Contralateral transcallosal transfalcine approach for bilateral intra-extraventricular anaplastic ganglioglioma via 'the trans-tumoral route': a technical case instruction.

BACKGROUND: Bilateral, biventricular lesions present a challenging scenario in neurosurgery, often requiring complex surgical techniques for management. Gangliogliomas (GG), while typically indolent, can manifest as anaplastic variants (AGG), necessitating comprehensive treatment strategies. This case study explores a unique surgical approach for a patient with bilateral, intra-extraventricular lesions infiltrating the corpus callosum, highlighting the complexities of managing such cases. METHODS: A 63-year-old female presented with a progressive intraventricular lesion infiltrating the left frontal lobe, diagnosed initially as a ganglioglioma. Following resection and histological examination, the lesion was confirmed as a WHO Grade 1 ganglioglioma. Subsequently, a contralateral lesion emerged, necessitating a novel surgical approach to achieve maximal safe resection while minimising neurological deficits. The technique involved extending the surgical corridor contralaterally along the tumour route, guided by neuronavigation and fluorescence imaging. RESULTS: The surgical approach enabled maximal safe resection of the lesion, with postoperative imaging confirming complete resection in most sites except for a known infiltration in the right posterior lateral ventricle. Histological examination revealed AGG, prompting subsequent adjuvant radiotherapy due to its aggressive nature. CONCLUSION: The management of bilateral, biventricular lesions such as AGG requires innovative surgical approaches tailored to individual patient characteristics. The case highlights the efficacy of a transtumoral approach in achieving maximal safe resection while minimising neurological sequelae. Moreover, it underscores the importance of comprehensive treatment strategies, including adjuvant therapies, in addressing aggressive histological variants of gangliogliomas.

Management of radiation-induced oral mucositis in head and neck cancer patients: a real-life survey among 25 Italian radiation oncology centers.

AIM: Radiation-induced oral mucositis (RIOM) is the most frequent side effect in head and neck cancer (HNC) patients treated with curative radiotherapy (RT). A standardized strategy for preventing and treating RIOM has not been defined. Aim of this study was to perform a real-life survey on RIOM management among Italian RT centers. METHODS: A 40-question survey was administered to 25 radiation oncologists working in 25 different RT centers across Italy. RESULTS: A total of 1554 HNC patients have been treated in the participating centers in 2021, the majority (median across the centers 91%) with curative intent. Median treatment time was 41 days, with a mean percentage of interruption due to toxicity of 14.5%. Eighty percent of responders provide written oral cavity hygiene recommendations. Regarding RIOM prevention, sodium bicarbonate mouthwashes, oral mucosa barrier agents, and hyaluronic acid-based mouthwashes were the most frequent topic agents used. Regarding RIOM treatment, 14 (56%) centers relied on literature evidence, while internal guidelines were available in 13 centers (44%). Grade (G)1 mucositis is mostly treated with sodium bicarbonate mouthwashes, oral mucosa barrier agents, and steroids, while hyaluronic acid-based agents, local anesthetics, and benzydamine were the most used in mucositis G2/G3. Steroids, painkillers, and anti-inflammatory drugs were the most frequent systemic agents used independently from the RIOM severity. CONCLUSION: Great variety of strategies exist among Italian centers in RIOM management for HNC patients. Whether different strategies could impact patients' compliance and overall treatment time of the radiation course is still unclear and needs further investigation.

Stereotactic boost on residual disease after external-beam irradiation in clinical stage III non-small cell lung cancer: mature results of stereotactic body radiation therapy post radiation therapy (SBRTpostRT) study.

PURPOSE: To evaluate the role of stereotactic body radiation therapy (SBRT) delivered after external-beam fractionated irradiation in non-small-cell lung cancer (NSCLC) patients with clinical stage III A, B. MATERIALS AND METHODS: All patients received three-dimensional conformal radiotherapy (3D-CRT) or intensity modulated radiation therapy (IMRT) (60-66 Gy/30-33 fractions of 2 Gy/5 days a week) with or without concomitant chemotherapy. Within 60 days from the end of irradiation, a SBRT boost (12-22 Gy in 1-3 fractions) was delivered on the residual disease. RESULTS: Here we report the mature results of 23 patients homogeneously treated and followed up for a median time of 5.35 years (range 4.16-10.16). The rate of overall clinical response after external beam and stereotactic boost was 100%. No treatment-related mortality was recorded. Radiation-related acute toxicities with a grade ≥ 2 were observed in 6/23 patients (26.1%): 4/23 (17.4%) had esophagitis with mild esophageal pain (G2); in 2/23 (8.7%) clinical radiation pneumonitis G2 was observed. Lung fibrosis (20/23 patients, 86.95%) represented a typical late tissue damage, which was symptomatic in one patient. Median disease-free survival (DFS) and overall survival (OS) were 27.8 (95% CI, 4.2-51.3) and 56.7 months (95% CI, 34.9-78.5), respectively. Median local progression-free survival (PFS) was 17 months (range 11.6-22.4), with a median distant PFS of 18 months (range 9.6-26.4). The 5-year actuarial DFS and OS rates were 28.7% and 35.2%, respectively. CONCLUSIONS: We confirm that a stereotactic boost after radical irradiation is feasible in stage III NSCLC patients. All fit patients who have no indication to adjuvant immunotherapy and presenting residual disease after curative irradiation could benefit from stereotactic boost because outcomes seem to be better than might be historically assumed.

Extended Endonasal Endoscopic (EEE) Surgery with Almost No Use of Adjuvant Radiotherapy for Juvenile Nasopharyngeal Angiofibroma (JNA).

Background and Objectives: Juvenile nasopharyngeal angiofibroma (JNA) is an angiomatous hamartoma of the nasal cavity. It is a benign but locally aggressive vascular tumor of the nasopharynx affecting adolescent males. Many surgical procedures are in practice, but the extended endonasal endoscopic (EEE) approach for JNAs is a suitable and effective technique. Materials and Methods: Fifteen adolescent patients having JNA who underwent extended endonasal endoscopic (EEE) surgery from January 2010 to January 2022 were studied retrospectively. Patients having residual and recurrent JNAs and those who underwent surgery other than EEE were excluded. Results: The average age of the patients was 18.3 years of age. A total of six patients (40%) each had stage V and IV while three patients (20%) had stage III JNAs. Gross total removal was achieved in eight (53.3%) patients and seven (43.7%) had partial removal. There was no per or postoperative mortality. All the patients had at least 3 years of postoperative follow-up and during follow-ups, seven patients were found to have residual tumors, and two had recurrences. Discussion: During the last decades, the endoscopic approach for the resection of JNAs has gained increasing popularity due to its obvious advantages over transfacial approaches. The magnified and angled field of view "behind the corner" helping in a more complete inspection for the resection and shorter hospitalization time makes it a better choice than the other approaches. Conclusions: Endoscopy is an excellent approach for primary JNA. It allows well visualization and precise removal of the angiofibroma. An endoscopic multiangle, multicorridor skull base approach including Denker's anteromedial maxillotomy is suitable and preferable for the resection of extensive JNAs.

Palliative Care and End-of-Life Issues in Patients with Brain Cancer Admitted to ICU.

Background and Objectives: Palliative care is an interdisciplinary medical specialty focused on improving the quality of life of critically ill patients, including those with frailty, during their illness. Materials and Methods: We conducted an extensive literature review on Pubmed focusing on palliative care in neuro-oncology patients admitted to intensive care units (ICUs). Results: We identified 967 articles and, after excluding 952 articles in accordance with the PRISMA flow chart, we included a total of 15 articles in the final selection. The potential role of palliative care in neuro-oncology appears necessary to ensure comprehensive end-of-life patient care. However, this seems underestimated and poorly applied, especially in the context of intensive care units. Medical personnel also face ethical dilemmas, considering not only the pathology but also the socio-spiritual context of the patient. In addition, caregivers' understanding of prognosis and realistic goals is critical for optimal end-of-life management. Conclusions: The provision of palliative care to neuro-oncological patients admitted to ICU is a complex challenge supported by fragmented evidence. Additional research on palliative care and communication about end-of-life care in the neuro-oncology and neuro-ICU setting is needed.

Stereotactic Body Radiotherapy for Lymph-Nodal Oligometastatic Prostate Cancer: A Multicenter Retrospective Experience.

Background: The favorable role of SBRT for lymph-nodal oligometastases from prostate cancer has been reported by several retrospective and prospective experiences, suggesting a more indolent natural history of disease when compared to patients with bone oligometastases. This retrospective multicenter study evaluates the outcomes of a cohort of patients treated with stereotactic body radiotherapy for lymph-nodal oligometastases. Methods: Inclusion criteria were up to five lymph-nodal oligometastases detected either with Choline-PET or PSMA-PET in patients naïve for ADT or already ongoing with systemic therapy and at least 6 Gy per fraction for SBRT. Only patients with exclusive lymph-nodal disease were included. The primary endpoint of the study was LC; a toxicity assessment was retrospectively performed following CTCAE v4.0. Results: A total of 100 lymph-nodal oligometastases in 69 patients have been treated with SBRT between April 2015 and November 2022. The median age was 73 years (range, 60-85). Oligometastatic disease was mainly detected with Choline-PET in 47 cases, while the remaining were diagnosed using PSMA-PET, with most of the patients treated to a single lymph-nodal metastasis (48/69 cases), two in 14 cases, and three in the remaining cases. The median PSA prior to SBRT was 1.35 ng/mL (range, 0.3-23.7 ng/mL). Patients received SBRT with a median total dose of 35 Gy (range, 30-40 Gy) in a median number of 5 (range, 3-6) fractions. With a median follow-up of 16 months (range, 7-59 months), our LC rates were 95.8% and 86.3% at 1 and 2 years. DPFS rates were 90.4% and 53.4%, respectively, at 1 and 2 years, with nine patients developing a sequential oligometastatic disease treated with a second course of SBRT. Polymetastatic disease-free survival (PMFS) at 1 and 2 years was 98% and 96%. Six patients needed ADT after SBRT for a median time of ADT-free survival of 15 months (range, 6-22 months). The median OS was 16 months (range, 7-59) with 1- and 2-year rates of both 98%. In multivariate analysis, higher LC rates and the use of PSMA-PET were related to improved DPFS rates, and OS was significantly related to a lower incidence of distant progression. No G3 or higher adverse events were reported. Conclusions: In our experience, lymph-nodal SBRT for oligometastatic prostate cancer is a safe and effective option for ADT delay with no severe toxicity.

Intensity-modulated radiotherapy does not induce volumetric changes of the Bichat fat pad in nasopharyngeal cancer.

PURPOSE: To evaluate morphological and functional changes in the Bichat fat pad (BFP) after curative concurrent chemoradiotherapy in nasopharyngeal cancer (NPC) patients. METHODS: We retrospectively analyzed the volumetric, metabolic, and dosimetry parameters of BFPs in 7 NPC patients who underwent intensity-modulated radiotherapy (IMRT) between 2015 and 2020. Inclusion criteria were i) histologically confirmed diagnosis of NPC, ii) follow-up period of at least 12 months, iii) no history of previous irradiation or surgery in the maxillofacial area, and ìv) availability of pre- and posttreatment MRI and 18F­FDG PET-CT performed in our Institution. All patients had stage III-IVA disease (n = 7) and received platinum-based chemotherapy. Planned doses in 30 daily fractions/5 days per week were 66 Gy (2.2 Gy/die 5 days/week) to the gross tumor volume, 66 Gy (2.1-2.2 Gy/die 5 days/week) to the gross nodal volume, 60 Gy (2 Gy/die 5 days week) to clinical target volume (CTV)1, and 54 Gy (1.8 Gy/die 5 days/week) to CTV2. All patients completed the planned radiotherapy course in a median time of 42 days (range 42-43). Relationships between BFP volumes and the following DVH parameters were evaluated: mean dose, maximum dose (Dmax), and percentage of BFP volume receiving more than 5 to 65 Gy (V5 to V65). RESULTS: The pre-RT volumes of the left and right BFPs were 12.24 cc (range 6.51-20.01 cc) and 11.55 cc (range 5.78-17.53 cc), respectively. The mean volumes of left BFPPRE and BFPPOST were 12.24 cc (range 6.51-20.01cc) and 13.85 cc (range 7.54-20.21 cc), respectively, with no significant statistical differences (P > 0.05). No statistically significant correlations were found between dosimetry features and BFP volumetric changes (all P > 0.05). CONCLUSION: Our original results showed that chemoradiotherapy does not induce significant volumetric changes of the BFP. Further investigations are needed to evaluate the effects of higher radiation doses on BFP. This is the first real-world study on this issue.

Endocrine disorders after primary gamma knife radiosurgery for pituitary adenomas: A systematic review and meta-analysis.

PURPOSE: Gamma Knife radiosurgery (GKRS) is feasible for pituitary adenomas, but post-surgery GKRS may cause severe hormone deficits. We reviewed the literature on primary GKRS for pituitary adenoma focusing on radiation-induced hormone deficiencies. METHODS: PubMed, Web-of-Science, Scopus, and Cochrane were searched upon the PRISMA guidelines to include studies describing primary GKRS for pituitary adenomas. Pooled-rates of GKRS-induced hormone deficiencies and clinical-radiological responses were analyzed with a random-effect model meta-analysis. RESULTS: We included 24 studies comprising 1381 patients. Prolactinomas were the most common (34.2%), and 289 patients had non-functioning adenomas (20.9%). Median tumor volume was 1.6cm3 (range, 0.01-31.3), with suprasellar extension and cavernous sinus invasion detected in 26% and 31.1% cases. GKRS was delivered with median marginal dose 22.6 Gy (range, 6-49), maximum dose 50 Gy (range, 25-90), and isodose line 50% (range, 9-100%). Median maximum point doses were 9 Gy (range, 0.5-25) to the pituitary stalk, 7 Gy (range, 1-38) to the optic apparatus, and 5 Gy (range, 0.4-12.3) to the optic chiasm. Pooled 5 year rates of endocrine normalization and local tumor control were 48% (95%CI 45-51%) and 97% (95%CI 95-98%). 158 patients (11.4%) experienced endocrinopathies at a median of 45 months (range, 4-187.3) after GKRS, with pooled 5-year rates of 8% (95%CI 6-9%). GKRS-induced hormone deficiencies comprised secondary hypothyroidism (42.4%) and hypogonadotropic hypogonadism (33.5%), with panhypopituitarism reported in 31 cases (19.6%). CONCLUSION: Primary GKRS for pituitary adenoma may correlate with lower rates of radiation-induced hypopituitarism (11.4%) than post-surgery GKRS (18-32%). Minimal doses to normal pituitary structures and long-term endocrine follow-up are of primary importance.

Spine eburnation in a metastatic lung cancer patient treated with immunotherapy and radiotherapy. The first case report of bystander effect on bone.

INTRODUCTION: Metastatic non-small cell lung cancer (NSCLC) is nowadays treated with a multimodal therapeutic approach including immunotherapy, targeted therapy and radiotherapy. Radiation therapy, in addition to immune checkpoint inhibitors, gives rise to a particular radiobiological effect known as "bystander effect" consisting of the radiation-induced damage in nearby unirradiated cells. CASE REPORT: We report a case of a 79-year-old female patient with stage IV NSCLC treated with concomitant immuno-radiotherapy who showed a bystander effect on bone.Management and outcome: Primary tumour biopsy revealed an adenocarcinoma with a PDL1 expression >50%, while staging exams showed a right pulmonary lesion with a partial involvement of the contiguous rib and a single brain metastasis. The patient refused chemotherapy, so that Pembrolizumab 2 mg/Kg was administered every 3 weeks. After two administrations, the single brain metastasis was treated using stereotactic radiosurgery while the site of primitive lung cancer received an 8 Gy-single fraction 3 D-conformal radiotherapy. Three months after irradiation a chest CT showed a radiological remission of about 10% of the GTV and a partial eburnation of the vertebra located nearby the target volume. The CT images of a PET/CT at six months showed a complete vertebral eburnation. At the last follow-up, the patient was free of disease (brain MRI, spinal MRI and PET/CT). DISCUSSION: The present case alerts for unusual side effects provoked by bystander phenomenon in patients treated with a combination of immunotherapy and irradiation. Immune activation exacerbates the bystander effect causing normal tissues toxicities beyond what immunotherapies are causing by themselves.

The role of radiation therapy in the treatment of spine metastases from hepatocellular carcinoma: a systematic review and meta-analysis.

OBJECTIVE: Spine hepatocellular carcinoma (HCC) metastases severely worsen quality of life and prognosis, with the role of radiotherapy being controversial. The authors systematically reviewed the literature on radiotherapy for spine metastatic HCCs. METHODS: The PubMed, Scopus, Web of Science, and Cochrane databases were searched according to the PRISMA guidelines to include studies of radiotherapy for spine metastatic HCCs. Outcomes, complications, and local control were analyzed with indirect random-effect meta-analyses. RESULTS: The authors included 12 studies comprising 713 patients. The median time interval from diagnosis of HCC to spine metastases was 12 months (range 0-105 months). Most lesions were thoracic (35.9%) or lumbar (24.7%). Radiotherapy was delivered with conventional external-beam (67.3%) or stereotactic (31.7%) techniques. The median dose was 30.3 Gy (range 12.5-52 Gy) in a median of 5 fractions (range 1-20 fractions). The median biologically effective dose was 44.8 Gy10 (range 14.4-112.5 Gy10). Actuarial rates of postradiotherapy pain relief and radiological response were 87% (95% CI 84%-90%) and 70% (95% CI 65%-75%), respectively. Radiation-related adverse events and vertebral fractures had actuarial rates of 8% (95% CI 5%-11%) and 16% (95% CI 10%-23%), respectively, with fracture rates significantly higher after stereotactic radiotherapy (p = 0.033). Fifty-eight patients (27.6%) had local recurrences after a median of 6.8 months (range 0.1-59 months), with pooled local control rates of 61.6% at 6 months and 40.8% at 12 months, and there were no significant differences based on radiotherapy type (p = 0.068). The median survival was 6 months (range 0.1-62 months), with pooled rates of 52.5% at 6 months and 23.4% at 12 months. CONCLUSIONS: Radiotherapy in spine metastatic HCCs shows favorable rates of pain relief, radiological responses, and local control. Rates of postradiotherapy vertebral fractures are higher after high-dose stereotactic radiotherapy.

A non-surgical COMBO-therapy approach for locally advanced unresectable pancreatic adenocarcinoma: preliminary results of a prospective study.

In this short report we present a series of thirteen patients with locally advanced, unresectable, pancreatic cancer treated with a COMBO-Therapy consisting of: STEP-1: induction chemotherapy; STEP-2: concomitant chemoradiotherapy; STEP-3: stereotactic body radiotherapy boost. After four weeks from the end of each step all patients had a re-staging and a surgical re-evaluation. All patients completed STEP-1 and STEP-2. STEP-3 has been successfully delivered to 8/13 patients with a median dose of 12 Gy (range 10-21 Gy) in 1-3 fractions. The median LC was 20 months (range 10-32) with a 2-year LC of 72.9%, and none of the patients developed G3 acute or late toxicities. The median OS was 21.5 months (range 12-34), and the 2-year OS was 53.9%; the median PFS was 17.5 months (range 10-27). Our non-surgical COMBO-Therapy has demonstrated a feasible profile with good tolerance. Further prospective protocols are needed to confirm our preliminary results.

Comment on Ivanov et al. Ultra-Hypofractionated vs. Moderate Fractionated Whole Breast Three Dimensional Conformal Radiotherapy during the COVID-19 Pandemic. Medicina 2022, 58, 745.

I read the paper by Ivanov et al. [...].

An Italian survey on "palliative intent" radiotherapy.

Background: The aim of this paper is to provide a comprehensive overview of the scenario on radiotherapy (RT) delivered with palliative intent in Italy. Materials and methods: A structured online questionnaire was submitted to Italian radiation oncologists in order to explore the clinical practice in different areas of palliation, namely: bone, lung, brain, liver, and emergencies suitable to RT. Results: 209 radiation oncologists took part in the study. Stereotactic body irradiation was found to be the preferred technique in lung and liver metastases, whereas 3D conformal RT was registered as the technique of choice for bone and brain metastases. The majority (98%) of participants stated to treat mainly radiotherapy emergencies with 3D conformal RT at doses ranging from 25 to 50 Gy. Re-irradiation is delivered by the majority of respondents, whereas post-treatment follow-up is done only by 51.4% of them. Conclusions: This nationwide study highlights some heterogeneity among Italian radiation oncologists regarding treatment and follow-up of metastatic cancer patients.

Volumetric Modulated Arc Therapy Capabilities for Treating Lower-Extremity Skin Affected by Several Merkel Cell Carcinoma Nodules: When Technological Advances Effectively Achieve the Palliative Therapeutic Goal while Minimising the Risk of Potential Toxicities.

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.

A small case series about safety and effectiveness of a hypofractionated electron beam radiotherapy schedule in five fractions for facial non melanoma skin cancer among frail and elderly patients.

BACKGROUND: The aim of the study was to evaluate local control and toxicities of strongly hypofractionated electron beam radiotherapy (RT) in elderly and fragile patients with facial nonmelanoma skin cancer (NMSC). MATERIALS AND METHODS: We enrolled patients aged ≥ 65 years with facial NMSC, Karnofsky Performance Status (KPS) ≥ 40 and life expectancy ≥ 6 months, amenable neither to daily RT nor surgery. Radiotherapy consisted of 35 Gy, delivered with 6 MeV electron beam, in 5 fractions of 7 Gy/day twice a week (tw). Prescription isodoses were 100% for cT1-cT2 and 90% for cT3-cT4. Objective response was assessed clinically 4 and 8 weeks after the end of RT and then monitored every 6 months. Side effects were assessed according to the CTCAE scale. RESULTS: 12 patients of median age 89.5 years with a total of 23 NMSC cN0 achieved a median follow-up time of 6 months (range 1-10), with total treatment compliance. 10/12 patients had a 40 ≤ KPS < 70 and 2/12 a 70 ≤ KPS < 90. 5/12 patients had synchronous lesions. 22/23 lesions were classified as T1-T2 and had complete response (CR), 1/23 as T4 with partial response (PR). Within 4 weeks after the end of treatment, G1 toxicity was reported for 12/23 lesions, G2 for 8/23, G3 for 3/23, G4 for 0/23, all disappeared 8 weeks later, with or without topical therapy. After last follow-up (1 June 2020) 1/12 patients died with PR from senile marasmus, 11/12 are alive with CR and widely tolerated toxicities. CONCLUSIONS: Extreme hypofractionation of radiotherapy dose for facial NMSC is effective, safe and suitable for elderly patients.

Stereotactic body radiation therapy and radiofrequency ablation for the treatment of liver metastases: How and when?

Limited liver metastases represent a clinical challenge. Surgical approach is the most frequently reported treatment option, however, some patients are not eligible for surgical interventions. Relatively recent technologic advances have permitted the safe use of ablative techniques employed in the cure of hepatic metastases. Among these, radiofrequency ablation (RFA) and stereotactic body radiotherapy (SBRT) have emerged as valid treatments in a significant proportion of patients with intrahepatic oligometastatic disease. This review offers an up-to-date of current available literature on this issue focusing on the use and outcomes of RFA and SBRT, according to the PICO (Population, Intervention, Comparison and Outcomes) criteria.

Effectiveness of radiotherapy in delaying treatment changes in primary or secondary immunorefractory oligoprogressive patients: preliminary results from a single-center study.

AIMS: To investigate whether the addition of radiotherapy could be an appropriate option to delay the time-to-next systemic treatment (TTNsT) in patients with oligoprogressive solid tumors who had acquired or innate resistance to immune checkpoint inhibitors (ICIs). MATERIAL AND METHODS: Patients with oligoprogressive disease treated with ICIs and radiotherapy at our Institute from January 2019 to June 2023 were retrospectively identified. Patients were stratified as primary or secondary immunorefractory according to the time of onset of ICI resistance. TTNsT and Time-To-Resistance (TTR) were the primary outcomes. Secondary outcomes included: post-radiotherapy first progression-free survival (pR-PFS), Local Control (LC), Overall Survival (OS), and treatment-related toxicities. In addition, out-of-field effects (such as the abscopal effect) of radiotherapy have been hypothesized. The survival rates were analyzed using the Kaplan-Meier method and long-rank test. RESULTS: 40 out of 105 screened patients with oligoprogressive disease met the inclusion criteria. Of these, 28 had an acquired drug resistance while 12 had an innate drug resistance. Radiotherapy was offered as a local treatment approach in all patients. RT techniques were classified into three regimens: standard palliative hypofractionated radiotherapy (hypo-RT), stereotactic radiotherapy (SRS/SBRT), and lattice radiotherapy (LRT). After a median follow-up of 22.5 months, the median TTR was 4 months (range 3-4) in patients with innate resistance vs 14 months (range 7-36) in patients with acquired resistance. Median TTNsT among patients with acquired and those with innate resistance was not reached (NR) vs 24 months (range 7-72). Overall, only six patients suffered from a local failure. Although out-of-field effects of radiotherapy were hypothesized, we were unable to record them as they did not occur during the observation period. Regardless of the radiation dose, there was no observable ≥ Grade 2 acute or late treatment-related toxicity. CONCLUSION: Our preliminary results seem to confirm that the integration of radiotherapy and ICIs may allow for the continuation of systemic therapy beyond progression, which can have a subsequent benefit in terms of survival outcomes even in patients with innate resistance.

Computational Approach for Spatially Fractionated Radiation Therapy (SFRT) and Immunological Response in Precision Radiation Therapy.

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.

Mathematical modeling of the synergistic interplay of radiotherapy and immunotherapy in anti-cancer treatments.

Introduction: While radiotherapy has long been recognized for its ability to directly ablate cancer cells through necrosis or apoptosis, radiotherapy-induced abscopal effect suggests that its impact extends beyond local tumor destruction thanks to immune response. Cellular proliferation and necrosis have been extensively studied using mathematical models that simulate tumor growth, such as Gompertz law, and the radiation effects, such as the linear-quadratic model. However, the effectiveness of radiotherapy-induced immune responses may vary among patients due to individual differences in radiation sensitivity and other factors. Methods: We present a novel macroscopic approach designed to quantitatively analyze the intricate dynamics governing the interactions among the immune system, radiotherapy, and tumor progression. Building upon previous research demonstrating the synergistic effects of radiotherapy and immunotherapy in cancer treatment, we provide a comprehensive mathematical framework for understanding the underlying mechanisms driving these interactions. Results: Our method leverages macroscopic observations and mathematical modeling to capture the overarching dynamics of this interplay, offering valuable insights for optimizing cancer treatment strategies. One shows that Gompertz law can describe therapy effects with two effective parameters. This result permits quantitative data analyses, which give useful indications for the disease progression and clinical decisions. Discussion: Through validation against diverse data sets from the literature, we demonstrate the reliability and versatility of our approach in predicting the time evolution of the disease and assessing the potential efficacy of radiotherapy-immunotherapy combinations. This further supports the promising potential of the abscopal effect, suggesting that in select cases, depending on tumor size, it may confer full efficacy to radiotherapy.