[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.

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.

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.

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.

Acute kidney injury in a patient with metabolic syndrome.

INTRODUCTION: The metabolic syndrome (MS) encompasses many metabolic abnormalities and the insulin resistance is considered as one of the most significant denominators. The chronic kidney disease (CKD) is an emerging health problem but only few patients would reach the end stage renal disease. There exists an increasing strong association between MS and CKD, but up until now the link between MS and CKD is unclear and there are few studies regarding the renal histology in MS. METHODS: We describe an acute tubulointerstitial nephritis case, due to both infective and pharmacological aetiology, overlapping relevant histological changes (focal segmental glomerulosclerosis [FSG], hyaline arteriosclerosis) in a patient with MS and previously normal renal function. Despite the severe vascular finding (elevated renal arterial resistive index), the patient recovered a normal renal function. RESULTS: We reviewed the kidney pathological studies in MS and analyzed the principal renal histological images of glomerulomegaly, segmental glomerulosclerosis, and obesity-related glomerulopathy. CONCLUSION: Despite the strong association, the renal involvement in MS has not been proven. A greater knowledge of the combination of histological renal changes in MS can help to understand the pathophysiological mechanism(s) of MS.

[Membranous glomerulonephritis with crescent overlapping]. / La Glomerulonefrite membranosa con sovrapposizione crescentica.

Acute crescentic transformation is a rare but well described event in patients with membranous glomerulonephritis. We report our experience with a 66-year-old Caucasian man presented for rapid decline in renal function. For nearly 10 years, he was suffering from hypertension and mixed sensori-motor polyneuropathy. He performed therapy with prednisone and azathioprine, suspended 1 year before presentation. Moreover, six months before presentation, laboratory tests showed a serum creatinine concentration 220 mol/L and a 24-h protein excretion 0,75 g/d. The physical examination showed oedema and severe hypertension; the 24-h protein excretion was 1,1 gr/d and creatinine concentration was 550.8 mol/L; ANCA and other immunological tests were negative. There was no evidence of SLE, infection or malignancy. The kidney biopsy highlighted a membranous GN with crescentic overlap. The patient was treated with steroid and cyclophosphamide. Because there was no sign of improvement after 2 months, we stopped the cyclophosphamide therapy and the patient started chronic haemodialysis treatment. Unlike membranous nephropathy, patients with superimposed crescentic glomerulonephritis appear to have a more aggressive clinical course. The importance of recognizing this group of patients with membranous nephropathy and crescentic glomerulonephritis is that immunosuppressive therapy may ameliorate the progression of renal damage and in some cases early treatment was associated with useful recovery of renal function.

A case of acute EPS with local cocoon formation in a patient on peritoneal dialysis.

Encapsulating peritoneal sclerosis is a rare and life-threatening complication of long-term peritoneal dialysis and until now there is no established medical treatment. Many factors have been incriminated in its pathogenesis but they do not explain all risk conditions. We report our experience and we investigate the predisposing factors. Probably unidentified factors make some patients more susceptible to developing encapsulating peritoneal sclerosis.