Quynh Nhu Nguyen

Management of Spinal Metastases From Renal Cell Carcinoma Using Stereotactic Body Radiotherapy

PURPOSE To evaluate the outcomes associated with stereotactic body radiotherapy (SBRT) in the management of spinal metastases from renal cell carcinoma (RCC). METHODS AND MATERIALS SBRT was used in the treatment of patients with spinal metastases from RCC. Patients received either 24 Gy in a single fraction, 27 Gy in three fractions, or 30 Gy delivered in five fractions. Effectiveness of SBRT with respect to tumor control and palliation of pain was assessed using patient-reported outcomes. RESULTS A total of 48 patients with 55 spinal metastases were treated with SBRT with a median follow-up time of 13.1 months (range, 3.3-54.5 months). The actuarial 1-year spine tumor progression free survival was 82.1%. At pretreatment baseline, 23% patients were pain free; at 1 month and 12 months post-SBRT, 44% and 52% patients were pain free, respectively. No Grade 3-4 neurologic toxicity was observed. CONCLUSIONS The data support SBRT as a safe and effective treatment modality that can be used to achieve good tumor control and palliation of pain associated with RCC spinal metastases. Further evaluation with randomized trials comparing SBRT to conventional radiotherapy may be warranted.

Patient-specific quality assurance for prostate cancer patients receiving spot scanning proton therapy using single-field uniform dose

PURPOSE To describe our experiences with patient-specific quality assurance (QA) for patients with prostate cancer receiving spot scanning proton therapy (SSPT) using single-field uniform dose (SFUD). METHODS AND MATERIALS The first group of 249 patients with prostate cancer treated with SSPT using SFUD was included in this work. The scanning-beam planning target volume and number of monitor units were recorded and checked for consistency. Patient-specific dosimetric measurements were performed, including the point dose for each plan, depth doses, and two-dimensional (2D) dose distribution in the planes perpendicular to the incident beam direction for each field at multiple depths. The γ-index with 3% dose or 3-mm distance agreement criteria was used to evaluate the 2D dose distributions. RESULTS We observed a linear relationship between the number of monitor units and scanning-beam planning target volume. The difference between the measured and calculated point doses (mean ± SD) was 0.0% ± 0.7% (range, -2.9% to 1.8%). In general, the depth doses exhibited good agreement except at the distal end of the spread-out Bragg peak. The pass rate of γ-index (mean ± SD) for 2D dose comparison was 96.2% ± 2.6% (range, 90-100%). Discrepancies between the measured and calculated dose distributions primarily resulted from the limitation of the model used by the treatment planning system. CONCLUSIONS We have established a patient-specific QA program for prostate cancer patients receiving SSPT using SFUD.

Spot Scanning Proton Beam Therapy for Prostate Cancer: Treatment Planning Technique and Analysis of Consequences of Rotational and Translational Alignment Errors

PURPOSE Conventional proton therapy with passively scattered beams is used to treat a number of tumor sites, including prostate cancer. Spot scanning proton therapy is a treatment delivery means that improves conformal coverage of the clinical target volume (CTV). Placement of individual spots within a target is dependent on traversed tissue density. Errors in patient alignment perturb dose distributions. Moreover, there is a need for a rational planning approach that can mitigate the dosimetric effect of random alignment errors. We propose a treatment planning approach and then analyze the consequences of various simulated alignment errors on prostate treatments. METHODS AND MATERIALS Ten control patients with localized prostate cancer underwent treatment planning for spot scanning proton therapy. After delineation of the clinical target volume, a scanning target volume (STV) was created to guide dose coverage. Errors in patient alignment in two axes (rotational and yaw) as well as translational errors in the anteroposterior direction were then simulated, and dose to the CTV and normal tissues were reanalyzed. RESULTS Coverage of the CTV remained high even in the setting of extreme rotational and yaw misalignments. Changes in the rectum and bladder V45 and V70 were similarly minimal, except in the case of translational errors, where, as a result of opposed lateral beam arrangements, much larger dosimetric perturbations were observed. CONCLUSIONS The concept of the STV as applied to spot scanning radiation therapy and as presented in this report leads to robust coverage of the CTV even in the setting of extreme patient misalignments.

Focal and craniospinal irradiation for patients with intracranial germinoma and patterns of failure

The authors compared the patterns of failure in patients with intracranial germinoma who were managed with either chemotherapy and focal irradiation or with craniospinal irradiation (CSI).

Long‐term outcomes for men with high‐risk prostate cancer treated definitively with external beam radiotherapy with or without androgen deprivation

Men with high‐risk prostate cancer are often thought to have very poor outcomes in terms of disease control and survival even after definitive treatment. However, results after external beam radiotherapy have improved significantly through dose escalation and the use of androgen deprivation therapy (ADT). This report describes long‐term findings after low‐dose (< 75.6 Gy) or high‐dose (≥ 75.6 Gy) external beam radiation, with or without ADT.

Long-term outcomes after proton therapy, with concurrent chemotherapy, for stage II-III inoperable non-small cell lung cancer

PURPOSE We report long-term disease control, survival, and toxicity for patients with locally advanced non-small cell lung cancer prospectively treated with concurrent proton therapy and chemotherapy on a nonrandomized case-only observational study. METHODS All patients received passive-scatter proton therapy, planned with 4D-CT-based simulation; all received proton therapy concurrent with weekly chemotherapy. Endpoints were local and distant control, disease-free survival (DFS), and overall survival (OS). RESULTS The 134 patients (21 stage II, 113 stage III; median age 69 years) had a median gross tumor volume (GTV) of 70 cm(3) (range, 5-753 cm(3)); 77 patients (57%) received 74 Gy(RBE), and 57 (42%) received 60-72 Gy(RBE) (range, 60-74.1 Gy(RBE)). At a median follow-up time of 4.7 years, median OS times were 40.4 months (stage II) and 30.4 months (stage III). Five-year DFS rates were 17.3% (stage II) and 18.0% (stage III). OS, DFS, and local and distant control rates at 5 years did not differ by disease stage. Age and GTV were related to OS and DFS. Toxicity was tolerable, with 1 grade 4 esophagitis and 16 grade 3 events (2 pneumonitis, 6 esophagitis, 8 dermatitis). CONCLUSION This report of outcomes after proton therapy for 134 patients indicated that this regimen produced excellent OS with tolerable toxicity.

Do Angiotensin-Converting Enzyme Inhibitors Reduce the Risk of Symptomatic Radiation Pneumonitis in Patients With Non-Small Cell Lung Cancer After Definitive Radiation Therapy? Analysis of a Single-Institution Database

PURPOSE Preclinical studies have suggested that angiotensin-converting enzyme inhibitors (ACEIs) can mitigate radiation-induced lung injury. We sought here to investigate possible associations between ACEI use and the risk of symptomatic radiation pneumonitis (RP) among patients undergoing radiation therapy (RT) for non-small cell lung cancer (NSCLC). METHODS AND MATERIALS We retrospectively identified patients who received definitive radiation therapy for stages I to III NSCLC between 2004 and 2010 at a single tertiary cancer center. Patients must have received a radiation dose of at least 60 Gy for a single primary lung tumor and have had imaging and dosimetric data available for analysis. RP was quantified according to Common Terminology Criteria for Adverse Events, version 3.0. A Cox proportional hazard model was used to assess potential associations between ACEI use and risk of symptomatic RP. RESULTS Of 413 patients analyzed, 65 were using ACEIs during RT. In univariate analysis, the rate of RP grade ≥2 seemed lower in ACEI users than in nonusers (34% vs 46%), but this apparent difference was not statistically significant (P=.06). In multivariate analysis of all patients, ACEI use was not associated with the risk of symptomatic RP (hazard ratio [HR] = 0.66; P=.07) after adjustment for sex, smoking status, mean lung dose (MLD), and concurrent carboplatin and paclitaxel chemotherapy. Subgroup analysis showed that ACEI use did have a protective effect from RP grade ≥2 among patients who received a low (≤20-Gy) MLD (P<.01) or were male (P=.04). CONCLUSIONS A trend toward reduction in symptomatic RP among patients taking ACEIs during RT for NSCLC was not statistically significant on univariate or multivariate analyses, although certain subgroups may benefit from use (ie, male patients and those receiving low MLD). The evidence at this point is insufficient to establish whether the use of ACEIs does or does not reduce the risk of RP.

PSA Response to Neoadjuvant Androgen Deprivation Therapy Is a Strong Independent Predictor of Survival in High-Risk Prostate Cancer in the Dose-Escalated Radiation Therapy Era

PURPOSE The aim of the study was to evaluate the prognostic value of prostate-specific antigen (PSA) response to neoadjuvant androgen deprivation therapy (ADT) prior to dose-escalated radiation therapy (RT) and long-term ADT in high-risk prostate cancer. METHODS AND MATERIALS We reviewed the charts of all patients diagnosed with high-risk prostate cancer and treated with a combination of long-term ADT (median, 24 months) and dose-escalated (median, 75.6 Gy) RT between 1990 and 2007. The associations among patient, tumor, and treatment characteristics with biochemical response to neoadjuvant ADT and their effects on failure-free survival (FFS), time to distant metastasis (TDM), prostate cancer-specific mortality (PCSM) and overall survival (OS) were examined. RESULTS A total of 196 patients met criteria for inclusion. Median follow-up time for patients alive at last contact was 7.0 years (range, 0.5-18.1 years). Multivariate analysis identified the pre-RT PSA concentration (<0.5 vs ≥0.5 ng/mL) as a significant independent predictor of FFS (P=.021), TDM (P=.009), PCSM (P=.039), and OS (P=.037). On multivariate analysis, pretreatment PSA (iPSA) and African-American race were significantly associated with failure to achieve a pre-RT PSA of <0.5 ng/mL. CONCLUSIONS For high-risk prostate cancer patients treated with long-term ADT and dose-escalated RT, a pre-RT PSA level≥0.5 ng/mL after neoadjuvant ADT predicts for worse survival measures. Both elevated iPSA and African-American race are associated with increased risk of having a pre-RT PSA level≥0.5 ng/mL. These patients should be considered for clinical trials that test newer, more potent androgen-depleting therapies such as abiraterone and MDV3100 in combination with radiation.

Prostate cancer-specific mortality after definitive radiation therapy: Who dies of disease?

BACKGROUND A competing risks analysis was undertaken to identify subgroups at greatest risk of dying from prostate cancer (PC) after definitive external beam radiation therapy (RT)±androgen deprivation therapy (ADT) in the prostate specific antigen (PSA) era. METHODS Outcomes of 2675 men with localised PC treated with RT±ADT from 1987-2007 were analysed. Prostate cancer-specific mortality (PCSM) and non-PCSM rates were calculated after stratifying patients according to National Comprehensive Cancer Network (NCCN) risk-group, RT dose, use of ADT and age at treatment. RESULTS Only 0.2% of low-risk men died of PC 10 years after treatment. All of these deaths occurred in patients treated with < 72 Gy, and only one patient ≥ 70 years old who received ≥ 72 Gy died of PC at last follow-up. Likewise, none of the patients with intermediate-risk disease treated with ≥ 72 Gy and ADT died of PC at 10 years, and the highest 10-year rate of PCSM was seen in men ≥ 70 years old treated with < 72 Gy without ADT (5.1%). Among high-risk men < 70 years old, treatment with RT dose < 72 Gy without ADT yielded similar 10-year rates of PCSM (15.2%) and non-PCSM (18.5%), whereas men treated with ≥ 72 Gy and ADT were twice as likely to die from other causes (16.2%) than PC (9.4%). In high-risk men ≥ 70 years old, dose-escalation with ADT reduced 10-year PCSM from 14% to 4%, and most deaths were due to other causes. CONCLUSION Low- and intermediate-risk patients treated with definitive RT are unlikely to die of PC. PCSM is higher in men with high-risk disease but may be reduced with dose-escalation and ADT, although patients are still twice as likely to die of other causes.

Salvage pulmonary resection after stereotactic body radiotherapy: A feasible and safe option for local failure in selected patients

Objective For inoperable patients with pulmonary malignancy, stereotactic body radiotherapy is a reasonable therapeutic option. Despite good early tumor control, local failure occurs in up to 10% of patients by 3 years. Because management of local recurrence after stereotactic body radiotherapy is unclear, we evaluated use of surgery as a salvage option. Methods A retrospective review was conducted of consecutive patients from a single institution who underwent salvage resection of primary and metastatic pulmonary malignancies previously treated with stereotactic body radiotherapy. In addition, a literature search was conducted to identify previous reports of pulmonary resection for local stereotactic body radiotherapy failures, to allow cumulative analyses with previously published cases. Results A total of 21 patients met inclusion criteria. The median time between stereotactic body radiotherapy and salvage surgery was 16.2 months (range, 6.4‐71.5). Postoperative complications occurred in 7 patients (18.9%), in whom atrial arrhythmias and prolonged air leaks (>5 days) were most frequent (n = 2 each, 5.4%). There was no local recurrence after salvage surgery. Distant failure occurred in 5 of 21 patients (23.8%) at a median of 36.2 months, and median disease‐free survival was 19.2 months. The 30‐ and 90‐day mortality was 4.8% (1 patient). Cumulative analysis included 37 patients from 4 institutions and comprised 26 (78.8%) primary non–small cell lung cancers and 11 (29.7%) lung metastases. Median overall survival after salvage surgery was 46.9 months, and 3‐year survival was 71.8%. Conclusions After local failure of stereotactic body radiotherapy, salvage resection remains a viable option for operable patients, with acceptable morbidity and survival. As use of stereotactic body radiotherapy continues to expand, further studies to evaluate the optimal management for local failure are needed.