Ramzi Abdulrahman

Excessive toxicity when treating central tumors in a phase II study of stereotactic body radiation therapy for medically inoperable early-stage lung cancer

PURPOSE Surgical resection is standard therapy in stage I non-small-cell lung cancer (NSCLC); however, many patients are inoperable due to comorbid diseases. Building on a previously reported phase I trial, we carried out a prospective phase II trial using stereotactic body radiation therapy (SBRT) in this population. PATIENTS AND METHODS Eligible patients included clinically staged T1 or T2 (< or = 7 cm), N0, M0, biopsy-confirmed NSCLC. All patients had comorbid medical problems that precluded lobectomy. SBRT treatment dose was 60 to 66 Gy total in three fractions during 1 to 2 weeks. RESULTS All 70 patients enrolled completed therapy as planned and median follow-up was 17.5 months. The 3-month major response rate was 60%. Kaplan-Meier local control at 2 years was 95%. Altogether, 28 patients have died as a result of cancer (n = 5), treatment (n = 6), or comorbid illnesses (n = 17). Median overall survival was 32.6 months and 2-year overall survival was 54.7%. Grade 3 to 5 toxicity occurred in a total of 14 patients. Among patients experiencing toxicity, the median time to observation was 10.5 months. Patients treated for tumors in the peripheral lung had 2-year freedom from severe toxicity of 83% compared with only 54% for patients with central tumors. CONCLUSION High rates of local control are achieved with this SBRT regimen in medically inoperable patients with stage I NSCLC. Both local recurrence and toxicity occur late after this treatment. This regimen should not be used for patients with tumors near the central airways due to excessive toxicity.

FOUR-DIMENSIONAL COMPUTED TOMOGRAPHY SCAN ANALYSIS OF TUMOR AND ORGAN MOTION AT VARYING LEVELS OF ABDOMINAL COMPRESSION DURING STEREOTACTIC TREATMENT OF LUNG AND LIVER

PURPOSE To investigate the effectiveness of different abdominal compression levels on tumor and organ motion during stereotactic body radiotherapy of lower lobe lung and liver tumors using four-dimensional (4D)-CT scan analysis. METHODS AND MATERIALS Three 4D-CT scans were acquired for 10 patients first using with no compression and then compared with two different levels of abdominal compression. The position of the tumor and various organs were defined at the peak inspiratory and expiratory phases and compared to determine the maximum motion. RESULTS Mean (+/-SD) medium compression force (MC) and high compression force (HC) were 47.6 +/- 16.0 N and 90.7 +/- 27.1 N, respectively. Mean overall tumor motion was 13.6 mm (2sigma [2 sigma] 11.5-15.6), 8.3 mm (2sigma 6.0-10.5), and 7.2 mm (2sigma 5.4-9.0) for no compression, MC, and HC, respectively. A significant difference in the control of both superior-inferior (SI) and overall motion of tumors was seen with the application of MC and HC when compared with no compression (p < 0.0001 for both). High compression force improved SI and overall tumor motion compared with MC, but this was only significant for SI motion (p = 0.04 and p = 0.06). Significant control of organ motion was only seen in the pancreas (p = 0.01). CONCLUSIONS Four-dimensional CT shows significant control of both lower lobe lung and liver tumors using abdominal compression. High levels of compression improve SI tumor motion when compared with MC.

Phase II Trial of Stereotactic Body Radiation Therapy Combined With Erlotinib for Patients With Limited but Progressive Metastatic Non–Small-Cell Lung Cancer

PURPOSE Patients with stage IV non-small-cell lung cancer (NSCLC) who progress through first-line therapy have poor progression-free survival (PFS) and overall survival (OS), most commonly failing in original sites of gross disease. Cytoreduction with stereotactic body radiation therapy (SBRT) may help systemic agents delay relapse. PATIENTS AND METHODS Patients in our single arm phase II study had stage IV NSCLC with no more than six sites of extracranial disease who failed early systemic chemotherapy and were able to receive SBRT and concurrent erlotinib until disease progression. After erlotinib commencement, SBRT with equipotent fractionation was delivered to all sites of disease. PFS, OS, and other end points were evaluated. RESULTS Twenty-four patients (13 men and 11 women) with a median age of 67 years (range, 56-86 years) were enrolled with median follow-up of 11.6 months. All patients had progressed through platinum-based chemotherapy. A total of 52 sites were treated with 16 of 24 patients receiving SBRT to more than one site. Lung parenchyma was most often irradiated. Median PFS was 14.7 months, and median OS was 20.4 months. Most patients progressed in new distant sites with only three of 47 measurable lesions recurring within the SBRT field. Two grade 3 toxicities were radiation related. Zero of 13 patients tested were positive for an EGFR mutation. CONCLUSION Use of SBRT with erlotinib for unselected patients with stage IV NSCLC as a second- or subsequent line therapy resulted in dramatic changes in patterns of failure, was well tolerated, and resulted in high PFS and OS, substantially greater than historical values for patients who only received systemic agents.

Accreditation and quality assurance for Radiation Therapy Oncology Group: Multicenter clinical trials using Stereotactic Body Radiation Therapy in lung cancer

Starting in 2002, the Radiation Therapy Oncology Group in North America began the process of developing multicenter prospective trials in lung cancer using Stereotactic Body Radiation Therapy (SBRT). Much of the work was based on the prospective single institution trials from Indiana University that had been presented and published. In late 2004, RTOG 0236 using SBRT for medically inoperable patients with clinical stage I non-small cell lung cancer (NSCLC) was activated for accrual. Prior to activation, representatives from the Lung, Image-Guided Therapy, Physics, and Radiobiology Committees met on regular occasions to design the multicenter study and quality assurance measures. SBRT is not a black box, and the essence of the therapy had to be distilled via guidelines. Issues related to patient selection, method of dosimetry construction, equipment requirements, motion assessments and control, site accreditation, data exchange, and follow-up policies were worked out by compromise and consensus. RTOG 0236 has nearly completed its accrual. The Lung Committee has initiated the development of several other trials, each building on the last, to investigate the therapy in central tumors, in combinations with systemic therapy, in operable patients, and in lung metastases patients. The guidelines developed for RTOG 0236 will be refined to take advantage of more modern innovations including heterogeneity corrections and intensity modulation when appropriate. The development of RTOG 0618 using SBRT in operable patients with early stage NSCLC is a testament to both the enthusiasm from already published works and prospective multicenter clinical testing using SBRT techniques.

Optimizing Dose and Fractionation for Stereotactic Body Radiation Therapy

Stereotactic body radiation therapy (SBRT) is a potent noninvasive means of administering high-dose radiation to demarcated tumor deposits in extracranial locations. The treatments use image guidance and related treatment delivery technology for the purpose of escalating the radiation dose to the tumor itself with as little radiation dose to the surrounding normal tissue as possible. The local tumor control for SBRT has been higher than anything previously published for radiotherapy in treating typical carcinomas. In addition, the pattern, timing and severity of toxicity have been very different than what was seen with conventional radiotherapy. In this review, the clinical characteristics and outcomes of SBRT are presented in the context of their underlying mechanisms. While much of the material is unproven and speculative, it at least qualitatively searches for understanding as to the biological basis for the observed clinical effects. Hopefully, it will serve as a motivation for more sophisticated biological research into the effects of SBRT.

Stereotactic body radiation therapy for early-stage non-small-cell lung cancer

Stereotactic body radiation therapy has emerged as a novel oncologic therapy and experience with the use of stereotactic body radiation therapy for the treatment of early-stage non-small-cell lung cancer has grown over the last 10 years. This article reviews the radiobiologic, physical/technical and clinical aspects of stereotactic body radiation therapy for early-stage non-small-cell lung cancer. The literature is also reviewed.

Optimizing dose and fractionation for stereotactic body radiation therapy. Normal tissue and tumor control effects with large dose per fraction.

: Stereotactic body radiation therapy (SBRT) is a potent noninvasive means of administering high-dose radiation to demarcated tumor deposits in extracranial locations. The treatments use image guidance and related treatment delivery technology for the purpose of escalating the radiation dose to the tumor itself with as little radiation dose to the surrounding normal tissue as possible. The local tumor control for SBRT has been higher than anything previously published for radiotherapy in treating typical carcinomas. In addition, the pattern, timing and severity of toxicity have been very different than what was seen with conventional radiotherapy. In this review, the clinical characteristics and outcomes of SBRT are presented in the context of their underlying mechanisms. While much of the material is unproven and speculative, it at least qualitatively searches for understanding as to the biological basis for the observed clinical effects. Hopefully, it will serve as a motivation for more sophisticated biological research into the effects of SBRT.

Lung Cancer: A Model for Implementing Stereotactic Body Radiation Therapy into Practice

Primary and metastatic tumors to the lung have been principle targets for the noninvasive high-doseper- fraction treatment programs now officially called stereotactic body radiation therapy (SBRT). Highly focused treatment delivery to moving lung targets requires accurate assessment of tumor position throughout the respiratory cycle. Measures to account for this motion, either by tracking (chasing), gating, or inhibition (breath hold and abdominal compression) must be employed in order to avoid large margins of error that would expose uninvolved normal tissues. The treatments use image guidance and related treatment delivery technology for the purpose of escalating the radiation dose to the tumor itself with as little radiation dose to the surrounding normal tissues as possible. Clinical trials have demonstrated superior local control with SBRT as compared with conventionally fractionated radiotherapy. While late toxicity requires further careful assessment, acute and subacute toxicity are remarkably infrequent. Radiographic and local tissue effects consistent with bronchial damage and downstream collapse with fibrosis are common, especially with adequate doses capable of ablating tumor targets. As such, great care must be taken when employing SBRT near the serially functioning central chest structures including the esophagus and major airways. While mechanisms of this injury remain elusive, ongoing prospective trials offer the hope of finding the ideal application for SBRT in treating pulmonary targets.

Primary osteosarcoma of the ribs: CT findings

We report the CT appearance of primary osteosarcoma of the ribs in three patients. CT evaluation is important because this lesion may present a diagnostic dilemma on chest radiographs. The tumor should be suspected if CT demonstrates dense calcification within a mass that is centered in a rib.

Stereotactic Body Radiation Therapy for Thoracic Cancers: Recommendations for Patient Selection, Setup and Therapy

Advanced technologies have facilitated the development of stereotactic body radiation therapy (SBRT) programs capable of delivering ablative radiation doses for the control of lung cancers. To date, experience with these programs has been highly favorable, as reflected in the results of careful clinical trials. The medically inoperable lung cancer patient, lacking more effective options, has served as the initial clinical base to test SBRT; the therapeutic outcomes have confirmed a significant role for this approach. For many patient groups, SBRT may become a noninvasive alternative to some thoracic surgeries, especially ones with more limited therapeutic goals such as wedge resection. Despite these results, long-term evaluation of the cases treated is required to allow greater understanding of the limitations and contributions of this new modality. The successful delivery of SBRT requires the development of a comprehensive, specialized clinical program providing advanced technology and the technical expertise of physicians, physicists and therapists specially trained in SBRT applications. To achieve successful clinical outcomes, careful patient selection and attention to therapy design and delivery are required since exacting clinical procedures are involved. This chapter will outline many details essential for establishing an effective SBRT program in clinical practice.