Stereotactic Body Radiotherapy for Large Unresectable Hepatocellular Carcinomas - A Single Institution Phase II Study.

AIMS: To evaluate the safety and efficacy of liver stereotactic body radiotherapy (SBRT) in the treatment of unresectable hepatocellular carcinomas (HCC) measuring >5 cm. MATERIALS AND METHODS: Between November 2013 and February 2016, 13 patients with unresectable HCC (>5 cm), ineligible for other local treatments, with a Child-Pugh score (CPS) ≤ B7, were enrolled into a single-institution phase II study. SBRT was delivered by volumetric-modulated arc radiotherapy. Radiological response was reported using modified Response Evaluation Criteria in Solid Tumours criteria and toxicities graded by Common Terminology Criteria for Adverse Events v4 criteria. RESULTS: Sixteen hepatomas (median size 7.5 cm, range 5.1-9.7 cm) were treated in 13 patients. The baseline CPS was A5/6 in nine patients (69%) and B7 in four patients (31%). Five patients (38%) received previous liver-directed treatment. The median prescribed dose was 45 Gy (range 40-45 Gy) in five fractions. The median follow-up was 17.7 months. The 1-year local control rate was 92%. The median overall survival was 17.7 months and the 1-year overall survival was 62%. The median time to local progression was not reached. Five patients (39%) had an increase in CPS by two or more points at 3 months. Overall, there were 10 grade 3 acute toxicities occurring in seven patients, of which six were haematological. Quality of life remained clinically stable or improved at 3 months in 61.5% and 53.8% of patients based on the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core-30 Global Health Score and Functional Assessment of Cancer Therapy - Hepatobiliary version 4 score, respectively. CONCLUSIONS: In our cohort, SBRT to unresectable large HCC tumours provided excellent local control with acceptable toxicities. Regional recurrence remained the major cause of failure. Further studies are warranted to examine the role for SBRT in combination with other modalities to maximise disease control in the liver.

Metabolic tumour volume is prognostic in patients with non-small-cell lung cancer treated with stereotactic ablative radiotherapy.

Introduction: Stereotactic ablative radiotherapy (sabr) is a relatively new technique for the curative-intent treatment of patients with inoperable early-stage non-small-cell lung cancer (nsclc). Previous studies have demonstrated a prognostic value for positron emission tomography-computed tomography (pet/ct) parameters, including maximal standardized uptake value (suvmax), metabolic tumour volume (mtv), and total lesion glycolysis (tlg) in lung cancer patients. We aimed to determine which pet/ct parameter is most prognostic of local control (lc) and overall survival (os) in patients treated with sabr for nsclc. Methods: We conducted a retrospective review of patients treated with sabr for stage I inoperable nsclc at BC Cancer between 2009 and 2013. The Akaike information criterion was used to compare the prognostic value of the various pet/ct parameters. Results: The study included 134 patients with a median age of 76 years. Median tumour diameter was 2.2 cm, gross tumour volume was 8.1 mL, suvmax was 7.9, mtv was 2.4 mL, and tlg was 10.9 suv·mL. The 2-year lc was 92%, and os was 66%. On univariate and multivariate analysis, imaging variables including tumour size, gross tumour volume, suvmax, mtv, and tlg were all associated with worse lc. Tumour size was not associated with significantly worse os, but other imaging variables were. The pet/ct parameter most prognostic of lc was mtv. Compared with suvmax, tlg and mtv were more prognostic of os. Conclusions: In patients with early-stage nsclc treated with sabr, mtv appears to be prognostic of lc and os.

Can peptide receptor radionuclide therapy be safely applied in florid bone metastases? A pilot analysis of late stage osseous involvement.

AIM: Highly advanced metastatic bone disease with extensive osseous infiltration of neuroendocrine tumours (NET) may preclude patients from treatment with peptide receptor radionuclide therapy (PRRT) in concern about haematotoxicity. This study aims to assess the safety and efficacy of PRRT with 177Lu-octreotate in a patient cohort with this condition. PATIENTS, METHODS: 41 PRRT courses were performed in 11 patients with gastroenteropancreatic neuroendocrine tumours (GEP-NET) and florid bone metastases (severely advanced widespread metastatic bone disease). A mean activity of 6.95 GBq 177Lu-octreotate was administered per treatment cycle, aimed at four courses with standard intervals of 3 months. Haematological parameters were determined prior to each treatment course, in 2-4 weeks intervals between the courses, 8-12 weeks after the last course of PRRT and in 3 monthly intervals thereafter. Toxicity was recorded using Common Terminology Criteria for Adverse Events v3.0. Restaging was performed 3 months after termination of PRRT with CT/MRI and functional imaging (modified MDA criteria). RESULTS: Significant (grade III-IV), reversible haematotoxicity occurred in 4 (35%) patients and after 10 (24%) administrations. It either resolved spontaneously (1 patient) or was controlled by supportive measures (3 patients), such as blood transfusions (3 patients) or deferral of the subsequent therapy cycle (1 patient). Patients returned to baseline blood values within up to 23 months after termination of PRRT. The observed treatment response of bone metastases consisted of a partial response in 2, a minor response in 1, stable disease in 7, and progressive disease in 1 patient. Of the 4 patients with metastatic bone pain, 1 experienced complete and 3 partial resolution of symptoms within 3-10 weeks after commencement of PRRT. CONCLUSION: These preliminary data indicate that PRRT with 177Lu-octreotate can be safely applied even in florid bone metastases with extensive, severely advanced osseous replacement. The higher myelosuppression rate was not associated with serious complications and should not preclude patients from being treated and potentially experiencing remarkable treatment efficacy despite the very advanced stage.

Early prediction of tumour response to PRRT. The sequential change of tumour-absorbed doses during treatment with 177Lu-octreotate.

UNLABELLED: [177Lu-DOTA0,Tyr3]-octreotate (177Lu-octreotate) in peptide receptor radionuclide therapy (PRRT) offers direct intra-therapeutic dosimetry. The aim of this study was to compare tumour and non-tumour parameters and assess intra-individual variations. PATIENTS, METHODS: Retrospective analysis of 53 consecutive PRRT treatment cycles (mean activity of 7.53 ± 0.46 GBq 177Lu-octreotate, intended four cycles at intervals of 10-14 weeks, standard nephroprotection) in 27 GEP NET patients. Extended planar dosimetry with serial whole-body imaging on selected, non-superimposed tumour and non-tumour regions; liver (LM), bone (BM), and other (OM) metastases. The per-cycle variation was compared with post-treatment response (CT/MRI three months post-treatment, modified SWOG criteria). RESULTS: Residence time in tumor lesions (133-147 h) exceeded that in kidneys (93 h). Tumour-to-kidney absorbed dose ratios ranged from 14 to 28 (LM, BM, OM). Intra-individual per-cycle dose variation was insignificant for kidneys, but significant for metastases (LM, BM, and OM; p < 0.05). The mean per-cycle decrease of tumour absorbed dose (ΔD/A0[%]) was linked to morphologic response after PRRT. A mean decrease of >20% was predictive of a partial or minor remission in all 11 evaluable patients, while absent significant dose reduction indicated stable or progressive disease in 4/5 patients. The dose decrease was unrelated to volume effects and also observed for BM. CONCLUSION: Besides confirmation of a favourable tumour-to-kidney parameter relation for 177Lu-octreotate, stepwise intra-lesional comparison seems to imply a prognostic impact of tumor dosimetry: The early per-cycle change ΔD/A0 between treatment cycles may predict the outcome after PRRT. Larger studies are needed to confirm this finding.

A reliable method for measurement and normalization of pediatric hippocampal volumes.

A robust standardized method for segmentation, quantification, and normalization of pediatric hippocampal volumes using magnetic resonance imaging is presented. The method will find application in time course measurements of hippocampal volumes in pediatric patients who suffer from temporal lobe epilepsy and was tested prospectively on six control patients (13-60 mo of age). The un-normalized hippocampal volumes obtained using our segmentation method ranged from 3.85 to 6.38 mL, in agreement with previously published results. Inter- and intraobserver variability of the segmentation method was determined to be 13.3% and 2.8%, respectively. Four different methods of volume normalization were tested. Normalization is required to adjust for age-related increases in hippocampal volume. The normalization approach that seemed to compensate best for growth-related hippocampal volume changes was based on a simple estimation of intracranial volumes. This is the first report of a consistent and reliable method for segmentation and normalization of hippocampi from pediatric patients that can be used to study the progression of neurologic diseases in children.