Ciro Franzese

Changes in neurocognitive functioning and quality of life in adult patients with brain tumors treated with radiotherapy

This review aims to summarize what is currently known about neurocognitive outcome and quality of life in patients with brain tumors treated with radiotherapy. Whether potential tumor-controlling benefits of radiotherapy outweigh its potential toxicity in the natural history of brain tumors is a matter of debate. This review focuses on some of the adult main brain tumors, for which the issue of neurocognitive decline has been thoroughly studied: low-grade gliomas, brain metastases, and primary central nervous system lymphomas. The aims of this review are: (1) the analysis of existing data regarding the relationship between radiotherapy and neurocognitive outcome; (2) the identification of strategies to minimize radiotherapy-related neurotoxicity by reducing the dose or the volume; (3) the evidence-based data concerning radiotherapy withdrawal; and (4) the definition of patients subgroups that could benefit from immediate radiotherapy. For high grade gliomas, the main findings from literature are summarized and some strategies to reduce the neurotoxicity of the treatment are presented. Although further prospective studies with adequate neuropsychological follow-up are needed, this article suggests that cognitive deficits in patients with brain tumor have a multifactorial genesis: radiotherapy may contribute to the neurocognitive deterioration, but the causes of this decline include the tumor itself, disease progression, other treatment modalities and comorbidities. Treatment variables, such as total and fractional dose, target volume, and irradiation technique can dramatically affect the safety of radiotherapy: optimizing radiation parameters could be an excellent approach to improve outcome and to reduce neurotoxicity. At the same time, delayed radiotherapy could be a valid option for highly selected patients.

Prognostic value of positive human epidermal growth factor receptor 2 status and negative hormone status in patients with T1a/T1b, lymph node-negative breast cancer.

The objective of this study was to evaluate prognostic factors of local and distant recurrence in patients diagnosed with T1a and T1b, lymph node‐negative breast carcinoma (BC) with emphasis on human epidermal growth factor receptor 2 (HER2) status.

A PPAR-gamma agonist attenuates pulmonary injury induced by irradiation in a murine model.

PURPOSE/OBJECTIVE(S) Due to its anti-inflammatory, antifibrotic and antineoplastic properties, the PPAR-γ agonist rosiglitazone is of interest in the prevention and therapy of radiation-induced pulmonary injury. We evaluated the radioprotective effects of rosiglitazone in a murine model of pulmonary damage to determine whether radioprotection was selective for normal and tumor tissues. METHODS Lungs in C57BL/6J mice were irradiated (19 Gy) with or without rosiglitazone (RGZ, 5mg/kg/day for 16 weeks, oral gavage). Computed tomography (CT) was performed and Hounsfield Units (HU) were determined during the observation period. Histological analysis and evaluation of fibrosis/inflammatory markers by western blot were performed at 16 weeks. A549 tumor-bearing CD1 mice were irradiated (16 Gy) with or without RGZ, and tumor volumes were measured at 35 days. RESULTS Rosiglitazone reduced radiologic and histologic signs of fibrosis, inflammatory infiltrate, alterations to alveolar structures, and HU lung density that was increased due to irradiation. RGZ treatment also significantly decreased Col1, NF-kB and TGF-β expression and increased Bcl-2 protein expression compared to the irradiation group and reduced A549 clonogenic survival and xenograft tumor growth. CONCLUSIONS Rosiglitazone exerted a protective effect on normal tissues in radiation-induced pulmonary injury, while irradiated lung cancer cells were not protected in vivo and in vitro. Thus, rosiglitazone could be proposed as a radioprotective agent in the treatment of lung cancer.

Low Prevalence of K-RAS, EGF-R and BRAF Mutations in Sinonasal Adenocarcinomas. Implications for Anti-EGFR Treatments

We have previously shown that a subset of sinonasal intestinal-type adenocarcinomas (ITAC) shows activation of the epidermal growth factor-receptor (EGFR) pathway. In this study we examine the status of the EGFR, KRAS and BRAF genes in a series of sinonasal intestinal (ITAC) and non-intestinal type adenocarcinomas (non-ITAC). Eighteen ITACs and 12 non-ITACs were studied immunohistochemically for EGFR expression. Point mutations were analyzed for EGFR exons 19 and 21, KRAS exon 2 and BRAF exon 15 by direct sequencing. Non-ITACs showed significantly higher expression of EGFR (p = 0.015). Mutation analysis revealed one ITAC with EGFR and one ITAC with KRAS mutation, while two non-ITACs presented mutation of BRAF. We conclude that a subset of sinonasal adenocarcinomas shows overexpression of EGFR, while activating mutations of the signaling cascade downstream of EGFR are rare, suggesting that these tumors could be good candidates for anti-EGFR therapies.

Management of inflammatory breast cancer: focus on radiotherapy with an evidence-based approach.

Inflammatory breast cancer represents a rare and extremely aggressive subtype of breast cancer. Due to its rarity, prospective studies are a difficult goal to obtain in this field. Nowadays a multimodal approach seems to be the standard approach. Role and timing of surgery, radiotherapy and chemotherapy are still debated issues. In this scenario interest is rising in molecular and target therapies. We performed a review analyzing the management of this unfavorable disease focusing on the role of radiotherapy, with particular emphasis on levels of evidence.

The role of stereotactic body radiation therapy (SBRT) in the treatment of oligometastatic disease in the elderly

OBJECTIVE To report about clinical outcome of stereotactic body radiation therapy (SBRT) in the treatment of oligometastatic disease in elderly patients. METHODS Patients with 1-4 inoperable metastases were treated with SBRT. Dose prescription ranged from 40 to 75 Gy in 3-8 fractions. SBRT was delivered using the volumetric modulated arc therapy technique with flattening filter-free photon beams. The primary end points were in-field local control (LC) and toxicity. Secondary end points were overall survival (OS) and disease-specific survival (DSS). RESULTS 82 patients with 111 total metastases were treated. Median age was 79 years. 64 patients (78%) had a single lesion; the remaining patients had 2-4 lesions. 16 (14.4%) lesions were localized in the abdomen, 50 (45.0%) in the liver and 45 (40.5%) in the lungs. Local response was observed for 87 lesions (78.4%) while local progression was observed in 24 lesions (21.6%). Actuarial 1-year LC was 86.8% ± 3.3%. Actuarial 1-year OS was 93.6% ± 2.7%. 2-year findings were 76.3% ± 4.4% and 72.0% ± 5.6%, respectively. Actuarial 1- and 2-year DSS results were 97.5% ± 2.0% and 81.6% ± 4.9%, respectively. Treatment-related Grade 2-3 toxicity was observed in five patients (4.2%); Grade 1 toxicity in seven patients (5.9%) and no toxicity was observed in 85.4% of the cases. CONCLUSION SBRT is a safe and effective therapeutic option for the treatment of oligometastatic disease in the elderly with acceptable rates of LC and low treatment-related toxicity. ADVANCES IN KNOWLEDGE The use of SBRT for oligometastatic disease in the elderly can be considered as a valuable approach, particularly for patients with fragile status or refusing other approaches.

Minimally Invasive Stereotactical Radio-ablation of Adrenal Metastases as an Alternative to Surgery

Purpose The purpose of this study was to study the clinical outcome for patients with metastases of the adrenal gland treated with stereotactic body radiation therapy. Materials and Methods Forty-six patients were studied retrospectively. The dose prescription was 40 Gy in four fractions. Dosimetric analysis was performed using the dose volume histograms while clinical outcome was assessed using actuarial analysis with determination of the overall survival (OS) and local control (LC) rates. Results The planning objectives were met for all patients. With a median follow-up period of 7.6 months, at the last follow-up 42 patients (91.3%) were alive and four had died because of distant progression. The actuarial mean OS was 28.5±1.6 months, the median was not reached. One-year and 2-year OS were 87.6±6.1%. None of the risk factors was significant in univariate analysis. Actuarial mean LC was 14.6±1.8 months (95% confidence interval [CI], 11.0 to 18.2) and median LC was 14.5±2.0 months (95% CI, 10.5 to 18.5). One-year and 2-year LC were 65.5±11.9% and 40.7±15.8%, respectively. A mild profile of toxicity was observed in the cohort of patients. Forty patients (86.9%) showed no complication (grade 0); two patients reported asthenia, six patients (13.1%) reported either pain, nausea, or vomiting. Of these six patients, five patients (10.9%) were scored as grade 1 toxicity while one patient (2.2%) was scored as grade 2. Conclusion Stereotactic body radiation therapy treatment provided an adequate clinical response in the management of adrenal gland metastases.

Isolated chest wall implantation of non-small cell lung cancer after fine-needle aspiration: a case report and review of the literature

Percutaneous fine-needle aspiration biopsy (FNAB) is a well-established and useful procedure in the diagnosis of lung squamous cell carcinoma (LSCC). Tumor seeding has been shown to be a potential risk. We report the case and management of a 78-year-old patient affected by LSCC who developed a chest wall metastasis in a straight line from the primary lesion along the FNAB needle track. Although tumor seeding after FNAB is a rare but possible complication, we suggest that careful examination for implantation (with periodical CT scans) should be performed for at least three years after FNAB.

Role of Stereotactic Body Radiation Therapy with Volumetric-Modulated Arcs and High-Intensity Photon Beams for the Treatment of Abdomino-Pelvic Lymph-Node Metastases

ABSTRACT Aim: To study clinical outcome for oligometastatic patients (abdominal lymph-node metastases) treated with stereotactic body radiation therapy. Materials and methods: Seventy-one patients were studied retrospectively. Dose prescription was 45 Gy in six fractions. Clinical outcome was assessed with actuarial analysis. Results: The median follow-up was 1.5 years; 45 patients (63.3%) had solitary metastasis, and 26 (36.6%) had multiple lesions. Local control was achieved in 97.5% with a 1-year actuarial rate of 83%. Two-year progression-free survival was 63.1%, and the overall survival was 76.9%. Two patients (3%) developed grade 2 gastro-enteric toxicity. Conclusions: The treatment provided adequate clinical response in the management of oligometastatic cases.

A Case of Focal Haematopoietic Hyperplasia of a Vertebral Body and Review of the Modern Literature

We report on a case of focal haematopoietic hyperplasia occurring in the haematopoietic marrow in a lumbar vertebral body, of a young man. The PET scan performed showed high uptake of the radiotracer in the vertebral body of L3 and a MRI of the lumbar spine confirmed the vertebral lesion. A biopsy of the L3 vertebral body lesion was performed and the histological result was of chronic myeloproliferative disease but the analysis performed consequently excluded the diagnosis of chronic myeloproliferative disorder, according to the WHO criteria. Focal benign hyperplasia is regarded a late reactive process after trauma, as well as the case reported