Andrea L. Arnett

Utility of 18F-FDG PET for Predicting Histopathologic Response in Esophageal Carcinoma following Chemoradiation

Introduction: For patients with esophageal cancer undergoing neoadjuvant chemoradiation (CRT) followed by surgical resection, complete histopathologic response (pCR) is associated with favorable overall survival (OS). The aim of this study was to evaluate the correlation between 18F‐fluorodeoxyglucose positron emission tomography (FDG PET) response to neoadjuvant CRT and pCR. Methods: Maximum standardized uptake values and standardized uptake ratios (SURs) were measured before and after CRT. SUR was normalized to liver uptake and mediastinal blood pool uptake. FDG PET complete response was defined as metabolic activity normalization to hepatic and blood pool activity. The correlation between FDG PET parameters and pCR was examined through logistic regression analyses. Results: In total, 193 patients were monitored for a median of 3.6 years after initiation of CRT. Most tumors were adenocarcinoma (85%) and stage T3 (75%). Complete FDG PET response and pCR occurred in 27% and 34% of patients, respectively. Histologic findings, chemotherapy type, tumor stage, and radiation dose were not significantly associated with complete radiographic response. The rates of pCR in patients with and without radiographic complete response were 42% and 31% (p = 0.17), respectively. No predictive correlation was found between pCR and change in maximum standardized uptake value (p = 0.25), in SUR normalized to blood pool uptake (p = 0.20), or in SUR normalized to liver uptake (p = 0.15). The 5‐year OS rate was 46% for patients with a complete FDG PET response versus 44% without a complete response (p = 0.78). The 5‐year OS rate of patients who achieved pCR was 49% versus 43% for patients with residual tumor (p = 0.04). Conclusion: For patients with esophageal cancer who received neoadjuvant chemoradiation, pretreatment and posttreatment FDG PET parameters did not correlate with pCR or OS.

18F-FDG PET response and clinical outcomes after stereotactic body radiation therapy for metastatic melanoma

Background Clinical data that support stereotactic body radiation therapy (SBRT) metastatic malignant melanoma (MM) are limited. Furthermore, functional imaging with 18F-fludeoxyglucose positron emission tomography (PET) may offer a more accurate post-SBRT assessment. Therefore, we assessed the clinical outcomes and metabolic response of metastatic MM after SBRT. Methods and materials Patients with MM who were treated with SBRT and had pre- and post-PET scans (>1) were included in this study. A total of 390 pre- and post-SBRT PET/computed tomography (CT) scans for 80 metastases were analyzed. The PET metabolic response was evaluated per the PET Response Criteria in Solid Tumors (PERCIST), version 1.0, criteria. Single-fraction equivalent dose (SFED) was calculated as per the standard. The Kaplan-Meier method was used for estimates of overall survival (OS) and progression-free survival. The cumulative incidence method was used to estimate metastasis control (MC). A Wilcoxon test was used to compare survival estimates. The prognostic factors for MC and OS were assessed using the Cox proportional hazards model, and the Likelihood Ratio was also used for comparisons between groups. Results A median of 6 PET scans (range, 2-6 scans) was evaluated for each metastasis. The median SFED was 42.8 Gy (range, 18-56.4 Gy) and the median biologically effective dose was 254.4 Gy2.5 (range, 100.8-540 Gy2.5). Twenty percent of patients received chemotherapy and 59% received immunotherapy: granulocyte-macrophage colony-stimulating factor (64%) and ipilimumab (34%). MC was 94% and 90% at 1 year and 3 years, respectively. The OS was 74% and 27% and 1 year and 3 years, respectively. Complete response was achieved in 90% at a median of 2.8 months (range, 0.4-25.2 months). SFED >24 Gy correlated with improved MC (93% vs 75%, P = .01). Acute and late grade 3+ toxicities were 4% and 11%, respectively, with no grade 5 toxicity. Conclusions Post-SBRT PET/CT for extracranial metastatic MM resulted in high rates of complete response at a median of 2.8 months, and durable MC was achieved with SFED >24 Gy. SBRT, in addition to surgery and ablation, should be discussed with patients with MM, especially those with oligometastases.

FDG-PET parameters as predictors of pathologic response and nodal clearance in patients with stage III non-small cell lung cancer receiving neoadjuvant chemoradiation and surgery

OBJECTIVE Pathologic complete response (pCR) following neoadjuvant chemoradiation (CRT) is associated with improved outcomes in stage III non-small cell lung cancer. Conflicting results exist regarding the value of 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) in predicting pCR. This study evaluated the association between post-CRT FDG-PET and pCR using novel FDG-PET parameters. METHODS AND MATERIALS This retrospective study included patients treated with CRT and resection. All underwent pre- and post-CRT FDG-PET imaging. Maximum standard uptake value (SUVmax), standard uptake ratio (SUR), metabolic tumor volume (MTV), and total lesion glycolysis (TLG) were measured. RESULTS In total, 44 patients were included for review. The majority had cT2 disease (59.0%). Median radiation dose was 60 Gy (45-70.2 Gy). Rate of pCR and near-pCR within the primary lesion was 29.5% and 45.5%, respectively. Average reduction in SUVmax was 9.2, whereas SUR normalized to mediastinum and liver showed mean reductions of 4.7 and 3.5, respectively. No association was found between pCR and either MTV or TLG. Reduction in SUVmax and SUR were significantly associated with increased rate of pCR (P ≤ .02). A threshold of >75% decrease in SUR-liver showed significant association with near-pCR (diagnostic odds ratio [DOR]: 8.3; P = .007). No correlation was found between nodal FDG-PET parameters and nodal pCR. CONCLUSIONS Our results indicate SUV and SUR have utility in predicting pCR after neoadjuvant CRT. SUR parameters trended toward higher DORs, suggesting improved predictive utility compared with SUVmax. Notably, no association was found with nodal pCR. Furthermore, MTV and TLG changes were not predictive, potentially resulting from inflammation after full-dose radiation, but this warrants further investigation.

Radiation Optic Neuropathy

Radiation-induced retinopathy and radiation-induced optic neuropathy (RION) are rare and disabling late-onset complications of ocular irradiation. Radiation-induced retinopathy is characterized by progressive, occlusive vasculopathy, leading to subsequent retinal inflammation, edema, ischemia, and neovascular proliferation. These changes ultimately lead to retinal hemorrhage, maculopathy, and gradual decline in visual acuity. In contrast, optic neuropathy involves the optic nerve or chiasm and may present with sudden onset of visual changes. Both can lead to profound and irreversible vision loss and substantial disability and are thus critically important to consider in the treatment of any intracranial or base of skull disease.

Increased utilization of external beam radiotherapy relative to cystectomy for localized, muscle-invasive bladder cancer: a SEER analysis

OBJECTIVE To assess recent utilization patterns of radiotherapy (RT) relative to cystectomy for muscle-invasive bladder cancer (MIBC) and evaluate survival trends over time in patients receiving RT. MATERIALS AND METHODS The surveillance, epidemiology, and end results program (SEER) was used to identify patients diagnosed between 1992 and 2013 with localized MIBC. Patients with a prior history of non-bladder malignancy, who received no treatment, or did not have available treatment information, were excluded. Treatment utilization patterns were assessed using Cochran-Armitage tests for trend, and patient characteristics were compared using chi-square tests. Overall survival (OS) and cause-specific survival (CSS) were estimated using the Kaplan-Meier method. All-cause (ACM) and cause-specific mortality (CSM) were evaluated with multivariable Cox proportional hazards regression. RESULTS Of 16175 patients analyzed, 11917 (74%) underwent cystectomy, and 4258 (26%) were treated with RT. Patients who received RT were older (median age 79 vs. 68, P < 0.01). Over time, the proportion of patients receiving RT relative to cystectomy increased (24% 1992–2002 vs. 28% 2003–2013, P < 0.01), despite median patient age throughout the study period remaining unchanged (71 for each 1992–2002 and 2003–2013, P = 0.41). For RT, compared with patients diagnosed earlier, those diagnosed from 2010–2013 showed improved OS (64% vs. 60% at 1 year, P < 0.01; 38% vs. 29% at 3 years, P < 0.01) and CSS (71% vs. 67% at 1 year, P = 0.01; 51% vs. 40% at 3 years, P < 0.01). On multivariable analysis, diagnosis from 2010–2013 was associated with a lower estimated risk of ACM (hazard ratio 0.77; 95% confidence interval 0.66–0.89, P < 0.001) and CSM (hazard ratio 0.81; 95% confidence interval 0.67–0.97, P = 0.02). CONCLUSION Utilization of RT for localized MIBC increased relative to cystectomy from 1992 to 2013, despite the median age of treated patients remaining unchanged. More recent survival outcomes for patients receiving RT were improved, supporting continued use of bladder preservation strategies utilizing RT.

Gamma Knife Stereotactic Radiosurgery for the Treatment of Primary and Metastatic Ocular Malignancies

Background: Gamma knife radiosurgery (GKR) can be used for precise targeting of malignant lesions of the CNS when brachytherapy is not an appropriate option. Objectives: This study reports treatment technique, efficacy, and radiation-induced adverse effects in patients with primary and metastatic ocular lesions treated with Leksell GKR. Methods: A retrospective, single-institution review was conducted of 28 patients with primary or metastatic ocular disease, treated from 2000 to 2014. The dose to margin was 17-27 Gy (maximum dose 28-54 Gy). Primary outcomes included overall survival (OS), local control, progression-free survival (PFS), and enucleation. Results: The median age at diagnosis was 70 years, and the median follow-up was 26.4 months. Of the 28 patients, 11 (39%) had metastatic ocular disease, and 17 (61%) were diagnosed with primary ocular melanoma (stage T2a-T4e). The average maximum dose and dose to margin were 41 and 21 Gy, respectively. The mean dose to the optic nerve was 12.6 Gy. The 5-year OS was 46% (95% CI: 23.6-68.4%) for the entire cohort; the 5-year PFS for M0 patients who presented with primary ocular melanoma lesions was 90% (95% CI: 71-100%). Only 1 patient required enucleation after radiation treatment. Conclusion: GKR is an effective option, with acceptable levels of toxicity, in the treatment of primary and metastatic ocular lesions.