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Radiation dose effect in locally advanced non-small cell lung cancer.

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Radiation is the foundation of treatment for locally advanced non-small cell lung cancer (NSCLC), and as such, optimal radiation dose is essential for successful treatment. This article will briefly review biological considerations of radiation dose and their effect in the context of three-dimensional conformal radiation therapy (3D-CRT) including intensity modulated radiation therapy (IMRT) and stereotactic body radiation therapy (SBRT) for NSCLC.

It will focus on literature review and discussions regarding radiation dose effect in locally advanced NSCLC including potential severe and lethal toxicities of high dose radiation given with concurrent chemotherapy. Potential new approaches for delivering safe and effective doses by individualizing treatment based on functional imaging are being applied in studies such as the PET boost trial and RTOG1106.

The RTOG concept of delivering high dose radiation to the more resistant tumors with the use of isotoxic dose prescription and adaptive planning will also be discussed in detail.

Electromagnetic navigation bronchoscopy-guided fine needle aspiration for the diagnosis of lung lesions.

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Many peripheral lung lesions are beyond the reach of conventional bronchoscopes, and require percutaneous CT-guided or open surgical biopsy, which carry increased risks to the patient. Electromagnetic navigation bronchoscopy (ENB) is a relatively new technique, which uses an image guided localization system to direct steerable bronchoscopic tools to predetermined points within the bronchial tree. This technology allows improved access to peripheral lesions in particular.

We investigated the sensitivity and specificity of ENB-guided fine needle aspiration (FNA) in the diagnosis of lung lesions. All ENB-guided FNAs performed at one institution were included in the study. The superDimension i-Logic System™ was used in all cases. Pathologic reports of the ENB-guided FNAs, as well as all other pulmonary sampling performed simultaneously with the FNA and within 1 year of the ENB-guided FNA were reviewed. Patients with a positive ENB-guided FNA or malignancy within the same lobe within the follow-up period were considered positive for malignancy. Patients with an atypical diagnosis but no definitive malignancy were considered negative for malignancy for statistical purposes. Ninety-one patients underwent 95 ENB-guided FNAs over a 3-year period. Thirty-five patients (38%) were positive for malignancy. ENB-guided FNA had a sensitivity of 63% for the detection of malignancy. The sensitivity for the detection of malignancy using all ENB-guided sampling methods, including FNA, bronchoscopic biopsy, and bronchial brushing was 83%.

Pathologists and cytotechnologists should be aware of ENB-guided FNA as an emerging technology with a relatively high sensitivity for the diagnosis of peripheral lung lesions. Diagn. Cytopathol. 2014. © 2014 Wiley Periodicals, Inc.

The use of bevacizumab in non-small cell lung cancer: an update.

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Lung cancer is the leading cause of cancer-related death worldwide, with approximately 1.2 million deaths annually. The standard-of-care in patients with advanced disease is platinum-based doublet chemotherapy. Recent advances in the understanding of biological mechanisms of tumor growth have allowed for identification of some molecular targets for cancer treatment, such as vascular endothelial growth factor (VEGF) and epidermal growth factor receptor (EGFR). VEGF is a pro-angiogenetic factor, which binds membrane receptors, and whose intra-cytoplasmatic domain presents tyrosine kinase activity. Pathological angiogenesis promotes tumor growth and metastasis.

Targeted action against angiogenesis can lead to regression or normalization of neovascular structures and to inhibition of new blood vessel growth. The most commonly used mechanism is mediated by bevacizumab, a monoclonal antibody that selectively binds to VEGF and prevents interaction with its receptor. Currently bevacizumab is the only anti-angiogenic agent approved for the first-line treatment of non-small cell lung cancer (NSCLC) in selected patients. In the present review, we discuss the most important trials that demonstrate the efficacy and safety of bevacizumab. We also present an overview of the types of patients eligible for this treatment and a cost-effectiveness analysis.

In conclusion, the possibility of administering a treatment with bevacizumab must be carefully analyzed case by case. It is important to identify those patients who can really benefit from the use of this drug, through the identification of specific response markers.

Stereotactic body radiotherapy (sbrt) in lung oligometastatic patients: role of local treatments.

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Data in the literature suggest the existence of oligometastatic disease, a state in which metastases are limited in number and site. Different kinds of local therapies have been used for the treatment of limited metastases and in the recent years reports on the use of Stereotactic Ablative radiotherapy (SABR) are emerging and the early results on local control are promising.

Patients and methods: From October 2010 to February 2012, 76 consecutive patients for 118 lung lesions were treated. SABR was performed in case of controlled primary tumor, long-term of progression disease, exclusion of surgery, and number of metastatic sites <= 5. Different kinds of primary tumors were treated, the most common were lung and colon-rectal cancer. The total dose prescribed varied according to tumor site and maximum diameter. Dose prescription was 48 Gy in 4 fractions for peripheral lesions, 60 Gy in 8 fractions for central lesions and 60 Gy in 3 fractions for peripheral lesions with diameter <= 2 cm.

RESULTS: Dosimetric planning objectives were met for the cohort of patients with in particular V98% = 98.1 +/- 3.4% for the CTV and mean lung dose of 3.7 +/- 3.8Gy. Radiological response was obtained in the vast majority of patients. The local control at 1, 2 and 3 years was 95%, 89% and 89% respectively. No major pulmonary toxicity, chest pain or rib fracture occurred. The median follow up was 20 months (range 6-45 months). Overall Survival (OS) at 1, 2 and 3 years was 84.1%, 73% and 73% respectively.

CONCLUSIONS: SABR is feasible with limited morbidity and promising results in terms of local contro, survival and toxicity.

Full-dose Cisplatin and Oral Vinorelbine Concomitant with Radiotherapy in Unresectable Stage III Non-small Cell Lung Cancer: A Multi-center Phase II Study.

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Aim: To evaluate the efficacy and toxicities of combination of cisplatin and oral vinorelbine given at full doses concomitantly with radiotherapy for non-small cell lung cancer (NSCLC).

PATIENTS AND METHODS: Untreated patients with locally advanced inoperable stage IIIA/IIIB NSCLC were eligible for study inclusion. Treatment consisted of four cycles of oral vinorelbine at 60 mg/m(2) on days 1 and 8, and cisplatin at 80 mg/m(2) on day 1 every three weeks plus radiotherapy 66 Gy starting on day 1 of cycle 2 in fractions of 2 Gy/day over 6.5 weeks.

RESULTS: Forty-eight patients were enrolled. Their characteristics included: median age 61 years; female gender 10%; stage IIIA 46% and IIIB 54%; squamous carcinoma 63%, performance status PS0 42%; PS1 58%. Selected grade 3/4 toxicities were as follows: neutropenia 33%, concomitant febrile neutropenia 14.6%, anemia 12.5%, thrombocytopenia 16.6%, and esophagitis 12.5%. Two treatment-related deaths were reported, both during cycle 1. Radiotherapy was administered to 87.5% of patients; 7.1% of them received less than 60 Gy and 23.8% had delays due to adverse events. The objective response rate was 77.3%, with two complete responses and 32 partial responses. With a median follow-up of 19 months, the median progression-free survival was 12 months, and the 1-year overall survival rate was 72.3%. Median overall survival was 27.8 months, although the 95% confidence interval has not yet been achieved.

CONCLUSION: Full doses of cisplatin and oral vinorelbine can be administered with concomitant radiotherapy, with good efficacy and an acceptable safety profile for patients with stage IIIA/IIIB NSCLC.

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