scholarly journals Feasibility of a multiparametric MRI protocol for imaging biomarkers associated with neoadjuvant radiotherapy for soft tissue sarcoma

BJR|Open ◽  
2021 ◽  
pp. 20200061
Author(s):  
Lucy Kershaw ◽  
Laura Forker ◽  
Darren Roberts ◽  
Benjamin Sanderson ◽  
Patrick Shenjere ◽  
...  

Objectives: Soft tissue sarcoma (STS) is a rare malignancy with a 5 year overall survival rate of 55%. Neoadjuvant radiotherapy is commonly used in preparation for surgery, but methods to assess early response are lacking despite pathological response at surgery being predictive of overall survival, local recurrence and distant metastasis. Multiparametric MR imaging (mpMRI) is used to assess response in a variety of tumours but lacks a robust, standardised method. The overall aim of this study was to develop a feasible imaging protocol to identify imaging biomarkers for further investigation. Methods: Fifteen patients with biopsy-confirmed STS suitable for preoperative radiotherapy and radical surgery were imaged throughout treatment. The mpMRI protocol included anatomical, diffusion weighted and dynamic contrast-enhanced imaging, giving estimates of apparent diffusion coefficient (ADC) and the area under the enhancement curve at 60 s (iAUC60). Histological analysis of resected tumours included detection of CD31, Ki67, HIF and calculation of a hypoxia score. Results: There was a significant reduction in T1 at visit 2 and in ADC at visit 3. Significant associations were found between hypoxia and pre-treatment iAUC60, pre-treatment ADC and mid-treatment iAUC60. There was also statistically significant association between mid-treatment ADC and Ki67. Conclusions: This work showed that mpMRI throughout treatment is feasible in patients with STS having neoadjuvant radiotherapy. The relationships between imaging parameters, tissue biomarkers and clinical outcomes warrant further investigation. Advances in knowledge : mpMRI based biomarkers have good correlation with STS tumour biology and are potentially of use for evaluation of radiotherapy response.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 11054-11054
Author(s):  
Mudit Chowdhary ◽  
Akansha Chowdhary ◽  
Neilayan Sen ◽  
Nicholas George Zaorsky ◽  
Kirtesh R. Patel ◽  
...  

11054 Background: Large, high-grade extremity/trunk (ET) non-rhabdomyosarcoma soft-tissue sarcoma (STS) is at high risk for distant recurrence and death. The integration of chemotherapy (C) to standard of care neoadjuvant radiotherapy (RT) remains controversial, even for these patients. This study examines the impact of adding C to neoadjuvant RT on overall survival (OS) in high risk ET-STS. Methods: The National Cancer Data Base (NCDB) was queried for patients ≥18 years with high risk (≥5 cm + high grade) non-rhabdomyosarcoma ET-STS (WHO histology) who received neoadjuvant RT and limb sparing surgery from 2006-2014. Patients were next stratified based upon receipt of C (RT and CRT cohorts). Overall survival (OS) for RT vs CRT cohorts was analyzed using the Kaplan-Meier (KM) method, log-rank test, and Cox proportional hazards models. Propensity score-matched analysis (PSM) was employed to account for potential treatment selection bias between cohorts. Results: A total of 848 (71.1%) and 344 (28.9%) patients received RT and CRT, respectively. Patient cohorts were well-balanced except for the CRT cohort having higher rates of treatment in the West (22.1% vs 10.6%) & Midwest (28.3% vs 22.7%), Charlson-Deyo [CD] score 0 vs ≥1 (85.5% vs 79.4%), younger age (≤50) (45.9% vs 21.7%), synovial sarcoma histology (18.9% vs 3.2%), earlier year of diagnosis (2006-2010) (39.5% vs 32.3%), and positive lymphovascular invasion (2.0 vs 1.51%), (p < 0.05 each). The KM 5-year OS was significantly higher in the CRT vs RT cohort: 69.2% vs 58.1% on univariate (p < 0.0001) and multivariate analysis (Hazard Ratio [HR]: 0.66; 95% Confidence Interval [CI]: 0.52-0.85; p = 0.001) even after adjusting for age, race, income, CD score, histology, tumor size, tumor grade, and primary site (lower extremity; upper extremity; trunk). PSM identified evenly matched cohorts of 300 patients each with respect to age, income, CD score, histology, grade, tumor size, and primary site. The addition of neoadjuvant C remained prognostic for OS on PSM (HR: 0.74 [0.56-0.99], p = 0.042). Conclusions: The addition of C to neoadjuvant RT was associated with improved OS in patients with high risk non-rhabdomyosarcoma ET-STS in the NCDB. These hypothesis generating results support prospective evaluation.


2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e23537-e23537
Author(s):  
Se Jun Park ◽  
Jinsoo Lee ◽  
Kabsoo Shin ◽  
Hyunho Kim ◽  
In-Ho Kim ◽  
...  

e23537 Background: Recent studies suggest that the neutrophil-to-lymphocyte ratio (NLR) may be associated with prognosis in several cancers. However, it has not been widely accepted in a clinical situation. In this study, we investigated the clinical significance of NLR as prognostic marker in patients with soft tissue sarcoma. Methods: Between January 2008 to December 2018, 168 patients with STS who had available blood counts at the time of diagnosis were retrospectively evaluated. Receiver operator characteristic (ROC) curve analysis was used to identify the optimal cut-off value for NLR in predicting overall survival. The association between NLR and overall survival (OS) and disease-free survival (DFS) was analyzed with Kaplan-meier method and multivariate Cox proportional models. Results: A total of 168 patients were analyzed, 116 (69.0%) patients were initially resectable disease. Based on the results of ROC curve analysis, patients were classified into two groups as; high-NLR ( > 1.8) and low-NLR (≤1.8). High-NLR was presented in 107 (63.7%) patients which was significantly associated initial disease status (HR 3.30; 95% CI 1.51-7.20, p= 0.002), but not with age at diagnosis ( p= 0.167). High-NLR was significantly correlated with worse OS (HR 3.14; 95% CI 1.62-6.10, p < 0.001). 3-year DFS was 26.2% for high-NLR group versus 37.3% for low-NLR group. DFS tended to be better in low-NLR group, though not statistically significant (HR 1.65; 95% CI 0.95-2.87, p= 0.078). Conclusions: Pre-treatment NLR is a useful predictive factor for prognosis in patients with soft tissue sarcoma. Further studies are needed to evaluate the association between factors representing of host inflammatory status and cancer prognosis.


Author(s):  
Cecilia Tetta ◽  
Maria Carpenzano ◽  
Areej Tawfiq J Algargoush ◽  
Marwah Algargoosh ◽  
Francesco Londero ◽  
...  

Background: Radio-frequency ablation (RFA) and Stereotactic Body Radiation Therapy (SBRT) are two emerging therapies for lung metastases. Introduction: We performed a literature review to evaluate outcomes and complications of these procedures in patients with lung metastases from soft tissue sarcoma (STS). Method: After selection, seven studies were included for each treatment encompassing a total of 424 patients: 218 in the SBRT group and 206 in the RFA group. Results: The mean age ranged from 47.9 to 64 years in the SBRT group and from 48 to 62.7 years in the RFA group. The most common histologic subtype was, in both groups, leiomyosarcoma. : In the SBRT group, median overall survival ranged from 25.2 to 69 months and median disease-free interval from 8.4 to 45 months. Two out of seven studies reported G3 and one G3 toxicity, respectively. In RFA patients, overall survival ranged from 15 to 50 months. The most frequent complication was pneumothorax. : Local control showed high percentage for both procedures. Conclusion: SBRT is recommended in patients unsuitable to surgery, in synchronous bilateral pulmonary metastases, in case of deep lesions and in patients receiving high-risk systemic therapies. RFA is indicated in case of a long disease-free interval, in oligometastatic disease, when only the lung is involved, in small size lesions far from large vessels. : Further large randomized studies are necessary to establish whether these treatments may also represent a reliable alternative to surgery.


2021 ◽  
Vol 41 (1) ◽  
pp. 527-532
Author(s):  
YASUYOSHI SATO ◽  
KENJI NAKANO ◽  
NAOKI FUKUDA ◽  
XIAOFEI WANG ◽  
TETSUYA URASAKI ◽  
...  

2021 ◽  
Vol 28 (1) ◽  
pp. 813-817
Author(s):  
Arielle Elkrief ◽  
Suzanne Kazandjian ◽  
Thierry Alcindor

Background: Myxofibrosarcoma is a type of soft-tissue sarcoma that is associated with high rates of local recurrence and distant metastases. The first-line treatment for metastatic soft-tissue sarcoma has conventionally been doxorubicin-based. Recent evidence suggests that myxofibrosarcoma may be molecularly similar to undifferentiated pleomorphic sarcoma (UPS), which is particularly sensitive to gemcitabine-based therapy. The goal of this study was to evaluate the activity of gemcitabine-containing regimens for the treatment of metastatic myxofibrosarcoma refractory to doxorubicin. Material and Methods: We retrospectively evaluated seven consecutive cases of metastatic myxofibrosarcoma at our institution treated with gemcitabine-based therapy in the second-line setting, after progression on doxorubicin. Baseline clinical and baseline characteristics were collected. Primary endpoints were objective response rate (ORR), progression-free survival (PFS) and overall survival (OS). Results: After progression on first-line doxorubicin, a partial, or complete radiological response was observed in four of seven patients who received gemcitabine-based chemotherapy. With a median follow-up of 14 months, median progression-free and overall survival were 8.5 months and 11.4 months, respectively. Conclusions: Gemcitabine-based chemotherapy was associated with encouraging response rates in this cohort, similar to those seen in UPS. Both entities could be studied together for novel gemcitabine-based regimens.


2017 ◽  
Vol 123 ◽  
pp. S21
Author(s):  
A. Cortesi ◽  
A. Arcelli ◽  
R. Frakulli ◽  
L. Giaccherini ◽  
S. Bisello ◽  
...  

Oncology ◽  
2020 ◽  
Vol 98 (12) ◽  
pp. 893-896
Author(s):  
Andrea Napolitano ◽  
Alessandro Minelli ◽  
Daniele Santini ◽  
Giuseppe Tonini ◽  
Bruno Vincenzi

<b><i>Background:</i></b> Circulating tumor cells (CTCs) have been identified and shown to have prognostic and predictive roles in several types of carcinoma. More recently, aneuploid CTCs have become subject of a growing interest, as aneuploidy is considered a hallmark of cancer often associated with poor prognosis. Here, we aimed to identify for the first time aneuploid CTCs in soft-tissue sarcoma (STS) patients and show supportive in silico evidence on the prognostic role of aneuploidy in mesenchymal cancers. <b><i>Methods:</i></b> In our pilot study, we collected blood from 4 metastatic STS patients and 4 age- and sex-matched healthy controls. After sample processing, cells were cyto-centrifuged onto glass slides and FISH was performed using 5 probes. The in silico analysis was performed using data from The Cancer Genome Atlas cohort of STS patients, using the validated Aneuploidy Score. We divided the patients in two populations (aneuploidy-high, Ane-Hi, and aneuploidy-low, Ane-Lo) using the median value of the Aneuploidy Score as a cutoff. Kaplan-Meier curves associated with log-rank test were used to compare progression-free and overall survival between groups. GraphPad Prism 8.0 (La Jolla, CA, USA) was used for statistical analyses. <b><i>Results:</i></b> Aneuploid CTCs were identified in all 4 STS patients and in none of the controls, with a median value of 4 (range 3–6) per 7 mL of blood. Ane-Hi patients showed a significantly worse progression-free and overall survival compared to Ane-Lo patients. The same trend was maintained when analyzing the data based on the different histologies. <b><i>Conclusions:</i></b> We identified for the first time aneuploid CTCs in STS patients using fluorescence in situ hybridization in a surface marker-independent way. We also showed that the Aneuploidy Score has a prognostic value both in terms of progression-free survival and overall survival in STS patients using The Cancer Genome Atlas data, regardless of the histology.


2020 ◽  
Vol 879 ◽  
pp. 173121 ◽  
Author(s):  
Jing Zhang ◽  
Maoshan Chen ◽  
Yuanyuan Zhao ◽  
Huihua Xiong ◽  
Tal Sneh ◽  
...  

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