Purpose: To evaluate feasibility, toxicities, and clinical response in Stage IV patients treated with palliative “metabolism-guided” lattice technique. Patients and Methods: From June 2020 to December 2021, 30 consecutive clinical stage IV patients with 31 bulky lesions were included in this study. All patients received palliative irradiation consisting of a spatially fractionated high radiation dose delivered in spherical deposits (vertices, Vs) within the bulky disease. The Vs were placed at the edges of tumor areas with different metabolisms at the PET exam following a non-geometric arrangement. Precisely, the Vs overlapped the interfaces between the tumor areas of higher ¹⁸F-FDG uptake (>75% SUV max) and areas with lower ¹⁸F-FDG uptake. A median dose of 15 Gy/1 fraction (range 10–27 Gy in 1/3 fractions) was delivered to the Vs. Within 7 days after the Vs boost, all the gross tumor volume (GTV) was homogeneously treated with hypo-fractionated radiation therapy (RT). Results: The rate of symptomatic response was 100%, and it was observed immediately after lattice RT delivery in 3/30 patients, while 27/30 patients had a symptomatic response within 8 days from the end of GTV irradiation. Radiation-related acute grade ≥1 toxicities were observed in 6/30 (20%) patients. The rate of overall clinical response was 89%, including 23% of complete remission. The 1-year overall survival rate was 86.4%. Conclusions: “Metabolism-guided” lattice radiotherapy is feasible and well-tolerated, being able to yield very impressive results both in terms of symptom relief and overall clinical response rate in stage IV bulky disease patients. These preliminary results seem to indicate that this kind of therapy could emerge as the best therapeutic option for this patient setting.

Background: Orbital metastases often lead to severe functional impairment. The role of resection, orbital exenteration, and complementary treatments is still debated. We systematically reviewed the literature on orbital metastases. Methods: PubMed, Scopus, Web-of-Science, and Cochrane were searched upon PRISMA guidelines to identify studies on orbital metastases. Clinical characteristics, management strategies, and survival were analyzed. Results: We included 262 studies comprising 873 patients. Median age was 59 years. The most frequent primary tumors were breast (36.3%), melanoma (10.1%), and prostate (8.5%) cancers, with median time interval of 12 months (range, 0–420). The most common symptoms were proptosis (52.3%) and relative-afferent-pupillary-defect (38.7%). Most metastases showed a diffuse location within the orbit (19%), with preferential infiltration of orbital soft tissues (40.2%). In 47 cases (5.4%), tumors extended intracranially. Incisional biopsy (63.7%) was preferred over fine-needle aspiration (10.2%), with partial resection (16.6%) preferred over complete (9.5%). Orbital exenteration was pursued in 26 patients (3%). A total of 305 patients (39.4%) received chemotherapy, and 506 (58%) received orbital radiotherapy. Post-treatment symptom improvement was significantly superior after resection (p = 0.005) and orbital radiotherapy (p = 0.032). Mean follow-up was 14.3 months, and median overall survival was 6 months. Fifteen cases (1.7%) demonstrated recurrence with median local control of six months. Overall survival was statistically increased in patients with breast cancer (p < 0.001) and in patients undergoing resection (p = 0.024) but was not correlated with orbital location (p = 0.174), intracranial extension (p = 0.073), biopsy approach (p = 0.344), extent-of-resection (p = 0.429), or orbital exenteration (p = 0.153). Conclusions: Orbital metastases severely impair patient quality of life. Surgical resection safely provides symptom and survival benefit compared to biopsy, while orbital radiotherapy significantly improves symptoms compared to not receiving radiotherapy.

Palliative radiotherapy has a great role in the treatment of large tumor masses. However, treating a bulky disease could be difficult, especially in critical anatomical areas. In daily clinical practice, short course hypofractionated radiotherapy is delivered in order to control the symptomatic disease. Radiation fields generally encompass the entire tumor mass, which is homogeneously irradiated. Recent technological advances enable delivering a higher radiation dose in small areas within a large mass. This goal, previously achieved thanks to the GRID approach, is now achievable using the newest concept of LATTICE radiotherapy (LT-RT). This kind of treatment allows exploiting various radiation effects, such as bystander and abscopal effects. These events may be enhanced by the concomitant use of immunotherapy, with the latter being ever more successfully delivered in cancer patients. Moreover, a critical issue in the treatment of large masses is the inhomogeneous intratumoral distribution of well-oxygenated and hypo-oxygenated areas. It is well known that hypoxic areas are more resistant to the killing effect of radiation, hence the need to target them with higher aggressive doses. This concept introduces the “oxygen-guided radiation therapy” (OGRT), which means looking for suitable hypoxic markers to implement in PET/CT and Magnetic Resonance Imaging. Future treatment strategies are likely to involve combinations of LT-RT, OGRT, and immunotherapy. In this paper, we review the radiobiological rationale behind a potential benefit of LT-RT and OGRT, and we summarize the results reported in the few clinical trials published so far regarding these issues. Lastly, we suggest what future perspectives may emerge by combining immunotherapy with LT-RT/OGRT.

Background: The development of [⁶⁸Ga]Ga-DOTA-SSTR PET tracers has garnered interest in neuro-oncology, to increase accuracy in diagnostic, radiation planning, and neurotheranostics protocols. We systematically reviewed the literature on the current uses of [⁶⁸Ga]Ga-DOTA-SSTR PET in brain tumors. Methods: PubMed, Scopus, Web of Science, and Cochrane were searched in accordance with the PRISMA guidelines to include published studies and ongoing trials utilizing [⁶⁸Ga]Ga-DOTA-SSTR PET in patients with brain tumors. Results: We included 63 published studies comprising 1030 patients with 1277 lesions, and 4 ongoing trials. [⁶⁸Ga]Ga-DOTA-SSTR PET was mostly used for diagnostic purposes (62.5%), followed by treatment planning (32.7%), and neurotheranostics (4.8%). Most lesions were meningiomas (93.6%), followed by pituitary adenomas (2.8%), and the DOTATOC tracer (53.2%) was used more frequently than DOTATATE (39.1%) and DOTANOC (5.7%), except for diagnostic purposes (DOTATATE 51.1%). [⁶⁸Ga]Ga-DOTA-SSTR PET studies were mostly required to confirm the diagnosis of meningiomas (owing to their high SSTR2 expression and tracer uptake) or evaluate their extent of bone invasion, and improve volume contouring for better radiotherapy planning. Some studies reported the uncommon occurrence of SSTR2-positive brain pathology challenging the diagnostic accuracy of [⁶⁸Ga]Ga-DOTA-SSTR PET for meningiomas. Pre-treatment assessment of tracer uptake rates has been used to confirm patient eligibility (high somatostatin receptor-2 expression) for peptide receptor radionuclide therapy (PRRT) (i.e., neurotheranostics) for recurrent meningiomas and pituitary carcinomas. Conclusion: [⁶⁸Ga]Ga-DOTA-SSTR PET studies may revolutionize the routine neuro-oncology practice, especially in meningiomas, by improving diagnostic accuracy, delineation of radiotherapy targets, and patient eligibility for radionuclide therapies.

In spinal surgery, 3D prothesis represents a useful instrument for spinal reconstruction after the removal of spinal tumors that require an “en bloc” resection. This represents a complex and demanding procedure, aiming to restore spinal length, alignment and weight-bearing capacity and to provide immediate stability. Thus, in this systematic review the authors searched the literature to investigate and discuss the advantages and limitations of using 3D-printed custom-made vertebral bodies in the treatment of spinal tumors. A systematic literature review was conducted following the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) statement, with no limits in terms of date of publication. The collected studies were exported to Mendeley. The articles were selected according to the following inclusion criteria: availability of full articles, full articles in English, studies regarding the implant of 3D custom-made prothesis after total or partial vertebral resection, studies regarding patients with a histologically confirmed diagnosis of primary spinal tumor or solitary bone metastasis; studies evaluating the implant of 3d custom-made prothesis in the cervical, thoracic, and lumbar spine. Nineteen published studies were included in this literature review, and include a total of 87 patients, 49 males (56.3%) and 38 females (43.7%). The main tumoral location and primary tumor diagnosis were evaluated. The 3D custom-made prothesis represents a feasible tool after tumor en-bloc resection in spinal reconstruction. This procedure is still evolving, and long-term follow-ups are mandatory to assess its safeness and usefulness.

Radiotherapy represents an essential part of the therapeutic algorithm for breast cancer patients after conservative surgery. The treatment of left-sided tumors has been associated with a non-negligible risk of developing late-onset cardiovascular disease. The cardiac risk perception has especially increased over the last years due to the prolongation of patients’ survival owing to the advent of new drugs and an ever earlier cancer detection through screening programs. Improvements in radiation delivery techniques could reduce the treatment-related heart toxicity. The deep-inspiration-breath-hold (DIBH) irradiation is one of the most advanced treatment approaches, which requires specific technical equipment and uses inspiration to displace the heart from the tangential radiation fields. However, not all patients benefit from its use. Moreover, DIBH irradiation needs patient compliance and accurate training. Therefore, such a technique may be unjustifiably cumbersome and time-consuming as well as unnecessarily expensive from a mere healthcare cost point of view. Hence the need to early select only the true beneficiaries while tailoring more effective heart-sparing techniques for the others and streamlining the workflow, especially in high-volume radiation oncology departments. In this literature overview, we collected some possible predictors of cardiac dose sparing in DIBH irradiation for left breast treatment in an effort to provide an easy-to-consult summary of simple instruments to insiders for identifying patients actually benefitting from this technique. We critically reviewed the reliability and weaknesses of each retrieved finding, aiming to inspire new insights and discussions on this much-debated topic.