Lech Papiez

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.

Stereotactic body radiation therapy: The report of AAPM Task Group 101

Task Group 101 of the AAPM has prepared this report for medical physicists, clinicians, and therapists in order to outline the best practice guidelines for the external-beam radiation therapy technique referred to as stereotactic body radiation therapy (SBRT). The task group report includes a review of the literature to identify reported clinical findings and expected outcomes for this treatment modality. Information is provided for establishing a SBRT program, including protocols, equipment, resources, and QA procedures. Additionally, suggestions for developing consistent documentation for prescribing, reporting, and recording SBRT treatment delivery is provided.

Stereotactic Body Radiation Therapy for Early-Stage Non–Small-Cell Lung Carcinoma: Four-Year Results of a Prospective Phase II Study

PURPOSE The 50-month results of a prospective Phase II trial of stereotactic body radiation therapy (SBRT) in medically inoperable patients are reported. METHODS AND MATERIALS A total of 70 medically inoperable patients had clinically staged T1 (34 patients) or T2 (36 patients) (< or =7 cm), N0, M0, biopsy-confirmed non-small-cell lung carcinoma (NSCLC) and received SBRT as per our previously published reports. The SBRT treatment dose of 60-66 Gy was prescribed to the 80% isodose volume in three fractions. RESULTS Median follow-up was 50.2 months (range, 1.4-64.8 months). Kaplan-Meier local control at 3 years was 88.1%. Regional (nodal) and distant recurrence occurred in 6 (8.6%) and 9 (12.9%) patients, respectively. Median survival (MS) was 32.4 months and 3-year overall survival (OS) was 42.7% (95% confidence interval [95% CI], 31.1-54.3%). Cancer-specific survival at 3 years was 81.7% (95% CI, 70.0-93.4%). For patients with T1 tumors, MS was 38.7 months (95% CI, 25.3-50.2) and for T2 tumors MS was 24.5 months (95% CI, 18.5-37.4) (p = 0.194). Tumor volume (< or =5 cc, 5-10 cc, 10-20 cc, >20 cc) did not significantly impact survival: MS was 36.9 months (95% CI, 18.1-42.9), 34.0 (95% CI, 16.9-57.1), 32.8 (95% CI, 21.3-57.8), and 21.4 months (95% CI, 17.8-41.6), respectively (p = 0.712). There was no significant survival difference between patients with peripheral vs. central tumors (MS 33.2 vs. 24.4 months, p = 0.697). Grade 3 to 5 toxicity occurred in 5 of 48 patients with peripheral lung tumors (10.4%) and in 6 of 22 patients (27.3%) with central tumors (Fishers exact test, p = 0.088). CONCLUSION Based on our study results, use of SBRT results in high rates of local control in medically inoperable patients with Stage I NSCLC.

Stereotactic Body Radiation Therapy in Multiple Organ Sites

INTRODUCTION Stereotactic body radiation therapy (SBRT) uses advanced technology to deliver a potent ablative dose to deep-seated tumors in the lung, liver, spine, pancreas, kidney, and prostate. METHODS SBRT involves constructing very compact high-dose volumes in and about the tumor. Tumor position must be accurately assessed throughout treatment, especially for tumors that move with respiration. Sophisticated image guidance and related treatment delivery technologies have developed to account for such motion and efficiently deliver high daily dose. All this serves to allow the delivery of ablative dose fractionation to the target capable of both disrupting tumor mitosis and cellular function. RESULTS Prospective phase I dose-escalation trials have been carried out to reach potent tumoricidal dose levels capable of eradicating tumors with high likelihood. These studies indicate a clear dose-response relationship for tumor control with escalating dose of SBRT. Prospective phase II studies have been reported from several continents consistently showing very high levels of local tumor control. Although late toxicity requires further careful assessment, acute and subacute toxicities are generally acceptable. Patterns of toxicity, both clinical and radiographic, are distinct from those observed with conventionally fractionated radiotherapy as a result of the unique biologic response to ablative fractionation. CONCLUSION Prospective trials using SBRT have confirmed the efficacy of treatment in a variety of patient populations. Although mechanisms of ablative-dose injury remain elusive, ongoing prospective trials offer the hope of finding the ideal application for SBRT in the treatment arsenal.

Stereotactic body radiation therapy: a novel treatment modality

Stereotactic body radiation therapy (SBRT) involves the delivery of a small number of ultra-high doses of radiation to a target volume using very advanced technology and has emerged as a novel treatment modality for cancer. The role of SBRT is most important at two cancer stages—in early primary cancer and in oligometastatic disease. This modality has been used in the treatment of early-stage non-small-cell lung cancer, prostate cancer, renal-cell carcinoma, and liver cancer, and in the treatment of oligometastases in the lung, liver, and spine. A large body of evidence on the use of SBRT for the treatment of primary and metastatic tumors in various sites has accumulated over the past 10–15 years, and efficacy and safety have been demonstrated. Several prospective clinical trials of SBRT for various sites have been conducted, and several other trials are currently being planned. The results of these clinical trials will better define the role of SBRT in cancer management. This article will review the radiobiologic, technical, and clinical aspects of SBRT.

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.

DOSIMETRIC EVALUATION OF HETEROGENEITY CORRECTIONS FOR RTOG 0236: STEREOTACTIC BODY RADIOTHERAPY OF INOPERABLE STAGE I-II NON-SMALL- CELL LUNG CANCER

PURPOSE Using a retrospective analysis of treatment plans submitted from multiple institutions accruing patients to the Radiation Therapy Oncology Group (RTOG) 0236 non-small-cell stereotactic body radiotherapy protocol, the present study determined the dose prescription and critical structure constraints for future stereotactic body radiotherapy lung protocols that mandate density-corrected dose calculations. METHOD AND MATERIALS A subset of 20 patients from four institutions participating in the RTOG 0236 protocol and using superposition/convolution algorithms were compared. The RTOG 0236 protocol required a prescription dose of 60 Gy delivered in three fractions to cover 95% of the planning target volume. Additional requirements were specified for target dose heterogeneity and the dose to normal tissue/structures. The protocol required each site to plan the patients treatment using unit density, and another plan with the same monitor units and applying density corrections was also submitted. These plans were compared to determine the dose differences. Two-sided, paired Students t tests were used to evaluate these differences. RESULTS With heterogeneity corrections applied, the planning target volume receiving >/=60 Gy decreased, on average, 10.1% (standard error, 2.7%) from 95% (p = .001). The maximal dose to any point >/=2 cm away from the planning target volume increased from 35.2 Gy (standard error, 1.7) to 38.5 Gy (standard error, 2.2). CONCLUSION Statistically significant dose differences were found with the heterogeneity corrections. The information provided in the present study is being used to design future heterogeneity-corrected RTOG stereotactic body radiotherapy lung protocols to match the true dose delivered for RTOG 0236.

Improved leaf sequencing reduces segments or monitor units needed to deliver IMRT using multileaf collimators

Leaf sequencing algorithms may use an unnecessary number of monitor units or segments to generate intensity maps for delivery of intensity modulated radiotherapy (IMRT) using multiple static fields. An integer algorithm was devised to generate a sequence with the fewest possible segments when the minimum number of monitor units are used. Special hardware related restrictions on leaf motion can be incorporated. The algorithm was tested using a benchmark map from the literature and clinical examples. Results were compared to sequences given by the routine of Bortfeld that minimizes monitor units by treating each row independently, and the areal or reducing routines that use fewer segments at the price of more monitor units. The Bortfeld algorithm used on average 58% more segments than provided by the integer algorithm with bidirectional motion and 32% more segments than did an integer algorithm admitting only unidirectional sequences. The areal algorithm used 48% more monitor units and the reducing algorithm used 23% more monitor units than did the bidirectional integer algorithm, while the areal and reducing algorithms used 23% more segments than did the integer algorithm. Improved leaf sequencing algorithms can allow more efficient delivery of static field IMRT. The integer algorithm demonstrates the efficiencies possible with an improved routine and opens a new avenue for development.

DMLC leaf-pair optimal control for mobile, deforming target.

Existing algorithms of dynamic control of independent pairs of leaves allow optimal DMLC delivery of IMRT to rigid targets translating parallel to leaf trajectories. However, in numerous cases of radiotherapy treatments simplifying assumptions of rigid-like motions of targets and surrounding tissues are clearly not satisfied. Therefore algorithms have to be developed that allow one to control MLC so that predetermined intensities are delivered to various points in targets that experience compression and expansion at the time of irradiation. Moreover, it is desirable for such algorithms to ensure that delivery of modulated intensity map will be done with minimal expense of monitor units. Derivation of the algorithm that optimizes the DMLC IMRT to mobile, deforming target is presented in this paper. [To illustrate the general algorithm two representative examples of DMLC IMRT delivery to deforming targets are presented in full detail.] Finally, similarities and differences between solutions for immobile targets, for moving, rigid targets and for moving, deforming targets are discussed.

Real‐time DMLC IMRT delivery for mobile and deforming targets

In numerous cases of radiotherapy delivery to moving targets, simplifying assumptions of identical pattern of motions of tissue for each fraction are not satisfied. Therefore, algorithms capable to respond in real time to motions of target registered at treatment should be developed to improve the precision of radiation intensity delivery. The DMLC delivery of predetermined intensity maps to moving and deforming targets in real time is developed in this paper. Algorithms are constructed so that constraints on maximum admissible speed of leaves are preserved during delivery. A sequence of examples is presented to illustrate behavior of leaf trajectories for representative cases of [dynamic multileaf collimator] (DMLC) [intensity modulated radiation therapy] (IMRT) real-time delivery. The examples presented show real-time deliveries to targets moving as rigid bodies and targets deforming uniformly over their volumes. Examples are admitting random perturbations of predefined target motions that are time dependent only, i.e., target motion perturbations are identical for all target points.