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.

Synchronous rectal adenocarcinoma and splenic marginal zone lymphoma.

Synchronous cancers of different primary origin are rare. Here, we describe the case of a patient with concomitant diagnoses of rectal adenocarcinoma and splenic marginal zone lymphoma (smzl). A 57-year-old woman initially presented with abdominal pain. Physical examination and computed tomography demonstrated massive splenomegaly, and a complete blood count revealed microcytic anemia and lymphopenia. During the subsequent evaluation, she presented with hematochezia, melena, and constipation, which prompted gastroenterology referral. Subsequent endoscopic rectal ultrasonography revealed a T3N1 moderately differentiated rectal adenocarcinoma, with computed tomography imaging of chest, abdomen, and pelvis confirming no metastasis. Thus, the cancer was classified as clinical stage T3N1M0, stage iii. Bone marrow biopsy confirmed co-existing marginal zone lymphoma, and with the clinical presentation of massive splenomegaly, a diagnosis of smzl was made. The patient's management was individually tailored for simultaneous optimal treatment of both conditions. Concurrent treatment with neoadjuvant rituximab and 5-fluorouracil chemotherapy, with external-beam radiation therapy to the pelvis, was administered, followed by surgery consisting of en bloc splenectomy and distal pancreatectomy, and low anterior resection. The patient completed a standard course of adjuvant folfox (fluorouracil-leucovorin-oxaliplatin) chemotherapy and has remained disease-free for 7 years. To our knowledge, this report is the first to specifically describe simultaneous diagnoses of locally advanced rectal cancer and smzl. We also describe the successful combined neoadjuvant treatment combination of 5-fluorouracil, rituximab, and pelvic radiation.

Carboplatin and paclitaxel as first-line treatment of unresectable or metastatic esophageal or gastric cancer.

Survival in patients with metastatic esophageal and gastric cancer is dismal. No standard treatment has been established. Carboplatin/paclitaxel is active in both advanced gastric and esophageal cancer. Here we retrospectively present our single center experience. Between 1998 and 2013, a total of 134 patients with metastatic esophageal and gastric adenocarcinoma treated with carboplatin/paclitaxel (carboplatin predominantly area under the curve 5 and paclitaxel predominantly 175 mg/m(2)) every 3 weeks as first-line therapy were identified. Baseline characteristics, response to therapy, toxicities, and survival in this patient population were evaluated. Overall survival was defined as date from diagnosis to death or last follow up, and progression-free survival was defined at time from cycle 1 to, progression or last follow up. Kaplan-Meier curves were fit to estimate overall and progression-free survival. Of the 134 patients evaluated, the median age at diagnosis was 65 years. Disease control rate was 62.6% (complete response: 11%, partial response: 28%, stable disease: 33%). Median overall survival from date of initial diagnosis was 15.5 months (95% confidence interval [CI] 1.06-1.5). Median progression-free survival from date of initiation of carboplatin and paclitaxel was 5.3 months (95% CI 0.34-0.5). Grade III or greater toxicity occurred in 26.1% of patients. The most common grade III toxicities were neutropenia and neuropathy, present in 14.2% and 3.7% of the total study population, respectively. In patients with metastatic or unresectable esophageal or gastric cancer, the combination of carboplatin and paclitaxel is well tolerated with comparable overall survival and progression-free survival to existing regimens in this population.

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.

Review of current best practice and priorities for research in radiation oncology for elderly patients with cancer: the International Society of Geriatric Oncology (SIOG) task force.

Radiotherapy (RT) is a key component of the management of older cancer patients. Level I evidence in older patients is limited. The International Society of Geriatric Oncology (SIOG) established a task force to make recommendations for curative RT in older patients and to identify future research priorities. Evidence-based guidelines are provided for breast, lung, endometrial, prostate, rectal, pancreatic, oesophageal, head and neck, central nervous system malignancies and lymphomas. Patient selection should include comorbidity and geriatric evaluation. Advances in radiation planning and delivery improve target coverage, reduce toxicity and widen eligibility for treatment. Shorter courses of hypofractionated whole breast RT are safe and effective. Conformal RT and involved-field techniques without elective nodal irradiation have improved outcomes in non-small-cell lung cancer (NSCLC) without increasing toxicity. Where comorbidities preclude surgery, stereotactic body radiotherapy (SBRT) is an option for early-stage NSCLC and pancreatic cancer. Modern involved-field RT for lymphoma based on pre-treatment positron emission tomography data has reduced toxicity. Significant comorbidity is a relative contraindication to aggressive treatment in low-risk prostate cancer (PC). For intermediate-risk disease, 4-6 months of hormones are combined with external beam radiotherapy (EBRT). For high-risk PC, combined modality therapy (CMT) is advised. For high-intermediate risk, endometrial cancer vaginal brachytherapy is recommended. Short-course EBRT is an alternative to CMT in older patients with rectal cancer without significant comorbidities. Endorectal RT may be an option for early disease. For primary brain tumours, shorter courses of postoperative RT following maximal debulking provide equivalent survival to longer schedules. MGMT methylation status may help select older patients for temozolomide alone. Stereotactic RT provides an alternative to whole-brain RT in patients with limited brain metastases. Intensity-modulated radiation therapy provides an excellent technique to reduce dose to the carotids in head and neck cancer and improves locoregional control in oesophageal cancer. Best practice and research priorities are summarised.

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.

SU-E-J-187: Evaluation of the Effects of Dose on 4DCT-Calculated Lung Ventilation.

PURPOSE: To investigate the effects of radiation therapy (RT) treatment dose on ventilation. METHODS: Optical flow deformable image registration of the normal end-expiration and end-inspiration phases of 4DCT images was used to correlate the voxels between the two phases. 4DCT sets from before and after RT were used to derive ventilation for 3 SBRT lung patients. Planning dose and normalized ventilation were superimposed on the CT volume resulting in each voxel having a volume, a normalized ventilation and a dose. From these values a 3D dose-ventilation-volume surfaces was created. The surface was integrated over dose to reduce the 3D surface to a 2D histogram that is easier to interpret. RESULTS: For lung tissue regions receiving more than 20 Gy, a decrease in ventilation was observed in the three patients. Patient A (time between scans, T=26 months) showed an increase in ventilation for regions receiving a dose smaller than 20 Gy, whereas patients B (T=3 months) and C (T=6 months) did not show any change for these regions. Mean ventilation within the 20 Gy region for patient A was 0.57 before RT and 0.51 after RT; and 0.54 before and 0.48 after RT for the 30 Gy region. Mean ventilation for the 20 Gy region for patient B was 0.49 before RT and 0.47 after RT, for the 30 Gy region mean ventilation was 0.49 Gy before and 0.45 Gy after RT. Patient C's mean ventilation for the 20 Gy region was 0.54 before RT and 0.50 after RT, for the 30 Gy region mean ventilation was 0.54 before RT and 0.49 after RT. CONCLUSIONS: Ventilation before and after radiation therapy can be measured using 4DCT and deformable image registration techniques. In a preliminary application of this approach for three patients, changes in ventilation were observed with a weak correlation between ventilation change and dose. Partially supported by a grant from Varian Medical Systems.