A Prospective Observational Cohort Study for Newly Diagnosed Osteosarcoma Patients in the UK: ICONIC Study Initial Results.

There has been little change to the standard treatment for osteosarcoma (OS) over the last 25 years and there is an unmet need to identify new biomarkers and novel therapeutic approaches if outcomes are to improve. Furthermore, there is limited evidence on the impact of OS treatment on patient-reported outcomes (PROs). ICONIC (Improving Outcomes through Collaboration in Osteosarcoma; NCT04132895) is a prospective observational cohort study recruiting newly diagnosed OS patients across the United Kingdom (UK) with matched longitudinal collection of clinical, biological, and PRO data. During Stage 1, which assessed the feasibility of recruitment and data collection, 102 patients were recruited at 22 sites with representation from patient groups frequently excluded in OS studies, including patients over 50 years and those with less common primary sites. The feasibility of collecting clinical and biological samples, in addition to PRO data, has been established and there is ongoing analysis of these data as part of Stage 2. ICONIC will provide a unique, prospective cohort of newly diagnosed OS patients representative of the UK patient population, with fully annotated clinical outcomes linked to molecularly characterised biospecimens, allowing for comprehensive analyses to better understand biology and develop new biomarkers and novel therapeutic approaches.

Separation Surgery, Fixation With Carbon-Fiber Implants, and Stereotactic Body Radiotherapy for Oligometastatic Spinal Disease.

The management of spinal metastases focuses on reducing symptoms and protecting the spinal cord, historically involving extracorporeal radiotherapy alone. The use of separation surgery techniques alongside high-dose radiotherapy to treat spinal metastases is a novel concept and has changed the treatment paradigm. Additionally, titanium implants have been increasingly used in cases of metastatic spinal tumours requiring adjuvant stereotactic radiotherapy (SBRT). We present the case of a 48-year-old female patient who was diagnosed with a metastatic deposit of breast cancer within L1 with an Epidural Spinal Cord Compression score greater than 1a. At the time of the diagnosis, her prognosis was estimated to be more than two years. She underwent a posterior instrumented fusion of T11-L3 vertebrae with a carbon-fibre fixation system and separation surgery (debulking of the tumour around the spinal cord). The patient was discharged on the second postoperative day achieving complete resolution of the mechanical back pain. SBRT was performed 12 weeks after the surgery. The patient regained ECOG status of 1 shortly after but sadly passed away due to multiple brain metastases 36 months following posterior fixation. Her spinal disease remained well-controlled throughout the follow-up. Carbon-fibre implants appear to be safe and relatively easy to apply. Their use, due to limited artefacts in both computed tomography and magnetic resonance imaging, makes SBRT much more straightforward and follow-up imaging easier to be interpreted. Our experience demonstrates that, in conjunction with separation surgery, the translucent, low perturbing properties of these implants can improve SBRT intervention and detection of recurrence on follow-up imaging.

Pelvic Ewing sarcoma: Should all patients receive pre-operative radiotherapy, or should it be delivered selectively?

BACKGROUND: Locally recurrent disease following surgical resection of Ewing sarcoma (ES) confers a poor prognosis. Limited evidence is available evaluating non-selective use of pre-operative radiotherapy (RT) for patients with pelvic ES and its effect on local control and survival. PATIENTS AND METHODS: 49 consecutive patients with pelvic ES were identified retrospectively from a prospectively collated database. Patients either received non-selective pre-operative RT and surgery (n = 27), or selective post-operative RT (n = 22) (surgery alone (n = 11) or surgery and post-operative RT (n = 11)). RESULTS: Patients who had non-selective pre-operative radiotherapy appeared to have a higher LRFS, 88.0% compared to 66.5% in the selective RT group (p = 0.096, Kaplan Meier; p = 0.028, Chi-squared). Administration of non-selective, pre-operative RT to all patients with pelvic ES elevates the LFRS to that of the good responder group (≥90% tumour necrosis and margins, p = 0.880). There was no difference in metastasis-free survival, 60.0% and 54.5% (p = 0.728) and overall survival (OS), 57.7% and 63.6% (p = 0.893). The majority of pre-operative RT patients had both good necrosis (≥90%) (p = 0.003) and widely excised tumours, 81.5% vs 59.1% (p = 0.080). Tumour volume ≥250 ml was associated with worse LRFS (p = 0.045) and post-operative complications (p = 0.017). There may be improved LRFS (p = 0.057) with pre-operative proton-beam RT compared to surgery and selective post-operative RT. CONCLUSION: Pre-operative photon or proton-beam RT to all pelvic ES may improve LRFS compared to the selective delivery of post-operative RT. Radiotherapy delivered to all patients results in a greater percentage of highly necrotic tumours at surgical excision, enabling a greater proportion of patients with wide resection margins.

Doxorubicin plus dacarbazine, doxorubicin plus ifosfamide, or doxorubicin alone as a first-line treatment for advanced leiomyosarcoma: A propensity score matching analysis from the European Organization for Research and Treatment of Cancer Soft Tissue and Bone Sarcoma Group.

BACKGROUND: The optimal treatment for advanced leiomyosarcoma is still debated. Given histotype-specific prospective controlled data lacking, this study retrospectively evaluated doxorubicin plus dacarbazine, doxorubicin plus ifosfamide, and doxorubicin alone as first-line treatments for advanced/metastatic leiomyosarcoma treated at European Organization for Research and Treatment of Cancer Soft Tissue and Bone Sarcoma Group (EORTC-STBSG) sites. METHODS: The inclusion criteria were a confirmed histological diagnosis, treatment between January 2010 and December 2015, measurable disease (Response Evaluation Criteria in Solid Tumors 1.1), an Eastern Cooperative Oncology Group performance status ≤2, and an age ≥ 18 years. The endpoints were progression-free survival (PFS), overall survival (OS), and overall response rate (ORR). PFS was analyzed with methods for interval-censored data. Patients were matched according to their propensity scores, which were estimated with a logistic regression model accounting for histology, grade, age, sex, performance status, tumor site, and tumor extent. RESULTS: Three hundred three patients from 18 EORTC-STBSG sites were identified. One hundred seventeen (39%) received doxorubicin plus dacarbazine, 71 (23%) received doxorubicin plus ifosfamide, and 115 (38%) received doxorubicin. In the 2:1:2 propensity score-matched population (205 patients), the estimated median PFS was 9.2 months (95% confidence interval [CI], 5.2-9.7 months), 8.2 months (95% CI, 5.2-10.1 months), and 4.8 months (95% CI, 2.3-6.0 months) with ORRs of 30.9%, 19.5%, and 25.6% for doxorubicin plus dacarbazine, doxorubicin plus ifosfamide, and doxorubicin alone, respectively. PFS was significantly longer with doxorubicin plus dacarbazine versus doxorubicin (hazard ratio [HR], 0.72; 95% CI, 0.52-0.99). Doxorubicin plus dacarbazine was associated with longer OS (median, 36.8 months; 95% CI, 27.9-47.2 months) in comparison with both doxorubicin plus ifosfamide (median, 21.9 months; 95% CI, 16.7-33.4 months; HR, 0.65; 95% CI, 0.40-1.06) and doxorubicin (median, 30.3 months; 95% CI, 21.0-36.3 months; HR, 0.66; 95% CI, 0.43-0.99). Adjusted analyses retained an effect for PFS but not for OS. None of the factors selected for multivariate analysis had a significant interaction with the received treatment for both PFS and OS. CONCLUSIONS: This is the largest retrospective study of first-line treatment for advanced leiomyosarcoma. In the propensity score-matched population, doxorubicin and dacarbazine showed favorable activity in terms of both ORR and PFS and warrants further evaluation in prospective trials.

Radiotherapy for the Palliation of Advanced Sarcomas-The Effectiveness of Radiotherapy in Providing Symptomatic Improvement for Advanced Sarcomas in a Single Centre Cohort.

Background: Sarcomas are rare and heterogeneous tumours with a large proportion of patients requiring palliative intervention. They are regarded as relatively radioresistant and therefore achieving good palliation with radiation may require larger doses than for more common solid tumour types. Limited data is available regarding appropriate palliative radiotherapy dose fractionation. This case series aims to assess the effectiveness of radiotherapy in providing symptomatic improvement for advanced sarcomas. Method: Data was retrospectively collected for patients treated with palliative radiotherapy between July 2010 and April 2019 at one institution. The primary outcome was documented symptomatic improvement following radiotherapy. Secondary outcome was overall survival. Results: One hundred and five patients had a total of 137 sites treated using 25 different dose fractionation schedules. The median patient age was 54 (range 8-90) years. Treated sites included 114 soft tissue and 23 bone sarcomas. Data on symptomatic improvement was available in 56% and 67% of cases respectively. A total of 70% of soft tissue and 55% of bone sarcoma patients reported symptomatic improvement. Symptomatic response rates appeared to increase to a biological effective dose (BED) of 50Grey4 (Gy4) (alpha beta ratio (α/ß) = 4 for tumour) but did not continue to improve with further rises in dose beyond this. Conclusion: Palliative radiotherapy offers symptomatic improvement for sarcoma patients with two-thirds of patients reporting reduction in symptoms. These results are limited by the heterogeneous study population including different sarcoma subtypes each with a probable different radio-sensitivity, treated with different radiotherapy schedules. Further prospective data collection is needed considering sarcoma subtype radio-sensitivity, to determine appropriate palliative dose fractionation schedules.