabitant, whereas lower mortality rates were found to be associated with higher income and more clinical oncologists available.
Educational webcast series targeted to the interprofessional bladder cancer care team improves clinician knowledge, confidence, and competence.
Authors: Gitzinger Susan H. , Taylor Bryan Carson , Carranza Vanessa , Fowler Joan B. , Trieu Tina , Lilly Ashley
Published: June 2022

e23002

Background: There are an estimated >81,000 new cases of metastatic urothelial bladder cancer (mUBC) diagnosed in the U.S each year, resulting in more than 17,000 deaths. mUBC has been shown to be susceptible to immune checkpoint inhibitors (ICIs), and beyond currently approved first and second line indications, these agents are being studied in bladder-sparing regimens and for high risk NMIBC patients who are BCG-unresponsive. Needs assessments demonstrate educational gaps involved in medication selection, dosing, and immune-related adverse event management as barriers to immunotherapy use by the interprofessional bladder cancer care team. The webcast series, “Key Issues for the Advanced Bladder Cancer Care Clinic: Incorporating Immunotherapy into your Community-Based Urology Practice” was designed specifically for the interprofessional team of bladder cancer clinicians to address unmet educational needs by focusing on the communities where the significant majority of patients are diagnosed, evaluated, and managed. Methods: Four online activities were designed to target urology and uro-oncology community physicians, physician assistants, nurse practitioners, nurses, and pharmacists focused on ICI therapies for bladder cancer, with a focus on the role of the team. Learning and confidence change were objectively assessed by analyzing pre- and post-test results before and after the educational activities. Statistical testing between pre- and post-tests were conducted via chi square analysis with a priori significance set at 0.05. Results: Evaluations were collected from N=706 participants. Knowledge advancements, as determined by significant ( P<0.05) increases in correct responses, were observed in several specific topic areas: recognition of ongoing clinical trials (29% pre-test vs. 69% post-test) biomarkers and treatment selection (43% pre-test vs. 81% post-test) logistical concerns for patients initiating ICIs (60% pre-test vs. 80% post-test) Participant self-reported mean confidence scores increased with statistical significance in implementation of appropriate immunotherapy and in recognizing and mitigating irAEs from pre- to post-test ( P<0.05). Conclusions: As the treatment paradigm for bladder cancer continuously evolves, all members of the oncology healthcare team must be equipped to evolve with it to ensure optimal patient care. This analysis shows that online accredited education can significantly improve the knowledge and confidence of the interprofessional bladder cancer care team in multiple areas surrounding the effective and appropriate use of ICIs.
Is a ‘cancer check-up’ near for high-risk adults? clinician attitudes and perspectives on multicancer early detection tests.
Authors: Ackbarali Tariqa , Marinac Catherine , Beer Tomasz M.
Published: June 2022

e23008

Background: Current screening guidelines for many cancers are limited and multiple cancer-screening tests are not yet FDA approved. The development and potential use of a pan-tumor or multi-cancer early detection (MCED) test has been met with both enthusiasm and hesitation, despite its potential for early detection and a resultant reduction in cancer-related mortality and morbidity. The lack of knowledge of clinician perceptions of MCED test and the need to educate a multidisciplinary team prompted the design of educational initiatives in 2020 and 2021. Methods: In September 2020 and July 2021; two 1-hour CME activities were launched live-online on OMedLive.com; the 2021 activity remains on-demand until July 2022. The 2020 activity introduced the value proposition and trial designs of MCED tests and reviewed the current cancer screening guidelines. Challenges revealed from the 2020 activity informed the multidisciplinary approach of the 2021 activity presenting epidemiology, oncology, and primary care perspectives. In both activities, participants were assessed at 3 time points (pre-, immediate post-, and 2 mos. post-activity) and McNemar tests compared paired responses with Cohen’s d for effect size. Behavioral impact, perception, and practice pattern questions were also assessed immediately post-activity and year-to-year data analyzed. Results: As of 02/13/22, 1,015 clinicians have participated in the 2020 activity and 3,372 in the 2021 activity. Across the eight CME test questions, seven exhibited improvements in knowledge/competence related to screening modalities, trial data, value of MCED tests, and clinical workflow following results. In the analysis of perception and practice pattern questions, 50% of clinicians were likely to integrate MCED tests into their practice; however, expectation of high costs and access/availability to utilize MCED tests at their practice were the top barriers identified. A lack of consensus in identifying adults at higher risk of cancer was observed in 2020 with improvements seen in 2021. At 2-mos. follow-up for the 2020 and 2021 activity, respectively, clinicians reported practice behavior changes as 89% and 73% related to clinical practice, while 89% and 72% reported improved patient experience/outcomes. Qualitative data including clinician write-in examples of specific practice behavior changes will be analyzed. Conclusions: These data provide real-world insight into clinician perspectives on MCED tests and the clinical, patient-care, and workflow challenges that should be considered before incorporating future approaches on multi-cancer screening. As the primary care setting is most suited for the introduction of novel cancer-screening tools, PCPs and oncologists will require continued education to apply practical strategies for point-of-care decision-making and transitions of care protocols.
Surgical subtype and survival in stage I chondrosarcoma: A National Cancer Database (NCDB) analysis.
Authors: Burdyny Michael , Eaton Vincent , Tupper Connor , Legenza Ashton , Silberstein Peter T.
Published: June 2022

e23502

Background: Chondrosarcoma is one of the most common primary malignancies of bone and commonly presents in adults in its early stages. Standard of care for chondrosarcoma is currently surgical intervention, with radiation therapy for cases where complete resection is not possible; chemotherapy is minimally effective. To the authors’ knowledge, there is little literature regarding different surgical subtypes for chondrosarcoma patients. To address this, the aim of our study is to assess survival outcomes in stage I chondrosarcoma patients based off of different surgical subtypes. Methods: Using the NCDB, patients diagnosed with stage I chondrosarcoma between 2004-2018 were identified using ICD-O-3 histology codes 9220 and 9221. The cohort was analyzed to determine if they received any form of surgical intervention and which surgical subtype they received. We then performed univariate analysis to assess patient length of survival for each surgical subtype. Data was analyzed using SPSS and statistical significance was set at α = 0.05. Results: A total of 5186 patients were included that had survival data, of which 4752 received surgical intervention. The mean survival time was 152.1 months for all patients. Surgical patients survived an average of 156.6 months while nonsurgical patients survived just 97.7 months (p < .0001). Analysis of surgical types revealed local destruction and local excision had the longest mean survival but were not different from each other (p > .05). Local excision had significantly longer survival than radical excision with limb sparing (p < .05). Local, partial, and radical excision all resulted in longer survival than limb and major amputations (all p < .01). Patients who underwent major amputation survived longer than limb amputation, but this difference was not significant (p > .05). Conclusions: This study found that receipt of surgery is associated with improved survival in chondrosarcoma patients. Receiving different surgical interventions may influence survival as patients receiving local excision survived longer than radical excision with limb sparing. Future studies should investigate additional variables that may influence receipt of surgery such as patient demographics, insurance status, and treatment facility type.[Table: see text]
Phase 2 trial of palbociclib and ganitumab in patients with relapsed Ewing sarcoma.
Authors: Shulman David Stephen , Merriam Priscilla , Choy Edwin , Guenther Lillian M. , Cavanaugh Kerri , Kao Pei-Chi , Posner Andrew , Fairchild Grace , Barker Emma , Stegmaier Kimberly , Crompton Brian D. , London Wendy B. , DuBois Steven G.
Published: June 2022

e23507

Background: Ewing sarcoma (EwS) is an aggressive sarcoma with few treatment options for patients with relapsed disease. CDK4 is a known genomic vulnerability in EwS, but an unappealing monotherapy target given propensity for innate resistance. In laboratory studies to identify targets synergistic with CDK4 inhibition, IGF-1R scored highly. We present the results of a phase 2 study combining palbociclib (CDK4/6 inhibitor) with ganitumab (IGF-1R monoclonal antibody) for patients with relapsed or refractory EwS. Methods: This was a prospective open-label, non-randomized, single-center, phase 2 study (NCT04129151) for patients with relapsed EwS and RECIST measurable disease. Patients with relapsed EwS ≥12 years and a documented fusion consistent with EwS were eligible. Patients initially received Palbociclib 125 mg on days 1-21 and ganitumab 18 mg/kg on days 1 and 15 of a 28-day cycle. The primary endpoints were objective response (complete or partial) per RECIST and toxicity by CTCAE. Secondary endpoints included progression-free survival (PFS) and overall survival (OS). A one-stage design required ≥4 responders out of 15 to evaluate an alternative hypothesis of 40% response rate against a null of 10%. Results: Ten evaluable patients enrolled between 5/2019-8/2021. The study closed 12/2021 due to lack of ganitumab drug supply. The median age at enrollment was 25.7 years (range 12.3-40.1; Table). The median duration of therapy was 2.5 months (range = 0.9-10.8). There were no complete or partial responders. Three of 10 patients had stable disease for > 4 cycles and 2 had stable disease at completion of planned therapy or study closure. 6-month PFS was 30±14.5%. Two patients had cycle 1 hematologic DLTs triggering the pre-defined toxicity rule; the palbociclib dose was subsequently reduced to 100 mg daily for 21 days. Among the remaining 8 patients, two had cycle 1 hematologic DLTs at the 100 mg dose. 80% of patients had grade 3/4 AEs; the most commons AEs were neutropenia (n = 8), white blood cell decreased (n = 7), and thrombocytopenia (n = 5). Total IGF-1 testing demonstrated intrapatient elevations in serum levels after a single cycle of therapy. Analysis of serial ctDNA samples is ongoing. Conclusions: Four responders out of 15 were required to reject the null hypothesis of a 10% response rate. With 0/10 responders, we concluded that this combination lacked adequate therapeutic activity for further study. The combination was tolerable at a palbociclib dose of 100 mg, with primarily hematologic toxicity in patients with relapsed EwS. Clinical trial information: NCT04129151. [Table: see text]
Role of anlotinib in the treatment of early advanced osteosarcoma of limbs in children.
Authors: Li Zhifan , Wang Junlan , Wen Zhuoyu , Long Zuoyao , Pan Kaili , Wang Zhen
Published: June 2022

e23509

Background: The prognosis of advanced or early advanced osteosarcoma during neoadjuvant chemotherapy is unfavorable. Many patients can only accept brutal amputation without a new and reliable limb rescue solution. There are no clinical data on the efficacy and safety of anlotinib in the treatment of osteosarcoma in children and adolescents. We investigate the efficacy of anotinib plus first-line chemotherapy (platinum + doxorubicin liposome/ifosfamide) in the treatment of early advanced osteosarcoma in children and adolescents. Methods: Early advanced osteosarcoma in this study was defined as pathologically identified osteosarcoma that progressed within 6 months after radical surgery, with neoadjuvant chemotherapy or adjuvant chemotherapy. 11 cases of limb osteosarcoma with Enneking stage IIB (8 cases in the lower femur and 3 cases in the upper tibia), aged 8-15 years, were selected from February 2018 to December 2021. After 1 cycle of first-line neoadjuvant chemotherapy, patients locally advanced received anlotinib (12mg/d) combined with first-line chemotherapy for 1-2 cycles. The tumor shrinkage rate, limb salvage rate, disease-free survival time (DFS), progression-free survival time (PFS), disease control rate (DCR), and safety were analyzed. Results: 9 patients had locally advanced during neoadjuvant chemotherapy. After 2 cycles of anlotinib combined with first-line chemotherapy, the tumor shrunked and was well demarcated from surrounding tissue. All patients underwent limb salvage surgery Postoperative chemotherapy lasted for 4-6 cycles, with a median DFS of 12 months. 2 patients who developed recurrence or metastasis after radical surgery continued to complete at least 8 cycles of standard first-line chemotherapy combined with anlotinib, PFS showed separately 6 months and 8 months. The tumor shrinkage rate was 54.55% and the DCR was 72.73%. The adverse reactions associated with anlotinib were epistaxis (8 cases, 72.72%) and oral ulcer (1 case, 9.09%), which were controlled immediately after withdrawal. Conclusions: Combination of anlotinib with first-line chemotherapy can shrink the tumor, improve limb salvage rate for children with early advanced osteosarcoma, and delay disease progression for children with recurrence and metastasis after radical surgery. The toxicity of anlotinib combined with first-line chemotherapy were tolerated which is expected to be a new approach for the treatment of early advanced osteosarcoma.
Surgical subtypes and survival in Ewing sarcoma: A National Cancer Database (NCDB) analysis.
Authors: Tupper Connor , Silberstein Peter T. , Eaton Vincent
Published: June 2022

e23511

Background: Ewing sarcoma (EWS) is the one of the most common primary malignancies of bone, more commonly affecting the pediatric population Standard of care for EWS currently involves surgical intervention in combination with chemotherapy, in addition to the potential use of preoperative and/or postoperative radiation on a case by case basis. To date, there is not much in the literature reported regarding different surgical subtypes in these patients. Thus, this study aims to analyze survival outcomes amongst the different surgical subtypes in EWS patients. Methods: Using the NCDB, patients diagnosed with EWS between 2004-2018 were identified using ICD-O-3 histology code 9260. The cohort was analyzed to determine if they received any surgical intervention and, if so, which surgical subtype was used. Univariate analysis was then performed assessing patient length of survival for each surgical subtype. Data was analyzed using SPSS and statistical significance was set at α = 0.05. Results: A total of 2208 patients were included that had survival data and had received surgical intervention. The mean survival time of all patients was 118.1 months. Surgical patients survived an average of 137.2 months while nonsurgical patients survived 96.0 months on average (p < .00001). Analysis of surgical subtypes revealed significantly longer survival in patients who underwent radical excision with limb salvage compared to patients who underwent partial resection (p < .05). Patients who received a partial limb amputation survived significantly longer than patients who received a total limb amputation (p < .01). Patients who underwent local tumor excision or radial excision with limb salvage also survived significantly longer than patients with total limb amputation (p < .05 and p < .01, respectively). Conclusions: This study found that receipt of surgery is associated with longer survival in Ewing sarcoma patients. Further, different surgical interventions may influence survival in Ewing sarcoma as patients receiving radical excision with limb salvage fared better than partial resection and partial limb amputation better than total limb amputation. Future studies would benefit from investigating additional variables that may influence receipt of surgical interventions including patient demographics, socioeconomic status, and surgical center type.[Table: see text]
Clinicopathologic characteristics and patient outcomes of malignant phyllodes tumors: A multi-institution experience.
Authors: Al-Awadhi Aydah , Hussein Mawada , Al Qawasmeh Khaled H , Trad Diaeddine Ahmad , Ansari Jawaher , Anwar Emad , Bennini Nouri , Azribi Fathi
Published: June 2022

e23528

Background: Phyllodes tumors (PT) are rare fibroepithelial neoplasm that start in the connective tissue of the breast. PTs are classified by their histologic features into benign, borderline, and malignant. Malignant PTs account for about 1 in 4 PTs and are most likely to come back after treatment and metastasize. This study was conducted to investigate the incidence, clinical presentation, pathological characteristics, treatment and outcome of malignant PTs in the Abu Dhabi Health Services Company (SEHA) institutions in the United Arab Emirates. This will provide a better insight on factors that influences outcome in these patients. Methods: We retrospectively analyzed data of malignant PT treated at Tawam Hospital, Sheikh Khalifa Medical City and Sheikh Shakbout Medical City between 2000 and 2020. Information was obtained from the SEHA Cancer Registry and analyzed using excel software. Results: A total of 36 patients with malignant PT were identified. All were females. The median age at diagnosis was 38 (17-60). Median BMI at diagnosis was 27 (21-47). Out of the 36 patients, 3 were diagnosed during pregnancy, 16 (44%) had a history of fibroadenoma and 8 had a family history of first degree relative with breast cancer. Initial symptom at presentation was breast mass in 30 patients and fungating breast mass in 6 patients. Out of the 26 patients, 4 (11%) had tumor < 5 cm, 10 (28%) had tumor ≥5 cm and < 10 cm, 22 (61%) had tumor ≥10 cm, 2 patients had heterogenous tumor with component of invasive ductal carcinoma, no patient had metastatic ipsilateral axillary adenopathy at diagnosis and 5 (14%) presented with de-novo metastatic disease (4 in the lung and 1 in the contralateral breast as the first metastatic site). Of the 31 patients with non-metastatic disease at presentation, 17 underwent mastectomy, 14 underwent lumpectomy, 14 had axillary lymph node dissection, 8 had no axillary surgery, 9 had sentinel lymph node biopsy, 16 had adjuvant radiation therapy and 2 had adjuvant chemotherapy. Of the 31 patients, 13 patients developed locoregional recurrence of which 9 had positive margin on initial surgery and 4 had negative closet margin of ≤1 cm, 7 patients developed metastatic disease of which lung and/or the chest are the main sites. Of the total population to date, 7 patients passed away from the disease. Conclusions: Malignant PT patients are a unique population with limited characterization to date. Our study demonstrates the clinical and pathological characteristics and the treatment pattern of these patients. Further analysis is underway to assess risks associated with surgical and survival outcome of this disease.
Comparison of prognostic reliability of TNM staging systems version 7/8 and SARCULATOR in primary localized liposarcomas of the extremity or trunk wall.
Authors: Kosela-Paterczyk Hanna , Teterycz Pawel , Mariuk-Jarema Anna , Wagrodzki Michal , Zdzienicki Marcin , Rutkowski Piotr
Published: June 2022

e23529

Background: The oncological staging system should provide meaningful information regarding the patients’ prognosis. For soft tissue sarcomas, available staging systems include AJCC version 8, AJCC version 7, and nomogram-based approaches such as SARCULATOR (which additionally includes age and subtype). This work compares these systems using a group of extremity/trunk wall cases of liposarcoma (LPS). Methods: We have included all (N = 147) consecutive, newly diagnosed LPS patients treated in our institution between 2010 and 2021. We have excluded atypical lipomatous tumors. Patients’ and tumor characteristics were collected, and AJCC staging and SARCULATOR risk assessment were performed. Appropriate Cox proportional hazard models were fitted. The results were compared using the concordance index, Akaike information criterion (AIC), and partial likelihood ratio (PLR) test for non-nested Cox models. Results: In this group, 81 (55.1%) patients were male; the mean age in the group was 54 years (SD:16). Most tumors (83%) were localized on the lower extremity, with 8.8% on the upper extremity and 8.2% on the trunk. 66% of cases were myxoid LPS, 17.7% - dedifferentiated and 16.3% - pleomorphic. The median tumor size was 12 cm (IQR 9 – 18). Patients’ prognostic groups are summarized in Table. The median follow-up was 43 months (95%CI:38-51). The median overall survival (OS) was not reached. The 5-year survival rate was 68% (95%CI:62-75). The concordance for AJCC version 7, AJCC version 8, and SARCULATOR were respectively 0.625, 0.705, and 0.778. The AIC in the same order were: 311, 301, 274. The PLR test showed that AJCC version 8 fits better than AJCC version 7 (p for superiority = 0.036) while SARCULATOR fits better than AJCC version 8 (p for superiority = 0.028). Conclusions: New staging systems improve in better predicting patients outcome. In rare diseases such as sarcomas, it is crucial to have access to more personalized nomograms such as SARCULATOR.[Table: see text]
A novel pan-RAS inhibitor for malignant peripheral nerve sheath tumors.
Authors: Arshad Tariq
Published: June 2022

e23531

Background: Malignant Peripheral Nerve Sheath Tumors (MPNST) are a rare but deadly form of sarcoma originating from the Schwann cell compartment. They are usually driven by loss of function of the NF1 tumor suppressor. This can happen spontaneously but is also the cause of disease in the inheritable syndrome of Neurofibromatosis. Neurofibromatosis is a member of the family of genetic diseases known as “Rasopathies” and is one of the most common inherited neurological disorders. NF1 serves as an important negative regulator or GAP for the RAS oncoprotein. Loss of function of NF1 thus results in the upregulation of non-mutant RAS activity and this appears to be a driving event in the disease. Therapeutic options remain poor. An obvious approach to effective treatment would be targeted therapy directed at non-mutant Ras proteins. There are currently no approved pan-RAS inhibitors. We have developed a small molecule pan-RAS inhibitor which binds directly to all forms of RAS. It acts to block the ability of RAS and to bind and signal through its effectors. It is active in vitro and in vivo against multiple models of MPNST. Methods: In silico screening of a virtual compound library was performed to identify an initial candidate inhibitor. Iterative rounds of Medicinal Chemistry informed by structural modeling and bioassay in 3D vs 2D growth assays were performed to identify an enhanced activity derivative. Target binding was confirmed by Microscale Thermophoresis and NMR. RAS/RAF complex status was measured by co-immunoprecipitation of the endogenous proteins. Ras signaling was assayed by Western analysis of Phospho-ERK and RAL-GTP pull down assays. In vitro activity was measured using 3D soft agar assays. In vivo activity was measured by ip or po administration against MPNST pdx systems. Results: The current lead, designated RAS-F binds all three main isoforms of RAS at low uM kd and modulates the RAS effector domain in NMR studies. It suppresses RAS signaling pathways in transient assays and suppresses MPNST tumor cell growth in soft agar with IC50s ̃ 250nM. It suppresses MPNST pdx growth. Conclusions: We have developed a pre-clinical pan-RAS inhibitor that is active in vitro and in vivo against MPNST cancer models. The agent also has potential uses against non-tumor manifestations of Neurofibromatosis such as Plexiform and Cutaneous neurofibromas. Funding: NIH 5U01HL127518-03, Kentucky Lung Cancer Research Program CDMRP NF180094 (GJC). Qualigen Therapeutics LLC (GJC, JOT).
Genomic co-genotype classification and clinical prognosis in Ewing sarcoma.
Authors: You Yang , Guo Xi , Zhuang Rongyuan , Li Wei , Zhang Chenlu , Wang Zhiming , Shen Feng , Zhou Qiwen , Song Zhengqing , Zhang Yong , Lu Weiqi , Jiang Zhengzeng , Zhou Xiaoyu , Sun Ying , Zhou Yuhong , Ji Yuan
Published: June 2022

e23532

Background: Ewing sarcoma is a highly aggressive round cell mesenchymal tumor that commonly occurs in children and young adults. It is molecularly characterized by chromosomal translocations, most commonly t (11;22), resulting in the abnormal EWSR1-FLI1 fusion. In addition to EWSR1-FLI1, patients may have other genomic variants that can be used for risk stratification. In the present study, we retrospectively investigated the association between co-variant genes and prognosis in patients with Ewing sarcoma. Methods: From 2019 to 2021, 10 patients with Ewing sarcoma were enrolled in the study, and their standard first-line treatment consisted of five-drug regimen chemotherapy including vincristine, doxorubicin (Adriamycin) and cyclophosphamide, alternating with ifosfamide and etoposide (VAC/IE). We carried out whole-exome sequencing on collected tumor samples and matched leukocyte DNA from these patients. Mutations, indels, gene deletions, and amplifications were identified, and survival analysis was performed. Results: In general, median progression-free survival (PFS) of the 10 confirmed Ewing sarcoma (with EWSR1-FLI1 fusion) patients was 10.5 months. We found that 60%, 30%, and 30% of patients had genetic variants (including mutation and copy number variation) in the three signaling pathways of cell cycle, WNT, and NOTCH, respectively. Their PFS was shorter than patients without these variants (log-rank test, p = 0.0345, 0.0053, and 0.0053, respectively). Median PFS was 7 vs 17 months in cell cycle pathway (the former with variants and the latter without variants), 5 vs 14 months in WNT pathway, and 5 vs 14 months in NOTCH pathway. However, there was no difference in PFS between patients with and without variants in other pathways (including TP53, RTK-RAS, MYC, DDR, PI3K) (log-rank test, p＞0.05). Conclusions: We found that the variants in cell cycle, WNT and NOTCH signaling pathway were associated with poor prognosis of Ewing sarcoma. This study provides important molecular markers for risk stratification in patients with Ewing sarcoma, which may provide insights into later clinical trials.