Predictors of Local Control for Stereotactic Ablative Radiotherapy (SAbR) in Pulmonary Oligometastases from Gastrointestinal Malignancies.

BACKGROUND/AIM: To assess predictors of local control (LC) for stereotactic ablative radiotherapy (SAbR) in pulmonary oligometastatic disease (OMD) from gastrointestinal (GI) malignancies. PATIENTS AND METHODS: Patients with pulmonary OMD treated with SAbR from January 2016 to December 2018 were included in this observational analysis. Primary endpoint was LC. Uni- and multivariate analyses to assess variable correlations were conducted. RESULTS: Thirty-seven patients and 59 lung metastases were evaluated. The delivered dose was 30-60 Gy in 3-8 fractions. After a median follow-up of 23.0 months (range=6.3-50.4 months), LC rate at 1/2 years was 89.7%/85.0%, and increased to 96.0%/91.0% for lesions treated with a biologically effective dose (BED10) ≥100 Gy (p=0.03). RECIST response at 6 months was predictive for LC (p=0.002). CONCLUSION: SAbR is an effective option for pulmonary OMD from GI malignancies. A BED10 ≥100 Gy and radiological response at 6 months can affect LC.

A single-institutional brachytherapy experience in the management of esophageal cancer.

PURPOSE: The aim of this work was to analyze the efficacy of high-dose-rate brachytherapy in the management of patients with esophageal cancer. METHODS AND MATERIALS: Between 2001 and 2008, 104 patients (88 males and 16 females) received a brachytherapy treatment as a part of a personalized multimodal approach. The median age was 72 years, and the median Karnofsky performance status was 60. Brachytherapy was used in different situations: to complete a primary treatment with radical intent in patients not suitable for surgery; to control local recurrences; or to obtain a rapid and durable palliation of dysphagia in patients with metastases or in poor general condition. In selected cases, endoscopic ultrasound images were integrated in treatment planning procedure to obtain a more accurate volume definition. Efficacy in controlling dysphagia was assessed 1 month after brachytherapy. RESULTS: Fifty-one patients received a radical treatment, and 53 patients were treated to relieve the symptoms. The median overall survival was 20.8 months. Lymph node involvement was found to be a significant prognostic factor for overall survival and dysphagia. Dysphagia was controlled in 88 patients (84.6%), and the median dysphagia-free interval was 17.5 months. Early and late adverse events were generally mild to moderate. The most severe effects were esophagotracheal fistulas, observed in 3 patients. CONCLUSIONS: Brachytherapy has an important role in the management of esophageal cancer with a low rate of complications. endoscopic ultrasound-assisted treatment planning can be useful for a better individualization of curative treatments.

A multimodal approach to the treatment of bilateral choroidal metastases from thyroid carcinoma.

A 58-year old man, affected by metastatic thyroid carcinoma, experienced a progressive bilateral visual impairment. Ophthalmic examination revealed the presence of a choroidal mass with an associated exudative retinal detachment in both eyes. Twelve years before, a diagnosis of metastatic thyroid carcinoma had been established and the patient had been subject to several therapeutic procedures.In May 2007, he received a radiotherapy treatment to the left eye with an episcleral plaque and bilateral bulbar injection of bevacizumab. The patient had a rapid and stable visual acuity recovery. Twenty months after treatment, the lesion treated with radiotherapy was still stable whereas the contra-lateral lesion had evolved and determined a vitreal hemorrhage.

High-dose-rate brachytherapy in a large squamous cell carcinoma of the hand.

PURPOSE: High-dose-rate (192)Ir-based brachytherapy can be used as an exclusive treatment of large skin tumors when teletherapy or surgery is not feasible. A case of an extended inoperable skin epithelioma of the hand is reported; the lesion involved the first finger, the tenar, the palm, and the back. METHODS AND MATERIALS: A detailed description of an individual case is reported. A customized mold was created for the patient, to administer a fractionated brachytherapy treatment in a reproducible way. RESULTS: A total dose of 50Gy was administered in 10 fractions, after a time schedule of three fractions per week. The treatment was well tolerated and the acute effects (mainly, epitheliolysis) were resolved completely within a month after the treatment. CONCLUSIONS: Nine months after the treatment, the malignant lesion completely disappeared and the cosmetic results are quite satisfactory. Therefore, we conclude that the treatment technique is well adaptable to any particular geometry and that the fractionation scheme has proven to be well tolerated and effective in tumor eradication.

Synergistic antitumor activity of ZD6474, an inhibitor of vascular endothelial growth factor receptor and epidermal growth factor receptor signaling, with gemcitabine and ionizing radiation against pancreatic cancer.

PURPOSE: Standard treatments have modest effect against pancreatic cancer, and current research focuses on agents targeting molecular pathways involved in tumor growth and angiogenesis. This study investigated the interactions between ZD6474, an inhibitor of tyrosine kinase activities of vascular endothelial growth factor receptor-2 and epidermal growth factor receptor (EGFR), gemcitabine, and ionizing radiation in human pancreatic cancer cells and analyzed the molecular mechanisms underlying this combination. EXPERIMENTAL DESIGN: ZD6474, ionizing radiation, and gemcitabine, alone or in combination, were given in vitro to MIA PaCa-2, PANC-1, and Capan-1 cells and in vivo to MIA PaCa-2 tumor xenografts. The effects of treatments were studied by the evaluation of cytotoxicity, apoptosis, cell cycle, EGFR and Akt phosphorylation, modulation of gene expression of enzymes related to gemcitabine activity (deoxycytidine kinase and ribonucleotide reductase), as well as vascular endothelial growth factor immunohistochemistry and microvessel count. RESULTS: In vitro, ZD6474 dose dependently inhibited cell growth, induced apoptosis, and synergistically enhanced the cytotoxic activity of gemcitabine and ionizing radiation. Moreover, ZD6474 inhibited phosphorylation of EGFR and Akt and triggered cell apoptosis. PCR analysis showed that ZD6474 increased the ratio between gene expression of deoxycytidine kinase and ribonucleotide reductase. In vivo, ZD6474 showed significant antitumor activity alone and in combination with radiotherapy and gemcitabine, and the combination of all three modalities enhanced MIA PaCA-2 tumor growth inhibition compared with gemcitabine alone. CONCLUSIONS: ZD6474 decreases EGFR and Akt phosphorylation, enhances apoptosis, favorably modulates gene expression in cancer cells, and acts synergistically with gemcitabine and radiotherapy to inhibit tumor growth. These findings support the investigation of this combination in the clinical setting.