Nam P. Nguyen

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.

Can stereotactic fractionated radiation therapy become the standard of care for early stage non-small cell lung carcinoma

Management of early stages non-small cell lung carcinoma has traditionally been surgery with radiation selected for medically inoperable patients. Recent emergence of stereotactic body radiation therapy allows for delivery of high radiation dose to the tumor while sparing normal lungs. This reviews compares loco-regional control, survival and complications rates between these two treatment modalities. Literature search identifies studies with stereotactic body radiation therapy and surgery for early stages non-small cell lung cancer. Effectiveness and toxicity of these two modalities was assessed. Stereotactic body radiation therapy is associated with minimal morbidity and provides comparable local control and survival in patients with multiple co-morbidities factors. Stereotactic body radiation therapy may become standard of care for operable early stages non-small cell lung cancer.

Prognostic value of nodal ratios in node-positive breast cancer: a compiled update

The number of positive axillary nodes is a strong prognostic factor in breast cancer, but is affected by variability in nodal staging technique yielding varying numbers of excised nodes. The nodal ratio of positive to excised nodes is an alternative that could address this variability. Our 2006 review found that the nodal ratio consistently outperformed the number of positive nodes, providing strong arguments for the use of nodal ratios in breast cancer staging and management. New evidence has continued to accrue confirming the prognostic significance of nodal ratios in various worldwide population settings. This review provides an updated summary of available data, and discusses the potential application of the nodal ratio to breast cancer staging and prognostication, its role in the context of modern surgical techniques such as sentinel node biopsy, and its potential correlations with new biologic markers such as circulating tumor cells and breast cancer stem cells.

Evaluation and management of swallowing dysfunction following chemoradiation for head and neck cancer.

Purpose of reviewConcurrent chemoradiation offers excellent local control and survival for patients with locally advanced head and neck cancer while allowing anatomic organ preservation. Treatment toxicity is significant, however, often resulting in long-term dysphagia and aspiration. We review the prevalence of post-treatment swallowing dysfunction, describe current thinking about its pathogenesis and management, and signal possible directions for future research. Recent findingsApoptosis from chemoradiation induces abnormal motility of the upper aerodigestive tract, resulting in stasis of the bolus in all phases of the swallow, and resulting in aspiration when the larynx is not protected during swallow. Long-term scarring may result in stenosis of the upper digestive tract. Recent findings suggest the role of transforming growth factor beta 1 in the pathogenesis of normal tissue damage and late scarring induced by radiation. Aspiration is often silent, and therefore a modified barium swallow or videofluoroscopy are required for its diagnosis. Swallowing therapy may improve swallowing efficiency and reduce the aspiration rate, and should be started immediately. SummarySuccessful management of swallowing dysfunction following chemoradiation is a complex undertaking requiring a team approach. Collaboration among different specialists (physicians, speech pathologist, dietitian, and psychologists) remains the key to a desirable outcome.

Analysis of factors influencing aspiration risk following chemoradiation for oropharyngeal cancer

Our aim was to identify risk factors for aspiration following concurrent chemoradiation for oropharyngeal cancer. 46 patients with locally advanced oropharyngeal carcinoma underwent concurrent chemoradiation at our institution. All patients underwent modified barium swallow to assess dysphagia severity and to determine the need for continued tube feedings after treatment. Dysphagia severity was graded as 1-7. There were 5 Grade 2, 11 Grade 3, 5 Grade 4, 5 Grade 5, 10 Grade 6 and 10 Grade 7 scores. 25 patients (54%) developed aspiration (5 trace, 20 severe). The aspiration rate for T1-T2 and T3-T4 tumours was 31% and 67%, respectively (p = 0.03). There was no statistical difference in the aspiration rate between the base of the tongue and tonsillar carcinoma (p = 0.23). Despite anatomical organ preservation, most patients with locally advanced oropharyngeal carcinoma had moderate to severe dysphagia after chemoradiation. Patients with large tumours had a significant risk of developing aspiration following treatment.

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.

Recombinant activated factor VII in patients with cancer and hemorrhagic disseminated intravascular coagulation

Hemorrhagic disseminated intravascular coagulation (DIC) associated with the presence of underlying advanced or metastatic tumors are often difficult to control by conventional methods. We report the use of recombinant activated factor VII (rFVIIa) in patients with cancer and bleeding secondary to DIC. A total of 18 patients with cancer met pre-defined criteria for DIC. All patients had failed to respond to transfusion with blood products and treatment of the underlying malignancy prior to the introduction of rFVIIa. The median laboratory data at the time of treatment with rFVIIa were as follows: hemoglobin, 7.7 g/dl; platelets, 54 × 109/l; prothrombin time, 21 s; activated partial thromboplastin time, 41 s fibrinogen, 83 mg/dl; D-dimer, 17 μg/ml; and antithrombin, 32%. The dose of rFVIIa was 90 μg/kg and the median number of doses administered was 5 (range, 3–10). Serial measurements of coagulation parameters were obtained at frequent intervals during treatment with rFVIIa. Of the 18 patients, 15 responded with cessation of bleeding and improvement in coagulation data. The prothrombin time and activated partial thromboplastin time normalized in all responding patients within 24 h of treatment. The median fibrinogen was 214 mg/dl while the median D-dimer was 6 μg/dl at 48 h following the administration of rFVIIa. No thromboembolic complications were observed following rFVIIa. Our data provide evidence that rFVIIa can be used successfully to control the hemorrhagic episodes associated with DIC. Although this type of treatment appears to be safe, close monitoring of the patients is warranted.

Impact of Tumor Board Recommendations on Treatment Outcome for Locally Advanced Head and Neck Cancer

Background/Aims: To identify physician selection factors in the treatment of locally advanced head and neck cancer and how treatment outcome is affected by Tumor Board recommendations. Methods: A retrospective analysis of 213 patients treated for locally advanced head and neck cancer in a single institution was performed. All treatments followed Tumor Board recommendations: 115 patients had chemotherapy and radiation, and 98 patients received postoperative radiation. Patient characteristics, treatment toxicity, locoregional control and survival between these two treat- ment groups were compared. Patient survival was compared with survival data reported in randomized studies of locally advanced head and neck cancer. Results: There were no differences in comorbidity factors, and T or N stages between the two groups. A statistically significant number of patients with oropharyngeal and oral cavity tumors had chemoradiation and postoperative radiation, respectively (p < 0.0001). Grade 3–4 toxicities during treatment were 48 and 87% for the postoperative radiation and chemoradiation groups, respectively (p = 0.0001). There were no differences in survival, locoregional recurrences and distant metastases between the two groups. Patient survival was comparable to survival rates reported by randomized studies of locally advanced head and neck cancer. Conclusion: Disease sites remained the key determining factor for treatment selection. Multidisciplinary approaches provided optimal treatment outcome for locally advanced head and neck cancer, with overall survival in these patients being comparable to that reported in randomized clinical trials.

Feasibility of Tomotherapy to spare the cochlea from excessive radiation in head and neck cancer

We would like to evaluate the effectiveness of Tomotherapy for decreasing radiation dose to the cochlea in head and neck cancer patients. A retrospective review of 72 patients undergoing radiation for head and neck cancer was performed. Cochlea dose was compared between 20 patients treated with conventional intensity modulated radiotherapy (IMRT) and 52 treated with Tomotherapy. A review of literature was performed to assess cochlea dose reported with the IMRT technique for head and neck cancer. Mean total cochlea dose was 36 Gy for IMRT compared to 12.1 Gy for Tomotherapy (p=0.002). Mean right cochlea dose was respectively, 16.6 and 6.2 Gy for IMRT and Tomotherapy (p=0.007), and 19.3 and 5.9 Gy for the left. Cochlea (p=0.002). Mean cochlea dose reported in the literature ranged from 16 to 55 Gy with IMRT for head and neck cancer. Helical Tomotherapy for head and neck cancer may significantly decrease radiation dose to the cochlea without sacrificing target volume coverage.

Feasibility of tomotherapy to reduce normal lung and cardiac toxicity for distal esophageal cancer compared to three-dimensional radiotherapy

PURPOSE To compare the effectiveness of tomotherapy and three-dimensional (3D) conformal radiotherapy to spare normal critical structures (spinal cord, lungs, and ventricles) from excessive radiation in patients with distal esophageal cancers. MATERIALS AND METHODS A retrospective dosimetric study of nine patients who had advanced gastro-esophageal (GE) junction cancer (7) or thoracic esophageal cancer (2) extending into the distal esophagus. Two plans were created for each of the patients. A three-dimensional plan was constructed with either three (anteroposterior, right posterior oblique, and left posterior oblique) or four (right anterior oblique, left anterior oblique, right posterior oblique, and left posterior oblique) fields. The second plan was for tomotherapy. Doses were 45 Gy to the PTV with an integrated boost of 5 Gy for tomotherapy. RESULTS Mean lung dose was respectively 7.4 and 11.8 Gy (p=0.004) for tomotherapy and 3D plans. Corresponding values were 12.4 and 18.3 Gy (p=0.006) for cardiac ventricles. Maximum spinal cord dose was respectively 31.3 and 37.4 Gy (p < 0.007) for tomotherapy and 3D plans. Homogeneity index was two for both groups. CONCLUSIONS Compared to 3D conformal radiotherapy, tomotherapy decreased significantly the amount of normal tissue irradiated and may reduce treatment toxicity for possible dose escalation in future prospective studies.