Delta radiomics analysis of Magnetic Resonance guided radiotherapy imaging data can enable treatment response prediction in pancreatic cancer.

BACKGROUND: Magnetic Resonance Image guided Stereotactic body radiotherapy (MRgRT) is an emerging technology that is increasingly used in treatment of visceral cancers, such as pancreatic adenocarcinoma (PDAC). Given the variable response rates and short progression times of PDAC, there is an unmet clinical need for a method to assess early RT response that may allow better prescription personalization. We hypothesize that quantitative image feature analysis (radiomics) of the longitudinal MR scans acquired before and during MRgRT may be used to extract information related to early treatment response. METHODS: Histogram and texture radiomic features (n = 73) were extracted from the Gross Tumor Volume (GTV) in 0.35T MRgRT scans of 26 locally advanced and borderline resectable PDAC patients treated with 50 Gy RT in 5 fractions. Feature ratios between first (F1) and last (F5) fraction scan were correlated with progression free survival (PFS). Feature stability was assessed through region of interest (ROI) perturbation. RESULTS: Linear normalization of image intensity to median kidney value showed improved reproducibility of feature quantification. Histogram skewness change during treatment showed significant association with PFS (p = 0.005, HR = 2.75), offering a potential predictive biomarker of RT response. Stability analyses revealed a wide distribution of feature sensitivities to ROI delineation and was able to identify features that were robust to variability in contouring. CONCLUSIONS: This study presents a proof-of-concept for the use of quantitative image analysis in MRgRT for treatment response prediction and providing an analysis pipeline that can be utilized in future MRgRT radiomic studies.

Dose escalated neoadjuvant chemoradiotherapy with dose-painting intensity-modulated radiation therapy and improved pathologic complete response in locally advanced esophageal cancer.

We compared pathologic complete response (pCR) rate, toxicity, and postoperative complications between patients treated preoperatively with 50.4 Gy versus dose escalation with dose-painting intensity-modulated radiation therapy (dp-IMRT) to 56 Gy in locally advanced esophageal cancer. We evaluated esophageal cancer patients treated between 2006 and 2014 with preoperative IMRT chemoradiation to a dose of 50.4 Gy versus 56 Gy. The endpoints were pCR and toxicity. We identified 113 patients (50.4 Gy: n = 40; 56 Gy: n = 73). There were no significant differences in tumor or patient characteristics. Patients treated with 56 Gy demonstrated a higher pCR rate (56.2% vs. 30.0%) and lower pathologic nonresponse rate (4.1% vs. 20.0%) compared to patients treated to 50.4 Gy (P = 0.008). This remained significant on multivariate analysis (OR 3.375 95%CI 1.3-8.8, P = 0.013). Patients treated to 56 Gy also had an improved 3-year locoregional control rate compared to those treated to 50.4 Gy (93.8% vs. 78.5%; P = 0.022). The estimated 3-year freedom from failure was also superior in the 56 Gy arm (73.7% vs. 52.2%; P = 0.051), approaching significance. There were no differences in treatment related grade ≥3 toxicities, hospital admissions, feeding tube, esophageal stent placement, or dilation. There was, however, a statistically significant increase in postoperative atrial fibrillation in patients treated with 56 Gy (30.1% vs. 12.5%; P = 0.036). There was no difference in postoperative 30 or 60 day mortality. Dose escalation to 56 Gy with dp-IMRT is safe and results in significantly higher complete pathologic response rates in esophageal cancer without an increase in treatment-related toxicity. Prospective trials using dp-IMRT are needed to address the role of dose escalation on pCR rate and survival in esophageal cancer.

Comparative outcomes for three-dimensional conformal versus intensity-modulated radiation therapy for esophageal cancer.

Emerging data suggests a benefit for using intensity modulated radiation therapy (IMRT) for the management of esophageal cancer. We retrospectively reviewed patients treated at our institution who received definitive or preoperative chemoradiation with either IMRT or 3D conformal radiation therapy (3DCRT) between October 2000 and January 2012. Kaplan Meier analysis and the Cox proportional hazard model were used to evaluate survival outcomes. We evaluated a total of 232 patients (138 IMRT, 94 3DCRT) who received a median dose of 50.4 Gy (range, 44-64.8) to gross disease. Median follow up for all patients, IMRT patients alone, and 3DCRT patients alone was 18.5 (range, 2.5-124.2), 16.5 (range, 3-59), and 25.9 months (range, 2.5-124.2), respectively. We observed no significant difference based on radiation technique (3DCRT vs. IMRT) with respect to median overall survival (OS) (median 29 vs. 32 months; P = 0.74) or median relapse free survival (median 20 vs. 25 months; P = 0.66). On multivariable analysis (MVA), surgical resection resulted in improved OS (HR 0.444; P < 0.0001). Superior OS was also associated on MVA with stage I/II disease (HR 0.523; P = 0.010) and tumor length ≤5 cm (HR 0.567; P = 0.006). IMRT was also associated on univariate analysis with a significant decrease in acute weight loss (mean 6% + 4.3% vs 9% + 7.4%, P = 0.012) and on MVA with a decrease in objective grade ≥3 toxicity, defined as any hospitalization, feeding tube, or >20% weight loss (OR 0.51; P = 0.050). Our data suggest that while IMRT-based chemoradiation for esophageal cancer does not impact survival there was significantly less toxicity. In the IMRT group there was significant decrease in weight loss and grade ≥3 toxicity compared to 3DCRT.

Overview of diagnosis and management of metastatic disease to bone.

BACKGROUND: Bone metastases occur frequently in patients with advanced cancer and are a serious complication of cancer. The decision to treat is often individualized, based on each patient's clinical presentation, life expectancy, and quality of life. METHODS: We reviewed the current literature pertaining to management of metastatic disease to bone, and the medical, radiotherapeutic, and surgical treatment options for management of bone metastasis are discussed. RESULTS: Current management of skeletal metastasis includes analgesia, systemic therapy, radiation therapy, and surgery. We propose treatment algorithms for management of vertebral and nonvertebral bone metastases and suggest individualized interventions based on clinical presentation. CONCLUSIONS: Management of bone metastases is complex and requires a multidisciplinary approach. The goal of treatment is often palliative, and intervention and treatment regimens should be individualized based on the specific clinical presentation of each patient.

Beyond the conventional role of external-beam radiation therapy for skeletal metastases: new technologies and stereotactic directions.

BACKGROUND: Radiation therapy is a common and effective treatment modality in the management of skeletal metastases. Recent advances in technology permitting delivery of an ablative radiation dose with an image-guided stereotactic approach improve the therapeutic threshold. METHODS: The authors reviewed the literature on conventional external-beam radiation therapy and summarized the emerging data about image-guided stereotactic body radiation therapy (SBRT) for vertebral oligometastasis. RESULTS: Pain control can be achieved effectively with conventional external-beam radiation therapy and may be further improved with image-guided spinal SBRT. Image-guided SBRT allows delivery of an ablative radiation dose with minimal toxicity, may potentially improve local tumor control, and may enhance clinical outcomes for histologies that are considered radioresistant. However, further understanding of long-term normal tissue toxicity is lacking. CONCLUSIONS: Radiotherapy options are expanding for patients with skeletal metastases. Image-guided spinal SBRT can deliver a safe ablative radiation dose to improve pain control and potentially local tumor control. Randomized clinical trials are ongoing to assess clinical benefits and outcome with spinal SBRT.