Ajay P. Sandhu

Toxicity analysis of postoperative image-guided intensity-modulated radiotherapy for prostate cancer.

PURPOSE To report on the acute and late gastrointestinal (GI) and genitourinary (GU) toxicity associated with a unique technique of image-guided radiotherapy (IGRT) in patients undergoing postprostatectomy irradiation. METHODS AND MATERIALS Fifty patients were treated with intensity-modulated radiation therapy (IMRT) after radical prostatectomy. Daily image guidance was performed to localize the prostate bed using kilovoltage imaging or cone-beam computed tomography. The median prescription dose was 68 Gy (range, 62-68 Gy). Toxicity was graded every 3 to 6 months according to the Common Terminology Criteria for Adverse Events version 3.0. RESULTS The median follow-up was 24 months (range, 13-38 months). Grade 2 acute GI and GU events occurred in 4 patients (8%) and 7 patients (14%), respectively. No Grade 3 or higher acute GI or GU toxicities were observed. Late Grade 2 GI and GU events occurred in 1 patient (2%) and 8 patients (16%), respectively. Only a single (2%) Grade 3 or higher late toxicity was observed. CONCLUSIONS Image-guided IMRT in the postprostatectomy setting is associated with a low frequency of acute and late GI/GU toxicity. These results compare more favorably to radiotherapy techniques that do not use in-room image-guidance, suggesting that daily prostate bed localization may reduce the incidence of adverse events in patients undergoing postprostatectomy irradiation.

Locoregional and distant failure following image-guided stereotactic body radiation for early-stage primary lung cancer

PURPOSE To report our institutional experience using image-guided stereotactic body radiation therapy (SBRT) for early stage lung cancer, including an analysis into factors associated with nodal and distant failures (NF, DF). METHODS Forty-eight patients with early-stage primary lung cancer were treated with image-guided SBRT between 2007 and 2009. Median prescription dose was 48 Gy in 4 fractions. Toxicity was graded according to the NCI CTCAE v3.0 scale. RESULTS Local failure was detected in two lesions and actuarial 24-month local control was 95%. At 24 months, the cumulative incidence of NF was 6%, and DF was 29%. Larger lesions (>3 cm) and younger age (<70 years) were the only factors found to be significantly correlated with increased DF (p=0.005 and p=0.015, respectively). A single grade ≥ 3 toxicity was observed. After adjusting for age and lesion size, distant failure was significantly associated with a poorer OS (Cox regression, p=0.0059). CONCLUSION Image-guided SBRT can produce excellent LC rates with minimal toxicity. Distant failure was a major determinant of OS and the most common pattern of failure, indicating a potential role for systemic therapy in younger patients with large lesions.

Recent Advances in Image-Guided Radiotherapy for Head and Neck Carcinoma

Radiotherapy has a well-established role in the management of head and neck cancers. Over the past decade, a variety of new imaging modalities have been incorporated into the radiotherapy planning and delivery process. These technologies are collectively referred to as image-guided radiotherapy and may lead to significant gains in tumor control and radiation side effect profiles. In the following review, these techniques as they are applied to head and neck cancer patients are described, and clinical studies analyzing their use in target delineation, patient positioning, and adaptive radiotherapy are highlighted. Finally, we conclude with a brief discussion of potential areas of further radiotherapy advancement.

Comparison of outcomes following stereotactic body radiotherapy for non-small cell lung cancer in patients with and without pathological confirmation.

Purpose/objective: Treatment of presumed early-stage lung cancer with definitive radiation therapy in the absence of a pathologically confirmed specimen frequently occurs. However, it is not well described in the literature, and there are few North American series reporting on this patient population. We report outcomes in patients treated with stereotactic body radiotherapy (SBRT) for presumed lung cancer and compare them to outcomes in patients treated with SBRT with pathologically confirmed non-small cell lung cancer (NSCLC). Materials/methods: This study is based on a retrospective review of 55 patients with presumed or confirmed lung cancer: 23 patients had nondiagnostic or absent pathologic specimens while 32 patients had pathologically confirmed NSCLC. All patients had hypermetabolic primary lesions on a positron emission tomography (PET) or PET/computed tomography (CT) scan. SBRT was delivered as 48–56 Gy in four to five fractions via a four-dimensional CT treatment plan. Results: Of the patients without pathological confirmation, the mean age was 78 (range 63–89 years) and 17 (74%) were men. The mean tumor size was 2.5 cm (range 1.0–5.1). Reasons for not having confirmed pathologic diagnosis included indeterminate biopsy specimen or an inability to tolerate a biopsy procedure due to poor respiratory status. SBRT was chosen due to noncandidacy for surgery in 17 patients (74%) or patient refusal of surgery in six (26%). Median follow up was 24.2 months (range 1.9–64.6): 2 of the 23 patients (8.7%) had local failure at the site of SBRT and 3 (13%) had regional failure. The actuarial 12-month overall survival was 83%. The median overall survival was 30.2 months. At last follow up, 12 patients (52%) were alive up to 64.6 months after treatment. SBRT was tolerated well in this series. Acute toxicity was noted in two patients (8.7%) and chronic toxicity in three (13%). These patient characteristics and results were shown to be similar to the 32 patients with pathologically confirmed NSCLC. On Kaplan–Meier analysis, there was no significant difference (p = 0.27) in overall survival between patients with pathologically confirmed NSCLC and those with presumed lung cancer (which was deemed most likely NSCLC). Conclusion: While biopsy confirmation remains a goal in the workup of suspected NSCLC, SBRT without pathologic confirmation may represent a safe and effective option for the treatment of presumed NSCLC among patients who cannot tolerate or refuse surgery.

Frameless Image-Guided Stereotactic Body Radiation Therapy for Lung Tumors with 4-Dimensional Computed Tomography or 4-Dimensional Positron Emission Tomography/ Computed Tomography

BACKGROUND/PURPOSE To augment the accuracy of stereotactic body radiation therapy (SBRT), a variety of image guidance systems are used for patient positioning and target localization. Clinical outcomes evaluating these systems, especially frameless image-guided systems, are still limited. This article aims to describe and evaluate our frameless image-guided SBRT technique for lung tumors. METHODS Between 2007 and 2009, 85 pulmonary tumors (50 primaries and 35 metastases) were treated with SBRT using daily image guidance for patient positioning and target localization in lieu of a body frame. Four-dimensional computed tomography (4DCT) or an in-house protocol for integrated 4D positron emission computed tomography (4DPET/CT) was used for planning simulation. RESULTS Median follow-up was 17 months (range, 4-42). Median overall survival (OS) was 31 months (95% CI, 26-34), and median local failure-free survival was 30 months (95% CI, 18-32). At last follow-up, 9 of 83 evaluable lesions failed locally. Actuarial local control at 24 months was 87% (95% CI, 75-98) and was significantly worse for metastatic lesions (95% vs. 74%; P = .045; log-rank test). No acute or late toxicities (grade ≥ 4) were observed. CONCLUSIONS Frameless image-guided SBRT is a feasible, safe, and effective treatment for lung tumors.

Hypofractionated radiotherapy as definitive treatment of stage I non-small cell lung cancer in older patients.

Purpose/Objective(s): We report our experience using hypofractionated radiotherapy in older patients. Materials/Methods: This analysis includes patients aged 60 years and older at our institution with inoperable Stage I (T1/T2 N0 M0) non–small-cell lung cancer that completed a curative course of radiotherapy alone using a hypofractionated schedule. Between 1991 and 2006, 75 such patients were identified with median age of 74 years (range, 60–86). Patient characteristics were as follows: male, 65/75 (86.7%); stage IA (T1N0), 47/75 (62.7%); stage IB (T2N0), 28/75 (37.3%). Patients received a median total dose of 6500 cGy using median daily dose fractions of 250 cGy. The following outcomes were analyzed: local failure free survival (time to local failure or death from any cause), time to distal failure as first event, and overall survival. Toxicities were evaluated using Common Terminology Criteria for Adverse Events v 3.0. Results: The median follow-up was 19.6 months (range: 4.0–128.8 months). Median local failure free survival was 19.6 months (95% confidence interval [CI]: 14.4–28.8 months); and median overall survival was 21.2 months (95% CI: 14.9–29.3 months). Analysis of competing risks showed that at 5 years, the probability of local failure as the first detected event was 22.1% (95% CI: 12.8%–32.9%); the probability of distal failure as the first detected event was 14.5% (95% CI: 7.3%–24.0%); and the probability of death without recording a failure was 48.6% (95% CI: 36.1%–60.1%). Radiation-related toxicity of grade 3 or greater was seen in 3 patients and there were no treatment-related deaths. Conclusions: Hypofractionated radiotherapy is an effective, safe treatment for older patients with stage I non–small-cell lung cancer.

Comparison of daily cone-beam computed tomography and kilovoltage planar imaging for target localization in prostate cancer patients following radical prostatectomy

PURPOSE To review our initial clinical experience with image-guided radiation therapy (IGRT) using cone-beam computed tomography (CBCT) for prostate bed localization in post-radical prostatectomy (RP) patients and to compare shift and acute toxicity results to our previously published IGRT experience with daily kV planar imaging. METHODS AND MATERIALS Fifty patients treated with intensity modulated radiation therapy (IMRT) who had image guidance using either CBCT (n = 23) or kV planar imaging (n = 27) following RP were analyzed. Shifts were recorded in anterior-posterior, superior-inferior, and left-right axes. Total error was defined as the shift from initial setup based on skin markings to isocenter. Prostate bed motion (PBM) was defined as the change in prostate bed position relative to bones. Acute toxicity was graded according to the Radiation Therapy Oncology Group morbidity criteria. RESULTS Total error (TE) was measured in 752 CBCTs and 725 kV planar image pairs. PBM was measured in 585 CBCTs and 384 kV planar image pairs. The average magnitudes of TE and PBM in the anterior-posterior, superior-inferior, and left-right axes were greater with kV planar imaging compared to CBCT. Frequencies of acute grade 2 gastrointestinal (13% vs 7%, P = .7) and genitourinary (9% vs 11%, P = 1.0) were similar for CBCT and kV planar imaging patients. No toxicities greater than grade 2 were seen. CONCLUSIONS These results suggest that although the magnitudes of TE and PBM were larger with kV planar compared to CBCT, the levels of acute toxicity were acceptable and comparable between the two. The reasons for the differences are unclear, but we postulate that discernment of the prostate bed on the CBCT is more difficult. Further investigation is necessary to determine the reason for the shift differences and to evaluate the benefits and risks of CBCT in this setting.

The role of positron emission tomography following radiosurgical treatment of malignant lung lesions.

Objective To establish response patterns in PET following stereotactic body radiotherapy (SBRT) of malignant lung lesions. Methods Patients with malignant lung lesions treated with SBRT were retrospectively reviewed. All patients received 40–52 Gy in three to five equal fractions. An independent, blinded radiologist reassessed all 18F-fluoro-deoxy-glucose PET/computed tomography scans to determine the tumor maximum standardized uptake value (SUVmax) and size changes. Results Thirty-nine patients were included in this study. Of the 47 lesions treated, there were 22 primary and 25 metastatic lung lesions. In total, 86 PET/computed tomography studies were reviewed. The mean SUVmax values decreased markedly and stabilized after 6 months following the treatment of primary lesions. Metastatic lesions showed greater variability, with an overall increase in SUVmax values until 6 months and decrease thereafter. Of the eight local failures, the mean SUVmax and size change from nadir values to biopsy-proven failure were 117 and 215%; however, it was difficult to measure the size of five lesions because of fibrotic changes. Statistical analysis revealed metastatic tumors to be associated with poorer local control (P=0.028). No correlation was found between size or pretreatment SUVmax and outcome. Conclusion Anticipated SUVmax and size patterns following SBRT remain a challenge due to surrounding tissue reactions. Nonetheless, marked SUVmax changes can aid in determining local failure. Increases in size were also observed in local failures; however, localized fibrosis challenges its utility in distinguishing failures from a normal tissue response. A larger series needs to be examined to better establish the correlation of PET responses to overall survival and local control.

Radiation therapy for older cancer patients

Cancer is the leading cause of death among the elderly. With the dramatic increase in life expectancy, treatment approach of older cancer patients poses major challenges. There is no consensus on treatment guidelines for elderly cancer patients with significant variability among physicians due to concerns for toxicity. The issue is further complicated by a lack of quality data on age-related issues of cancer management. This review highlights important factors relevant to treatment decision making in older cancer patients with special emphasis on radiation therapy for lung, prostate and breast cancer. The potential benefits of recent innovations and emerging radiotherapeutic technologies and their application to elderly cancer patients is also presented.

Lung stereotactic body radiotherapy (SBRT): a single institution's outcomes and methodology in the context of a literature review

Lung cancer is the leading cause of cancer death in the United States and worldwide, with the incidence of early stage lung cancer anticipated to rise with increasing use of screening CT. Improvements in systemic therapy have increased the need for durable local control both in primary lung cancer as well as oligometastatic disease to the lung. Since 2007, the University of California San Diego (UCSD) has employed SBRT in the treatment of early stage primary non-small cell histology (NSCLC), intrapulmonary oligometastases, and multiple primary lung cancers (MPLCs) with high efficacy and low toxicity using a frameless technique that involves non-invasive image guidance. We review our center’s general approach to management including our experience with clinical outcomes and toxicity in the context of a review of the literature, details of our preferred technique (including simulation and real-time tumor tracking), as well as our results and strategy for patient follow-up using PET to monitor tumor response in the post-SBRT setting.