Tumor heterogeneity can be elucidated by mapping subregions of the lesion with differential imaging characteristics, called habitats. Dynamic Contrast Enhanced (DCE-)MRI can depict the tumor microenvironments by identifying areas with variable perfusion and vascular permeability, since individual tumor habitats vary in the rate and magnitude of the contrast uptake and washout. Of particular interest is identifying areas of hypoxia, characterized by inadequate perfusion and hyper-permeable vasculature. An automatic procedure for delineation of tumor habitats from DCE-MRI was developed as a two-part process involving: (1) statistical testing in order to determine the number of the underlying habitats; and (2) an unsupervised pattern recognition technique to recover the temporal contrast patterns and locations of the associated habitats. The technique is examined on simulated data and DCE-MRI, obtained from prostate and brain pre-clinical cancer models, as well as clinical data from sarcoma and prostate cancer patients. The procedure successfully identified habitats previously associated with well-perfused, hypoxic and/or necrotic tumor compartments. Given the association of tumor hypoxia with more aggressive tumor phenotypes, the obtained in vivo information could impact management of cancer patients considerably.

In transarterial radioembolization (TARE) of hepatocellular carcinoma (HCC) with Yttrium-90 (Y-90) microspheres, recent studies correlate dosimetry from bremsstrahlung single photon emission tomography (SPECT/CT) with treatment outcomes; however, these studies focus on measures of central tendency rather than volumetric coverage metrics commonly used in radiation oncology. We hypothesized that three-dimensional (3D) isodose coverage of gross tumor volume (GTV) is the driving factor in HCC treatment response to TARE and is best assessed using advanced dosimetry techniques applied to nuclear imaging of actual Y-90 biodistribution. We reviewed 51 lobar TARE Y-90 treatments of 43 HCC patients. Dose prescriptions were 120 Gy for TheraSpheres and 85 Gy for SIR-Spheres. All patients underwent post-TARE Y-90 bremsstrahlung SPECT/CT imaging. Commercial software was used to contour gross tumor volume (GTV) and liver on post-TARE SPECT/CT. Y-90 dose distributions were calculated using the Local Deposition Model based on post-TARE SPECT/CT activity maps. Median gross tumor volume (GTV) dose; GTV receiving less than 100 Gy, 70 Gy and 50 Gy; minimum dose covering the hottest 70%, 95%, and 98% of the GTV (D70, D95, D98); mean dose to nontumorous liver, and disease burden (GTV/liver volume) were obtained. Clinical outcomes were collected for all patients by chart and imaging review. HCC treatment response was assessed according to the modified response criteria in solid tumors (mRECIST) guidelines. Kaplan-Meier (KM) survival estimates and multivariate regression analyses (MVA) were performed using STATA. Median survival was 22.5 months for patients achieving objective response (OR) in targeted lesions (complete response (CR) or partial response (PR) per mRECIST) vs. 7.6 months for non-responders (NR, stable disease or disease progression per mRECIST). On MVA, the volume of underdosed tumor (GTV receiving less than 100 Gy) was the only significant dosimetric predictor for CR (p = 0.0004) and overall survival (OS, p = 0.003). All targets with less than CR (n = 39) had more than 20 cc of underdosed tumor. D70 (p = 0.038) correlated with OR, with mean D70 of 95 Gy for responders and 60 Gy for non-responders (p = 0.042). On MVA, mean dose to nontumorous liver trended toward significant association with grade 3+ toxicity (p = 0.09) and correlated with delivered activity (p < 0.001) and burden of disease (p = 0.05). Dosimetric models supplied area under the curve estimates of > 0.80 predicting CR, OR, and ≥grade 3 acute toxicity. Dosimetric parameters derived from the retrospective analysis of post-TARE Y-90 bremsstrahlung SPECT/CT after lobar treatment of HCC suggest that volumetric coverage of GTV, not a high mean or median dose, is the driving factor in treatment response and that this is best assessed through the analysis of actual Y-90 biodistribution.

Objectives: People over the age of 75 years account for approximately 40% of patients diagnosed with pancreatic cancer, many with comorbidities that may limit their treatment options. This study reports on the use of stereotactic body radiation therapy (SBRT) in this population. Materials and Methods: Twenty consecutively treated patients over the age of 75 with pathologically proven localized pancreatic cancer were included in this retrospective review. All had been evaluated by a multidisciplinary team as unable to tolerate surgery or combined chemoradiation therapy. Patient outcomes were analyzed to determine the safety and efficacy of SBRT in this elderly cohort. Results: The median age was 83.2 years (minimum 77 y, maximum 90 y). Eighteen patients were treated at time of initial diagnosis, and 2 for recurrence after surgery. Eleven (55%) of the patients had an Adult Comorbidity Evaluation-27 comorbidity index score of 3 (severe) and 6 (30%) had a score of 2 (moderate). Fourteen patients were treated with 35 Gy in 5 fractions, 5 with 30 Gy in 5 fractions, and 1 patient with 36 Gy in 3 fractions. Seven (35%) patients had common terminology criteria for adverse events (CTCAE) V4.0 toxicity grade of 1-2, and 3 patients had a CTCAE V4.0 toxicity grade of 3-4, 2 with dehydration, and 1 had episodes of gastrointestinal bleeding. Three patients recurred locally, 10 had distant metastases, 4 of whom were found on the first posttreatment scan. Median overall survival was 6.4 months (95% confidence interval, 3.5-10.8 mo). Median recurrence-free survival was 6.8 months (95% confidence interval, 1.3-23.5 mo). Two patients survived >23 months. Conclusion: SBRT for pancreatic cancer appears to be a safe and effective method for treatment of elderly patients, even in the setting of severe comorbidities.

Small randomized trials have not shown an overall survival (OS) difference among local treatment modalities for patients with extremity soft‐tissue sarcomas (E‐STS) but were underpowered for OS. We examine the impact of local treatment modalities on OS and sarcoma mortality (SM) using two national registries. The National Cancer Database (NCDB) and the Surveillance, Epidemiology, and End Results (SEER) Program were analyzed separately to identify patients with stage II‐III, high‐grade E‐STS diagnosed between 2004 and 2013 and treated with (1) amputation alone, (2) limb‐sparing surgery (LSS) alone, (3) preoperative radiation therapy (RT) and LSS, or (4) LSS and postoperative RT. Multivariable analyses (MVAs) and 1:1 matched pair analyses (MPAs) examined treatment impacts on OS (both databases) and SM (SEER only). From the NCDB and SEER, 7828 and 2937 patients were included. On MVAs, amputation was associated with inferior OS and SM. Relative to LSS alone, both preoperative RT and LSS (HR, 0.70; 95% CI: 0.62‐0.78) and LSS and postoperative RT (HR, 0.69; 95% CI: 0.63‐0.75) improved OS in NCDB analyses with confirmation by SEER. Estimated median survivals from MPA utilizing NCDB data were 7.2 years with LSS alone (95% CI: 6.5‐8.9 years) vs 9.8 years (95% CI: 9.0‐11.2 years) with LSS and postoperative RT. A MPA comparing preoperative RT and LSS to LSS alone found median survivals of 8.9 years (95% CI: 7.9‐not estimable) and 6.6 years (95% CI: 5.4‐7.8 years). Optimal high‐grade E‐STS management includes LSS with preoperative or postoperative RT as evidenced by superior OS and SM.