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Aims This review aims to synthesize the existing literature on palliative radiotherapy (RT) delivered in two daily fractions for patients with advanced cancer, focusing on its impact on symptom alleviation, treatment tolerance, and the implications for clinical practice and future research. Methods An international team conducted this narrative review, adhering to SANRA guidelines. Studies published in English on palliative RT delivered in two daily fractions were selected without date restrictions. The literature search, using a combination of specific key terms, led to a comprehensive examination of relevant studies. Data on study objectives, treatment approaches, palliative effectiveness, and toxicity were extracted and qualitatively analyzed. Results The review included 29 publications, showing consistent efficacy in symptom reduction (63.0%–100% palliative response rate) and general tolerability across various cancer types. These studies highlighted the potential radiobiological advantages and practicality of accelerated multi-fractionated regimens, which provide rapid tumor response with reduced late toxicity risks. Furthermore, the logistical benefits of such treatments, including shorter hospital stays and minimized travel requirements, were noted as particularly valuable during challenging times such as recent pandemics. Conclusions The evidence supports the integration of evidence-based, accelerated-hypofractionated RT into palliative care strategies, ensuring effective symptom management with minimal patient burden. Future research should focus on comparative studies on single versus multiple-cycle treatments, optimal intervals between treatment cycles, and the integration of advanced RT techniques.

Objective: The SHARON (Short course RadiatiON therapy for palliative treatment) Bone trial is a phase III randomized non-inferiority multicentric study comparing symptom relief for complicated bone metastases (BMs) achieved through hypofractionated accelerated palliative radiotherapy (RT) to a standard RT regimen. Methods: Eligible participants were adults with ECOG PS ≤ 3 who were referred for palliative RT for painful BMs. Patients were assigned to receive either 30 Gy delivered in 10 daily fractions or 20 Gy in 4 fractions over two consecutive days. The primary outcome was pain relief one month post-treatment. Pain relief and adverse events were also evaluated at 2, 3, 6, and 12 months after RT. This trial was registered at clinicaltrials.gov (NCT03503682). Results: Between February 2018 and November 2021, 83 patients were enrolled (30 Gy: 41; 20 Gy: 42). In the standard RT group, five patients did not complete the prescribed RT, while none in the experimental arm discontinued treatment (p = 0.026). Due to early mortality, the primary endpoint was evaluable in 73 patients (35 and 38 in the standard and experimental arms, respectively). The rate of complete pain response at one month was 22.9% and 28.9% in the 30 Gy and 20 Gy arms, respectively (p: 0.571). The overall pain response rates, which included complete and partial responses, were 74.3% and 78.9% in the 30 Gy and 20 Gy arms, respectively (p = 0.638), when considering at least a 2-point reduction in the numerical rating scale. In both arms, 4.8% of patients experienced Grade >2 toxicity. Conclusions: Administering 20 Gy in four fractions twice a day is non-inferior to the standard 30 Gy delivered in 10 fractions for pain relief in the context of complicated BMs. Furthermore, this regimen demonstrated comparable safety in terms of acute toxicity, with a lower incidence of definitive interruptions of radiotherapy.

Background/Objectives. To evaluate T&N-staging diagnostic performance of [68Ga]Ga-FAPI-46 PET/CT (FAPI) in a suspected/confirmed lung cancer surgical cohort. Methods: Patients were enrolled in a prospective monocentric trial (EudraCT: 2021-006570-23) to perform FAPI, in addition to conventional-staging-flow-chart (including [18F]F-FDG PET/CT-FDG). For the current purpose, only surgical patients were included. PET-semiquantitative parameters were measured for T&N: SUVmax, target-to-background-ratios (using mediastinal blood pool-MBP, liver-L and pulmonary-parenchyma-P). Visual and semiquantitative T&N PET/CT performances were analysed per patient and per region for both tracers, with surgical histopathology as standard-of-truth. Results: 63 FAPI scans were performed in 64 patients enrolled (26 May 2022–30 November 2023). A total of 50/63 patients underwent surgery and were included. Agreement (%) with histopathological-T&N-StagingAJCC8thEdition was slightly in favour of FAPI (T-66% vs. 58%, N-78% vs. 70%), increasing when T&N dichotomised (T-92% vs. 80%, N-78% vs. 72%). The performance of Visual-Criteria for T-per patient (n = 50) resulted higher FAPI than FDG. For N-per patient (n = 46), sensitivity and NPV were slightly lower with FAPI. Among 59 T-regions surgically examined, malignancy was excluded in 6/59 (10%). FAPI showed (vs. FDG): sensitivity 85% (vs. 72%), specificity 67% (vs. 50%), PPV 96% (vs. 93%), NPV 33% (vs. 17%), accuracy 83% (vs. 69%). Among 217 N-stations surgically assessed (overall 746 ln removed), only 15/217 (7%) resulted malignant; FAPI showed (vs. FDG): sensitivity 53% (vs. 60%), PPV 53% (vs. 26%), NPV 97% (vs. 97%), and significantly higher specificity (97% vs. 88%, p = 0.001) and accuracy (94% vs. 86%, p = 0.018). Semiquantitative-PET parameters performed similarly, better for N (p < 0.001) than for T, slightly in favour (although not significantly) of FAPI over FDG. Conclusions: In a suspected/confirmed lung cancer surgical cohort, PET/CT performances for preoperative T&Nstaging were slightly in favour of FAPI than FDG (except for suboptimal N-sensitivity), significantly better only for N (region-based) specificity and accuracy using visual assessment. The trial’s conventional follow-up is still ongoing; future analyses are pending, including non-surgical findings and theoretical impact on patient management.

Immune checkpoint inhibitors (ICIs) have transformed the therapeutic landscape of advanced non-small cell lung cancer (NSCLC), offering durable survival in selected patients. However, ICIs can induce immune-related adverse events (irAEs), among which pneumonitis represents one of the most clinically significant due to its potential severity and diagnostic challenges. Different radiological patterns have been reported, although they may overlap with infectious or radiation-induced lung injury, complicating a timely diagnosis. We report two cases of young patients with metastatic NSCLC and high PD-L1 expression who achieved long-term benefit from first-line pembrolizumab but were burdened by severe immune-related pneumonitis. Imaging findings in both patients were suggestive of organizing pneumonia associated with the presence of the so-called \"atoll sign\" (or reversed halo sign), a radiological feature rarely reported in the context of ICI-related pneumonitis. In both cases, the diagnosis was supported by imaging, microbiological tests, and histology. The subsequent administration of high-dose steroids led to rapid relief of symptoms associated with radiological improvement. Despite pembrolizumab discontinuation, both patients maintained durable systemic disease control. These cases emphasize the importance of recognizing uncommon radiological patterns such as the atoll sign in patients receiving ICIs, highlighting the need for vigilance even after prolonged therapy and underscoring the potential for sustained oncologic benefit despite treatment discontinuation.

Background: Thoracic ultrasound (TUS) has emerged as a viable alternative of computed tomography (CT) for pneumothorax diagnosis. Ultrasound elastography (USE), a technique assessing tissue elasticity, has recently been proposed as a novel tool for pneumothorax evaluation. Methods: This prospective, monocentric, observational study aimed to compare the diagnostic accuracy of static and dynamic USE with TUS in detecting iatrogenic pneumothorax after CT-guided transthoracic needle aspiration (TTNA). Results: Thirty-two patients were enrolled, with pneumothorax confirmed via CT in 40.63% of cases. The results showed that elastographic-mode images had significantly higher sensitivity (76.9% vs. 21.2%, p < 0.001) and improved positive and negative predictive values (67.8% vs. 52.4%, p-value 0.01, 82.6% vs. 61.7%, p-value < 0.001, respectively), compared to B-mode images. Concordance between expert and non-expert evaluators was also higher for elastographic images, suggesting improved interpretability. However, dynamic USE did not demonstrate a statistically significant advantage over B-mode videos. Conclusions: These findings suggest that USE may enhance static ultrasound-based pneumothorax detection and provide an objective imaging marker for reports. Further multicenter studies are needed to confirm these findings and explore the potential role of USE in other settings.

To evaluate T&N-staging diagnostic performance of [68Ga]Ga-FAPI-46 PET/CT (FAPI) in a suspected/confirmed lung cancer surgical cohort.BACKGROUND/OBJECTIVESTo evaluate T&N-staging diagnostic performance of [68Ga]Ga-FAPI-46 PET/CT (FAPI) in a suspected/confirmed lung cancer surgical cohort.Patients were enrolled in a prospective monocentric trial (EudraCT: 2021-006570-23) to perform FAPI, in addition to conventional-staging-flow-chart (including [18F]F-FDG PET/CT-FDG). For the current purpose, only surgical patients were included. PET-semiquantitative parameters were measured for T&N: SUVmax, target-to-background-ratios (using mediastinal blood pool-MBP, liver-L and pulmonary-parenchyma-P). Visual and semiquantitative T&N PET/CT performances were analysed per patient and per region for both tracers, with surgical histopathology as standard-of-truth.METHODSPatients were enrolled in a prospective monocentric trial (EudraCT: 2021-006570-23) to perform FAPI, in addition to conventional-staging-flow-chart (including [18F]F-FDG PET/CT-FDG). For the current purpose, only surgical patients were included. PET-semiquantitative parameters were measured for T&N: SUVmax, target-to-background-ratios (using mediastinal blood pool-MBP, liver-L and pulmonary-parenchyma-P). Visual and semiquantitative T&N PET/CT performances were analysed per patient and per region for both tracers, with surgical histopathology as standard-of-truth.63 FAPI scans were performed in 64 patients enrolled (26 May 2022-30 November 2023). A total of 50/63 patients underwent surgery and were included. Agreement (%) with histopathological-T&N-StagingAJCC8thEdition was slightly in favour of FAPI (T-66% vs. 58%, N-78% vs. 70%), increasing when T&N dichotomised (T-92% vs. 80%, N-78% vs. 72%). The performance of Visual-Criteria for T-per patient (n = 50) resulted higher FAPI than FDG. For N-per patient (n = 46), sensitivity and NPV were slightly lower with FAPI. Among 59 T-regions surgically examined, malignancy was excluded in 6/59 (10%). FAPI showed (vs. FDG): sensitivity 85% (vs. 72%), specificity 67% (vs. 50%), PPV 96% (vs. 93%), NPV 33% (vs. 17%), accuracy 83% (vs. 69%). Among 217 N-stations surgically assessed (overall 746 ln removed), only 15/217 (7%) resulted malignant; FAPI showed (vs. FDG): sensitivity 53% (vs. 60%), PPV 53% (vs. 26%), NPV 97% (vs. 97%), and significantly higher specificity (97% vs. 88%, p = 0.001) and accuracy (94% vs. 86%, p = 0.018). Semiquantitative-PET parameters performed similarly, better for N (p < 0.001) than for T, slightly in favour (although not significantly) of FAPI over FDG.RESULTS63 FAPI scans were performed in 64 patients enrolled (26 May 2022-30 November 2023). A total of 50/63 patients underwent surgery and were included. Agreement (%) with histopathological-T&N-StagingAJCC8thEdition was slightly in favour of FAPI (T-66% vs. 58%, N-78% vs. 70%), increasing when T&N dichotomised (T-92% vs. 80%, N-78% vs. 72%). The performance of Visual-Criteria for T-per patient (n = 50) resulted higher FAPI than FDG. For N-per patient (n = 46), sensitivity and NPV were slightly lower with FAPI. Among 59 T-regions surgically examined, malignancy was excluded in 6/59 (10%). FAPI showed (vs. FDG): sensitivity 85% (vs. 72%), specificity 67% (vs. 50%), PPV 96% (vs. 93%), NPV 33% (vs. 17%), accuracy 83% (vs. 69%). Among 217 N-stations surgically assessed (overall 746 ln removed), only 15/217 (7%) resulted malignant; FAPI showed (vs. FDG): sensitivity 53% (vs. 60%), PPV 53% (vs. 26%), NPV 97% (vs. 97%), and significantly higher specificity (97% vs. 88%, p = 0.001) and accuracy (94% vs. 86%, p = 0.018). Semiquantitative-PET parameters performed similarly, better for N (p < 0.001) than for T, slightly in favour (although not significantly) of FAPI over FDG.In a suspected/confirmed lung cancer surgical cohort, PET/CT performances for preoperative T&Nstaging were slightly in favour of FAPI than FDG (except for suboptimal N-sensitivity), significantly better only for N (region-based) specificity and accuracy using visual assessment. The trial's conventional follow-up is still ongoing; future analyses are pending, including non-surgical findings and theoretical impact on patient management.CONCLUSIONSIn a suspected/confirmed lung cancer surgical cohort, PET/CT performances for preoperative T&Nstaging were slightly in favour of FAPI than FDG (except for suboptimal N-sensitivity), significantly better only for N (region-based) specificity and accuracy using visual assessment. The trial's conventional follow-up is still ongoing; future analyses are pending, including non-surgical findings and theoretical impact on patient management.

Background It has been suggested that withdrawal of inhaled corticosteroids (ICS) in COPD patients on maintenance treatment results in deterioration of symptoms, lung function and exacerbations. The aim of this real-life, prospective, multicentric study was to investigate whether withdrawal of ICS in COPD patients at low risk of exacerbation is linked to a deterioration in lung function and symptoms and to a higher frequency of exacerbations. Methods 914 COPD patients, on maintenance therapy with bronchodilators and ICS, FEV 1 >50% predicted, and <2 exacerbations/year were recruited. Upon decision of the primary physicians, 59% of patients continued their ICS treatment whereas in 41% of patients ICS were withdrawn and regular therapy was continued with long-acting bronchodilators mostly (91% of patients). FEV 1 , CAT (COPD Assessment Test), and occurrence of exacerbations were measured at the beginning (T0) and at the end (T6) of the 6 months observational period. Results 816 patients (89.3%) concluded the study. FEV 1 , CAT and exacerbations history were similar in the two groups (ICS and no ICS) at T0 and at T6. We did not observe any deterioration of lung function symptoms, and exacerbation rate between the two groups at T0 and T6. Conclusions We conclude that the withdrawal of ICS, in COPD patients at low risk of exacerbation, can be safe provided that patients are left on maintenance treatment with long-acting bronchodilators.