Recent advances in the management of gastrointestinal stromal tumors

This report focuses mainly on the major reduction of the risk of relapse of gastrointestinal stromal tumor (GIST) treated with imatinib, as identified in the American College of Surgeons Oncology Group (ACOSOG) Z9001 trial. It also focuses on the many unknowns associated with adjuvant imatinib therapy despite approvals by the US Food and Drug Administration and the European Medicines Agency, and on a new marker for the diagnosis of GIST

Systemic therapies in advanced epithelioid haemangioendothelioma: A retrospective international case series from the World Sarcoma Network and a review of literature

[Background] This observational, retrospective effort across Europe, US, Australia, and Asia aimed to assess the activity of systemic therapies in EHE, an ultra-rare sarcoma, marked by WWTR1-CAMTA1 or YAP1-TFE3 fusions.[Methods] Twenty sarcoma reference centres contributed data. Patients with advanced EHE diagnosed from 2000 onwards and treated with systemic therapies, were selected. Local pathologic review and molecular confirmation were required. Radiological response was retrospectively assessed by local investigators according to RECIST. Progression free survival (PFS) and overall survival (OS) were estimated by Kaplan-Meier method.[Results] Overall, 73 patients were included; 21 had more than one treatment. Thirty-three patients received anthracyclines regimens, achieving 1 (3%) partial response (PR), 25 (76%) stable disease (SD), 7 (21%) progressive disease (PD). The median (m-) PFS and m-OS were 5.5 and 14.3 months respectively. Eleven patients received paclitaxel, achieving 1 (9%) PR, 6 (55%) SD, 4 (36%) PD. The m-PFS and m-OS were 2.9 and 18.6 months, respectively. Twelve patients received pazopanib, achieving 3 (25%) SD, 9 (75%) PD. The m-PFS and m-OS were.2.9 and 8.5 months, respectively. Fifteen patients received INF-α 2b, achieving 1 (7%) PR, 11 (73%) SD, 3 (20%) PD. The m-PFS and m-OS were 8.9 months and 64.3, respectively. Among 27 patients treated with other regimens, 1 PR (ifosfamide) and 9 SD (5 gemcitabine +docetaxel, 2 oral cyclophosphamide, 2 others) were reported.[Conclusion] Systemic therapies available for advanced sarcomas have limited activity in EHE. The identification of new active compounds, especially for rapidly progressive cases, is acutely needed.Peer reviewe

Systemic treatments in MDM2 positive intimal sarcoma: A multicentre experience with anthracycline, gemcitabine, and pazopanib within the World Sarcoma Network

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/152621/1/cncr32508_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/152621/2/cncr32508.pd

Selinexor in Advanced, Metastatic Dedifferentiated Liposarcoma: A Multinational, Randomized, Double-Blind, Placebo-Controlled Trial

PURPOSE Antitumor activity in preclinical models and a phase I study of patients with dedifferentiated liposarcoma (DD-LPS) was observed with selinexor. We evaluated the clinical benefit of selinexor in patients with previously treated DD-LPS whose sarcoma progressed on approved agents. METHODS SEAL was a phase II-III, multicenter, randomized, double-blind, placebo-controlled study. Patients age 12 years or older with advanced DD-LPS who had received two-five lines of therapy were randomly assigned (2:1) to selinexor (60 mg) or placebo twice weekly in 6-week cycles (crossover permitted). The primary end point was progression-free survival (PFS). Patients who received at least one dose of study treatment were included for safety analysis (ClinicalTrials.gov identifier: ). RESULTS Two hundred eighty-five patients were enrolled (selinexor, n = 188; placebo, n = 97). PFS was significantly longer with selinexor versus placebo: hazard ratio (HR) 0.70 (95% CI, 0.52 to 0.95; one-sided P = .011; medians 2.8 v 2.1 months), as was time to next treatment: HR 0.50 (95% CI, 0.37 to 0.66; one-sided P < .0001; medians 5.8 v 3.2 months). With crossover, no difference was observed in overall survival. The most common treatment-emergent adverse events of any grade versus grade 3 or 4 with selinexor were nausea (151 [80.7%] v 11 [5.9]), decreased appetite (113 [60.4%] v 14 [7.5%]), and fatigue (96 [51.3%] v 12 [6.4%]). Four (2.1%) and three (3.1%) patients died in the selinexor and placebo arms, respectively. Exploratory RNA sequencing analysis identified that the absence of CALB1 expression was associated with longer PFS with selinexor compared with placebo (median 6.9 v 2.2 months; HR, 0.19; P = .001). CONCLUSION Patients with advanced, refractory DD-LPS showed improved PFS and time to next treatment with selinexor compared with placebo. Supportive care and dose reductions mitigated side effects of selinexor. Prospective validation of CALB1 expression as a predictive biomarker for selinexor in DD-LPS is warranted. (C) 2022 by American Society of Clinical Oncolog

Determinants of the access to remote specialised services provided by national sarcoma reference centres

BACKGROUND: Spatial inequalities in cancer management have been evidenced by studies reporting lower quality of care or/and lower survival for patients living in remote or socially deprived areas. NETSARC+ is a national reference network implemented to improve the outcome of sarcoma patients in France since 2010, providing remote access to specialized diagnosis and Multidisciplinary Tumour Board (MTB). The IGéAS research program aims to assess the potential of this innovative organization, with remote management of cancers including rare tumours, to go through geographical barriers usually impeding the optimal management of cancer patients. METHODS: Using the nationwide NETSARC+ databases, the individual, clinical and geographical determinants of the access to sarcoma-specialized diagnosis and MTB were analysed. The IGéAS cohort (n = 20,590) includes all patients living in France with first sarcoma diagnosis between 2011 and 2014. Early access was defined as specialised review performed before 30 days of sampling and as first sarcoma MTB discussion performed before the first surgery. RESULTS: Some clinical populations are at highest risk of initial management without access to sarcoma specialized services, such as patients with non-GIST visceral sarcoma for diagnosis [OR 1.96, 95% CI 1.78 to 2.15] and MTB discussion [OR 3.56, 95% CI 3.16 to 4.01]. Social deprivation of the municipality is not associated with early access on NETSARC+ remote services. The quintile of patients furthest away from reference centres have lower chances of early access to specialized diagnosis [OR 1.18, 95% CI 1.06 to 1.31] and MTB discussion [OR 1.24, 95% CI 1.10 to 1.40] but this influence of the distance is slight in comparison with clinical factors and previous studies on the access to cancer-specialized facilities. CONCLUSIONS: In the context of national organization driven by reference network, distance to reference centres slightly alters the early access to sarcoma specialized services and social deprivation has no impact on it. The reference networks' organization, designed to improve the access to specialized services and the quality of cancer management, can be considered as an interesting device to reduce social and spatial inequalities in cancer management. The potential of this organization must be confirmed by further studies, including survival analysis

Spirituality and Cancer: a Qualitative Study

International audienceAims: Patients suffering from cancer are often confronted with an awareness of their own finiteness and with the fact that their life is now ruled by the cancer. This existential upheaval can be accompanied by spiritual “work” which contributes to the adjustment to the disease and to the conditions of the end of life. Spirituality can be defined as a process through which individuals seek for and give meaning to their life, feel connected to the self, to others, at the present moment and in what is sacred. Few studies in France have studied spirituality in the context of cancer. So, the aim of our research was to identify and to study the role of spiritual components in the experience of cancer.Procedure: We carried out 15 semi-directed interviews with patients at the medical oncology and palliative care department at the CHU in Timone (Marseille). A double analysis was performed: 1) a lexicographical analysis and 2) a thematic content analysis of the most typical interviews from the lexicographical analysis.Results: The lexicographical analysis highlighted three lexical classes. Class 1 represented the illness of cancer as a personal transformation (40.5%), Class 2 concerned the biographical disruption experience (13.4%) and Class 3 corresponded to daily life with the illness (46.1%). Moreover, the thematic content analysis revealed different themes testifying to spirituality in the lived experience of cancer, in particular the experience of and the relationship with the sacred, the relationship with transcendence and the role of spirituality in the lived experience of patients who are suffering from cancer.Conclusion: The two analyses of the interviews allowed us to identify the expression of spirituality. Spirituality was expressed as a resource, an “invisible spring,” allowing people to adjust to the extreme experience of the disease of cancer. Both “secular” and “central” dimensions of spirituality: the transcendence and the relationship with the sacred open perspectives for the integration of spirituality into the care of patients suffering from cancer, without threatening the principle of secularism in French hospitals.Contexte : Les malades du cancer sont souvent confrontés à une prise de conscience de leur propre finitude et au fait de composer avec une vie désormais rythmée par le cancer. Ce bouleversement existentiel peut s’accompagner d’un « travail » spirituel qui contribue à l’ajustement à la maladie et aux conditions de la fin de la vie. La spiritualité peut être définie comme un processus par lequel les individus cherchent et donnent du sens à leur vie, se sentent connectés à soi, aux autres, au moment présent et à ce qui est sacré. Très peu d’études en France s’intéressent à la spiritualité dans le contexte du cancer. Ainsi, l’objectif de notre étude était d’identifier et d’étudier le rôle des composantes spirituelles dans le vécu de la maladie cancéreuse.Méthodologie : Nous avons réalisé 15 entretiens semidirectifs auprès de patients du service d’oncologie médicale et de soins palliatifs du CHU de la Timone (Marseille). Une double analyse a été réalisée : 1) une analyse lexicographique et 2) une analyse thématique ciblée sur les entretiens les plus typiques issus de l’analyse lexicographique.Résultats : L’analyse lexicographique a mis en évidence trois classes lexicales. La classe 1 renvoie à l’expérience vécue du cancer ainsi qu’aux transformations et réaménagements internes (40,5 %), la classe 2 est relative à la rupture biographique constitutive du vécu expérientiel du cancer (13,4 %) et la classe 3 correspond à la description du vécu quotidien du cancer (46,1 %). En complément, l’analyse thématique fait apparaître différents thèmes témoignant de la spiritualité dans l’expérience vécue du cancer, notamment l’expérimentation et la relation au sacré, la relation à la transcendance et le rôle de la spiritualité dans le vécu expérientiel des patients.Conclusion : L’analyse des entretiens a permis d’identifier l’expression de composantes spirituelles. Elles s’expriment comme une ressource, un « ressort invisible » afin de permettre l’ajustement à l’expérience extrême de la maladie cancéreuse. Les deux dimensions centrales « laïques » de la spiritualité : la transcendance et la relation au sacré ouvrent des perspectives pour l’intégration de la spiritualité dans la prise en charge des patients atteints de cancer, sans remettre en cause le principe de laïcité des hôpitaux français

“Fortunately I felt pain, or I would have thought I was on my way out”: experiencing pain and negotiating analgesic treatment in the context of cancer

International audienceObjectives: To explore cancer patients' experience of pain and coping strategies as well as beliefs and representations associated with pain, pain management and treatments.Method and participants: A qualitative study based on semi-structured interviews was conducted among 16 patients with cancer. The inductive research strategy adopted derived from the Grounded Theory approach and the data transcribed verbatim were gradually analyzed involving researcher triangulation.Findings: The experience of pain and the coping strategies developed by patients to deal with it are shaped by the experience and representations of cancer associated with death and suffering. Pain acts both as an indication to the patients that they are still alive and as an indicator of the progression of the disease. Cancer also models patients' relationships to analgesic treatments and health care providers, since pain is an area in which patients can take back control of what is happening to them. Patients' expression of reluctance to accept analgesic treatments is also influenced by the significance of opioid treatments in this context, which are perceived as an indication that the end of life is close.Conclusions: The contextualization of pain through the particularities of cancer is critical in order to understand cancer patients' experience of pain.Implications for psychosocial providers: Not only patients' knowledge but also the meaning-making of pain should be incorporated in interventions targeting pain management