Unconventional radiotherapy to enhance immunotherapy efficacy in bulky tumors: a case report

Determining the most appropriate management strategy for patients with large tumor masses is a very challenging issue. Unconventional radiotherapy modalities, such as spatially fractionated radiation therapy (SFRT), are associated with dramatic responses. Recent studies have suggested that systemic immune activation may be triggered by SFRT delivery to primary tumor lesion. This report describes the case of a patient treated with a novel form of immune-sparing partially ablative irradiation (ISPART) for a bulky peritoneal metastasis from renal cell cancer, refractory to anti-PD-1 therapy (nivolumab) as third-line therapy after sequential therapy with sunitinib and cabozantinib. The observed response suggests that there may be a synergistic effect between ISPART and immunotherapy. This case report supports the inclusion of ISPART in patients presenting with bulky lesions treated with checkpoint inhibitors .

Comparison of stereotactic body radiation therapy versus fractionated radiation therapy for primary liver cancer with portal vein tumor thrombus

Background To compare the clinical outcomes of stereotactic body radiation therapy (SBRT) and fractionated radiation therapy (FRT) for primary liver cancer with portal vein tumor thrombus (PVTT). Methods This retrospective study included 36 patients who underwent SBRT and 36 patients who underwent FRT from August 2016 to June 2018. Patients were evaluated for short-term efficacy, long-term efficacy, AEs, and quality of life before and after treatment. Results With a median follow-up of 28.8 months (26–36 months), 27 patients survived in the SBRT group while 19 patients survived in the FRT group. The survival rate in the SBRT group was statistically higher than that of the FRT group after 6 months (80.56% vs. 58.33%; P = 0.041), 12 months (77.78% vs. 55.56%; P = 0.046) and 24 months 75.00% vs. 52.78%; P = 0.049). The median whole survival time of the SBRT group was 13.3 months (95% CI 12.83–13.97), which was statistically longer than 9.8 months in the FRT group (95% CI 8.83–10.97, P < 0.05) based on the Kaplan–Meier method. The SBRT group had better survival quality and fewer adverse events than the FRT group. Conclusion SBRT had better clinical outcomes than FRT for primary liver cancer with PVTT.

Long-term survival in patients with long-segment complex meningiomas occluding the dural venous sinuses: illustrative cases

BACKGROUND Invasive sagittal sinus meningiomas are difficult tumors to cure by resection alone. Stereotactic radiosurgery (SRS) can be used as an adjuvant management strategy to improve tumor control after incomplete resection. OBSERVATIONS The authors reported the long-term retrospective follow-up of two patients whose recurrent parasagittal meningiomas eventually occluded their superior sagittal sinus. Both patients underwent staged radiosurgery and fractionated radiation therapy to achieve tumor control that extended to 20 years after their initial surgery. After initial subtotal resection of meningiomas that had invaded major cerebral venous sinuses, adjuvant radiosurgery was performed to enhance local tumor control. Over time, adjacent tumor progression required repeat SRS and fractionated radiation therapy to boost long-term tumor response. Staged multimodality intervention led to extended survival in these patients with otherwise unresectable meningiomas. LESSONS Multimodality management with radiosurgery and fractionated radiation therapy was associated with long-term survival of two patients with otherwise surgically incurable and invasive meningiomas of the dural venous sinuses.

Towards an Image-Informed Mathematical Model of In Vivo Response to Fractionated Radiation Therapy

Fractionated radiation therapy is central to the treatment of numerous malignancies, including high-grade gliomas where complete surgical resection is often impractical due to its highly invasive nature. Development of approaches to forecast response to fractionated radiation therapy may provide the ability to optimize or adapt treatment plans for radiotherapy. Towards this end, we have developed a family of 18 biologically-based mathematical models describing the response of both tumor and vasculature to fractionated radiation therapy. Importantly, these models can be personalized for individual tumors via quantitative imaging measurements. To evaluate this family of models, rats (n = 7) with U-87 glioblastomas were imaged with magnetic resonance imaging (MRI) before, during, and after treatment with fractionated radiotherapy (with doses of either 2 Gy/day or 4 Gy/day for up to 10 days). Estimates of tumor and blood volume fractions, provided by diffusion-weighted MRI and dynamic contrast-enhanced MRI, respectively, were used to calibrate tumor-specific model parameters. The Akaike Information Criterion was employed to select the most parsimonious model and determine an ensemble averaged model, and the resulting forecasts were evaluated at the global and local level. At the global level, the selected model’s forecast resulted in less than 16.2% error in tumor volume estimates. At the local (voxel) level, the median Pearson correlation coefficient across all prediction time points ranged from 0.57 to 0.87 for all animals. While the ensemble average forecast resulted in increased error (ranging from 4.0% to 1063%) in tumor volume predictions over the selected model, it increased the voxel wise correlation (by greater than 12.3%) for three of the animals. This study demonstrates the feasibility of calibrating a model of response by serial quantitative MRI data collected during fractionated radiotherapy to predict response at the conclusion of treatment.

Investigating chemopotentiation by low-dose fractionated radiation therapy for disseminated intra-abdominal gastric cancer.

242 Background: Treatment options are rather limited for gastrointestinal cancer patients whose disease has disseminated into the intra-abdominal cavity. There is currently no modality that has been shown to prolong survival of this patient sub-population. Here, we designed pre-clinical studies to evaluate the potential application of chemopotentiation by Low Dose Fractionated Radiation Therapy (LDFRT) for disseminated gastric cancer and evaluate the role of a likely biomarker, the Dual Oxidase 2 (DUOX2) enzyme. Methods: Nude mice were injected orthotopically with human gastric cancer cells expressing endogenous or lower levels of DUOX2 and randomly assigned to four treatment groups: 1; vehicle alone, 2; chemotherapy consisting of a modified regimen of docetaxel, cisplatin and 5’-fluorouracil (mDCF) for three consecutive days, 3; Low Dose- Whole Abdomen Radiation Therapy (LD-WART) (5 fractions of 15 cGy in three days), 4; mDCF and LD-WART. Blood was harvested at day 14 and 45 and cancer progression was evaluated by fluorescence imaging (Xenogen). Results: The combined regimen was well tolerated in all animals and led to DUOX2 upregulation, increased serum protein oxidation and reduced cancer progression in the DUOX2 positive tumors. Tumors expressing lower DUOX2 levels were more sensitive to chemotherapy but no additional benefit was obtained with LD-WART. The potential clinical significance of these findings is exemplified by a tumor microarray demonstrating that only about 46% of human gastric tumors expressed DUOX2. The molecular mechanisms underlying DUOX2 effects in response to the combined regimen include NF-kB upregulation and VEGF down regulation. Moreover, the combined regimen of mDCF and LDFRT was also effective on a Cancer Stem Cell (CSC)-Like subpopulation of mouse gastric cancer cells. Conclusions: Taken together these data suggest that DUOX2 could be used as a potential biomarker for patient stratification for chemopotentiation by LD-WART for positive tumors while chemotherapy alone would be more effective for DUOX2 negative tumors. The absence of added toxicity suggests that these cycles could be repeated.