Sterotactic Body Radiation Therapy for Liver Tumors

As a common deposit for tumor cells, the liver is second only to the lymph nodes as a site of metastatic disease. Unfortunately, by the time patients present with liver metastases there is usually evidence of the systemic spread of the disease, and patients can not longer be considered as candidates for surgery or other local ablative treatments. Because the liver is the first major organ reached by venous blood draining from the intestinal tract, it is the most common site of metastatic disease in cancers of the large intestine. It is involved in as many as 50-70% of colorectal cancer patients who develop metastatic disease, in approximately half of whom it is the only site of recurrence. While the role of local treatments such as surgery and radiofrequency ablation (RFA) is relatively well defined for colorectal metastases, their indications and benefits are less clear in metastases from other tumor types. However, due to concomitant medical diseases or to poor anatomical location or performance status, few patients with colorectal liver metastases are considered eligible for resection

Individualized automated planning for dose bath reduction in robotic radiosurgery for benign tumors

Object To explore the use of automated planning in robotic radiosurgery of benign vestibular schwannoma (VS) tumors for dose reduction outside the planning target volume (PTV) to potentially reduce risk of secondary tumor induction. Methods A system for automated planning (AUTOplans) for VS patients was set up. The goal of AUTO- planning was to reduce the dose bath, including the occurrence of high dose spikes leaking from the PTV into normal tissues, without worsening PTV coverage, OAR doses, or treatment time. For 20 VS patients treated with 1x12 Gy, the AUTOplan was compared with the plan generated with conventional, manual trial-and-error planning (MANplan). Results With equal PTV coverage, AUTOplans showed clinically negligible differences with MANplans in OAR sparing (largest mean difference for all OARs: ΔD2% = 0.2 Gy). AUTOplan dose distributions were more compact: mean/maximum reductions of 23.6/53.8% and 9.6/ 28.5% in patient volumes receiving more than 1 or 6 Gy, respectively (p<0.001). AUTOplans also showed smaller dose spikes with mean/maximum reductions of 22.8/37.2% and 14.2/ 40.4% in D2% for shells at 1 and 7 cm distance from the PTV, respectively (p<0.001). Conclusion Automated planning for benign VS tumors highly outperformed manual planning with respect to the dose bath outside the PTV, without deteriorating PTV coverage or OAR sparing, or significantly increasing treatment time

Progression of hearing loss after LINAC-based stereotactic radiotherapy for vestibular schwannoma is associated with cochlear dose, not with pre-treatment hearing level

BACKGROUND: Although stereotactic radiotherapy (SRT) for vestibular schwannoma has demonstrated excellent local control rates, hearing deterioration is often reported after treatment. We therefore wished to assess the change in hearing loss after SRT and to determine which patient, tumor and treatment-related factors influence deterioration. METHODS: We retrospectively analyzed progression of hearing loss in patients with vestibular schwannoma who had received stereotactic radiosurgery (SRS) or fractionated stereotactic radiotherapy (FSRT) as a primary treatment between 2000 and 2014. SRS had been delivered as a single fraction of 12 Gy, and patients treated with FSRT had received 30 fractions of 1.8 Gy. To compare the effects of SRS and FSRT, we converted cochlear doses into EQD2. Primary outcomes were loss of functional hearing, Gardner Robertson (GR) classes I and II, and loss of baseline hearing class. These events were used in Kaplan Meier plots and Cox regression. We also calculated the rate of change in Pure Tone Average (PTA) in dB per month elapsed after radiation-a measure we use in linear regression-to assess the associations between the rate of change in PTA and age, pre-treatment hearing level, tumor size, dose scheme, cochlear dose, and time elapsed after treatment (time-to-first-audiogram). RESULTS: The median follow-up was 36 months for 67 SRS patients and 63 months for 27 FSRT patients. Multivariate Cox regression and in linear regression both showed that the cochlear V90 was significantly associated with the progression of hearing loss. But although pre-treatment PTA correlated with rate of change in Cox regression, it did not correlate in linear regression. The time-to-first-audiogram was also significantly associated, indicating time dependency of the rate of change. None of the analysis showed a significant difference between dose schemes. CONCLUSIONS: We found no significant difference between SRS and FSRT. As the deterioration in hearing after radiotherapy for vestibular schwannoma was associated with the cochlea V90, restricting the V90 may reduce progression of hearing loss. The association between loss of functional hearing and baseline PTA seems to be biased by the use of a categorized variable for hearing loss

Protocol for the STRONG trial: stereotactic body radiation therapy following chemotherapy for unresectable perihilar cholangiocarcinoma, a phase I feasibility study

INTRODUCTION: For patients with perihilar cholangiocarcinoma (CCA), surgery is the only treatment modality that can result in cure. Unfortunately, in the majority of these patients, the tumours are found to be unresectable at presentation due to either local invasive tumour growth or the presence of distant metastases. For patients with unresectable CCA, palliative chemotherapy is the standard treatment yielding an estimated median overall survival (OS) of 12-15.2 months. There is no evidence from randomised trials to support the use of stereotactic body radiation therapy (SBRT) for CCA. However, small and most often retrospective studies combining chemotherapy with SBRT have shown promising results with OS reaching up to 33-35 months.METHODS AND ANALYSIS: This study has been designed as a single-centre phase I feasibility trial and will investigate the addition of SBRT after standard chemotherapy in patients with unresectable perihilar CCA (T1-4 N0-1 M0). A total of six patients will be included. SBRT will be delivered in 15 fractions of 3-4.5 Gy (risk adapted). The primary objective of this study is to determine feasibility and toxicity. Secondary outcomes include local tumour control, progression-free survival (PFS), OS and quality of life. Length of follow-up will be 2 years. As an ancillary study, the personalised effects of radiotherapy will be measured in vitro, in patient-derived tumour and bile duct organoid cultures.ETHICS AND DISSEMINATION: Ethics approval for the STRONG trial has been granted by the Medical Ethics Committee of Erasmus MC Rotterdam, the Netherlands. It is estimated that all patients will be included between October 2017 and October 2018. The results of this study will be published in a peer-reviewed journal, and presented at national and international conferences.TRIAL REGISTRATION NUMBER: NCT03307538; Pre-results

Institutional experience in the treatment of colorectal liver metastases with stereotactic body radiation therapy

Aim: To investigate whether the impact of dose escalation in our patient population represented an improvement in local control without increasing treatment related toxicity. Materials and methods: A cohort of consecutive patients with colorectal liver metastases treated with stereotactic body radiation therapy (SBRT) between December 2002 and December 2013 were eligible for this study. Inclusion criteria were a Karnofsky performance status ≥80% and, according to the multidisciplinary tumor board, ineligibility for surgery or radiofrequency ablation. Exclusion criteria were a lesion size>6. cm, more than 3 metastases, and treatment delivered with other fractionation scheme than 3 times 12.5. Gy or 16.75. Gy prescribed at the 65-67% isodose. To analyze local control, CT or MRI scans were acquired during follow-up. Toxicity was scored using the Common Toxicity Criteria Adverse Events v4.0. Results: A total of 40 patients with 55 colorectal liver metastases were included in this study. We delivered 37.5. Gy to 32 lesions, and 50.25. Gy to 23 lesions. Median follow-up was 26 and 25 months for these two groups. Local control at 2 and 3 years was 74 and 66% in the low dose group while 90 and 81% was reached in the high dose group. No significant difference in local control between the two dose fractionation schemes could be found. Grade 3 toxicity was limited and was not increased in the high dose group. Conclusions: SBRT for colorectal liver metastases offers a high chance of local control at long term. High irradiation doses may contribute to enhance this effect without increasing toxicity