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Background: Radiation dermatitis (RD) is the most frequent side effect in patients undergoing adjuvant radiotherapy (RT) for breast cancer. Despite the skin-sparing benefits of new RT techniques, most patients develop RD. There is currently no standard treatment to prevent and soothe RD, which is generally managed with emollients, moisturizers, or corticosteroids. We conducted a prospective observational study to evaluate the rate and grade of RD with the application of a cleansing mousse and a non-steroidal emulsion during the adjuvant RT program in patients with breast cancer submitted to surgery. Materials and Methods: A cleansing mousse containing vegetable glycerin (12%), phytoextract of chamomile (0.5%), yarrow phytoextract (0.5%), sweet almond (0.1%), Oenothera oil (0.1%), and rice protein hydrolyzate (0.1%), and an emulsion containing micronized zinc oxide (3.7%), rapeseed phytosterols (1.7%), aloe (0.5%), 18-beta glycyrrhetinic acid (0.5%), alpha bisabolol (0.5%), and zanthalene (0.5%) were offered to breast cancer patients undergoing adjuvant RT to prevent the onset of RD and mitigate its severity. These specific ingredients were selected for their well-known anti-inflammatory, antioxidant, and moisturizing properties. Skin toxicities were recorded photographically and graded according to the RTOG scoring system. Results: From March 2023 to July 2023, a total of 24 patients with a median age of 59 years (range 42–75) were enrolled. Halfway through the RT treatment, 20 patients (83.3%) had G0 skin toxicity, three (12.5%) G1, one (4.2%) G2. None showed G3–G4 toxicity. At the end of RT, seven patients (29.2%) exhibited G0 skin toxicity, 14 (58.3%) G1, two (8.3%) G2, one (4.2%) G3. No patient developed G4 toxicity. Fifteen days after the end of RT, 13 patients (54.2%) had G0 skin toxicity, 10 (41.1%) G1, one (4.2%) G2, with none showing G3–G4 toxicity. Conclusions: Our data suggest that the tested topicals might be an effective option for preventing and alleviating RD. Further prospective randomized studies are needed to confirm our findings. [ABSTRACT FROM AUTHOR]

The field of precision radiation therapy has seen remarkable advancements in both experimental and computational methods. Recent literature has introduced various approaches such as Spatially Fractionated Radiation Therapy (SFRT). This unconventional treatment, demanding high-precision radiotherapy, has shown promising clinical outcomes. A comprehensive computational scheme for SFRT, extrapolated from a case report, is proposed. This framework exhibits exceptional flexibility, accommodating diverse initial conditions (shape, inhomogeneity, etc.) and enabling specific choices for sub-volume selection with administrated higher radiation doses. The approach integrates the standard linear quadratic model and, significantly, considers the activation of the immune system due to radiotherapy. This activation enhances the immune response in comparison to the untreated case. We delve into the distinct roles of the native immune system, immune activation by radiation, and post-radiotherapy immunotherapy, discussing their implications for either complete recovery or disease regrowth. [ABSTRACT FROM AUTHOR]

Purpose: To investigate the ability of radiotherapy (RT) to prolong progression-free survival (PFS) and to report treatment-related toxicities among oligoprogressive metastatic Merkel cell carcinoma (mMCC) patients on avelumab. Methods: We retrospectively collected clinical data on mMCC patients who underwent radiotherapy for limited progression on avelumab. Patients were categorized as primary or secondary immune refractory depending on the time of onset of resistance to immunotherapy (at the first or subsequent follow-up visits after avelumab initiation). Pre- and post-RT PFS were calculated. Overall survival (OS) from the first progression treated with RT was also reported. Radiological responses and toxicities were evaluated according to the irRECIST criteria and RTOG scoring system, respectively. Results: Eight patients, including five females, with a median age of 75 years, met our inclusion criteria. The median gross tumor and clinical target volumes at first progression on avelumab were 29.85 cc and 236.7 cc, respectively. The treatment sites included lymph node, skin, brain, and spine metastases. Four patients received more than one course of RT. Most patients were treated with palliative radiation doses (mainly 30 Gy in 3 Gy/day fractions). Two patients were treated with stereotactic RT. Five/eight patients were primary immune refractory. The objective response rate at the first post-RT assessment was 75%, whereas no local failure was reported. The median pre-RT PFS was 3 months. The pre-RT PFS was 37.5% at 6 months and 12.5% at 1 year. The median post-RT PFS was not reached. The post-RT PFS was 60% at 6 months and 1 year. The post-RT OS was 85.7% at 1 year and 64.3% at 2 years. No relevant treatment-related toxicity was observed. After a median follow-up of 18.5 months, 6/8 patients are still alive and continuing on avelumab therapy. Conclusions: Adding radiotherapy to mMCC patients with limited progression on avelumab seems to be safe and effective in prolonging the successful use of immunotherapy, regardless of the type of immune refractoriness. [ABSTRACT FROM AUTHOR]

Simple Summary: The lattice technique is a particular form of spatially fractionated radiation therapy, which was demonstrated to be safe and effective for treating advanced cancers. Bulky tumor disease is difficult to treat. In this clinical scenario, radiotherapy has a role in the palliation of symptoms. The lattice technique allows high doses to be delivered within tumor masses. Combining lattice delivery with IMRT/VMAT to bulky tumors offers optimal symptom control and could emerge as the best therapeutic option in this setting of patients. 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. [ABSTRACT FROM AUTHOR]

Simple Summary: Adjuvant radiotherapy could damage the heart in left-sided breast cancer patients. The deep-inspiration-breath-hold technique may limit the heart exposure to radiation. As non-beneficiaries exist, there is some need to do an upfront cost-effective selection. Some easy-to-use anatomical predictors may help insiders in the treatment decision. The awareness of such findings may improve the efficiency of practitioners' workflows. 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. [ABSTRACT FROM AUTHOR]

Simple Summary: Nodal and distant metastases of cutaneous squamous cell carcinomas are very rare and lead to dismal prognoses. Immunotherapy is approved only for cutaneous squamous cell carcinoma patients not amenable to surgery or curative radiation therapy. Radiation therapy has a clear role as an adjuvant treatment for locally advanced disease. Radiation therapy may also have an important role in inoperable and metastatic disease. Oligometastatic disease is a condition that needs to be defined for this carcinoma. This review aims to offer to the readers a comprehensive overview of studies about the role of radiotherapy in the management of advanced or metastatic cutaneous squamous cell carcinomas, also assuming possible further developments in the light of the recent discoveries about tumor biology. The present paper has the merit of re-focusing great attention on the efficacy and cost-effectiveness of radiotherapy in these not yet properly explored scenarios. Radiation therapy (RT) is an effective therapeutic option for small localized cutaneous squamous cell carcinoma (cSCC) among patients who are not eligible for or refuse surgery. RT also has a defined role as an adjuvant treatment in cases of adverse features that predispose to tumor recurrence after local excision. Since the development of cSCC is often a late consequence of chronic sun exposure, its occurrence is more common among elderly patients whose comorbidities may contraindicate surgical procedures. These could be impeded not only by frail medical conditions but also by technical issues. Indeed, an aggressive locoregional behavior of cSCC may culminate in unresectability due to widespread invasion of neighboring tissues. Moreover, cSCC could develop distant metastases. Both locally advanced and metastatic cSCCs carry a poor prognosis. In these scenarios, recent discoveries of tumor molecular targets are promoting the use of promising systemic therapies, especially immunotherapy, over RT. However, the results from using immunotherapy and, even more so, of chemotherapy are still not optimal. By contrast, advances in radiation delivery equipment can safely treat even large and complex-shaped cSCC targets in challenging body sites. In addition, RT could also have a role in metastatic cSCC settings by enhancing the effectiveness of concomitant immunotherapy. The aim of this review is to summarize and comment on the body of literature about the use of radiotherapy for operable and inoperable locally advanced cSCCs and for metastatic ones in an attempt to define its current and future role. [ABSTRACT FROM AUTHOR]

Spine represents the most common site for metastatic disease involvement. Due to the close relationship between the spinal cord and critical structures, therapeutical management of metastatic spinal cord disease remains challenging. Spinal localization can lead to neurological sequelae, which can significantly affect the quality of life in patients with a limited life expectancy. The authors conducted a systematic literature review according to PRISMA guidelines in order to determine the impact of the most updated palliative care on spinal metastases. The initial literature search retrieved 2526 articles, manually screened based on detailed exclusion criteria. Finally, 65 studies met the inclusion criteria and were finally included in the systematic review. In the wide scenario of palliative care, nowadays, recent medical or surgical treatments represent valuable options for ameliorating pain and improving patients QoL in such this condition. [ABSTRACT FROM AUTHOR]

Tumor volume regression during and after chemo and radio therapy is a useful information for clinical decisions. Indeed, a quantitative, patient oriented, description of the response to treatment can guide towards the modification of the scheduled doses or the evaluation of the best time for surgery. We propose a macroscopic algorithm which permits to follow quantitatively the time evolution of the tumor volume during and after radiochemotherapy. The method, initially validated with different cell-lines implanted in mice, is then successfully applied to the available data for partially responding and complete recovery patients. [ABSTRACT FROM AUTHOR]

33813420 5 Ferini G., Pergolizzi S. A Ten-year-long Update on Radiation Proctitis Among Prostate Cancer Patients Treated with Curative External Beam Radiotherapy. Such an inference is wrong since the risk of adverse radiation events is strongly dependent not only on the total dose but also on each fraction dose size [[3]]. For example and for better clarity, when I along with other authors published some papers about the risk of radiation proctitis among prostate cancer patients [[4], [6]], we referred to different dose constraints during the plan evaluation based on the diversity of the dose prescriptions. [Extracted from the article]

Simple Summary: Spine giant cell tumors (SGCTs) are intermediate malignant bone tumors, sometimes aggressive and responsible for debilitating axial pain and sensorimotor impairments. Non-surgical therapies, including denosumab, radiotherapy, and selective arterial embolization (SAE), have shown promising results in the treatment of patients with inoperable SGCTs. In this systematic review, we aimed to comprehensively analyze the current literature on denosumab, radiotherapy, and SAE for inoperable SGCTs, comparing treatment outcomes and complications using a random-effect model meta-analysis. We found that all three treatments were equally effective in providing symptom improvement and radiological tumor response, also showing low and comparable rates of treatment-related complications. Patients treated with denosumab showed lower rates of local recurrences and distant metastases. Background: Surgical resection remains the preferred treatment in spine giant cell tumors (SGCTs), but it is not always feasible. Conservative strategies have been studied for inoperable cases. We systematically reviewed the literature on inoperable SGCTs treated with denosumab, radiotherapy or selective arterial embolization (SAE). Methods: PubMed, Scopus, Web-of-Science, Ovid-EMBASE, and Cochrane were searched following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines to include studies of inoperable SGCTs treated with denosumab, radiotherapy or SAE. Treatment outcomes were analyzed and compared with a random-effect model meta-analysis. Results: Among the 17 studies included, 128 patients received denosumab, 59 radiotherapy, and 43 SAE. No significant differences in baseline patient characteristics were found between the three groups. All strategies were equally effective in providing symptom improvement (p = 0.187, I2 = 0%) and reduction in tumor volume (p = 0.738, I2 = 56.8%). Rates of treatment-related complications were low (denosumab: 12.5%; radiotherapy: 8.5%; SAE: 18.6%) and comparable (p = 0.311, I2 = 0%). Patients receiving denosumab had significantly lower rates of local tumor recurrence (10.9%) and distant metastases (0%) compared to patients receiving radiotherapy (30.5%; 8.5%) or SAE (35.6%; 7%) (p = 0.003, I2 = 32%; p = 0.002, I2 = 47%). Denosumab was also correlated with significantly higher overall survival rates at 18 months (99.2%) and 24 months (99.2%) compared to radiotherapy (91.5%; 89.6%) and SAE (92.5%; 89.4%) (p = 0.019, I2 = 8%; p = 0.004, I2 = 23%). Mortality was higher in patients receiving SAE (20.9%) or radiotherapy (13.6%) compared to denosumab (0.8%) (p < 0.001), but deaths mostly occurred for unrelated diseases. Conclusions: Denosumab, radiotherapy, and SAE are safe and effective for inoperable SGCTs. Clinical and radiological outcomes are mostly comparable, but denosumab may provide superior tumor control. [ABSTRACT FROM AUTHOR]

The peculiar and rare clinical condition below clearly requires a customized care approach in the context of personalized medicine. An 80-year-old female patient who was subjected in 2018 to surgical removal of a cutaneous Merkel cell carcinoma (MCC) nodule located on the posterior surface of the left thigh and to three subsequent palliative radiotherapy treatments developed a fourth relapse in October 2020, with fifteen nodular metastases located in the left thigh and leg. Since the overall macroscopic disease was still exclusively regionally located and microscopic spread was likely extended also to clinically negative skin of the thigh and leg, we performed an irradiation of the whole left lower extremity. For this purpose the total target (65.5 cm) was divided into three sub-volumes. Dose prescription was 30 Gy in 15 daily fractions. A sequential boost of 10 Gy in 5 daily fractions was planned for macroscopic nodules. Plans were calculated by means of volumetric modulated arc therapy (VMAT) with the field overlap technique. Thanks to this, we obtained a homogeneous dose distribution in the field junction region; avoidance structures were delineated in the central part of the thigh and leg with the aim of achieving an optimal superficial dose painting and to reduce bone exposure to radiation. This case study demonstrates that VMAT allows for a good dose coverage for circumferential cutaneous targets while sparing deeper organs at risk. A reproducible image-guided set-up is fundamental for an accurate and safe dose delivery. However, local treatments such as radiotherapy for very advanced MCC of the lower extremities might have limited impact due to the high probability of systemic progression, as illustrated in this case. Radiation is confirmed as being effective in preventing MCC nodule progression toward skin wounding. [ABSTRACT FROM AUTHOR]

Simple Summary: Oxygen-guided radiotherapy is a new modality for cancer irradiation. Spatially Fractionated Radiation Therapy allows the treatment of hypoxic tumor areas with high radiation doses. Radiotherapy enhances immunotherapy effectiveness. Abscopal and bystander effects are important radiobiological issues. The aim of this paper was to analyze the recent development of a particular kind of radiation therapy that is based on high-dose delivery in small areas within large tumor masses. We performed a narrative review of the radiobiological rationale behind a potential benefit by using these techniques combined with immunotherapy and employing personalized target definition according to hypoxic areas. 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. [ABSTRACT FROM AUTHOR]

Tumor regrowth and heterogeneity are important clinical parameters during radiotherapy, and the probability of treatment benefit critically depends on the tumor progression pattern in the interval between the fractional irradiation treatments. We propose an analytic, easy-to-use method to take into account clonal subpopulations with different specific growth rates and radiation resistances. The different strain regrowth effects, as described by Gompertz law, require a dose-boost to reproduce the survival probability of the corresponding homogeneous system and for uniform irradiation. However, the estimate of the survival fraction for a tumor with a hypoxic subpopulation is more reliable when there is a slow specific regrowth rate and when the dependence on the oxygen enhancement ratio of radiotherapy is consistently taken into account. The approach is discussed for non-linear two-population dynamics for breast cancer and can be easily generalized to a larger number of components and different tumor phenotypes. [ABSTRACT FROM AUTHOR]