Outcome of rare primary malignant bone sarcoma treated with multimodal therapy: Results from the EUROpean Bone Over 40 Sarcoma Study (EURO-B.O.S.S.).

BACKGROUND: Rare primary malignant bone sarcomas (RPMBS) account for 5%-10% of primary high-grade bone tumors and represent a major treatment challenge. The outcome of patients with RPMBS enrolled in the EUROpean Bone Over 40 Sarcoma Study (EURO-B.O.S.S) is presented. METHODS: Inclusion criteria were as follows: age from 41 to 65 years and a diagnosis of high-grade spindle cell, pleomorphic, or vascular RPMBS. The chemotherapy regimen included doxorubicin 60 mg/m2 , ifosfamide 9 g/m2 , and cisplatin 90 mg/m2 ; postoperative methotrexate 8 g/m2 was added in case of a poor histologic response. Version 2.0 of the Common Terminology Criteria for Adverse Events, Kaplan-Meier curves, log-rank tests, and univariate Cox regression models were used. RESULTS: In total, 113 patients were evaluable for analysis. The median patient age was 52 years (range, 40-66 years), and 67 patients were men. Eighty-eight tumors were categorized as undifferentiated pleomorphic sarcomas (UPS), 20 were categorized as leiomyosarcomas, three were categorized as fibrosarcomas, and two were categorized as angiosarcomas. Eighty-three of 113 tumors were located in the extremities. Ninety-five of 113 patients presented with no evidence of metastases. After a median follow-up of 6.8 years (interquartile range [IQR], 3.5-9.8 years), the 5-year overall survival rate for patients with localized disease was 68.4% (IQR, 56.9%-77.5%), and it was 71.7% (IQR, 58.1%-81.6%) for patients with UPS and 54.9% (IQR, 29.5%-74.5%) for patients with leiomyosarcoma. Grade III-IV hematologic toxicity was reported in 81% patients; 23% had grade II-III neurotoxicity, and 37.5% had grade I-II nephrotoxicity. Five-year overall survival was significantly better for patients with localized disease, for patients who obtained surgical complete remission, and when the primary tumor was located in the extremities. CONCLUSIONS: The survival of patients who had RPMBS in the current series was similar to that of age-matched patients who had high-grade osteosarcoma treated according to the same protocol. An osteosarcoma-like chemotherapy may be proposed in patients who have RPMBS.

Psychological and social challenges of patients with locally advanced and metastatic gastrointestinal stromal tumours (GIST) on long-term treatment with tyrosine kinase inhibitors: a qualitative study with patients and medical oncologists.

PURPOSE: Tyrosine kinase inhibitors (TKIs) have revolutionized the treatment of locally advanced and metastatic gastrointestinal stromal tumours (GISTs). Patients are experiencing prolonged survival but often at the expense of their health-related quality of life. It is not only the physical side effects that impact GIST patients' daily lives but also the psychological and social challenges they have to deal with. This qualitative study aimed to explore the psychological and social life challenges of GIST patients with locally advanced and metastatic disease on ≥ 5 years TKI treatment. METHODS: Semi-structured interviews with 15 locally advanced and/or metastatic GIST patients and 10 medical oncologists with experience of delivering care to this specific patient group were conducted. Thematic analysis was used to interpret the data. RESULTS: Psychological challenges expressed by participants concerned fears, scanxiety, negative change in emotion and mood, doubts about their treatment and follow-up, living with uncertainty, lack of understanding from others or healthcare professionals, and constantly being reminded of their illness. Challenges regarding social health included financial difficulties, challenges in relationships, concerns about fertility and parenting, work, and impact on social activities. CONCLUSION: The reported psychological and social challenges can significantly hamper the overall quality of life of GIST patients. Some challenges were clearly underreported and hardly recognized by medical oncologist, as they may tend to focus on the physical side effects and clinical outcomes of treatment. Therefore, it is essential to take the patient's perspective into account in research and clinical practice to ensure optimal care for this patient group.

Real-world evidence on perioperative chemotherapy in localized soft tissue sarcoma of the extremities and trunk wall; a population-based study.

BACKGROUND: Data from the real-world setting on perioperative chemotherapy in high-risk, localized soft tissue sarcoma (STS) is limited. Real-world data (RWD) includes data derived from patients treated outside clinical trials and often captures long-term follow-up not recorded in clinical trials. The aim of this study was to provide population-based, real-world evidence on perioperative chemotherapy in localized STS. MATERIAL AND METHODS: Adult patients with localized STS in the extremities or trunk wall treated at Oslo University Hospital, Oslo, Norway from 1998 to 2017 were included in the study. Data were extracted from a prospectively maintained database, supplemented by retrospective review of medical records. RESULTS: The total study cohort included 806 patients, of whom 154 (19%) received perioperative chemotherapy. A regimen with anthracycline and ifosfamide was given in 141 of 154 cases (92%). During long-term follow-up two patients developed secondary malignancies, cardiac toxicity was registered in 11 patients (7%) and renal toxicity in 12 patients (8%). Seventy-one of 154 patients (46%) were treated outside of clinical trials and constituted the RWD cohort. The median age at surgery was slightly lower and there were more synovial sarcomas and fewer myxofibrosarcomas in the RWD cohort. No difference in chemotherapy dose intensity was observed. The estimated 5-year metastasis-free survival (MFS) in all patients receiving perioperative chemotherapy was 58%. In the RWD cohort 5-year MFS was 53% and in the clinical study cohort 61% (HR 1.24; 95% CI 0.77-2.00). CONCLUSION: Long-term outcome after perioperative chemotherapy was comparable for patients treated in routine clinical practice to those in clinical trials. Secondary malignancy and cardiac toxicity were observed. The risk of serious late side effects should be included in the decision process on perioperative chemotherapy.

Multimodal functional imaging for early response assessment in patients with gastrointestinal stromal tumor treated with tyrosine kinase inhibitors.

BACKGROUND: Several imaging modalities are used in the early work-up of patients with gastrointestinal stromal tumor (GIST) receiving tyrosine kinase inhibitor (TKI) treatment and there is a need to establish whether they provide similar or complimentary information. PURPOSE: To compare 18F-fluorodeoxyglucose positron emission tomography (FDG PET), computed tomography (CT) and magnetic resonance imaging (MRI) as early predictors of three-month outcomes for patients with GIST receiving TKI treatment. MATERIAL AND METHODS: Thirty-five patients with advanced GIST were prospectively included between February 2011 and June 2017. FDG PET, contrast-enhanced CT (CECT), and MRI were performed before and early after onset of TKI treatment (range 8-18 days). Early response was categorized according to mRECIST (CT), the Choi criteria (CECT), and PERCIST (FDG PET/CT). For MRI, volumetry from T2-weighted images and change in apparent diffusion coefficient (ADC) from diffusion-weighted imaging was used. The reference standard for early assessment was the three-month mRECIST evaluation based on CT. At three months, both stable disease (SD) and partial response (PR) were categorized as response. Clinical usefulness was defined as agreement between early and three-month assessment. RESULTS: At the three-month assessment, 91% (32/35) were responders, 37% (13/35) PR, 54% (19/35) SD, and 9% (3/35) had progressive disease (PD). Early assessment correctly predicted three-month response in 93% (27/29) for MRI, 80% (28/35) for PERCIST, 74% (26/35) for Choi, and 23% (8/35) for mRECIST. Six patients had non-FDG-avid tumors. For the FDG-avid tumors, PET/CT correctly predicted three-month response in 97% (28/29). CONCLUSION: MRI was superior to CECT for early assessment of TKI-treatment response in GIST. If the tumor was FDG-avid, PET and MRI were equally good. Changes in functional parameters were superior to changes in longest tumor diameter (mRECIST).

Cancer therapy with isolated limb perfusion. / Kreftbehandling med isolert ekstremitetsperfusjon.

For locally advanced soft tissue sarcomas and metastases from melanoma located in the extremities, mutilating surgery or amputation may be necessary to achieve local control. Isolated limb perfusion with high-dose chemotherapy may represent an alternative to amputation for this patient group.

Ra-224 labeling of calcium carbonate microparticles for internal α-therapy: Preparation, stability, and biodistribution in mice.

Internal therapy with α-emitters should be well suited for micrometastatic disease. Radium-224 emits multiple α-particles through its decay and has a convenient 3.6 days of half-life. Despite its attractive properties, the use of 224 Ra has been limited to bone-seeking applications because it cannot be stably bound to a targeting molecule. Alternative delivery systems for 224 Ra are therefore of considerable interest. In this study, calcium carbonate microparticles are proposed as carriers for 224 Ra, designed for local therapy of disseminated cancers in cavitary regions, such as peritoneal carcinomatosis. Calcium carbonate microparticles were radiolabeled by precipitation of 224 Ra on the particle surface, resulting in high labeling efficiencies for both 224 Ra and daughter 212 Pb and retention of more than 95% of these nuclides for up to 1 week in vitro. The biodistribution after intraperitoneal administration of the 224 Ra-labeled CaCO3 microparticles in immunodeficient mice revealed that the radioactivity mainly remained in the peritoneal cavity. In addition, the systemic distribution of 224 Ra was found to be strongly dependent on the amount of administered microparticles, with a reduced skeletal uptake of 224 Ra with increasing dose. The results altogether suggest that the 224 Ra-labeled CaCO3 microparticles have promising properties for use as a localized internal α-therapy of cavitary cancers.

Multimodal treatment of craniofacial osteosarcoma with high-grade histology. A single-center experience over 35 years.

High-grade craniofacial osteosarcoma (CFOS) is an aggressive malignancy with a poor prognosis. Our goals were to evaluate treatment outcomes in those treated at a single referral institution over 35 years and to compare our results to the available literature. A retrospective analysis of all 42 patients treated between 1980 and 2015 at Oslo University Hospital, Norway, identified in a prospectively collected database, was conducted. Mean follow-up was 79.6 months. Overall survival at 2 and 5 years was 70.5 and 44.7%, respectively. The corresponding disease-specific survival rates were 73.0 and 49.8%. Treatment was surgery only in eight cases. Additional therapy was administered in 34 patients: chemotherapy in nine, radiotherapy in seven, and a combination of these in 18 cases. Stratified analysis by resection margins demonstrated significantly better survival at 2 and 5 years after radical surgical treatment. Neoadjuvant chemotherapy and subsequent adequate surgery resulted in better survival than surgery alone. Half of the patients either had a primary or familial cancer predisposition. This is the largest single-center study conducted on high-grade CFOS to date. Our experience indicates that neoadjuvant chemotherapy with complete surgical resection significantly improved survival, compared to surgery alone.

Time-trends on incidence and survival in a nationwide and unselected cohort of patients with skeletal osteosarcoma.

BACKGROUND: This study describes time-trends on epidemiology, subtypes and histopathological entities of osteosarcoma (OS) in a nationwide and unselected cohort of OS patients in Norway between 1975 and 2009. Few nationwide studies are published, and we still have particularly limited knowledge regarding patients not included in clinical trials comprising about half of the OS population. METHOD: Histologically verified skeletal OS for all subgroups were included, resulting in 473 eligible cases from a total of 702 evaluated patients. To ensure completeness, the present cohort was based on all cases reported to the Norwegian Cancer Registry, complemented with data from all Norwegian hospitals involved in sarcoma management. Survival analyses were performed with overall and sarcoma-specific survival as endpoints. RESULTS: Mean annual age-standard incidence amounted to about 3.8 per million in male and 2.8 per million in female with no clear time-trends. The male to female ratio was 1.4. Peak incidence was observed in the second decade for both genders. Conventional OS comprised 71.2% of all cases, while low grade OS represented 10.4% and telangiectatic OS only 1.3%. The most common primary site of OS was femur and tibia, respectively. The axial to appendicular ratio increased with the age. The overall 10-year survival did increase from about 30% during the late 1970s to around 50% 20 years later, with no subsequent improvement during the last two decades. Axial tumours, age above 40 years and overt metastatic disease at time of diagnosis were all negative prognostic factors. CONCLUSION: No improvement in the overall survival for OS since the 1990s was documented. The survival rates are still poor for elderly people, patients with axial disease and in the primary metastatic setting. The average incidence rate of skeletal OS in Norway was in line with international figures.

Influence of multiple UV exposures on serum cobalamin and vitamin D levels in healthy females.

AIMS: Ultraviolet (UV) radiation is a major source for vitamin D production. Furthermore, UV destroys cobalamins (also called vitamin B12) in solution. However, data from humans are scarce. The aim of the present study was to clarify if UV exposure has any effect on serum cobalamins, as compared to vitamin D levels, in healthy volunteers. METHODS: This single-center, open observational study was conducted in a research institute: 23 non-pregnant, non-lactating, healthy, fair-skinned female subjects had their serum cobalamin and 25-hydroxyvitamin D (25(OH)D, the marker for vitamin D status) levels measured before and after exposure to UV. RESULTS: UV exposure increased serum 25(OH)D levels from 61.6 nmol/L to 88.5 nmol/L (44%; p < 0.001). A statistically insignificant decay in serum cobalamin levels from 300 pmol/L to 260 pmol/L (13%; p = 0.142) was observed in the volunteers after the first UV exposure; however, no additional decline of statistical significance was seen after subsequent exposures. CONCLUSIONS: Multiple exposure to UV radiation give a significant increase in 25(OH)D levels, but has no detrimental effect on cobalamin concentrations.

Effect of radium-223 dichloride on symptomatic skeletal events in patients with castration-resistant prostate cancer and bone metastases: results from a phase 3, double-blind, randomised trial.

BACKGROUND: Bone metastases frequently cause skeletal events in patients with metastatic castration-resistant prostate cancer. Radium-223 dichloride (radium-223) selectively targets bone metastases with high-energy, short-range α-particles. We assessed the effect of radium-223 compared with placebo in patients with castration-resistant prostate cancer and bone metastases. METHODS: In this phase 3, double-blind, randomised ALSYMPCA trial, we enrolled patients who had symptomatic castration-resistant prostate cancer with two or more bone metastases and no known visceral metastases, who were receiving best standard of care, and had previously either received or were unsuitable for docetaxel. Patients were stratified by previous docetaxel use, baseline total alkaline phosphatase level, and current bisphosphonate use, then randomly assigned (2:1) to receive either six intravenous injections of radium-223 (50 kBq/kg) or matching placebo; one injection was given every 4 weeks. Randomisation was done with an interactive voice response system, taking into account trial stratification factors. Participants and investigators were masked to treatment assignment. The primary endpoint was overall survival, which has been reported previously. Here we report on time to first symptomatic skeletal event, defined as the use of external beam radiation to relieve bone pain, or occurrence of a new symptomatic pathological fracture (vertebral or non-verterbal), or occurence of spinal cord compression, or tumour-related orthopeadic surgical intervention. All events were required to be clinically apparent and were not assessed by periodic radiological review. Statistical analyses of symptomatic skeletal events were based on the intention-to-treat population. The study has been completed and is registered with ClinicalTrials.gov, number NCT00699751. FINDINGS: Between June 12, 2008, and Feb 1, 2011, 921 patients were enrolled, of whom 614 (67%) were randomly assigned to receive radium-223 and 307 (33%) placebo. Symptomatic skeletal events occurred in 202 (33%) of 614 patients in the radium-223 group and 116 (38%) of 307 patients in the placebo group. Time to first symptomatic skeletal event was longer with radium-223 than with placebo (median 15·6 months [95% CI 13·5-18·0] vs 9·8 months [7·3-23·7]; hazard ratio [HR]=0·66, 95% CI 0·52-0·83; p=0·00037). The risks of external beam radiation therapy for bone pain (HR 0·67, 95% CI 0·53-0·85) and spinal cord compression (HR=0·52, 95% CI 0·29-0·93) were reduced with radium-233 compared with placebo. Radium-223 treatment did not seem to significantly reduce the risk of symptomatic pathological bone fracture (HR 0·62, 95% CI 0·35-1·09), or the need for tumour-related orthopaedic surgical intervention (HR 0·72, 95% CI 0·28-1·82). INTERPRETATION: Radium-223 should be considered as a treatment option for patients with castration-resistant prostate cancer and symptomatic bone metastases. FUNDING: Algeta and Bayer HealthCare Pharmaceuticals.

Response to preoperative chemotherapy in patients undergoing resection of pulmonary metastasis from soft tissue sarcoma - a predictor of outcome?

UNLABELLED: Approximately 50% of patients with high-grade soft tissue sarcoma (STS) will develop pulmonary metastasis. This is the most frequent cause of death and improving treatment is warranted. Preoperative chemotherapy is used for selected patients, usually those with less favorable prognosis and mainly outside clinical trials. The predicted value of histological and radiological response to preoperative chemotherapy on outcome was the main focus for this investigation. PATIENTS AND METHODS: This retrospective study comprises 93 patients with metachronous lung metastasis from STS who underwent complete metastasectomy alone (n = 41) or metastasectomy following preoperative chemotherapy (n = 52). Clinical data, histological and radiological responses to chemotherapy were recorded and survival analyses performed. RESULTS: The time from initial STS diagnosis to the appearance of metastasis was shorter in the preoperative chemotherapy group than in those treated with surgery alone (p = 0.02). However, no statistical differences in post-metastasis disease-specific survival (DSS) or progression-free survival (PFS) between the groups were demonstrated. Patients in the preoperative chemotherapy group with good (complete) histological response had improved PFS compared with poor responders (p = 0.04). Radiological partial response was an independent, favorable prognostic factor for improved PFS and DSS (p = 0.003). CONCLUSION: Despite having unfavorable disease characteristics, some patients may benefit from preoperative chemotherapy. Both histological and radiological responses to preoperative chemotherapy seem to be prognostic in STS patients undergoing complete pulmonary metastasectomy.

Denosumab induction and Zoledronic acid maintenance therapy for recurrent unresectable giant cell tumour of the distal tibia: A case report with sustained tumour control after drug withdrawal.

A 31-year-old woman was diagnosed with a recurrent and rapidly growing giant cell tumour of distal tibia with skin ulceration after intralesional curettage. The patient started on Denosumab 120 mg subcutaneously, once per month with additional loading doses on Days 8 and 15 attempting to avoid below-knee amputation. Twelve doses of Denosumab were administered in 9 months, resulting in resolution of pain, reduction of tumour size and calcification. Hence, the local surgical treatment was delayed and bisphosphonate maintenance therapy was initiated as skin healing was incomplete. The patient was given Zoledronic acid infusions at a dose of 4 mg. After the third infusion, the skin healed. As tumour remained stable, it was decided to continue maintenance. Overall, six doses of Zoledronic acid at 6 months intervals were administrated over 3 years. At the end of the maintenance, the patient experienced no pain and satisfied with her limb function. Since the lesion remained stable over 3 years after Denosumab discontinuation, it was suggested to stop further medical treatment and proceed to active surveillance. The patient's disease is still stable clinical remission with no serious adverse events 41 months after Denosumab cessation and 10 months after the last bisphosphonate infusion. The present case confirmed the high effectiveness of denosumab as induction therapy in advanced recurrent giant cell tumour. We speculate that following the Denosumab-induced tumour ossification, high Zoledronic acid uptake in lesion may prevent tumour reactivation due to its improved pharmacodynamics with an assumed irreversible anti-tumoral effect on residual mutated cells. This hypothesis requires confirmation in future studies.

Biologic targets identified from dynamic 18FDG-PET and implications for image-guided therapy.

PURPOSE: The outcome of biologic image-guided radiotherapy depends on the definition of the biologic target. The purpose of the current work was to extract hyperperfused and hypermetabolic regions from dynamic positron emission tomography (D-PET) images, to dose escalate either region and to discuss implications of such image guided strategies. METHODS: Eleven patients with soft tissue sarcomas were investigated with D-PET. The images were analyzed using a two-compartment model producing parametric maps of perfusion and metabolic rate. The two image series were segmented and exported to a treatment planning system, and biological target volumes BTVper and BTVmet (perfusion and metabolism, respectively) were generated. Dice's similarity coefficient was used to compare the two biologic targets. Intensity-modulated radiation therapy (IMRT) plans were generated for a dose painting by contours regime, where planning target volume (PTV) was planned to 60 Gy and BTV to 70 Gy. Thus, two separate plans were created for each patient with dose escalation of either BTVper or BTVmet. RESULTS: BTVper was somewhat smaller than BTVmet (209 ± 170 cm(3) against 243 ± 143 cm(3), respectively; population-based mean and s.d.). Dice's coefficient depended on the applied margin, and was 0.72 ± 0.10 for a margin of 10 mm. Boosting BTVper resulted in mean dose of 69 ± 1.0 Gy to this region, while BTVmet received 67 ± 3.2 Gy. Boosting BTVmet gave smaller dose differences between the respective non-boost DVHs (such as D98). CONCLUSIONS: Dose escalation of one of the BTVs results in a partial dose escalation of the other BTV as well. If tumor aggressiveness is equally pronounced in hyperperfused and hypermetabolic regions, this should be taken into account in the treatment planning.

Quantitative dynamic ¹8FDG-PET and tracer kinetic analysis of soft tissue sarcomas.

PURPOSE: To study soft tissue sarcomas using dynamic positron emission tomography (PET) with the glucose analog tracer [(18)F]fluoro-2-deoxy-D-glucose ((18)FDG), to investigate correlations between derived PET image parameters and clinical characteristics, and to discuss implications of dynamic PET acquisition (D-PET). MATERIAL AND METHODS: D-PET images of 11 patients with soft tissue sarcomas were analyzed voxel-by-voxel using a compartment tracer kinetic model providing estimates of transfer rates between the vascular, non-metabolized, and metabolized compartments. Furthermore, standard uptake values (SUVs) in the early (2 min p.i.; SUVE) and late (45 min p.i.; SUVL) phases of the PET acquisition were obtained. The derived transfer rates K1, k2 and k3, along with the metabolic rate of (18)FDG (MRFDG) and the vascular fraction νp, was fused with the computed tomography (CT) images for visual interpretation. Correlations between D-PET imaging parameters and clinical parameters, i.e. tumor size, grade and clinical status, were calculated with a significance level of 0.05. RESULTS: The temporal uptake pattern of (18)FDG in the tumor varied considerably from patient to patient. SUVE peak was higher than SUVL peak for four patients. The images of the rate constants showed a systematic pattern, often with elevated intensity in the tumors compared to surrounding tissue. Significant correlations were found between SUVE/L and some of the rate parameters. CONCLUSIONS: Dynamic (18)FDG-PET may provide additional valuable information on soft tissue sarcomas not obtainable from conventional (18)FDG-PET. The prognostic role of dynamic imaging should be investigated.

Exploring the Patient Perspective of Bone Sarcoma Survivors Who Have Undergone Particle Radiotherapy Abroad.

BACKGROUND/AIM: Sarcoma patients' experiences of their health-related quality of life and late effects following particle therapy are sparse. Such knowledge is essential to optimize treatment compliance and follow-up care related to this rapidly developing, but still centralized treatment modality. PATIENTS AND METHODS: This qualitative study has an explorative design and applies a phenomenological and hermeneutical approach based on semi-structured interviews with 12 bone sarcoma patients who had undergone particle therapy abroad. The data were interpreted using thematic analysis. RESULTS: Several of the participants called for more information about how the treatment would be carried out, its acute side effects and late complications. Most participants had positive experiences from the treatment and their stay abroad, but several struggled with late effects and other challenges. Themes that emerged from the analysis were "importance of being prepared", "treatment and stay abroad", "basically healthy, but with health problems and challenges". CONCLUSION: Oncologists who inform and refer patients to particle therapy abroad must have sufficient experience of this treatment modality, prognoses, acute side effects, and late complications. Findings derived from this study may improve treatment preparation and compliance, enhance understanding of individual patient challenges to reduce stress and worry, and lead to better follow-up care and consequently quality of life of this selected group of bone sarcoma patients.

ALPL-1 is a target for chimeric antigen receptor therapy in osteosarcoma.

Osteosarcoma (OS) remains a dismal malignancy in children and young adults, with poor outcome for metastatic and recurrent disease. Immunotherapies in OS are not as promising as in some other cancer types due to intra-tumor heterogeneity and considerable off-target expression of the potentially targetable proteins. Here we show that chimeric antigen receptor (CAR) T cells could successfully target an isoform of alkaline phosphatase, ALPL-1, which is highly and specifically expressed in primary and metastatic OS. The target recognition element of the second-generation CAR construct is based on two antibodies, previously shown to react against OS. T cells transduced with these CAR constructs mediate efficient and effective cytotoxicity against ALPL-positive cells in in vitro settings and in state-of-the-art in vivo orthotopic models of primary and metastatic OS, without unexpected toxicities against hematopoietic stem cells or healthy tissues. In summary, CAR-T cells targeting ALPL-1 show efficiency and specificity in treating OS in preclinical models, paving the path for clinical translation.

Global gene expression profiling of human osteosarcomas reveals metastasis-associated chemokine pattern.

Global gene expression analysis was performed on a panel of 23 osteosarcoma samples of primary and metastatic origin using the Applied Biosystems Gene Expression Array System. When comparing the primary tumours with the metastases, we found a significantly increased expression of genes involved in immunological processes, for example coding for cytokines and chemokines, in the metastatic samples. In addition, a comparison of the gene expression in primary samples from patients with or without metastases demonstrated that patients who later developed metastases had high expression of the chemokine (C-X-C motif) receptor 4 (CXCR4), similar to the metastatic samples, suggesting that these signal molecules play an important role in promoting metastasis. Increased knowledge of mechanisms and interactions between specified molecular signalling pathways in osteosarcomas could lead to a more rational strategy for development of targeted therapy.

Hope as a Lifeline: Imatinib Discontinuation in Patients With Oligometastatic Gastrointestinal Stromal Tumours.

BACKGROUND/AIM: This study explored how highly selected oligometastatic gastrointestinal stromal tumour (GIST) patients subjectively experienced the discontinuation of imatinib (IM) treatment. PATIENTS AND METHODS: Being an exploratory qualitative study, we applied a phenomenological and hermeneutical approach. We conducted in-depth semi-structured interviews with nine oligometastatic GIST patients who were in long-term clinical remission. The gathered data were interpreted using a thematic analysis. RESULTS: The analysis of the interview data revealed four main themes; getting one's life back, fear of recurrence, hope as a lifeline and the pros/cons of participating in this clinical trial. The participants disclosed that hope of being cancer free and without the side-effects of IM was essential for both participating in this study and enduring the uncertainty of drug discontinuation. CONCLUSION: Use of a qualitative approach in clinical trials can result in a better understanding of patients' perspectives and therefore lead to improved clinical practice.

Particle Therapy in Adult Patients with Pelvic Ewing Sarcoma-Tumor and Treatment Characteristics and Early Clinical Outcomes.

PURPOSE: To report dosimetric characteristics and early clinical outcomes in patients with pelvic Ewing sarcoma undergoing particle therapy. METHODS: Patients ≥ 18 years old with pelvic Ewing sarcoma treated in adjuvant or definitive settings were considered for this retrospective analysis. Proton therapy was carried out with 45-60 Gy (RBE) (1.5-2 Gy (RBE) per fraction) and carbon ion therapy for recurrent disease with 51 Gy (RBE) (3 Gy (RBE) per fraction). Local control (LC), disease control (DC) and overall survival (OS) were calculated using the Kaplan-Meier method. RESULTS: For our sample, 21 patients were available, 18 of whom were treated for primary, 3 for locally recurrent and 16 for inoperable disease. The median CTV and PTV were 1215 cm3 and 1630 cm3. Median Dmean values for the PTV, bladder and rectum and median V40 Gy for the bowel for patients undergoing proton therapy were 56 Gy (RBE), 0.6 Gy (RBE), 9 Gy (RBE) and 15 cm3, respectively. At the end of particle therapy, G 1-2 skin reactions (n = 16/21) and fatigue (n = 9/21) were the main reported symptoms. After a median follow-up of 21 months, the 2-year LC, DC and OS were 76%, 56% and 86%, respectively. CONCLUSIONS: Particle therapy in adult pelvic Ewing sarcoma is feasible and provides excellent dosimetric results. First clinical outcomes are promising; however, further long-term follow-up is needed.