[Concurrent simultaneous integrated boost radiotherapy and cetuximab in head and neck squamous cell cancer patients: is it feasible in daily clinical practice?] / Radioterapia a intensità modulata con boost simultaneo più cetuximab in pazienti con carcinoma a cellule squamose in stadio localmente avanzato del distretto testa collo: è fattibile nella pratica clinica quotidiana?

INTRODUCTION AND AIM: Locally advanced head and neck squamous cell carcinoma (LA-Hnscc) is a true therapeutical challenge in the modern era and the scientific community is trying to face this challenge with new therapeutical strategies, including combinations of monoclonal antibodies and radiation therapy. The aim of this study is to evaluate clinical outcomes in LA-Hnscc patients unfit to receive platinum-based chemotherapy, treated with concurrent simultaneous integrated boost-intensity modulated radiotherapy (Sib-Imrt) + cetuximab (Ctx) in daily clinical practice. METHODS: LA-Hnscc patients not included in other prospective studies treated in 4 Italian radiotherapy units (2 Messina, 1 Rome, and 1 Lecce) using Sib-Imrt and Ctx were included in this study. Acute and late toxicities and overall survival (OS) have been evaluated. RESULTS: Data regarding 27 patients with squamous tumour were collected and reviewed. The primary tumour sites were oropharynx in 14 patients (51.9%), oral cavity in 7 (25.9%), larynx in 3 (11%) and other sites in 3(11%). There were 20 (74%) patients had stage IV (16 IVa and 4 IVb). Complete remission was observed in 18 patients (66.7%), a partial remission in 4 (14.8%) whilst 4 had a progression disease (14.8%). After 3 year of follow-up 7/27 patients were deaths. The OS was 95.5%, 62.5% and 52.9% respectively at 1,2 and 3 years. Acute toxicities were observed in all treated patients (mucositis, dermatitis and dysphagia) while 66.7% of patients developed late toxicities. All observed toxicities were grade 1 to 3 and just 1 patient developed a G4 toxicity. CONCLUSION: The concurrent bio-radiotherapy of Sib-Imrt and cetuximab is feasible in real-life daily clinical practice for LA-Hnscc patients unfit for platinum-based chemoradiotherapy.

Image-guided moderately hypofractionated radiotherapy for localized prostate cancer: a multicentric retrospective study (IPOPROMISE).

BACKGROUND: Moderate hypofractionated radiotherapy is a treatment option for the cure of localized prostate cancer (PCa) patients based on the results of randomized prospective trials, but there is a clinical concern about the relatively short length of follow-up, and real-world results on outcome and toxicity based on cutting-edge techniques are lacking. The objective of this study is to present the long-term results of a large multicentric series. MATERIALS AND METHODS: We retrospectively evaluated 1325 PCa patients treated with daily volumetric image-guided hypofractionated radiotherapy between 2007 and 2020 in 16 Centers. For survival endpoints, we used Kaplan-Meier survival curves and fitted univariate and multivariable Cox's proportional hazards regression models to study the association between the clinical variables and each survival type. RESULTS: At the end of the follow-up, 11 patients died from PCa. The 15-year values of cancer-specific survival (CSS) and biochemical relapse-free survival (b-RFS) were 98.5% (95%CI 97.3-99.6%) and 85.5% (95%CI 81.9-89.4%), respectively. The multivariate analysis showed that baseline PSA, Gleason score, and the use of androgen deprivation therapy were significant variables for all the outcomes. Acute gastrointestinal (GI) and genitourinary (GU) toxicities of grade ≥ 2 were 7.0% and 16.98%, respectively. The 15-year late grade ≥ 2 GI and GU toxicities were 5% (95%CI 4-6%) and 6% (95%CI 4-8%), respectively. CONCLUSION: Real-world long-term results of this multicentric study on cutting-edge techniques for the cure of localized PCa demonstrated an excellent biochemical-free survival rate of 85.5% at 15 years, and very low rates of ≥ G3 late GU and GI toxicity (1.6% and 0.9% respectively), strengthening the results of the available published trials.

Radiotherapy of Orbital and Ocular Adnexa Lymphoma: Literature Review and University of Catania Experience.

Orbital and ocular adnexa lymphomas are rare neoplasms confined to the orbital region. The prognosis is generally favorable, with a high proportion of localized disease, indolent clinical course, prolonged disease-free intervals, and low lymphoma-related mortality rate. We report our experience on eleven patients with confirmed histological diagnosis of lymphoma stage IE-IIE, treated between 2010 and 2021 with radiotherapy alone or in association with chemotherapy or immunotherapy. Eight patients were treated with primary radiotherapy only, while three received previous systemic treatments. Six patients were treated with Proton beam therapy (PBT), and five with external beam radiotherapy (EBRT). The five-year local control rate was 98%; only one patient developed an out-of-field recurrence. We also conducted a comprehensive literature review using electronic databases (PubMed, EMBASE, and Cochrane Library). Articles were selected based on their pertinence to treatment of the ocular and adnexal lymphoma focusing on radiotherapy techniques (electron beam radiotherapy, photon beam radiotherapy, or proton beam radiotherapy), treatment total dose, fractionation schedule, early and late radio-induced toxicities, and patient's clinical outcome. Radiotherapy is an effective treatment option for orbital lymphoma, especially as standard treatment in the early stage of orbital lymphoma, with excellent local control rate and low rates of toxicity.

Stereotactic Body Radiation Therapy and Abiraterone Acetate for Patients Affected by Oligometastatic Castrate-Resistant Prostate Cancer: A Randomized Phase II Trial (ARTO).

PURPOSE: ARTO (ClinicalTrials.gov identifier: NCT03449719) is a multicenter, phase II randomized clinical trial testing the benefit of adding stereotactic body radiation therapy (SBRT) to abiraterone acetate and prednisone (AAP) in patients with oligometastatic castrate-resistant prostate cancer (CRPC). MATERIALS AND METHODS: All patients were affected by oligometastatic CRPC as defined as three or less nonvisceral metastatic lesions. Patients were randomly assigned 1:1 to receive either AAP alone (control arm) or AAP with concomitant SBRT to all the sites of disease (experimental arm). Primary end point was the rate of biochemical response (BR), defined as a prostate-specific antigen (PSA) decrease ≥50% from baseline measured at 6 months from treatment start. Complete BR (CBR), defined as PSA < 0.2 ng/mL at 6 months from treatment, and progression-free survival (PFS) were secondary end points. RESULTS: One hundred and fifty-seven patients were enrolled between January 2019 and September 2022. BR was detected in 79.6% of patients (92% v 68.3% in the experimental v control arm, respectively), with an odds ratio (OR) of 5.34 (95% CI, 2.05 to 13.88; P = .001) in favor of the experimental arm. CBR was detected in 38.8% of patients (56% v 23.2% in the experimental v control arm, respectively), with an OR of 4.22 (95% CI, 2.12 to 8.38; P < .001). SBRT yielded a significant PFS improvement, with a hazard ratio for progression of 0.35 (95% CI, 0.21 to 0.57; P < .001) in the experimental versus control arm. CONCLUSION: The trial reached its primary end point of biochemical control and PFS, suggesting a clinical advantage for SBRT in addition to first-line AAP treatment in patients with metastatic castration-resistant prostate cancer.

Modulation of Radiation Doses and Chimeric Antigen Receptor T Cells: A Promising New Weapon in Solid Tumors-A Narrative Review.

Tumor behavior is determined by its interaction with the tumor microenvironment (TME). Chimeric antigen receptor (CART) cell therapy represents a new form of cellular immunotherapy (IT). Immune cells present a different sensitivity to radiation therapy (RT). RT can affect tumor cells both modifying the TME and inducing DNA damage, with different effects depending on the low and high doses delivered, and can favor the expression of CART cells. CART cells are patients' T cells genetically engineered to recognize surface structure and to eradicate cancer cells. High-dose radiation therapy (HDRT, >10-20 Gy/fractions) converts immunologically "cold" tumors into "hot" ones by inducing necrosis and massive inflammation and death. LDRT (low-dose radiation therapy, >5-10 Gy/fractions) increases the expansion of CART cells and leads to non-immunogenetic death. An innovative approach, defined as the LATTICE technique, combines a high dose in higher FDG- uptake areas and a low dose to the tumor periphery. The association of RT and immune checkpoint inhibitors increases tumor immunogenicity and immune response both in irradiated and non-irradiated sites. The aim of this narrative review is to clarify the knowledge, to date, on CART cell therapy and its possible association with radiation therapy in solid tumors.

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.

Hypofractionated Radiotherapy in Localized, Low-Intermediate-Risk Prostate Cancer: Current and Future Prospectives.

At the time of diagnosis, the vast majority of prostate carcinoma patients have a clinically localized form of the disease, with most of them presenting with low- or intermediate-risk prostate cancer. In this setting, various curative-intent alternatives are available, including surgery, external beam radiotherapy and brachytherapy. Randomized clinical trials have demonstrated that moderate hypofractionated radiotherapy can be considered as a valid alternative strategy for localized prostate cancer. High-dose-rate brachytherapy can be administered according to different schedules. Proton beam radiotherapy represents a promising strategy, but further studies are needed to make it more affordable and accessible. At the moment, new technologies such as MRI-guided radiotherapy remain in early stages, but their potential abilities are very promising.

Integrated Intensified Chemoradiation in the Setting of Total Neoadjuvant Therapy (TNT) in Patients with Locally Advanced Rectal Cancer: A Retrospective Single-Arm Study on Feasibility and Efficacy.

While surgery is considered the main treatment for early-stage rectal cancer, locally advanced rectal cancer needs to be handled with a multidisciplinary approach. Based on literature data suggesting promising advantages of total neoadjuvant therapy (TNT), we performed a retrospective, single-arm, single-center study on 45 patients affected by histologically and radiologically proven locally advanced rectal cancer, with the aim of analyzing the feasibility and short-term efficacy of an integrated intensified treatment in the setting of TNT. Each analyzed patient performed three cycles of FOLFOX4 or De Gramont induction chemotherapy (iCT), followed by concurrent chemoradiotherapy (CRT) with long course radiotherapy (LCRT) plus concomitant boost and continuous 5-FU infusion, followed by three cycles of FOLFOX4 or De Gramont consolidation chemotherapy (conCT) and then surgery with total mesorectal excision. At a median follow-up of 30 months, this strategy has shown to be feasible and effective in terms of pathological complete response (pCR) and short-term disease-free survival (DFS).

The "Combo" radiotherapy treatment for high-risk grade 2 meningiomas: dose escalation and initial safety and efficacy analysis.

PURPOSE: The subgroup "high-risk" WHO grade 2 (hRG2) meningiomas may benefit from adjuvant radiation therapy (RT), but results are still suboptimal with high rates of local progression. A dose escalation using high-conformal RT techniques needs to be evaluated in terms of efficacy and safety. We report the results of a dose-escalation study, named "Combo-RT", combining Intensity Modulated Radiotherapy (IMRT) or Volumetric Arc Therapy (VMAT) with Hypofractionated Stereotactic Radiotherapy (hSRT) boost. PATIENTS AND METHODS: From November 2015 to January 2019, we prospectively enrolled 16 patients with hRG2. Seven patients had subtotal resection (STR) and 9 patients had a recurrent tumor. All patients received Combo-RT: LINAC-IMRT/ VMAT on the surgical bed and CyberKnife-hSRT boost on residual/recurrent meningioma Toxicity and initial efficacy were evaluated. RESULTS: The median age was 62 years (range, 31-80 years). The median cumulative dose delivered was 46 Gy For IMRT or VMAT and 15 Gy in 3 fractions at a median isodose line of 77% for hSRT. The median cumulative BED and EQD2 were 108.75 Gy and 72.5 Gy respectively. 3-year-PFS was 75% for the whole cohort,100% for patients with STR, and 55.5% for recurrent patients. Negligible toxicities, and stable or improved symptoms during long-term follow-up were observed. Salvage treatment for recurrence was an independent predictor of treatment failure (P = 0.025). CONCLUSIONS: With the limitation of a small series of patients, our results suggest that a dose escalation for hRG2 meningiomas, using a Combo-RT approach, is safe and particularly effective in the subgroup of patients with STR. Further studies are warranted.

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.

Impressive Results after "Metabolism-Guided" Lattice Irradiation in Patients Submitted to Palliative Radiation Therapy: Preliminary Results of LATTICE_01 Multicenter Study.

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.

First-ever Clinical Experience With Magnetic Resonance-based Lattice Radiotherapy for Treating Bulky Gynecological Tumors.

BACKGROUND/AIM: Bulky gynecological tumors are a rare entity of large primary tumors, for which only a limited range of therapeutic options is available. Among these, when surgical approach is deemed unsuitable based on comorbidities and/or technical feasibility, radiotherapy is administered at low doses with palliative intent only. Aggressive treatment of such large primary tumors might significantly prolong patient survival and improve their quality of life by effectively delaying tumor progression to extra-pelvic sites. Lattice radiotherapy is a type of Spatially Fractionated Radiation Therapy, specifically devoted to treat and debulk large tumor masses, which are not candidates for normofractionated homogeneous high-dose radiotherapy schedules due to potential harmful dose-volume effects. The aim of this case study was to report on the feasibility of a Magnetic Resonance Imaging-based Lattice approach. CASE REPORT: Herein we report a case of a patient with a locally advanced uterine serous papillary carcinoma submitted to radical surgery and rapidly experiencing a painful large pelvic recurrence eroding the sacrum. The patient was submitted to Magnetic Resonance Imaging-based Lattice radiotherapy consisting of an Apparent Diffusion Coefficient Map-Based boost followed by a normofractionated radiotherapy course. The patient impressively developed an almost complete clinical response with a long-lasting symptom relief. Subsequently, the disease course was burdened by limited extra- and in-field recurrences amenable of re-irradiation as long as the cumulative radiation dose did not seriously threaten the tolerance of neighboring organs at risk (especially the bowel). The patient is still alive 20 months after Lattice radiotherapy delivery with no radiation-related toxicities. CONCLUSION: Magnetic resonance imaging (MRI)-based Lattice radiotherapy might be safe and effective for the treatment of inoperable bulky gynecological tumors.

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.

Non-stereotactic radiotherapy in older cancer patients.

Old or very old oncological patients represent a heterogeneous and frail population due to concomitant comorbidities. Whether radiotherapy alone or in combination with novel cancer drugs may provide a clear benefit in this setting of patients is still a matter of debate. The aim of our review is to analyze the evaluation process and the different therapeutic possibilities in older cancer patients, focusing on the different and most disparate applications of radiotherapy. We reviewed the most recent literature on radiotherapy in older patients providing clinical evidence of treatment related toxicity, tolerance and outcomes using standard fractionated and/or hypofractionated irradiation alone or in combination with chemotherapy, targeted and immunotherapy. In older cancer patients unfit for systemic therapy or surgery, radiotherapy represents a valid therapeutic approach, both with curative and palliative intents, ensuring excellent patient compliance in terms of local toxicity and adherence to therapy.

Advanced or Metastatic Cutaneous Squamous Cell Carcinoma: The Current and Future Role of Radiation Therapy in the Era of Immunotherapy.

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.

Stereotactic radiotherapy for bone oligometastases.

About 60-90% of cancer patients are estimated to develop bone metastases, particularly in the spine. Bone scintigraphy, computed tomography (CT ) and magnetic resonance imaging (MRI ) are currently used to assess metastatic bone disease; positron emission tomography/computed tomography (PET-CT ) has become more widespread in clinical practice because of its high sensitivity and specificity with about 95% diagnostic accuracy. The most common and well-known radiotracer is 18F-fluorodeoxyglucose (18FDG); several other PET-radiotracers are currently under investigation for different solid tumors, such as 11C or 18FDG-choline and prostate specific membrane antigen (PSMA)-PET/CT for prostate cancer. In treatment planning, standard and investigational imaging modalities should be registered with the planning CT so as to best define the bone target volume. For target volume delineation of spine metastases, the International Spine Radiosurgery Consortium (ISRC ) of North American experts provided consensus guidelines. Single fraction stereotactic radiotherapy (SRT ) doses ranged from 12 to 24 Gy; fractionated SRT administered 21-27 Gy in 3 fractions or 20-35 Gy in 5 fractions. After spine SRT, less than 5% of patients experienced grade ≥ 3 acute toxicity. Late toxicity included the extremely rare radiation-induced myelopathy and a 14% risk of de novo vertebral compression fractures.

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.

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.

18F-FDG PET/CT Imaging of Immune Checkpoint Inhibitor-Related "Retroperitoneal Panniculitis".

ABSTRACT: A 71-year-old woman was operated on for undifferentiated lung adenocarcinoma. Four months after surgery, she developed bone and adrenal metastases. She underwent palliative radiation therapy of left scapula and right iliac bone. Thereafter, she started immune checkpoint inhibitor (ICI) therapy with anti-PD-1 antibodies achieving complete tumor response. Twenty months later, a follow-up 18F-FDG PET/CT confirmed tumor response and revealed high radiotracer accumulation in correspondence of retroperitoneal and subcutaneous fat opacities. The contiguous fasciae were mildly thickened. The temporal relation with ICI therapy together with tumor response and corticosteroids therapy effectiveness led to conclude for ICI-related adverse events.