Alexander Chi

Systemic review of the patterns of failure following stereotactic body radiation therapy in early-stage non-small-cell lung cancer: Clinical implications

PURPOSE To analyze the patterns of failure, the toxicity profile, and the factors influencing efficacy of stereotactic body radiation (SBRT) for early-stage non-small-cell lung cancer (NSCLC). METHODS AND MATERIALS A search was based on PubMed electronic databases. All searches were conducted in May, 2009. RESULTS The local control ranged from 80% to 100% in most studies with adequate isocentric or peripheral biologically effective dose (BED). Recurrences were associated with increased tumor size. The main pattern of failure after SBRT was distant metastasis. Grades 3-5 toxicity occurred mostly in centrally located tumors, and adjuvant chemotherapy may further decrease all recurrences; possibly translating to a survival benefit in large or centrally located tumors where high BED cannot be safely reached. CONCLUSION SBRT is an excellent treatment option for early-stage, and mostly medically inoperable, NSCLC. BED at both the isocenter and the tumor periphery is very important for optimal tumor control; higher doses are required for large (T2) lesions; SBRT for centrally located tumors can be feasible with a much less aggressive dose regimen than 60-66Gy/3 fractions and adjacent critical structures excluded from the target volume; chemotherapy may optimize the clinical outcome in large or centrally located lesions.

Treatment of Brain Metastasis from Lung Cancer

Brain metastases are not only the most common intracranial neoplasm in adults but also very prevalent in patients with lung cancer. Patients have been grouped into different classes based on the presence of prognostic factors such as control of the primary tumor, functional performance status, age, and number of brain metastases. Patients with good prognosis may benefit from more aggressive treatment because of the potential for prolonged survival for some of them. In this review, we will comprehensively discuss the therapeutic options for treating brain metastases, which arise mostly from a lung cancer primary. In particular, we will focus on the patient selection for combined modality treatment of brain metastases, such as surgical resection or stereotactic radiosurgery (SRS) combined with whole brain irradiation; the use of radiosensitizers; and the neurocognitive deficits after whole brain irradiation with or without SRS. The benefit of prophylactic cranial irradiation (PCI) and its potentially associated neuro-toxicity for both small cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC) are also discussed, along with the combined treatment of intrathoracic primary disease and solitary brain metastasis. The roles of SRS to the surgical bed, fractionated stereotactic radiotherapy, WBRT with an integrated boost to the gross brain metastases, as well as combining WBRT with epidermal growth factor receptor (EGFR) inhibitors, are explored as well.

Intensity-Modulated Radiotherapy After Extrapleural Pneumonectomy in the Combined-Modality Treatment of Malignant Pleural Mesothelioma

Introduction: Local therapy is becoming increasingly important as a part of the definitive treatment for malignant pleural mesothelioma after extrapleural pneumonectomy (EPP) because of the emergence of trimodality therapy consisted of chemotherapy, EPP, and adjuvant radiotherapy. Herein, we explore the current evidence and indications for adjuvant intensity-modulated radiotherapy (IMRT), as well as how to further improve this technique and adapt new technology in the delivering adjuvant radiotherapy in the setting of trimodality therapy. Methods: A systematic review of relevant studies identified through PubMed, ISI Web of Knowledge (Web of Science), the Cochrane Library, and the National Guideline Clearinghouse search engines was performed. Results: Local control remains poor despite the inclusion of conventional adjuvant radiation therapy in trimodality therapy. This can be improved by the delivery of adjuvant IMRT. However, IMRT can be associated with severe pulmonary toxicity if the radiation dose to the remaining lung is not kept to a very low level. This is especially true when patients are receiving chemotherapy. New advances in technology can allow for lower doses to the contralateral lung, decreased treatment delivery time, and improved target dose coverage. Conclusion: Excellent local control can be achieved through adjuvant IMRT after EPP for malignant pleural mesothelioma. Severe pulmonary toxicity may be avoided by setting stringent dose constraints for the contralateral lung. This can be aided by the advances in technology. Post-treatment surveillance may be reliably conducted by periodical [18F]-fluorodeoxyglucose-positron emission tomography imaging.

EGFR inhibition in non-small cell lung cancer: current evidence and future directions.

EGFR inhibition has emerged to be an important strategy in the treatment of non-small cell lung cancer (NSCLC). Small molecule tyrosine kinase inhibitors (TKIs) and mono-clonal antibodies (mAbs) to the EGFR have been tested in multiple large randomized phase III studies alone or combined with chemotherapy, as well as small phase I-II studies which investigated their efficacy as radiosensitizers when combined with radiotherapy. In this review, we described the current clinical outcome after treatment with EGFR TKIs and mAbs alone or combined with chemotherapy in advanced stage NSCLC, as well as the early findings in feasibility/phase I or II studies regarding to whether EGFR TKI or mAb can be safely and effectively combined with radiotherapy in the treatment of locally advanced NSCLC. Furthermore, we explore the potential predictive biomarkers for response to EGFR TKIs or mAbs in NSCLC patients based on the findings in the current clinical trials; the mechanisms of resistance to EGFR inhibition; and the strategies of augmenting the antitumor activity of the EGFR inhibitors alone or when combined with chemotherapy or radiotherapy.

Feasibility of Helical Tomotherapy in Stereotactic Body Radiation Therapy for Centrally Located Early Stage Non‒Small-Cell Lung Cancer or Lung Metastases

PURPOSE To investigate the ability of helical tomotherapy (HT) to spare critical organs immediately adjacent to the tumor target in stereotactic body radiation therapy (SBRT) for centrally located lung lesions. METHODS AND MATERIALS HT SBRT plans for 10 patients with centrally located lesions or lesions immediately adjacent to a critical structure were generated. A total of 70 Gy in 10 fractions was prescribed to the planning target volume (PTV) to satisfy a target volume coverage of ≥95% PTV receiving 70 Gy and an established set of dose constraints for the organs at risk (OARs). Quality assurance (QA) of the HT plans was performed with both ion chamber and film measurements. RESULTS The PTV coverage criteria was met with 95% of the PTV receiving 70.68 ± 0.33 Gy for all cases even though the OARs immediately adjacent to the PTV ranged from 0.38 to 0.85 cm away. The mean lung dose (MLD), and V(20) were 7.15 ± 1.44 Gy, and 11.93 ± 3.24 % for the total lung, respectively. The dose parameters of MLD, V(5), V(10), and V(20) for the contralateral lung were significantly lower than those for the ipsilateral lung (p < 0.05). An average dose fall off from the PTV periphery to the edge of the immediately adjacent OAR was 47.6% over an average distance of 4.87 mm. Comparison of calculated and measured doses with the ion chamber showed an average of 1.85% point dose error, whereas an average mean gamma and the area with a gamma larger than 1 of 0.20 and 0.94% were observed, respectively. CONCLUSION HT allows the sparing of critical structures immediately adjacent to the tumor target, thus making SBRT for these centrally located lesions feasible.

Effectiveness of intensity-modulated and image-guided radiotherapy to spare the mandible from excessive radiation

We would like to assess the effectiveness of intensity-modulated radiotherapy (IMRT) or image-guided radiotherapy (IGRT) to decrease the risk of osteoradionecrosis in locally advanced head and neck cancer. We conducted a retrospective study of 83 patients with head and neck cancer undergoing concurrent definitive chemoradiation, post-operative radiotherapy or chemoradiation, or radiotherapy alone with IMRT or IGRT. Mean mandibular dose was, respectively, 43.6Gy and 43.8Gy for the IMRT and IGRT technique. At a median follow-up of 28 months (5-55 months), only one patient developed osteoradionecrosis requiring hyperbaric oxygen. Sharp dose falloff associated with IMRT and IGRT decreased excessive radiation of the mandible and may reduce the risks of osteoradionecrosis.

Feasibility of Intensity-Modulated and Image-Guided Radiotherapy for Functional Organ Preservation in Locally Advanced Laryngeal Cancer

Purpose The study aims to assess the feasibility of intensity-modulated and image-guided radiotherapy (IMRT, and IGRT, respectively) for functional preservation in locally advanced laryngeal cancer. A retrospective review of 27 patients undergoing concurrent chemoradiation for locally advanced laryngeal cancers (8 IMRT, 19 IGRT) was undertaken. In addition to regular clinical examinations, all patients had PET imaging at 4 months and 10 months after radiotherapy, then yearly. Loco-regional control, speech quality and feeding-tube dependency were assessed during follow-up visits. Results At a median follow-up of 20 months (range 6–57 months), four out of 27 patients (14.8%) developed local recurrence and underwent salvage total laryngectomy. One patient developed distant metastases following salvage surgery. Among the 23 patients who conserved their larynx with no sign of recurrence at last follow-up, 22 (95%) reported normal or near normal voice quality, allowing them to communicate adequately. Four patients (14.8%) had long-term tube feeding-dependency because of severe dysphagia (2 patients) and chronic aspiration (2 patients, with ensuing death from aspiration pneumonia in one patient). Conclusions and Clinical Relevance Functional laryngeal preservation is feasible with IMRT and IGRT for locally advanced laryngeal cancer. However, dysphagia and aspiration remain serious complications, due most likely to high radiation dose delivery to the pharyngeal musculatures.

Stereotactic body radiation therapy in non-small-cell lung cancer: linking radiobiological modeling and clinical outcome.

For patients with peripheral, early-stage non–small-cell lung cancer, it has been found feasible to deliver 5 or fewer fractions of large doses through stereotactic body radiation therapy (SBRT) without causing severe early or late injury and with impressive tumor control. In this review, we employ radiobiological modeling with the linear quadratic formulation to explore the adequacy of various dose schedules used for tumor control in the lung as supported by clinical evidence, the influence of dose distribution and delivery time on local control, and how to decrease the likelihood of severe toxicity following SBRT. Furthermore, the validity of the linear quadratic formalism in the high dose range of SBRT for lung cancer is explored.

Impact of image-guided radiotherapy to reduce laryngeal edema following treatment for non-laryngeal and non-hypopharyngeal head and neck cancers

We would like to determine the effectiveness of image-guided radiotherapy (IGRT) to reduce laryngeal edema following treatment for head and neck cancer and to assess patient perception of voice and speech after treatment. We conducted a retrospective review of 44 patients undergoing radiation for non-laryngeal and non-hypopharyngeal head and neck cancers. Endoscopic and/or mirror examinations of the larynx were performed following radiotherapy at each follow-up visit. Laryngeal edema was assessed based on the Radiation Therapy Oncology Group grading scale. Patients were also asked to rate about the voice and speech quality relative to their pre-radiotherapy status. The mean laryngeal dose was 16.3 Gy (range: 11.7-45.5 Gy). At a median follow-up of 14 months (range: 2-31 months), three patients (7%) developed laryngeal edema (one grade 1, two grade 2). The mean laryngeal dose was respectively 20.3 Gy in two patients and 20.7 Gy in the third patient developing laryngeal edema. Except for one patient who continued to smoke and drink after radiotherapy, no patient reported any significant change in voice and speech quality after treatment. IGRT results in low rates and low severity of laryngeal edema following treatment for non-laryngeal and non-hypopharyngeal head and neck cancers and may preserve voice quality.

The potential role of magnetic resonance spectroscopy in image-guided radiotherapy.

Magnetic resonance spectroscopy (MRS) is a non-invasive technique to detect metabolites within the normal and tumoral tissues. The ability of MRS to diagnose areas of high metabolic activity linked to tumor cell proliferation is particularly useful for radiotherapy treatment planning because of better gross tumor volume (GTV) delineation. The GTV may be targeted with higher radiation dose, potentially improving local control without excessive irradiation to the normal adjacent tissues. Prostate cancer and glioblastoma multiforme (GBM) are two tumor models that are associated with a heterogeneous tumor distribution. Preliminary studies suggest that the integration of MRS into radiotherapy planning for these tumors is feasible and safe. Image-guided radiotherapy (IGRT) by virtue of daily tumor imaging and steep dose gradient may allow for tumor dose escalation with the simultaneous integrated boost technique (SIB) and potentially decrease the complications rates in patients with GBM and prostate cancers.