We provide an overview of imaging, histopathology, genetics, and multidisciplinary treatment of giant cell tumor of bone (GCTB), an intermediate, locally aggressive but rarely metastasizing tumor. ...Overexpression of receptor activator of nuclear factor κB ligand (RANKL) by mononuclear neoplastic stromal cells promotes recruitment of numerous reactive multinucleated giant cells. Conventional radiographs show a typical eccentric lytic lesion, mostly located in the meta‐epiphyseal area of long bones. GCTB may also arise in the axial skeleton and very occasionally in the small bones of hands and feet. Magnetic resonance imaging is necessary to evaluate the extent of GCTB within bone and surrounding soft tissues to plan a surgical approach. Curettage with local adjuvants is the preferred treatment. Recurrence rates after curettage with phenol and polymethylmethacrylate (PMMA; 8%–27%) or cryosurgery and PMMA (0%–20%) are comparable. Resection is indicated when joint salvage is not feasible (e.g., intra‐articular fracture with soft tissue component). Denosumab (RANKL inhibitor) blocks and bisphosphonates inhibit GCTB‐derived osteoclast resorption. With bisphosphonates, stabilization of local and metastatic disease has been reported, although level of evidence was low. Denosumab has been studied to a larger extent and seems to be effective in facilitating intralesional surgery after therapy. Denosumab was recently registered for unresectable disease. Moderate‐dose radiotherapy (40–55 Gy) is restricted to rare cases in which surgery would lead to unacceptable morbidity and RANKL inhibitors are contraindicated or unavailable.
The authors provide an overview of imaging, histopathology, genetics, and multidisciplinary treatment of giant cell tumor of bone (GCTB), an intermediate, locally aggressive but rarely metastasizing tumor. This review addresses most relevant issues concerning diagnosis and multidisciplinary treatment of GCTB and future perspectives.
Background
The objective of this study was to report on the long‐term effects of pexidartinib on tenosynovial giant cell tumor (TGCT).
Methods
This was a pooled analysis encompassing 3 ...pexidartinib‐treated TGCT cohorts: 1) a phase 1 extension study (NCT01004861; 1000 mg/d; n = 39), 2) ENLIVEN patients randomized to pexidartinib (1000 mg/d for 2 weeks and then 800 mg/d; n = 61), and 3) ENLIVEN crossover patients (NCT02371369; 800 mg/d; n = 30). Eligible patients were 18 years old or older and had a histologically confirmed TGCT that was unresectable and symptomatic. Efficacy endpoints included the best overall response (complete or partial response) and the duration of response (DOR) by the Response Evaluation Criteria in Solid Tumors (RECIST) and the tumor volume score (TVS). The safety assessment included the frequency of treatment‐emergent adverse events (TEAEs) and hepatic laboratory abnormalities (aminotransferase elevations and mixed/cholestatic hepatotoxicity). The data cutoff was May 31, 2019.
Results
One hundred thirty patients with TGCT received pexidartinib (median treatment duration, 19 months; range, 1 to 76+ months); 54 (42%) remained on treatment at the end of the analysis (26 months after initial data cut of March 2017). The RECIST overall response rate (ORR) was 60%; the TVS ORR was 65%. The median times to response were 3.4 (RECIST) and 2.8 months (TVS), with 48 of the responding patients (62%) achieving a RECIST partial response by 6 months and with 72 (92%) doing so by 18 months. The median DOR was reached for TVS (46.8 months). Reported TEAEs were mostly low‐grade, with hair color changes being most frequent (75%). Most liver abnormalities (92%) were aminotransferase elevations; 4 patients (3%) experienced mixed/cholestatic hepatotoxicity (all within the first 2 months of treatment), which was reversible in all cases (recovery spanned 1‐7 months).
Conclusions
This study demonstrates the prolonged efficacy and tolerability of long‐term pexidartinib treatment for TGCT.
This analysis further illustrates that systemic therapy targeting the CSF1/CSF1R pathway is an effective therapeutic strategy in patients with tenosynovial giant cell tumor. Because of the limited availability of long‐term prospective data for tenosynovial giant cell tumor, these findings are encouraging and demonstrate the overall long‐term benefit of continued treatment with pexidartinib.
Background
Solitary fibrous tumor (SFT) is a rare mesenchymal malignancy. Although surgery is potentially curative, the local relapse risk is high after marginal resections. Given the lack of ...prospective clinical trial data, the objective of the current study was to better define the role of perioperative radiotherapy (RT) in various SFT presentations by location.
Methods
This was retrospective study performed across 7 sarcoma centers. Clinical information was retrieved from all adult patients with extrameningeal, primary, localized SFT who were treated between 1990 and 2018 with surgery alone (S) compared with those who also received perioperative RT (S+RT). Differences in treatment characteristics between subgroups were tested using analysis of variance statistics and propensity score matching. Local control and overall survival rates were calculated from the start of treatment until progression or death from any cause.
Results
Of all 549 patients, 428 (78%) underwent S, and 121 (22%) underwent S+RT. The median follow‐up was 52 months. After correction for mitotic count and surgical margins, S+RT was significantly associated with a lower risk of local progression (hazard ratio, 0.19: P = .029), an observation further confirmed by propensity score matching (P = .012); however, this association did not translate into an overall survival benefit.
Conclusions
The results from this retrospective study investigating perioperative RT in patients with primary extrameningeal SFT suggest that combining RT with surgery in the management of this patient population is significantly associated with a reduced risk of local failures, especially in patients who have less favorable resection margins and in those who have tumors with a high mitotic count.
This retrospective study of perioperative radiotherapy in patients with primary extrameningeal solitary fibrous tumors suggests that combining radiotherapy with surgery in the management of this population significantly reduces the risk of local failures, especially in patients who have less favorable resection margins or tumors with a high mitotic count.
Background
Patients diagnosed with sarcoma are hypothesized to experience a prolonged route to a cancer diagnosis. This route, the total interval, can be divided into a patient interval (the time ...from the appearance of symptoms to physician consultation) and diagnostic interval (time from the first consultation to diagnosis). In the current study, the authors investigated these intervals among survivors of sarcoma and identified factors associated with prolonged intervals.
Methods
A cross‐sectional study was conducted among adult patients with sarcoma 2 to 10 years after diagnosis. Patients completed a questionnaire regarding their total interval, which was linked to clinical data from the Netherlands Cancer Registry. Descriptive statistics were used to describe intervals. Based on Dutch clinical guidelines, a diagnostic interval ≥1 month was considered to be prolonged and an interval ≥3 months was considered as very long. Multivariable regression analyses investigated associations between patient and tumor characteristics and interval length.
Results
A total of 1099 participants were included (response rate, 58%); approximately 60% reported a patient interval ≥1 month and 36% reported a patient interval ≥3 months. Risk factors for a very long patient interval were sarcoma of the skin or pelvis, liposarcoma, or rhabdomyosarcoma. Stage III disease was associated with a shorter patient interval. The diagnostic interval length was ≥1 month in 55% of patients and ≥3 months in 28% of patients. Risk factors for a very long diagnostic interval were female sex, age <70 years, or having a synovial sarcoma or chordoma.
Conclusions
The patient and diagnostic interval lengths were prolonged in a substantial percentage of this sarcoma survivorship population. Factors found to be associated with the length of the patient interval or the diagnostic interval differed. Creating awareness among (especially young) patients to consult a physician and awareness among physicians to consider a sarcoma diagnosis will contribute to optimization of the total interval.
The lengths of the patient interval and diagnostic interval are found to be prolonged in a substantial percentage of the sarcoma survivorship population in the current study. The findings highlight the need for longitudinal research among patients newly diagnosed with sarcoma to develop early diagnosis strategies for these individuals.
Background
Sarcomas account for almost 11% of all cancers in adolescents and young adults (AYAs; 18–39 years). AYAs are increasingly recognized as a distinct oncological age group with its own ...psychosocial challenges and biological characteristics. Social functioning has been shown to be one of the most severely affected domains of health‐related quality of life in AYA cancer survivors. This study aims to identify AYA sarcoma survivors with impaired social functioning (ISF) and determine clinical and psychosocial factors associated with ISF.
Methods
AYAs from the population‐based cross‐sectional sarcoma survivorship study (SURVSARC) were included (n = 176). ISF was determined according to the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 social functioning scale, and age‐ and sex‐matched norm data were used as reference.
Results
The median time since diagnosis was 6.2 years (range, 1.8–11.2). More than one‐quarter (28%) of AYA sarcoma survivors experienced ISF. Older age, higher tumor stage, comorbidities, lower experienced social support, uncertainty in relationships, feeling less attractive, sexual inactivity, unemployment, and financial difficulties were associated with ISF. In a multivariable analysis, unemployment (OR, 3.719; 95% CI, 1.261–10.967) and having to make lifestyle changes because of financial problems caused by one's physical condition or medical treatment (OR, 3.394; 95% CI, 1.118–10.300) were associated with ISF; better experienced social support was associated with non‐ISF (OR, 0.739; 95% CI, 0.570–0.957).
Conclusion
More than one‐quarter of AYA sarcoma survivors experience ISF long after diagnosis. These results emphasize the importance of follow‐up care that is not only disease‐oriented but also focuses on the psychological and social domains.
Plain Language Summary
Sarcomas account for almost 11% of all cancers in adolescents and young adults (AYAs; 18–39 years). The AYA group is increasingly recognized as a distinct oncological age group with its own psychosocial challenges and biological characteristics.
Social functioning has been shown to be severely affected in AYA cancer survivors.
A population‐based questionnaire study to identify AYA sarcoma survivors with impaired social functioning (ISF) and determine factors associated with ISF was conducted. More than one‐quarter of AYA sarcoma survivors experience ISF long after diagnosis. These results emphasize the importance of follow‐up care that is not only disease‐orientated but also focuses on the psychological and social domains.
More than one‐quarter of adolescent sarcoma survivors experience impaired social functioning long after diagnosis. These results emphasize the importance of follow‐up care that is not only disease‐oriented but also focuses on the psychological and social domains.
Changes in health-related quality of life (HRQoL) during the diagnostic and treatment trajectory of high-grade extremity soft-tissue sarcoma (eSTS) has rarely been investigated for adults (18-65 y) ...and the elderly (aged ≥65 y), despite a potential variation in challenges from diverse levels of physical, social, or work-related activities. This study assesses HRQoL from time of diagnosis to one year thereafter among adults and the elderly with eSTS.
HRQoL of participants from the VALUE-PERSARC trial (
= 97) was assessed at diagnosis and 3, 6 and 12 months thereafter, utilizing the PROMIS Global Health (GH), PROMIS Physical Function (PF) and EQ-5D-5L.
Over time, similar patterns were observed in all HRQoL measures, i.e., lower HRQoL scores than the Dutch population at baseline (PROMIS-PF:46.8, PROMIS GH-Mental:47.3, GH-Physical:46.2, EQ-5D-5L:0.76, EQ-VAS:72.6), a decrease at 3 months, followed by an upward trend to reach similar scores as the general population at 12 months (PROMIS-PF:49.9, PROMIS GH-Physical:50.1, EQ-5D-5L:0.84, EQ-VAS:81.5), except for the PROMIS GH-Mental (47.5), where scores remained lower than the general population mean (T = 50). Except for the PROMIS-PF, no age-related differences were observed.
On average, eSTS patients recover well physically from surgery, yet the mental component demonstrates no progression, irrespective of age. These results underscore the importance of comprehensive care addressing both physical and mental health.
Despite curative intents of treatment in localized malignant peripheral nerve sheath tumours (MPNSTs), prognosis remains poor. This study investigated survival and prognostic factors for overall ...survival in non-retroperitoneal and retroperitoneal MPNSTs in the Netherlands.
Data were obtained from the Netherlands Cancer Registry and the Dutch Pathology Database. All primary MPNSTs were collected. Paediatric cases (age ≤18 years) and synchronous metastases were excluded from analyses. Separate Cox proportional hazard models were made for retroperitoneal and non-retroperitoneal MPNSTs.
A total of 629 localized adult MPNSTs (35 retroperitoneal cases, 5.5%) were included for analysis. In surgically resected patients (88.1%), radiotherapy and chemotherapy were administered in 44.2% and 6.7%, respectively. In retroperitoneal cases, significantly less radiotherapy and more chemotherapy were applied. In non-retroperitoneal MPNSTs, older age (60+), presence of NF1, size >5 cm, and deep-seated tumours were independently associated with worse survival. In retroperitoneal MPNSTs, male sex and age of 60+ years were independently associated with worse survival. Survival of R1 and that of R0 resections were similar for any location, whereas R2 resections were associated with worse outcomes. Radiotherapy and chemotherapy administrations were not associated with survival.
In localized MPNSTs, risk stratification for survival can be done using several patient- and tumour-specific characteristics. Resectability is the most important predictor for survival in MPNSTs. No difference is present between R1 and R0 resections in both retroperitoneal and non-retroperitoneal MPNSTs. The added value of radiotherapy and chemotherapy is unclear.
•Resectability is the most prognostic factor for survival in localized MPNSTs.•In MPNSTs, NF1, older age, tumour size, and depth are associated with poorer survival.•Retroperitoneal MPNST is a small subgroup with a worse prognosis.•R0 and R1 resections have similar survival in MPNSTs of any location.•The added value of radiotherapy and chemotherapy is unclear for survival in MPNSTs.
Bone and soft-tissue tumor patients experience long-lasting physical and psychological challenges. It is unknown to what extent Health-Related Quality of Life (HRQoL) is already affected during the ...diagnostic process. This study assesses the HRQoL of bone and soft-tissue tumor patients around time of diagnosis and explores which patient or tumor characteristics are associated with a reduced HRQoL.
All patients with a suspected benign/malignant bone tumor (BT), benign soft-tissue tumor (STT), or malignant soft-tissue sarcoma (STS) visiting the Leiden University Medical Center between 2016 and 2020 were invited to complete the Patient-Reported Outcomes Measurement Information System (PROMIS) 29-item profile questionnaire. Mean scores of all included patients and per diagnosis group were compared to mean scores of the general population using one-sample
-tests.
Overall, patients (
= 637) reported statistically significantly worse HRQoL-scores on anxiety (51.3 ± 9.6), pain (55.3 ± 10.1), physical functioning (46.0 ± 9.7), and social functioning (48.1 ± 10.8) with the difference in pain and physical functioning being clinically relevant (based on a 3-point difference on t-metric). HRQoL-scores differed between diagnosis subgroups, i.e., patients with malignant tumors had higher anxiety levels and experienced more pain, where patients with bone tumors had worse physical functioning.
The HRQoL of patients with suspected bone and soft-tissue tumors is already affected during the diagnostic process.
Background: Sarcoma patients often experience a long time to diagnosis, known as the total interval. This interval can be divided into the patient (time from symptoms to doctor consultation) and ...diagnostic intervals (time from first consultation to diagnosis). In other cancers, a long total interval has been associated with worse outcomes, but its effect on health-related quality of life (HRQoL) has never been investigated among sarcoma patients. This study investigates the association between (1) the actual time to diagnosis and HRQoL; (2) the perceived impact of the diagnostic interval length and HRQoL; (3) the actual length and perceived impact of the length and the HRQoL of sarcoma survivors. Methods: A cross-sectional study was performed among sarcoma patients aged ≥18, diagnosed 2–10 years ago in the Netherlands. The participants completed a questionnaire on HRQoL, the time to diagnosis, the perceived impact of the diagnostic interval on HRQoL, and coping. Results: 1099 participants were included (response rate, 58%). The mean time since diagnosis was 67.4 months. More than half reported a patient (60%) or diagnostic interval (55%) ≥1 month. A third (31%) perceived a negative impact of the diagnostic interval length on HRQoL. Patient or diagnostic interval length was not associated with HRQoL. By contrast, participants perceiving a negative impact (32%) had lower HRQoL scores than those perceiving a positive (11%) or no impact (58%) (p = 0.000). This association remained significant in a multivariable model, in which maladaptive coping strategies and tumour characteristics were also found to be associated with HRQoL. Participants perceiving a negative impact of the length of the diagnostic interval related this to high psychological distress levels, more physical disabilities, and worse prognosis. Conclusion: The perceived impact of the diagnostic interval length was associated with the HRQoL of sarcoma survivors, whereas the actual length was not associated with HRQoL. Maladaptive coping strategies were independently associated with HRQoL. This offers opportunities for early intervention to improve HRQoL.
Introduction: Follow-up (FU) in soft-tissue sarcoma (STS) patients is designed for early detection of disease recurrence. Current guidelines are not evidenced-based and not tailored to patient or ...tumor characteristics, so they remain debated, particularly given concerns about cost, radiation frequency, and over-testing. This study assesses the extent to which STS patients received guideline-concordant FU and to characterize which type of patients received more or fewer visits than advised. Methods: All STS patients surgically treated at the Leiden University Medical Center between 2000–2020 were included. For each patient, along with individual characteristics, all radiological examinations from FU start up to 5 years were included and compared to guidelines. Recurrence was defined as local/regional recurrence or metastasis. Results: A total of 394 patients was included, of whom 250 patients had a high-grade tumor (63.5%). Only 24% of patients received the advised three FU visits in the first year. More FU visits were observed in younger patients and those diagnosed with a high-grade tumor. Among patients with a recurrence, 10% received fewer visits than advised, while 28% of patients without a recurrence received more visits than advised. Conclusions: A minority of STS patients received guideline-concordant FU visits, suggesting that clinicians seem to incorporate recurrence risk in decisions on FU frequency.
PDF
