Clinical benefit of systemic therapies for recurrent ovarian cancer-ESMO-MCBS scores

BACKGROUND: Licensed systemic treatment options for platinum-sensitive recurrent ovarian cancer are platinum-based chemotherapy and maintenance treatment with bevacizumab and poly (ADP-ribose) polymerase inhibitors. For platinum-resistant disease, several non-platinum options are available. We aimed to assess the clinical benefit of these treatments according to the European Society of Medical Oncology (ESMO)-Magnitude of Clinical Benefit Scale (MCBS). MATERIALS AND METHODS: A PubMed search was carried out including all studies evaluating systemic treatment of recurrent epithelial ovarian cancer, from 1990 onwards. Randomised trials with an adequate comparator and design showing a statistically significant benefit of the study arm were independently scored by two blinded observers using the ESMO-MCBS. RESULTS: A total of 1127 papers were identified, out of which 61 reported results of randomised trials of sufficient quality. Nineteen trials showed statistically significant results and the studied treatments were graded according to ESMO-MCBS. Only three treatments showed substantial benefit (score of 4 on a scale of 1-5) according to the ESMO-MCBS: platinum-based chemotherapy with paclitaxel in the platinum-sensitive setting and the addition of bevacizumab to chemotherapy in the platinum-resistant setting. The WEE1 inhibitor adavosertib (not licensed) also scores a 4, based on a recent small phase II study. Assessment of quality-of-life data and toxicity using the ESMO-MCBS showed to be complex, which should be taken into account in using this score for clinical decision making. CONCLUSION: Only a few licensed systemic therapies for recurrent ovarian cancer show substantial clinical benefit based on ESMO-MCBS scores. Trials demonstrating overall survival benefit are sparse

Treatment goals and changes over time in older patients with non-curable cancer

PURPOSE: To investigate the treatment goals of older patients with non-curable cancer, whether those goals changed over time, and if so, what triggered those changes. METHODS: We performed a descriptive and qualitative analysis using the Outcome Prioritization Tool (OPT) to assess patient goals across four conversations with general practitioners (GPs) over 6 months. Text entries from electronic patient records (hospital and general practice) were then analyzed qualitatively for this period. RESULTS: Of the 29 included patients, 10 (34%) rated extending life and 9 (31%) rated maintaining independence as their most important goals. Patients in the last year before death (late phase) prioritized extending life less often (3 patients; 21%) than those in the early phase (7 patients; 47%). Goals changed for 16 patients during follow-up (12 in the late phase). Qualitative analysis revealed three themes that explained the baseline OPT scores (prioritizing a specific goal, rating a goal as unimportant, and treatment choices related to goals). Another three themes related to changes in OPT scores (symptoms, disease course, and life events) and stability of OPT scores (stable situation, disease-unrelated motivation, and stability despite symptoms). CONCLUSION: Patients most often prioritized extending life as the most important goal. However, priorities differed in the late phase of the disease, leading to changed goals. Triggers for change related to both the disease (e.g., symptoms and course) and to other life events. We therefore recommend that goals should be discussed repeatedly, especially near the end of life. TRIAL REGISTRATION: OPTion study: NTR5419

Web-based information and support for patients with a newly diagnosed neuroendocrine tumor:A feasibility study

Purpose: Patients with a neuroendocrine tumor (NET) frequently experience physical and psychosocial complaints. Novel strategies to provide information to optimize supportive care in these patients are of interest. The aim of this study was to examine whether the use of a web-based system consisting of self-screening of problems and care needs, patient education, and self-referral to professional health care is feasible in NET patients and to evaluate their opinion on this. Methods: Newly diagnosed NET patients were randomized between standard care (n = 10) or intervention with additional access to the web-based system (n = 10) during 12 weeks. Patients completed questionnaires regarding received information, distress, quality of life (QoL), and empowerment. The intervention group completed a semi-structured interview to assess patients' opinion on the web-based system. Results: The participation rate was 77% (20/26 invited patients) with no dropouts. The use of the web-based system had a negative effect on patients' perception and satisfaction of received information (range Cohen's d -0.88 to 0.13). Positive effects were found for distress (Cohen's d 0.75), global QoL (subscale European Organization for Research and Treatment of Cancer (EORTC) QLQ-C30, Cohen's d 0.46), resolving problems with social functioning and finding information (subscales EORTC QLQ-GINET 21, Cohen's d 0.69, respectively, 1.04), and feeling informed (subscale empowerment questionnaire, Cohen's d 0.51). The interview indicated that the web-based system was of additional value to standard care. Conclusions: Use of this web-based system is feasible. Contradictory effects on informing and supporting NET patients were found and should be subject of further research

Clinical benefit of controversial first line systemic therapies for advanced stage ovarian cancer - ESMO-MCBS scores

Background . The magnitude of clinical benefit scale (MCBS) was introduced by the European Society of Medical Oncology (ESMO) to quantify the clinical benefit of therapeutic regimens and to prioritise therapies. It distinguishes curative from palliative treatments and ranks their benefit based on overall survival (OS), progression free survival (PFS), quality of life (QoL) and toxicity. Objective of this study on the first line treatment of ovarian cancer was to evaluate the evidence for the current standard of care using the ESMO-MCBSv1.1 with an emphasis on controversial therapeutic options: intraperitoneal chemotherapy, dose-dense paclitaxel and bevacizumab. Methods: Phase III trials, published since 1992, investigating first line systemic treatment of Federation Internationale de Gynecologie et d'Obstetrique (FIGO) stage IIB-IV epithelial ovarian cancer were included. Since most studies included patients with FIGO stage IV disease or incomplete debulking, all treatments were judged to be palliative. Treatments were graded 5 to 1 on the ESMO-MCBSv1.1, where grades 5 and 4 represent a high level of clinical benefit. Results: 55 studies met the inclusion criteria. ESMO-MCBS scores were calculated for eleven studies that showed a statistically significant benefit of the experimental treatment. Intraperitoneal (ip) cisplatin scored a 4 and 3, but two other studies were negative and therefore not scored on the ESMO-MCBS. Dose-dense paclitaxel showed substantial clinical benefit in one study (score 4), but three studies were negative. Addition of bevacizumab also scored a 4 in one study subgroup including high-risk patients but a 2 in another trial with a larger study population. Conclusion: Based on ESMO-MCBS scores, dose-dense paclitaxel and intraperitoneal chemotherapy cannot be recommended as standard treatment. Bevacizumab should be considered only in the high-risk population. The ESMO-MCBSv1.1. helps to summarise reported studies on controversial treatment regimens, and identifies their weaknesses

Fore-arc deformation and underplating at the northern Hikurangi margin, New Zealand

Geophysical investigations of the northern Hikurangi subduction zone northeast of New Zealand, image fore‐arc and surrounding upper lithospheric structures. A seismic velocity (Vp) field is determined from seismic wide‐angle data, and our structural interpretation is supported by multichannel seismic reflection stratigraphy and gravity and magnetic modeling. We found that the subducting Hikurangi Plateau carries about 2 km of sediments above a 2 km mixed layer of volcaniclastics, limestone, and chert. The upper plateau crust is characterized by Vp = 4.9–6.7 km/s overlying the lower crust with Vp > 7.1 km/s. Gravity modeling yields a plateau thickness around 10 km. The reactivated Raukumara fore‐arc basin is >10 km deep, deposited on 5–10 km thick Australian crust. The fore‐arc mantle of Vp > 8 km/s appears unaffected by subduction hydration processes. The East Cape Ridge fore‐arc high is underlain by a 3.5 km deep strongly magnetic (3.3 A/m) high‐velocity zone, interpreted as part of the onshore Matakaoa volcanic allochthon and/or uplifted Raukumara Basin basement of probable oceanic crustal origin. Beneath the trench slope, we interpret low‐seismic‐velocity, high‐attenuation, low‐density fore‐arc material as accreted and recycled, suggesting that underplating and uplift destabilizes East Cape Ridge, triggering two‐sided mass wasting. Mass balance calculations indicate that the proposed accreted and recycled material represents 25–100% of all incoming sediment, and any remainder could be accounted for through erosion of older accreted material into surrounding basins. We suggest that continental mass flux into the mantle at subduction zones may be significantly overestimated because crustal underplating beneath fore‐arc highs have not properly been accounted for

Early response evaluation using F-18-FDG-PET/CT does not influence management of patients with metastatic gastrointestinal stromal tumors (GIST) treated with palliative intent

Aim The aim of this study was to investigate the impact of F-18-FDG-PET/CT on treatment decision making in metastatic gastrointestinal stromal tumor (GIST) patients.Methods This study retrospectively evaluated F-18-FDG-PET/CT scans to monitor response of metastatic GIST patients treated with palliative intent. Data from the Dutch GIST Registry was used. Early scans ( 10 weeks after start of treatment) were scored on the impact in change of treatment.Results Sixty-one PET/CTscans were performed for treatment evaluation in 39 patients with metastatic GIST of which 36 were early scans and 25 were late scans. Early PET/CT scans led to a change in management in 5.6 % of patients and late PET/CT scans led to a change in management in 56 % of patients. Change in management was more often seen after scans with lack of metabolic response (48 % vs. 11 % in scans with metabolic response, p = 0.002). Neither metabolic response nor change in treatment were more often seen in patients with KIT mutations compared to patients with non-KIT mutations (metabolic response 65 % KIT vs. 46 % non-KIT, p = 0.33, and change in management 28 % KIT vs. 21 % nonKIT, p = 0.74).Conclusion(18)F-FDG-PET/CT is not recommended for early response evaluation in an unselected patient population with metastatic GIST, since it does not influence treatment decisions. F-18-FDG- PET/ CT, however, can be useful for late response assessment, especially in case of indeterminate CT results.Imaging- and therapeutic targets in neoplastic and musculoskeletal inflammatory diseas