Clinical Applications of Magnetic Resonance-Guided Radiotherapy: A Narrative Review.

Magnetic resonance-guided radiotherapy (MRgRT) represents a promising new image guidance technology for radiation treatment delivery combining an onboard MRI scanner with radiation delivery technology. By enabling real-time low-field or high-field MRI acquisition, it facilitates improved soft tissue delineation, adaptive treatment, and motion management. Now that MRgRT has been available for nearly a decade, research has shown the technology can be used to effectively shrink treatment margins to either decrease toxicity (in breast, prostate cancer, and pancreatic cancer) or facilitate dose-escalation and improved oncologic outcomes (in pancreatic and liver cancer), as well as enabling indications that require clear soft tissue delineation and gating (lung and cardiac ablation). In doing so, the use of MRgRT has the potential to significantly improve the outcomes and quality of life of the patients it treats. The present narrative review aims to describe the rationale for MRgRT, the current and forthcoming state of technology, existing studies, and future directions for the advancement of MRgRT, including associated challenges.

Improved Survival Outcomes in Medically Fit Patients With Early-Stage Non-Small-Cell Lung Cancer Undergoing Stereotactic Body Radiotherapy.

INTRODUCTION: Stereotactic body radiotherapy (SBRT) has been shown to result in excellent disease control rates for early-stage non-small-cell lung cancer (NSCLC). It remains unknown which patients would most benefit from SBRT in treating NSCLC. PATIENTS AND METHODS: We conducted a retrospective analysis of 346 patients treated with SBRT for early-stage NSCLC at 2 institutions (86 patients from City of Hope National Medical Center and 260 patients from The Newport Beach Radiosurgery Center/Hoag Hospital) from February 2010 to July 2019. The primary endpoint was overall survival (OS). The omnibus test of model coefficients was performed to study the associations between clinical factors and OS. Survival analyses were performed by the log-rank test and Cox proportional hazards regression. RESULTS: Under the univariate analysis, variables associated with a decreased likelihood of death included age < 65 years (P = .040) and being a surgical candidate (P = .010). Multivariate analysis found that surgical candidates still had a significantly decreased likelihood of death compared to nonsurgical candidates (Hazard ratio 0.360, 95% confidence interval 0.153-0.848, P = .019). Median OS was significantly increased for surgical candidates versus nonsurgical candidates (83 vs 53 months, P = .017). The local failure rate was 9.1%, the locoregional failure rate was 12.7%, and the distant failure rate was 10.7%. CONCLUSION: Patients who are deemed to be candidates for surgery have improved OS compared to those who are not when treated with SBRT. This raises the question of selection bias in trials comparing surgery with SBRT in NSCLC, as patients who are deemed to be surgical candidates and then go on to undergo surgery may have an inherent OS benefit.

Complex Oncological Decision-Making Utilizing Fast-and-Frugal Trees in a Community Setting-Role of Academic and Hybrid Modeling.

Non-small cell lung cancer is a devastating disease and with the advent of targeted therapies and molecular testing, the decision-making process has become complex. While established guidelines and pathways offer some guidance, they are difficult to utilize in a busy community practice and are not always implemented in the community. The rationale of the study was to identify a cohort of patients with lung adenocarcinoma at a City of Hope community site (n = 11) and utilize their case studies to develop a decision-making framework utilizing fast-and-frugal tree (FFT) heuristics. Most patients had stage IV (N = 9, 81.8%) disease at the time of the first consultation. The most common symptoms at initial presentation were cough (N = 5, 45.5%), shortness of breath (N = 3, 27.2%), and weight loss (N = 3, 27.2%). The Eastern Cooperative Oncology Group (ECOG) performance status ranged from 0-1 in all patients in this study. Distribution of molecular drivers among the patients were as follows: EGFR (N = 5, 45.5%), KRAS (N = 2, 18.2%), ALK (N = 2, 18.2%), MET (N = 2, 18.2%), and RET (N = 1, 9.1%). Seven initial FFTs were developed for the various case scenarios, but ultimately the decisions were condensed into one FFT, a molecular stage IV FFT, that arrived at accurate decisions without sacrificing initial information. While these FFT decision trees may seem arbitrary to an experienced oncologist at an academic site, the simplicity of their utility is essential for community practice where patients often do not get molecular testing and are not assigned proper therapy.

Dosimetric Analysis of Neural and Vascular Structures in Skull Base Tumors Treated with Stereotactic Radiosurgery.

Objective To examine the relationship between the prescribed target dose and the dose to healthy neurovascular structures in patients with vestibular schwannomas treated with stereotactic radiosurgery (SRS). Study Design Case series with chart review. Setting SRS center from 2011 to 2013. Subjects Twenty patients with vestibular schwannomas treated at the center from 2011 to 2013. Methods Twenty patients with vestibular schwannomas were included. The average radiation dose delivered to healthy neurovascular structures (eg, carotid artery, basilar artery, facial nerve, trigeminal nerve, and cochlea) was analyzed. Results Twenty patients with vestibular schwannomas who were treated with fused computed tomography/magnetic resonance imaging-guided SRS were included in the study. The prescribed dose ranged from 10.58 to 17.40 Gy over 1 to 3 hypofractions to cover 95% of the target tumor volume. The mean dose to the carotid artery was 5.66 Gy (95% confidence interval [CI], 4.53-6.80 Gy), anterior inferior cerebellar artery was 8.70 Gy (95% CI, 4.54-12.86 Gy), intratemporal facial nerve was 3.76 Gy (95% CI, 3.04-4.08 Gy), trigeminal nerve was 5.21 Gy (95% CI, 3.31-7.11 Gy), and the cochlea was 8.70 Gy (95% CI, 7.81-9.59 Gy). Conclusions SRS for certain vestibular schwannomas can expose the anterior inferior cerebellar artery (AICA) and carotid artery to radiation doses that can potentially initiate atherosclerotic processes. The higher doses to the AICA and carotid artery correlated with increasing tumor volume. The dose delivered to other structures such as the cochlea and intratemporal facial nerve appears to be lower and much less likely to cause immediate complications when shielded.

Diagnosis-specific prognostic factors, indexes, and treatment outcomes for patients with newly diagnosed brain metastases: a multi-institutional analysis of 4,259 patients.

PURPOSE: Controversy endures regarding the optimal treatment of patients with brain metastases (BMs). Debate persists, despite many randomized trials, perhaps because BM patients are a heterogeneous population. The purpose of the present study was to identify significant diagnosis-specific prognostic factors and indexes (Diagnosis-Specific Graded Prognostic Assessment [DS-GPA]). METHODS AND MATERIALS: A retrospective database of 5,067 patients treated for BMs between 1985 and 2007 was generated from 11 institutions. After exclusion of the patients with recurrent BMs or incomplete data, 4,259 patients with newly diagnosed BMs remained eligible for analysis. Univariate and multivariate analyses of the prognostic factors and outcomes by primary site and treatment were performed. The significant prognostic factors were determined and used to define the DS-GPA prognostic indexes. The DS-GPA scores were calculated and correlated with the outcomes, stratified by diagnosis and treatment. RESULTS: The significant prognostic factors varied by diagnosis. For non-small-cell lung cancer and small-cell lung cancer, the significant prognostic factors were Karnofsky performance status, age, presence of extracranial metastases, and number of BMs, confirming the original GPA for these diagnoses. For melanoma and renal cell cancer, the significant prognostic factors were Karnofsky performance status and the number of BMs. For breast and gastrointestinal cancer, the only significant prognostic factor was the Karnofsky performance status. Two new DS-GPA indexes were thus designed for breast/gastrointestinal cancer and melanoma/renal cell carcinoma. The median survival by GPA score, diagnosis, and treatment were determined. CONCLUSION: The prognostic factors for BM patients varied by diagnosis. The original GPA was confirmed for non-small-cell lung cancer and small-cell lung cancer. New DS-GPA indexes were determined for other histologic types and correlated with the outcome, and statistical separation between the groups was confirmed. These data should be considered in the design of future randomized trials and in clinical decision-making.

Radiographic and histopathologic observations after combined EGFR inhibition and hypofractionated stereotactic radiosurgery in patients with recurrent malignant gliomas.

PURPOSE: To describe the radiographic and histopathologic changes after stereotactic radiosurgery (SRS) and epidermal growth factor receptor inhibition in patients with recurrent malignant gliomas. METHODS AND MATERIALS: A total of 15 patients with recurrent high-grade gliomas were treated on a prospective Phase I trial combining SRS and gefitinib. The SRS dose was escalated from 18 to 36 Gy in three fractions. The planning target volume was the T(1)-weighted contrast-enhancing (T(1)C) lesion plus 2 mm. Gefitinib was given at 250 mg daily. Serial brain magnetic resonance imaging scans were analyzed to characterize the volumetric changes in the T(1)C and T(2) abnormalities after treatment. Two patients underwent resection for suspected recurrence. RESULTS: The median pretreatment magnetic resonance imaging T(1)C and T(2) volume was 40.9 and 184.1 cm(3), respectively. The median post-SRS percentage of increases in the T(1)C volume at 1, 2-4, and 5-7 months was 8.9%, 41.3%, and 99.6%, respectively. The median percentage increase in the T(2) volume likewise showed a trend upward after SRS, from 18.0% at 1 month to 37.8% at 5-7 months. For the 2 patients who underwent resection after SRS for an increasing T(1)C volume, the histopathologic analysis revealed therapy-induced vascular injury and necrosis. One patient with an asymptomatic increase in the T(1)C volume after SRS was treated conservatively. After a peak T(1)C volume increase at 9 months, the T(1)C volume had declined to 50% of the maximal volume at 15 months. The patients with the most dramatic increase in T(1)C volume experienced the longest overall survival. CONCLUSION: Patients experienced a notable increase in magnetic resonance imaging T(1)C and T(2) volumes after the combination of SRS and epidermal growth factor receptor inhibition. The tissue changes were consistent with a potent treatment effect.

Survival effect of neoadjuvant radiotherapy before esophagectomy for patients with esophageal cancer: a surveillance, epidemiology, and end-results study.

PURPOSE: The role of neoadjuvant radiotherapy (NeoRT) before definitive surgery for esophageal cancer remains controversial. This study used a large population-based database to assess the effect of NeoRT on survival for patients treated with definitive surgery. METHODS AND MATERIALS: The overall survival (OS) and cause-specific survival for patients with Stage T2-T4, any N, M0 (cT2-T4M0) esophageal cancer who had undergone definitive surgery between 1998 and 2004 were analyzed by querying the Surveillance, Epidemiology, and End-Results database. Kaplan-Meier survival curves were generated and univariate comparisons were made using the log-rank test. Cox proportional hazards survival regression multivariate analysis was performed with NeoRT, T stage (T2 vs. T3-T4), pathologic nodal status (pN0 vs. pN1), number of nodes dissected (>10 vs. /=65 years), and gender as covariates. RESULTS: A total of 1,033 patients were identified. Of these, 441 patients received NeoRT and 592 underwent esophagectomy alone; 77% were men, 67% had adenocarcinoma, and 72% had Stage T3-T4 disease. The median OS and cause-specific survival were both significantly greater for patients who received NeoRT compared with esophagectomy alone (27 vs. 18 months and 35 vs. 21 months, respectively, p <0.0001). The 3-year OS rate was also significantly greater in the NeoRT group (43% vs. 30%). On multivariate analysis, NeoRT, age <65 years, adenocarcinoma histologic type, female gender, pN0 status, >10 nodes dissected, and Stage T2 disease were all independently correlated with increased OS. CONCLUSION: These results support the use of NeoRT for patients with esophageal cancer. Prospective studies are needed to confirm these results.

Impact of postmastectomy radiotherapy in T3N0 invasive carcinoma of the breast: a Surveillance, Epidemiology, and End Results database analysis.

BACKGROUND: Randomized trials provide evidence for improved outcomes with postmastectomy radiotherapy (PMRT) in high-risk patients. It has been suggested that patients with T3N0 breast cancer represent a favorable subgroup for which PMRT renders little benefit. In the current study, the authors used a United States population database to evaluate PMRT in this subgroup. METHODS: The cause-specific survival (CSS) and overall survival (OS) of women with T3N0M0 breast cancer in the Surveillance, Epidemiology, and End Results database after mastectomy and axillary staging from 1988 to 2002 were analyzed. Univariate analysis was performed to relate CSS with PMRT (yes vs no), tumor size (< or =7 cm vs >7 cm), grade (1 vs 2 or 3), patient age (< or =50 years vs >50 years), the number of lymph nodes dissected (< or =13 vs >13), and the era treated (1988-1997 vs 1998-2002). Multivariate analyses for CSS and OS were also performed. RESULTS: In total, 1865 women met the analysis criteria for OS; CSS data were available for 98.8% of those women. Of the women who were diagnosed during the era from 1988 to 1997, 22% received PMRT, and that rate increased to 41% during the era from 1998 to 2002. The actuarial 10-year CSS for those who received PMRT versus those who did not receive PMRT was 81.6% versus 79.8%, respectively (P = .38). PMRT was not associated with a CSS benefit in any subgroup, a finding that persisted in multivariate analyses. Women who received PMRT had an increased 10-year OS rate (70.7% vs 58.4%; P < .001) that was confined to women aged >50 years in a subgroup analysis. CONCLUSIONS: This retrospective, population-based analysis demonstrated no increase in CSS with PMRT for women with T3N0 breast cancer, lending further support to the hypothesis that T3N0 disease postmastectomy represents a favorable subset of locally advanced breast cancer. The increased OS associated with PMRT in the absence of improved CSS likely reflects patient selection in this nonrandomized dataset. Prospective evaluation of PMRT in this population subset is warranted.

Outcomes and effect of radiotherapy in patients with stage I or II diffuse large B-cell lymphoma: a surveillance, epidemiology, and end results analysis.

PURPOSE: To assess disease-specific survival (DSS), overall survival (OS), and the effect of radiotherapy (RT) in patients with localized diffuse large B-cell lymphoma (DLBCL). PATIENTS AND METHODS: The Surveillance, Epidemiology, and End Results database was queried for all patients diagnosed with Stage I, IE, II, or IIE DLBCL between 1988 and 2004. The analyzable data included gender, age, race, stage, presence of extranodal disease, and RT administration. Patients who had died or were lost to follow-up within 6 months of diagnosis were excluded. RESULTS: A total of 13,420 patients met the search criteria. Of these, 5,547 (41%) had received RT and 7,873 (59%) had not. RT was associated with a significant DSS (hazard ratio, 0.82, p <0.0001) and OS benefit that persisted during the 15 years of follow-up. Elderly patients, defined either as those >60 or >70 years old, had significantly improved DSS and OS associated with RT. On multivariate analysis, RT was significantly associated with increased DSS and OS. The 5-year DSS outcomes were highly variable among patient subsets, defined by age, stage, and extranodal disease (range for RT-treated patients, 70% for Stage II, age >60 years to 87% for Stage I, age

A phase I dose-escalation study of fractionated stereotactic radiosurgery in combination with gefitinib in patients with recurrent malignant gliomas.

PURPOSE: To determine the maximum tolerated dose (MTD) of fractionated stereotactic radiosurgery (SRS) with gefitinib in patients with recurrent malignant gliomas. METHODS AND MATERIALS: A Phase I clinical trial was performed. Eligible patients had pathologically proved recurrent anaplastic astrocytoma or glioblastoma. Patients started gefitinib (250 mg/day) 7 days before SRS and continued for 1 year or until disease progression. SRS was delivered in three fractions over 3 days. The planning target volume (PTV) was the T1-weighted MRI postcontrast enhancing lesion+2 mm. The first cohort received an SRS dose of 18 Gy, and subsequent cohorts received higher doses up to the maximum dose of 36 Gy. Dose-limiting toxicity (DLT) was any Grade 3 toxicity. The MTD was exceeded if 2 of 6 patients in a cohort experienced DLT. RESULTS: Characteristics of the 15 patients enrolled were: 9 men, 6 women; median age, 47 years (range, 23-65 years); 11 glioblastoma, 4 AA; median prior RT dose, 60 Gy (range, 54-61.2 Gy); median interval since RT, 12 months (range, 3-57 months); median PTV, 41 cc (range, 12-151 cc). Median follow-up time was 7 months (range, 2-28 months). Median time on gefitinib was 5 months (range, 2-12 months). No patient experienced a DLT, and the SRS dose was escalated from 18 to 36 Gy. Grade 1-2 gefitinib-related dermatitis and diarrhea were common (10 and 7 patients, respectively). CONCLUSION: Fractionated SRS to a dose of 36 Gy in three fractions is well tolerated with gefitinib at daily dose of 250 mg. Further studies of SRS and novel molecular targeted agents are warranted in this challenging clinical setting.

Update in the treatment of brain metastases from lung cancer.

Brain metastases from lung cancer represent a prevalent and challenging clinical dilemma. The brain is an extremely common site of failure for non-small-cell lung cancer and small-cell lung cancer, often as a solitary site of disease. Despite steady research developments during recent years, survival rates remain poor. Some research suggests that the outcomes and characteristics of brain metastases that result from lung cancer primary sites are perhaps different than those from other primary sites. Clinical treatment strategies should therefore be adjusted accordingly. This article reviews the clinical characteristics, prognostic factors, and treatment strategies of brain metastases from lung cancer with a particular emphasis on recent research developments in the field.