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Treatment schedule. ADM = Adriamycin 60 mg/m 2 , 24 hours IV; CDP = cisplatin 100 mg/m 2 , 48-to 72-hour continuous infusion IV; IFO = ifosfamide 3 g/m 2 /day 1-to 2-hour infusions, 2 days, dose per cycle 6 g/m²; IV = intravenous; MTX = methotrexate 8 g/m 2 , 4-hour infusion IV.
Source publication
Introduction:
The EUROpean Bone Over 40 Sarcoma Study (EURO-B.O.S.S.) was the first prospective international study for patients 41-65 years old with high-grade bone sarcoma treated with an intensive chemotherapy regimen derived from protocols for younger patients with high-grade skeletal osteosarcoma.
Methods:
Chemotherapy based on doxorubicin,...
Contexts in source publication
Context 1
... outline of the scheme of the suggested chemothera- py regimen is reported in Figure 1. Details are available at http://www.italiansarcomagroup.org/wp-content/uploads/ 2014/04/EUROBOSS-testo-Version-2_1-05Sep2012.pdf. ...
Context 2
... our study, patients with nonmetastatic high-grade os- teosarcoma achieved a 5-year OS of 66%, those with extrem- ity tumors a 5-year OS of 70%, which is similar to reports from studies in younger patients (2-7). Our study confirmed the poor prognosis of patients with pelvic osteosarcoma, as re- ported in other studies (20, 21); whereas those patients with TABLE III -Probability of survival by clinical characteristics in 151 patients with localized disease at diagnosis 63% and 53% of patients, respectively. Blood or PLT transfu- sions were reported for 52% and 31% of patients, respectively. ...
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Citations
... The study found that in adolescent patients with osteosarcoma, the younger the age, the worse the prognosis (7). However, the impact of age on disease characteristics and outcomes has become a focal point of recent research, with studies suggesting that older age may correlate with a higher frequency of adverse histologic response to chemotherapy and inferior survival (11,12). ...
Background
Osteosarcoma is a leading subtype of bone tumor affecting adolescents and adults. Comparative molecular characterization among different age groups, especially in pediatric, adolescents and adults, is scarce.
Methods
We collected samples from 194 osteosarcoma patients, encompassing pediatric, adolescent, and adult cohorts. Genomic analyses were conducted to reveal prevalent mutations and compare molecular features in pediatric, adolescent, and adult patients.
Results
Samples from 194 osteosarcoma patients across pediatric to adult ages were analyzed, revealing key mutations such as TP53, FLCN, NCOR1, and others. Children and adolescents showed more gene amplifications and HRD mutations, while adults had a greater Tumor Mutational Burden (TMB). Mutations in those over 15 were mainly in cell cycle and PI3K/mTOR pathways, while under 15s had more in cell cycle and angiogenesis with higher VEGFA, CCND3, TFEB mutations. CNV patterns varied with age: VEGFA and XPO5 amplifications more in under 25s, and CDKN2A/B deletions in over 25s. Genetic alterations in genes like MCL1 and MYC were associated with poor prognosis, with VEGFA mutations also indicating worse outcomes. 58% of patients had actionable mutations, suggesting opportunities for targeted therapies. Age-specific patterns were observed, with Multi-TKI mutations more common in younger patients and CDK4/6 inhibitor mutations in adults, highlighting the need for personalized treatment approaches in osteosarcoma. In a small group of patients with VEGFR amplification, postoperative treatment with multi-kinase inhibitors resulted in a PR in 3 of 13 cases, especially in patients under 15. A significant case involved a 13-year-old with a notable tumor size reduction achieving PR, even with other genetic alterations present in some patients with PD.
Conclusion
This study delineates the molecular differences among pediatric, adolescent, and adult osteosarcoma patients at the genomic level, emphasizing the necessity for precision diagnostics and treatment strategies, and may offer novel prognostic biomarkers for patients with osteosarcoma. These findings provide a significant scientific foundation for the development of individualized treatment approaches tailored to patients of different age groups.
... Details of the group's recruitment strategies and treatment protocols have been described previously [15][16][17][18]. By necessity, all information regarding the hematological malignancies was collected retrospectively. ...
Simple Summary
Osteosarcoma may arise as a secondary malignant neoplasm following a previous hematologic malignancy. We set out to identify potential risk factors, treatments given, and outcomes. Thirty-three eligible patients were identified in the database of our Cooperative Osteosarcoma Study Group. On average, the osteosarcomas developed close to a decade after the hematologic cancer, when patients were mostly still pediatric. Radiotherapy administered to battle the hematologic cancer seemed to be a major risk factor, and genetic tumor predispositions were identified in a subset of patients. Modern interdisciplinary osteosarcoma treatment, with adaptations for previous therapies, seemed feasible. The prognosis of the affected patients was inferior to patients without preceding cancers, but was far from being universally fatal. Additional malignancies complicated the course in a subset of patients. These results will help us to interpret the findings and to guide treatment in future patients.
Abstract
Purpose: Osteosarcoma may arise as a secondary cancer following leukemias or lymphomas. We intended to increase the knowledge about such rare events. Patients and methods: We searched the Cooperative Osteosarcoma Study Group’s database for individuals who developed their osteosarcoma following a previous hematological malignancy. The presentation and treatment of both malignancies was investigated, and additional neoplasms were noted. Outcomes after osteosarcoma were analyzed and potential prognostic factors were searched for. Results: A total of 33 eligible patients were identified (male: 23, female: 10; median age: 12.9 years at diagnosis of hematological cancer; 20 lymphomas, 13 leukemias). A cancer predisposition syndrome was evident in one patient only. The hematological cancers had been treated by radiotherapy in 28 (1 unknown) and chemotherapy in 26 cases, including bone-marrow transplantation in 9. The secondary bone sarcomas (high-grade central 27, periosteal 2, extra-osseous 2, undifferentiated pleomorphic sarcoma of bone 2) arose after a median lag-time of 9.4 years, when patients were a median of 19.1 years old. Tumors were considered radiation-related in 26 cases (1 unknown). Osteosarcoma-sites were in the extremities (19), trunk (12), or head and neck (2). Metastases at diagnosis affected eight patients. Information on osteosarcoma therapy was available for 31 cases. All of these received chemotherapy. Local therapy involved surgery in 27 patients, with a good response reported for 9/18 eligible patients. Local radiotherapy was given to three patients. The median follow-up was 3.9 (0.3–12.0) years after bone tumor diagnosis. During this period, 21 patients had developed events as defined, and 15 had died, resulting in 5-year event-free and overall survival rates of 40% (standard error: 9%) and 56% (10%), respectively. There were multiple instances of additional neoplasms. Several factors were found to be of prognostic value (p < 0.05) for event-free (osteosarcoma site in the extremities) or overall (achievement of a surgical osteosarcoma-remission, receiving chemotherapy for the hematologic malignancy) survival. Conclusions: We were able to prove radiation therapy for hematological malignancies to be the predominant risk factor for later osteosarcomas. A resulting overrepresentation of axial and a tendency towards additional neoplasms affects prognosis. Still, selected patients may become long-term survivors with appropriate therapies, which is an argument against therapeutic negligence.
... Chemotherapy was administered to 7 patients (44%) both before and after surgery, 4 patients (25%) preoperatively only, 3 patients (19%) postoperatively only, and the 2 patients with primary metastases underwent palliative chemotherapy (13%). Among the 11 patients who underwent chemotherapy before surgery, 1 patient (9%) had <10% vital tumor cells in the histologic evaluation of the surgical specimen after treatment with doxorubicin/dacarbazine, 2 patients (18%) had 10-50% vital tumor cells after treatment within the EURO-B.O.S.S.-protocol (doxorubicin/cisplatin/ifosfamide +/− MTX) [25], and the remaining 4 patients (36%; 3 of whom were treated within the EURO-B.O.S.S.-protocol, and 1 received doxorubicin/ifosfamide) had >50% vital tumor cells according to the response classification by Salzer-Kuntschik [26]. The respective data on histological response were missing for 4 patients (36%). ...
... The 5-year OS rate for their 20 patients with localized disease of leiomyosarcoma of bone was 54.9% (IQR, 29.5-74.5%), which is slightly lower than the reported 5-year OS rate of 66% for localized high-grade skeletal osteosarcoma from the EURO-B.O.S.S.-group [25], and even lower than the reported 5-year OS rate of 80% in our 15 patients receiving different chemotherapeutical regimens. Due to the standardized therapy protocol, their findings might represent a benchmark to compare to future histologydriven therapeutical approaches. ...
Simple Summary
Primary leiomyosarcoma of bone constitutes less than 0.7% of all primary malignant bone tumors. Currently, there is no consensus on whether therapeutic approaches should align with the biological characteristics seen in soft tissue leiomyosarcoma or be tailored to the bone location. The efficacy of perioperative chemotherapy for this rare tumor type remains uncertain. Our study aimed to assess various treatment modalities across multiple centers. Surgical intervention emerged as the most significant prognostic factor for patient survival in our analysis, with tumors situated axially, indicating poorer prognosis. A considerable portion of patients experienced secondary metastases. Additionally, the perioperative chemotherapy regimens administered did not correlate with enhanced survival outcomes. Hence, the efficacy of perioperative chemotherapy in bone leiomyosarcoma warrants further investigation, alongside the identification of appropriate agents for treatment.
Abstract
Primary leiomyosarcoma of bone (LMSoB) is extremely rare, comprising only <0.7% of primary malignant bone tumors, and is therefore considered an ultra-rare tumor entity. There is currently no consensus as to whether therapeutic strategies should be based on the biological characteristics of soft tissue leiomyosarcoma or on primary tumor localization in the bone. The use of perioperative chemotherapy and its effectiveness in this rare tumor entity remains unclear. We aimed to evaluate the impact of different treatment approaches in a multicenter setting with a total of 35 patients included. The 5-year overall survival (OS) was 74%. Patients with localized disease undergoing surgery had a significantly higher 5-year OS compared to patients who did not undergo surgical treatment (82% vs. 0%, p = 0.0015). Axial tumor localization was associated with worse event-free survival (EFS) probability (p < 0.001) and OS (p = 0.0082). A high proportion of our patients developed secondary metastases. Furthermore, the perioperative chemotherapy protocols applied to our patients were not associated with an improved EFS or OS. Therefore, the benefit of perioperative chemotherapy in LMSoB needs to be further investigated, and the choice of agents still needs to be clarified.
... In recent decades, SO has become a major concern, the 5-year OS probability is only 14.6% [22] . Surgery is an important treatment for osteosarcoma. ...
... Zheng et al. [32] determined that tumour grade and histology are independent prognostic indicators for patients with osteosarcoma. Ferrari et al. [22] reported that the 5-year OS of patients with osteosarcoma over the age of 40 and those with synchronous metastasis was 22%. Iwata S. found that 25% of patients with distant metastases, when diagnosed, showed poor surgery due to a lack of confidence [33] . ...
Background
Surgical excision is considered as one of the effective treatments for secondary osteosarcoma (SO). It remain unclear that whether the survival of patients with SO could be associated with their surgical willingness.
Materials and Methods
The statistics of the patients diagnosed with SO between 1975 and 2008 were gathered from the surveillance epidemiology and end results (SEER) database. The patients were divided into three subgroups according to their surgical compliance. We used the multivariable Logistic regression analysis and cox regression method to reveal the influence of surgical compliance on prognosis and the risk factors of surgical compliance as well. Additionally, we formulated a nomogram model to predict the overall survival (OS) of patients. The concordance index (C-index) was used to evaluate the accuracy and practicability of the above prediction model.
Results
63(9.2%) of the 688 patients with SO who were recommended for surgical treatment refused to undergo surgery. Lower surgical compliance can be ascribed to earlier time of diagnosis and refused chemotherapy. The lower OS ([Hazard ratio (HR)] 1.733, [Confidential interval (CI)] 1.205-2.494, P -value ( P )=0.003) of not surgical compliant patients was verified by the multivariate cox regression method, compared with surgical compliant patients. In addition, the discernibility of the nomogram model was proven to be relatively high (C-index=0.748), by which we can calibrate 3 year- and 5 year-OS prediction plots to obtain good concordance to actual situation.
Conclusion
The surgical compliance was proved to be an independent prognostic factor to survival of patients with SO.
... For soft tissue sarcomas, this predominantly encompassed AI (Adriamycin and Ifosfamide) or EIA (Etoposid, Ifosamid and Adriamycin), and occasionally included other regimens, incorporating local hyperthermia for the majority of these cases [6,11]. In bone sarcomas, diverse protocols such as EURAMOS [12] and EURO-B.O.S.S. [13] were applied for osteosarcomas and bone sarcoma patients aged over 40, and EURO-EWING [14] was applied for Ewing sarcomas. Decisions regarding the administration and timing of chemotherapy were carefully tailored and discussed on a regular basis within an interdisciplinary tumor board. ...
Simple Summary
In a cohort of 828 patients undergoing surgery for sarcomas of the extremities, pelvis, and trunk, approximately half of them were advised to receive radiotherapy. Notably, 4.7% declined the recommended treatment regimen, resulting in a decrease of both overall survival and local recurrence-free survival. Similarly, 40% of patients within the same group were advised to undergo chemotherapy; 8.8% of these patients rejected the recommendation, leading to a reduced local recurrence-free survival. Enhancing physician-patient communication and addressing underutilization of recommended therapies in sarcoma patients should be a priority for surgeons and oncologists alike.
Abstract
Background: In soft tissue or bone sarcomas, multimodal therapeutic concepts represent the standard of care. Some patients reject the therapeutic recommendations due to several reasons. The aim of this study was to assess the impact of that rejection on both prognosis and local recurrence. Methods: Between 2012 and 2019, a total of 828 sarcoma patients were surgically treated. Chemotherapy was scheduled as a neoadjuvant, and adjuvant multi-agent therapy was performed following recommendations from an interdisciplinary tumor board. Radiotherapy, if deemed appropriate, was administered either in a neoadjuvant or an adjuvant manner. The recommended type of therapy, patient compliance, and the reasons for refusal were documented. Follow-ups included local recurrences, diagnosis of metastatic disease, and patient mortality. Results: Radiotherapy was recommended in 407 (49%) patients. A total of 40 (10%) individuals did not receive radiation. A reduction in overall survival and local recurrence-free survival was evident in those patients who declined radiotherapy. Chemotherapy was advised for 334 (40%) patients, 250 (75%) of whom did receive all recommended cycles. A total of 25 (7%) individuals did receive a partial course while 59 (18%) did not receive any recommended chemotherapy. Overall survival and local recurrence-free survival were reduced in patients refusing chemotherapy. Overall survival was worst for the group of patients who received no chemotherapy due to medical reasons. Refusing chemotherapy for non-medical reasons was seen in 8.8% of patients, and refusal of radiotherapy for non-medical reasons was seen in 4.7% of patients. Conclusions: Divergence from the advised treatment modalities significantly impacted overall survival and local recurrence-free survival across both treatment modalities. There is an imperative need for enhanced physician-patient communication. Reducing treatment times, as achieved with hypofractionated radiotherapy and with therapy in a high-volume sarcoma center, might also have a positive effect on complying with the treatment recommendations.
... Surgery, chemotherapy, and radiation are the standard treatments for Ewing sarcoma; however, protocols are not well established for older patients [21]. Previous studies have suggested older patients with EWS may exhibit a poorer response to chemotherapy and are more susceptible to treatment-associated toxicities [22]. Furthermore, the role of treatment differences between old and young EWS patients has never been studied before in a large, retrospective study. ...
Background
Ewing sarcoma (EWS) is a malignancy which primarily arises in adolescence and has been studied extensively in this population. Much less is known about the rare patient cohort over the age of 40 at diagnosis. In this study, we describe the survival outcomes and clinical characteristics of this population.
Methods
This retrospective cohort study utilized the National Cancer Database (NCDB) to identify 4600 patients diagnosed between 2004 through 2019. Of these patients, 4058 were under the age of 40 and 542 were over 40. Propensity score 1:1 matching was performed according to sex and race. Univariate and multivariate logistic regression was performed to generate odds ratios (OR) and a Multivariate Cox regression model was used to generate a hazard ratio (HR) for patients over 40. Kaplan–Meier curves were used to estimate survival from diagnosis to death between age groups. Chi-square tests were used to compare demographic and socioeconomic patient characteristics. IBM statistics version 27.0 was used. p < 0.05 was used to indicate statistical significance.
Results
EWS patients older than 40 experienced worse survival outcomes compared to patients under the age of 40. 5-year survival was 44.6% for older patients vs. 61.8% for younger patients (p < 0.05). A multivariate Cox proportional hazards model showed that age was independently associated with inferior survival. (HR 1.96; p < 0.05). EWS patients over the age of 40 were more likely to have tumors originating from the vertebral column (16.1% vs 8.9%; p < 0.05) and cranium (5.3% vs. 2.9%; p < 0.05) and had a higher rate of axial tumors (31.6% vs. 18.5%; p < 0.05) compared to patients under 40. Additionally, patients older than 40 experienced a significantly longer delay between the date of diagnosis and initiation of systemic treatment (36.7 days vs. 24.8 days; p < 0.05) and were less likely to receive adjuvant chemotherapy (93.4% vs. 97.9%; p < 0.05).
Conclusion
An age over 40 is associated with decreased survival for patients with EWS. Due to the rarity of EWS in this cohort, the optimal role of systemic treatment remains unknown and has yet to be clearly elucidated. Consequently, our findings suggest that older patients receive disparities in treatment which may be contributing to decreased survival rates.
... The local recurrence and metastatic rates are high at 45-50% and 62-75%, respectively [6][7][8]. Therapeutic options are often surgery followed by single or combination chemotherapy [5,[9][10][11]. Unfortunately, ESOS often shows chemotherapy resistance compared to classical osteosarcomas of the bone and, therefore, more effective systemic treatment options are urgently needed. Given the rarity of ESOS, it has been challenging to conduct formal randomized trials or prospective cohorts to establish an optimal treatment strategy and there have been limited advancements in the testing of new biological agents. ...
Extraskeletal osteosarcoma (ESOS) is a rare malignant mesenchymal tumor that originates in the soft tissue. ESOS accounts for less than 1% of all soft tissue sarcomas and exhibits an aggressive behavior with a high propensity for local recurrence and distant metastasis. Despite advances in treatment, the prognosis for ESOS remains poor, with a five-year survival rate of less than 50% and 27% for metastatic patients. Ex vivo models derived from patient samples are critical tools for studying rare diseases with poor prognoses, such as ESOS, and identifying potential new treatment strategies. In this work, we established a novel ESOS ex vivo sarco-sphere model from a metastatic lesion to the dermis for research and functional testing purposes. The ex vivo cell model accurately recapitulated the native tumor, as evidenced by histomorphology and molecular profiles. Through a functional screening approach, we were able to identify novel individual anti-cancer drug sensitivities for different drugs such as romidepsin, miverbresib and to multiple kinase inhibitors. Overall, our new ESOS ex vivo cell model represents a valuable tool for investigating disease mechanisms and answering basic and translational research questions.
... The Cooperative Osteosarcoma Study Group (COSS) has been running a comprehensive osteosarcoma registry for more than four decades (11)(12)(13). In addition to patients eligible for prospective trials, the registry has always been open for all other patients with osteosarcoma (14), thereby also enabling analyses of secondary tumors (15). ...
... For osteosarcoma, patients were treated according to one of the various COSS-regimens active at the time of enrolment. These included neoadjuvant and adjuvant multidrug chemotherapy and complete surgery wherever feasible (11)(12)(13). Adjustment for previous Ewing sarcoma treatments was allowed and the COSSstudy center was available for guidance. ...
Background/aim:
Ewing sarcoma can arise in patients after osteosarcoma or vice versa. Our aim was to learn more about which patients develop these secondary tumors, which treatments may be effective, and which patients might survive.
Patients and methods:
The database of the Cooperative Osteosarcoma Study Group (1980-09/2022) was searched for all patients with an osteosarcoma (including undifferentiated pleomorphic sarcoma of the bone) who also suffered from Ewing sarcoma (incl. peripheral neuroectodermal tumor) at any time, previously or thereafter. The identified patients were then analyzed for patient, tumor, and treatment-related variables as well as their disease- and survival-status at the last follow-up.
Results:
A total of 20 eligible patients [17 Ewing sarcoma prior to osteosarcoma, 3 vice versa; 10 males, 10 females; median age at 1st cancer 10.5 (2.4-20.6), at 2nd cancer 20.5 (9.9-42.4) years] were identified. None of the patients developed a 3rd cancer and none had a known tumor-predisposition syndrome. Sixteen/17 secondary osteosarcomas and no secondary Ewing sarcoma developed in sites that had previously been irradiated. Nineteen/20 (95%) patients received primary multi-agent chemotherapy for their 1st and 2nd cancers. Actuarial overall and event-free survival probabilities at five years after the diagnosis of the secondary cancer were 69% and 42%, respectively.
Conclusion:
Secondary osteosarcoma arising after Ewing sarcoma is almost exclusively associated with radiation. This is not the case vice versa. Either way, long-term survival is a realistic possibility with appropriate multidisciplinary treatment; thus, therapeutic negligence is clearly inadequate.
... An analysis of 1702 patients with high-grade osteosarcoma from the Cooperative German-Austrian-Swiss Osteosarcoma Study Group found that older age was not associated with outcomes in a multivariate model, despite univariate analysis suggesting that it was a negative prognostic indicator [7], and age similarly did not impact the survival outcomes in a large series from a single center in Italy [18,19]. One of the only prospective trials on osteosarcoma in patients above the age of 40, EURO-BOSS, suggests that adults over 40 and younger patients may even share similar survival rates with aggressive chemotherapy and surgery [20]. However, the 208 adult patients in this trial had higher rates of significant chemotherapy-related toxicities, including peripheral neuropathy and nephrotoxicity, despite receiving lower doses of methotrexate compared to younger patients [20]. ...
... One of the only prospective trials on osteosarcoma in patients above the age of 40, EURO-BOSS, suggests that adults over 40 and younger patients may even share similar survival rates with aggressive chemotherapy and surgery [20]. However, the 208 adult patients in this trial had higher rates of significant chemotherapy-related toxicities, including peripheral neuropathy and nephrotoxicity, despite receiving lower doses of methotrexate compared to younger patients [20]. To explore why adults have different outcomes than children, we herein examine the etiology of osteosarcoma, discussing the known distinctions between pediatric and adult patients. ...
... Methotrexate similarly presents with an increased risk of kidney injury. Overall renal function declines with older age; therefore, methotrexate dosages are reduced or it is omitted entirely to limit toxic drug accumulation and kidney damage [20,25,26]. Other notable age-related toxicities include cardiotoxicity from doxorubicin treatment, with older patients experiencing significantly increased risks of congestive heart failure and cardiomyopathy [27,28]. ...
Simple Summary
Osteosarcoma is an aggressive cancer of the bone that can present in children or adults. It has historically been thought that adults have worse clinical outcomes than children. However, current treatment strategies for adults are largely extrapolated from pediatric studies since the majority of clinical trials for osteosarcoma treatments are based on younger patient populations. We summarize the current understanding of the molecular etiology of osteosarcoma and how it may differ between age groups, hypothesizing why adult patients have worse outcomes compared to children.
Abstract
Malignant bone tumors are commonly classified as pediatric or adolescent malignancies, and clinical trials for these diseases have generally focused on these populations. Of primary bone cancers, osteosarcoma is among the most common. Osteosarcoma has a bimodal age distribution, with the first peak occurring in patients from 10 to 14 years old, and the second peak occurring in patients older than 65, with about 25% of cases occurring in adults between 20 and 59 years old. Notably, adult osteosarcoma patients have worse outcomes than their pediatric counterparts. It remains unclear whether age itself is a poor prognostic factor, or if inherent differences in tumor biology exist between age groups. Despite these unknowns, current treatment strategies for adults are largely extrapolated from pediatric studies since the majority of clinical trials for osteosarcoma treatments are based on younger patient populations. In light of the different prognoses observed in pediatric and adult osteosarcoma, we summarize the current understanding of the molecular etiology of osteosarcoma and how it may differ between age groups, hypothesizing why adult patients have worse outcomes compared to children.
... The only FDA-approved first-line targeted therapy in STS represents tyrosine kinase inhibitors (TKI) including imatinib for gastrointestinal stroma tumors (GIST) and dermatofibrosarcoma protuberans (DeMatteo et al. 2009). Systemic therapy for BS includes conventional chemotherapeutic agents as part of subtype specific protocols (Ferrari et al. 2018;Brennan et al. 2020;Smeland et al. 2019). Drug resistance is believed to cause treatment failure in over 90% of patients with metastatic cancer, which underlines the need for additional therapy lines and novel therapeutic approaches in patients with BS/STS (Longley and Johnston 2005). ...
Purpose
Due to poor outcomes and limited treatment options, patients with advanced bone and soft tissue sarcomas (BS/STS) may undergo comprehensive molecular profiling of tumor samples to identify possible therapeutic targets. The aim of this study was to determine the impact of routine molecular profiling in the setting of a dedicated precision oncology program in patients with BS/STS in a German large-volume sarcoma center.
Methods
92 BS/STS patients who received comprehensive genomic profiling (CGP) and were subsequently discussed in our molecular tumor board (MTB) between 2016 and 2022 were included. Patient records were retrospectively reviewed, and the clinical impact of NGS-related findings was analyzed.
Results
89.1% of patients had received at least one treatment line before NGS testing. At least one molecular alteration was found in 71 patients (82.6%). The most common alterations were mutations in TP53 (23.3% of patients), followed by PIK3CA and MDM2 mutations (9.3% each). Druggable alterations were identified, and treatment recommended in 32 patients (37.2%). Of those patients with actionable alterations, ten patients (31.2%) received personalized treatment and six patients did benefit from molecular-based therapy in terms of a progression-free survival ratio (PFSr) > 1.3.
Conclusion
Our single-center experience shows an increasing uptake of next-generation sequencing (NGS) and highlights current challenges of implementing precision oncology in the management of patients with BS/STS. A relevant number of patients were diagnosed with clinically actionable alterations. Our results highlight the potential benefit of NGS in patients with rare cancers and currently limited therapeutic options.
