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Background: The Surprise Question ('Would I be surprised if this patient died within 12 months?') identifies patients in the last year of life. It is unclear if 'surprised' means the same for each clinician, and whether their responses are internally consistent. Aim: To determine the consistency with which the Surprise Question is used. Design: A cross-sectional online study of participants located in Belgium, Germany, Italy, The Netherlands, Switzerland and UK. Participants completed 20 hypothetical patient summaries ('vignettes'). Primary outcome measure: continuous estimate of probability of death within 12 months (0% [certain survival]–100% [certain death]). A threshold (probability estimate above which Surprise Question responses were consistently 'no') and an inconsistency range (range of probability estimates where respondents vacillated between responses) were calculated. Univariable and multivariable linear regression explored differences in consistency. Trial registration: NCT03697213. Setting/participants: Registered General Practitioners (GPs). Of the 307 GPs who started the study, 250 completed 15 or more vignettes. Results: Participants had a consistency threshold of 49.8% (SD 22.7) and inconsistency range of 17% (SD 22.4). Italy had a significantly higher threshold than other countries (p = 0.002). There was also a difference in threshold levels depending on age of clinician, for every yearly increase, participants had a higher threshold. There was no difference in inconsistency between countries (p = 0.53). Conclusions: There is variation between clinicians regarding the use of the Surprise Question. Over half of GPs were not internally consistent in their responses to the Surprise Question. Future research with standardised terms and real patients is warranted. [ABSTRACT FROM AUTHOR]

Background: Home palliative care services have played an essential role during the first wave of the SARS-CoV-2 outbreak by providing symptom control, drug procurement, and psychological support for frail patients and their families unable to leave their homes. Aim: To understand how home palliative care professionals were affected by the outbreak, describing changes and challenges in their daily work as well as their reactions to the Covid-19 pandemic in Italy. Design: Qualitative study conducted using telephone semi-structured interviews, with thematic analysis. Setting/participants: Thirty home care professionals working for an Italian non-profit organization which provides home palliative care for cancer patients and their families. Results: Three main themes were identified. The first theme showed both patient-related and practice-related challenges participants faced in their daily work, requiring the implementation of different communication methods and patient and family education on risk prevention. The second theme showed the perception of increased responsibility and being the only landmark for family played a decisive role in participants' positive attitude. The third theme highlighted the participants' perception of the critical role of a home care setting in this emergency situation. Conclusions: The first wave of the Covid-19 pandemic brought many challenges and stressors for home palliative care professionals. On the other side, they reported a satisfaction with their critical role in carrying out their work with patients at risk. [ABSTRACT FROM AUTHOR]

Background: Regorafenib (REG) has now been approved as the standard third-line therapy in metastatic gastrointestinal stromal tumour (GIST) patients at the recommended dose and schedule of 160 mg once daily for the first 3 weeks of each 4-week cycle. However, it has a relevant toxicity profile that mainly occurs within the first cycles of therapy, and dose and schedule adjustments are often required to reduce the frequency or severity of adverse events and to avoid early treatment discontinuation. To date, large amounts of data on the use of REG in metastatic GIST patients in daily clinical practice are not available, and we lack information about how this treatment personalization really affects the quality of life (QoL) of patients. The aim of the present retrospective study is to build a comprehensive picture of all alternative REG strategies adopted in daily clinical practice for use in metastatic GIST patients. Methods: Metastatic GIST patients treated with dose adjustment or alternative schedules of REG at seven reference Italian centres were retrospectively included. Results: For a total of 62 metastatic GIST patients, we confirmed that REG treatment adjustment is common in clinical practice and that it is very heterogeneous, with approximately 20 different strategies being adopted. Independent of which strategy is chosen, treatment personalization has led to a clinical benefit defined as complete or partial resolution of side effects in almost all patients, affecting the duration of REG treatment. Conclusions: The personalization of REG, even if it is heterogeneous, seems to be crucial to maximize the overall treatment duration. [ABSTRACT FROM AUTHOR]

MET and its ligand HGF are involved in many biological processes, both physiological and pathological, making this signaling pathway an attractive therapeutic target in oncology. Downstream signaling effects are transmitted via mitogen-activated protein kinase (MAPK), PI3K (phosphoinositide 3-kinase protein kinase B)/AKT, signal transducer and activator of transcription proteins (STAT), and nuclear factor-κB. The final output of the terminal effector components of these pathways is activation of cytoplasmic and nuclear processes leading to increases in cell proliferation, survival, mobilization and invasive capacity. In addition to its role as an oncogenic driver, increasing evidence implicates MET as a common mechanism of resistance to targeted therapies including EGFR and VEGFR inhibitors. In the present review, we summarize the current knowledge on the role of the HGF-MET signaling pathway in cancer and its therapeutic targeting (HGF activation inhibitors, HGF inhibitors, MET antagonists and selective/nonselective MET kinase inhibitors). Recent advances in understanding the role of this pathway in the resistance to current anticancer strategies used in lung, kidney and pancreatic cancer are discussed. [ABSTRACT FROM AUTHOR]

Gastrointestinal stromal tumors (GISTs) are rare, but represent the most common mesenchymal neoplasms of the gastrointestinal tract. Tumor resection is the treatment of choice for localized disease. Tyrosine kinase inhibitors (imatinib, sunitinib) are the standard therapy for metastatic or unresectable GISTs. GISTs usually metastasize to the liver and peritoneum. Bone metastases are uncommon. We describe three cases of bone metastases in patients with advanced GISTs: two women (82 and 54 years of age), and one man (62 years of age). Bones metastases involved the spine, pelvis and ribs in one patient, multiple vertebral bodies and pelvis in one, and the spine and iliac wings in the third case. The lesions presented a lytic pattern in all cases. Two patients presented with multiple bone metastases at the time of initial diagnosis and one patient after seven years during the follow-up period. This report describes the diagnosis and treatment of the lesions and may help clinicians to manage bones metastases in GIST patients. [ABSTRACT FROM AUTHOR]

Gastrointestinal stromal tumors (GISTs) are known to be poorly responsive to conventional chemotherapy and historically considered resistant to radiotherapy. In the past the mainstay of GIST treatment was surgery, but the introduction of tyrosine kinase inhibitors (TKIs) imatinib and sunitinib marked the beginning of a new era in the treatment of GIST patients. To date, radiotherapy for GIST has not been administered in clinical practice except for limited palliative settings and there are no clear data on the administration of radiotherapy, alone or in combination with TKIs, with a purely cytoreductive intent. We describe the clinical case of a 48-year-old woman with metastatic GIST treated with external radiotherapy in a critical supraclavicular tumor localization progressively increasing in size with several symptoms and not responsive to systemic TKI therapies. We obtained an initial shrinkage of the mass and subsequent stabilization with an immediate and clear clinical benefit. Although the historical medical literature considered GISTs resistant to radiation therapy, our clinical case suggests this treatment may be appropriate in selected patients. [ABSTRACT FROM AUTHOR]