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.

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.

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.

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.

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.

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.

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.

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.

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).

Health-Related Quality of Life Issues Experienced by Thoracic and Breast Sarcoma Patients: A Rare and Understudied Group.

Thoracic and breast sarcomas constitute a rare subgroup within the sarcoma population. There is limited knowledge about their health-related quality of life (HRQoL) and a valid disease-specific HRQoL instrument is lacking. This qualitative study aimed to investigate the HRQoL issues experienced by a small group of thoracic and breast sarcoma patients. Semi-structured interviews with 19 thoracic and four breast sarcoma patients were conducted and thematically analysed. Physical issues mentioned by both groups were fatigue, sleep disturbances, pain, wound infections, and symptoms related to chemotherapy and radiotherapy. Tightness in the back and restrictions in performing tasks above arm height were specific physical issues for breast sarcoma patients, whereas respiratory problems were only mentioned by thoracic sarcoma patients. Body image issues, changes in mood, fear of recurrence, and living with uncertainty were important mental health issues for both subgroups. Social issues in both groups included challenges in work and relationships, financial difficulties, loss of independence, and limitations in social activities. The identified physical, mental, and social health challenges can significantly impact thoracic and breast sarcoma patients' HRQoL. Results of this qualitative study will guide personalised supportive care for breast and thoracic sarcoma patients and help in determining the best possible HRQoL measurement strategy for sarcoma patients with different primary sarcoma locations.

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.

Does the Lightning Process Training Programme Reduce Chronic Fatigue in Adolescent and Young Adult Cancer Survivors? A Mixed-Methods Pilot Study.

BACKGROUND: We report on a pilot intervention study exploring the efficacy of the Lightning Process® training programme for reducing chronic fatigue and improving health-related quality of life in cancer survivors. METHODS: 13 adolescent and young adult cancer survivors previously treated for sarcoma or Hodgkin lymphoma were enrolled. A mixed-methods approach was applied. This involved the use of five validated patient-reported outcome measure (PROM) questionnaires at baseline and the three- and six-month follow-up points to obtain quantitative data. Semi-structured interviews were conducted after the intervention with emphasis on the participants' experiences and outcomes. A reflexive thematic analysis was applied to the transcripts. RESULTS: A significant reduction (p < 0.001) in the total fatigue score from baseline to the three- and six-month follow-up points was documented. The correlation coefficients between the various PROMs at baseline and the six-month follow-up point indicated considerable overlap between the measures. The qualitative findings of the interviews corresponded well with the PROM findings. Most participants experienced both less fatigue and explicit improvement in their energy level. The aspects of the intervention found to be particularly helpful were the theoretical rationale and the coping techniques mediated. CONCLUSION: These encouraging results here reported should be of interest to the general oncological community, although they require confirmation through a larger and controlled study.

Radon-220 diffusion from 224Ra-labeled calcium carbonate microparticles: Some implications for radiotherapeutic use.

Alpha-particle emitting radionuclides continue to be the subject of medical research because of their high energy and short range of action that facilitate effective cancer therapies. Radium-224 (224Ra) is one such candidate that has been considered for use in combating micrometastatic disease. In our prior studies, a suspension of 224Ra-labeled calcium carbonate (CaCO3) microparticles was designed as a local therapy for disseminated cancers in the peritoneal cavity. The progenies of 224Ra, of which radon-220 (220Rn) is the first, together contribute three of the four alpha particles in the decay chain. The proximity of the progenies to the delivery site at the time of decay of the 224Ra-CaCO3 microparticles can impact its therapeutic efficacy. In this study, we show that the diffusion of 220Rn was reduced in labeled CaCO3 suspensions as compared with cationic 224Ra solutions, both in air and liquid volumes. Furthermore, free-floating lead-212 (212Pb), which is generated from released 220Rn, had the potential to be re-adsorbed onto CaCO3 microparticles. Under conditions mimicking an in vivo environment, more than 70% of the 212Pb was adsorbed onto the CaCO3 at microparticle concentrations above 1 mg/mL. Further, the diffusion of 220Rn seemed to occur whether the microparticles were labeled by the surface adsorption of 224Ra or if the 224Ra was incorporated into the bulk of the microparticles. The therapeutic benefit of differently labeled 224Ra-CaCO3 microparticles after intraperitoneal administration was similar when examined in mice bearing intraperitoneal ovarian cancer xenografts. In conclusion, both the release of 220Rn and re-adsorption of 212Pb are features that have implications for the radiotherapeutic use of 224Ra-labeled CaCO3 microparticles. The release of 220Rn through diffusion may extend the effective range of alpha-particle dose deposition, and the re-adsorption of the longer lived 212Pb onto the CaCO3 microparticles may enhance the retention of this nuclide in the peritoneal cavity.

Dose Reduction of Preoperative Radiotherapy in Myxoid Liposarcoma: A Nonrandomized Controlled Trial.

IMPORTANCE: Currently, preoperative radiotherapy for all soft-tissue sarcomas is identical at a 50-Gy dose level, which can be associated with morbidity, particularly wound complications. The observed clinical radiosensitivity of the myxoid liposarcoma subtype might offer the possibility to reduce morbidity. OBJECTIVE: To assess whether a dose reduction of preoperative radiotherapy for myxoid liposarcoma would result in comparable oncological outcome with less morbidity. DESIGN, SETTING, AND PARTICIPANTS: The Dose Reduction of Preoperative Radiotherapy in Myxoid Liposarcomas (DOREMY) trial is a prospective, single-group, phase 2 nonrandomized controlled trial being conducted in 9 tertiary sarcoma centers in Europe and the US. Participants include adults with nonmetastatic, biopsy-proven and translocation-confirmed myxoid liposarcoma of the extremity or trunk who were enrolled between November 24, 2010, and August 1, 2019. Data analyses, using both per-protocol and intention-to-treat approaches, were conducted from November 24, 2010, to January 31, 2020. INTERVENTIONS: The experimental preoperative radiotherapy regimen consisted of 36 Gy in once-daily 2-Gy fractions, with subsequent definitive surgical resection after an interval of 4 or more weeks. MAIN OUTCOMES AND MEASURES: As a short-term evaluable surrogate for local control, the primary end point was centrally reviewed pathologic treatment response. The experimental regimen was regarded as a success when 70% or more of the resection specimens showed extensive treatment response, defined as 50% or greater of the tumor volume containing treatment effects. Morbidity outcomes consisted of wound complications and late toxic effects. RESULTS: Among the 79 eligible patients, 44 (56%) were men and the median (interquartile range) age was 45 (39-56) years. Two patients did not undergo surgical resection because of intercurrent metastatic disease. Extensive pathological treatment response was observed in 70 of 77 patients (91%; posterior mean, 90.4%; 95% highest probability density interval, 83.8%-96.4%). The local control rate was 100%. The rate of wound complication requiring intervention was 17%, and the rate of grade 2 or higher toxic effects was 14%. CONCLUSIONS AND RELEVANCE: The findings of the DOREMY nonrandomized clinical trial suggest that deintensification of preoperative radiotherapy dose is effective and oncologically safe and is associated with less morbidity than historical controls, although differences in radiotherapy techniques and follow-up should be considered. A 36-Gy dose delivered in once-daily 2-Gy fractions is proposed as a dose-fractionation approach for myxoid liposarcoma, given that phase 3 trials are logistically impossible to execute in rare cancers. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02106312.

Preoperative accelerated radiotherapy combined with chemotherapy in a defined cohort of patients with high risk soft tissue sarcoma: a Scandinavian Sarcoma Group study.

BACKGROUND: We recently reported outcomes from a Scandinavian Sarcoma Group adjuvant study (SSG XX group A) conducted on localized and operable high risk soft tissue sarcoma (STS) of the extremities and trunk wall. SSG XX, group B, comprised of patients in a defined cohort with locally advanced STS considered at high risk for intralesional surgery. These patients received preoperative accelerated radiotherapy, together with neoadjuvant and adjuvant chemotherapy. Herein we report the results of this group B. METHODS: Twenty patients with high-grade, locally advanced and deep STS located in lower extremities (n = 12), upper extremities (5) or trunk wall (3) were included. The median age was 59 years and 14 patients were males. The treatment regimen consisted of 6 cycles of doxorubicin (60 mg/m2) and ifosfamide (6 g/m2), with three cycles given neoadjuvantly, and preoperative radiotherapy (1, 8 Gyx2/daily to 36 Gy) between cycles 2 and 3. After a repeated MRI surgery was then conducted, and the remaining 3 chemotherapy cycles were given postoperatively at 3 weeks intervals. Survival data, local control, toxicity of chemotherapy and postoperative complications are presented. RESULTS: Median follow-up time for metastasis-free survival (MFS) was 2.8 years (range 0.3-10.4). The 5-year MFS was 49.5% (95% confidence interval [CI] 31.7-77.4). The median follow-up time was 5.4 years (range 0.3-10.4) for overall survival (OS). The 5-year OS was 64.0% (95% CI 45.8-89.4). The median tumour size was 13 cm, with undifferentiated pleomorphic sarcoma (n = 10) and synovial sarcoma (n = 6) diagnosed most frequently. All patients completed surgery. Resection margins were R0 in 19 patients and R1 in 1 patient. No patients had evidence of disease progression preoperatively. Three patients experienced a local recurrence, in 2 after lung metastases had already been diagnosed. Eleven patients (55%) had postoperative wound problems (temporary in 8 and persistent in 3). CONCLUSIONS: Preoperative chemotherapy and radiotherapy were associated with temporary wound-healing problems. Survival outcomes, local control and toxicities were deemed satisfactory when considering the locally advanced sarcoma disease status at primary diagnosis. Trial registration This study was registered at ClinicalTrials.gov Identifier NCT00790244 and with European Union Drug Regulating Authorities Clinical Trials No. EUDRACT 2007-001152-39.

Calibration of sodium iodide detectors and reentrant ionization chambers for 212Pb activity in different geometries by HPGe activity determined samples.

Lead-212 is a promising radionuclide for cancer therapy, but no primary 212Pb activity standardization has been published. A need therefore exists for accurate estimation of injected doses of 212Pb activity in equilibrium with progeny, when it comes to preclinical and clinical trials. In this study, 212Pb activity was determined using a high purity germanium (HPGe) detector, which allowed the determination of geometry-specific calibration factors for commercially available reentrant ionization chambers (ICs) and sodium iodide (NaI) detectors.

In situ Generated 212Pb-PSMA Ligand in a 224Ra-Solution for Dual Targeting of Prostate Cancer Sclerotic Stroma and PSMA-positive Cells.

BACKGROUND: New treatments combating bone and extraskeletal metastases are needed for patients with metastatic castration-resistant prostate cancer. The majority of metastases overexpress prostate-specific membrane antigen (PSMA), making it an ideal candidate for targeted radionuclide therapy. OBJECTIVE: The aim of this study was to test a novel liquid 224Ra/212Pb-generator for the rapid preparation of a dual-alpha targeting solution. Here, PSMA-targeting ligands are labelled with 212Pb in the 224Ra-solution in transient equilibrium with daughter nuclides. Thus, natural bone-seeking 224Ra targeting sclerotic bone metastases and 212Pb-chelated PSMA ligands targeting PSMA-expressing tumour cells are obtained. METHODS: Two PSMA-targeting ligands, the p-SCN-Bn-TCMC-PSMA ligand (NG001), specifically developed for chelating 212Pb, and the most clinically used DOTA-based PSMA-617 were labelled with 212Pb. Radiolabelling and targeting potential were investigated in situ, in vitro (PSMA-positive C4-2 human prostate cancer cells) and in vivo (athymic mice bearing C4-2 xenografts). RESULTS: NG001 was rapidly labelled with 212Pb (radiochemical purity >94% at concentrations of ≥15 µg/ml) using the liquid 224Ra/212Pb-generator. The high radiochemical purity and stability of [212Pb]Pb- NG001 were demonstrated over 48 hours in the presence of ascorbic acid and albumin. Similar binding abilities of the 212Pb-labelled ligands were observed in C4-2 cells. The PSMA ligands displayed comparable tumour uptake after 2 hours, but NG001 showed a 3.5-fold lower kidney uptake than PSMA- 617. Radium-224 was not chelated and, hence, showed high uptake in bones. CONCLUSION: A fast method for the labelling of PSMA ligands with 212Pb in the 224Ra/212Pb-solution was developed. Thus, further in vivo studies with dual tumour targeting by alpha-particles are warranted.

Use of a simple form to facilitate communication on long-term consequences of treatment in sarcoma survivors.

BACKGROUND: To report on our experience using a simple optional form to facilitate communication on late effects between the patients and the oncologists during outpatient follow-up and to detail on the spectrum of challenges reported by sarcoma survivors. METHODS: The form was presented for the patients to complete before their consultation and covered topics related to late effects and unmet needs that the patient wished to discuss with the medical personnel. Logistic regression analysis examined how the distribution of the topics varied with age, gender, diagnosis and type of treatment received. RESULTS: The form was manageable in a busy outpatient clinic. Of the 265 patients that received the form, 236 (89%) returned it. Patients in a palliative setting and those with other diagnosis than bone sarcoma (BS) and soft-tissue sarcoma (STS) were excluded for subsequent analyses. The final study-cohort comprised 160 patients, 54 (34%) with BS and 106 (66%) with STS. Among these, 140 (88%) had late-effect topics they wanted to discuss with their oncologist. Fatigue was raised by 39% of the patients, pain by 29% and impaired mobility by 23%. BS patients raised fatigue more often (P < 0.005) than those with STS. Patients who had undergone multimodal treatment with chemotherapy raised fatigue more frequently (P < 0.001) than those who had only undergone surgery, radiotherapy or both. CONCLUSIONS: A simple form on the long-term consequences of sarcoma treatment achieved a high response rate, was feasible to use in an outpatient clinic and facilitated communication on these issues. Fatigue was the most frequent topic raised and it was raised significantly more often in patients who had undergone chemotherapy.

Perspectives on treatment side effects in patients with metastatic gastrointestinal stromal tumour: a qualitative study.

BACKGROUND: This study aims to explore how patients with metastatic gastrointestinal stromal tumour (GIST) experience the adverse effects of treatment, as expressed by the individuals themselves. METHODS: A qualitative, phenomenological and hermeneutic design was applied. Twenty patients with metastatic GIST participated in the study. In-depth and semi-structured interviews were conducted and then analysed by means of an inductive thematic analysis. RESULTS: The majority of participants reported experiencing a changed life after being diagnosed with metastatic GIST and commencing systemic medical treatment. More than half of them described partially debilitating self-reported side effects and complaints that had a detrimental impact on their lives. The life-prolonging tyrosine kinase inhibitor treatment prompted the participants to adapt to 'a new normal'. Several participants also emphasised having an ambivalent relationship with the pill, although most looked upon it as 'a friend' because it kept them alive. Paradoxically, while the participants struggled with the side effects of treatment as well as the consequences of living with a chronic cancer, half of them considered themselves to be healthy and, thus, to not actually be cancer patients. CONCLUSIONS: We observed a gap between the biomedical perspective on disease that health professionals typically adopt and the individual experiences of patients living with metastatic GIST. For those patients who are living in limbo between having metastatic cancer and offered an effective treatment, a holistic view of health on the part of their healthcare providers seems crucial. A vital goal should hence be to improve communication between healthcare professionals and GIST patients so as to secure an individualised follow-up with guidance on coping with, and adapting to, their new normal.Trial registration The study was approved by the data protection officer of the Oslo University Hospital (Approval Number 2016/15358).

Prognostic Impact of Proximal Versus Distal Localization in Extremity Long Bone Osteosarcomas.

BACKGROUND/AIM: This study aimed to identify the prognostic factors and outcomes of osteosarcoma (OS) located in proximal versus distal extremity long bones. PATIENTS AND METHODS: A nationwide cohort comprising all Norwegian high-grade OSs in extremity long bones between 1982 and 2009 was investigated. RESULTS: The univariate analysis results identified no significant differences in survival between patients with OS in proximal long bones (101 cases) as a group in comparison to patients with OS in the distal part of these bones (120 cases). However, proximal femur and primary metastasis were both independent adverse prognostic factors for sarcoma-specific survival in multivariate analyses, while elevated LDH and secondary OS were inferior prognostic factors for event-free survival. Adequate surgery and chemotherapy had a positive impact on survival. CONCLUSION: OS of the proximal femur had an unfavorable outcome in comparison to OS in other anatomical locations in extremity long bones.