Dosimetric Benefits and Practical Pitfalls of Daily Online Adaptive MRI-Guided Stereotactic Radiation Therapy for Pancreatic Cancer.

PURPOSE: Magnetic resonance imaging guided (MRI-g) radiation therapy provides visualization of the target and organs at risk (OARs), allowing for daily online adaptive radiation therapy (OART). We hypothesized that MRI-g OART would improve OAR sparing and target coverage in patients with pancreatic cancer treated with stereotactic body radiation therapy (SBRT). METHODS AND MATERIALS: Ten patients received pancreas SBRT to a dose of 33 to 40 Gy in 5 fractions. The dose was prescribed to 90% coverage of the planning target volume at 100% isodose (PTV100). After each fraction's setup magnetic resonance imaging scan, the target position was aligned by 3-dimensional shifts, the normal anatomy was recontoured, and the original radiation therapy plan was recalculated to create a nonadaptive plan. A reoptimized (adaptive) plan was then generated for each fraction and renormalized to 90% coverage of PTV100. Target and OAR doses between nonadaptive and adaptive plans were compared to assess the dosimetric impact of daily adaptation. RESULTS: The PTV100 mean for adaptive and nonadaptive techniques was 90% and 80.4% (range, 46%-97%), respectively (P = .0008). Point maximum (Dmax) 38 Gy duodenum objectives were met in 43 adaptive fractions compared with 32 nonadaptive fractions (P = .022). Both PTV100 ≥90% and all OAR objectives were achieved in 28 adaptive fractions compared with only 3 nonadaptive fractions. For nonadaptive plans, interfraction increases in stomach volume correlated with higher stomach V33 (P = .004), stomach Dmax (P = .009), duodenum V33 (P = .021), and duodenum Dmax (P = .105). No correlation was observed between stomach volume and OAR doses for adaptive plans. OART plans with Dmax violations of the spinal cord (20 Gy) in 4 fractions and large bowel (38 Gy) in 5 fractions were identified (although not delivered). CONCLUSIONS: MRI-g OART improves target coverage and OAR sparing for pancreas SBRT. This benefit partially results from mitigation of interfraction variability in stomach volume. Caution must be exercised to evaluate all OARs near the treatment area.

Seed loss in prostate brachytherapy : Operator dependency and impact on dosimetry.

INTRODUCTION: The aim of our study was to review seed loss and its impact on dosimetry as well as the influence of the treating physician on seed loss and dosimetry in patients treated with prostate brachytherapy using permanent loose (125)I implant. PATIENTS AND METHODS: We analyzed 1087 consecutive patients treated by two physicians between July 2005 and April 2015 at a single institution. Pelvic fluoroscopic imaging was done 30 days post implant and a chest X-ray when seed loss was observed. RESULTS: Seed loss occurred in 19.4 % of patients: in 20.0 % of implants done by the most experienced physician and in 17.2 % by the less experienced physician (p = 0.4) and migration to the thorax occurred in 5.9 % (6.9 vs. 2.2 %, p = 0.004). The mean seed loss rate was 0.57 % [standard deviation (SD) 1.39] and the mean rate of seeds in the thorax was 0.14 % (SD 0.65). The most experienced physician had a higher mean number of seeds lost: 0.36 versus 0.25 (p = 0.055), and a higher mean number of seed migration to the thorax: 0.1 versus 0.02 (p < 0.001). When at least one seed was lost, a decrease of 4.2 Gy (p < 0.001) in the D90 and a decrease of 3.5 % (p = 0.002) in the V150 was observed. CONCLUSION: We found a significant decrease in V150 and D90 with the occurrence of seed loss. Furthermore, we found a difference in seed migration among the physicians demonstrating that seed loss is operator dependant.

Soft tissue sarcoma and radiation therapy advances, impact on toxicity.

OPINION STATEMENT: Since adjuvant radiotherapy was introduced in the 1970s for soft tissue sarcoma (STS), sequential clinical trials characterized the toxicities induced by radiotherapy when given post-operatively and pre-operatively. Gradual technological advancements led to more precise radiotherapy delivery through intensity-modulated radiation therapy (IMRT) and more accurate targeting through image-guided radiotherapy (IGRT) to minimize normal tissues from high-dose irradiation. These improvements ultimately reduced the long-term toxicities from radiotherapy. Due to the rarity and complexity of the disease, patients with STS should be treated at institutes where multidisciplinary discussion and care can be provided. Patients with STS should ideally be offered the choice of participating in clinical trials. International phase III trials are ongoing through COG-NRG Oncology (Pazopanib Neoadjuvant Trial in Non-Rhabdomyosarcoma Soft Tissue Sarcomas (PAZNTIS)) to define the role of radiotherapy in combination with pazopanib in the clinical care of extremity STS and through EORTC (STRASS) to define the role of pre-operative radiotherapy in the treatment of retroperitoneal STS. Outside of clinical trials, extremity STS should be treated at centers of expertise where high-quality IMRT-IGRT is administered to lessen acute and long-term toxicities. In patients with extremity STS, pre-operative IMRT-IGRT is preferred as better target delineation and image guidance can be achieved. While acute wound complication remains a concern, patients treated using pre-operative IMRT-IGRT are largely spared of severe chronic irreversible radiation-related side effects such as bone fracture, fibrosis, edema, and joint stiffness that alter limb functions. For STS originating from the retroperitoneum, if radiotherapy is recommended following multidisciplinary case discussion, pre-operative radiotherapy is preferred over post-operative radiotherapy. Post-operatively, normal radiosensitive organs fill the surgical cavity, which is the targeted volume of radiotherapy; hence, post-operative radiotherapy for retroperitoneal STS is associated with severe to fatal toxicities. Pre-operative radiotherapy has a more favorable toxicity profile as the retroperitoneal STS displaces, and thus spares, normal structures and organs from the high-dose irradiation volume.

Preoperative intensity modulated radiation therapy for retroperitoneal sarcoma.

The use of intensity modulated radiation therapy (IMRT) has allowed for the administration of high doses to retroperitoneal sarcomas (RSTS) while limiting toxicity to adjacent organs. The purpose of our study is to assess the outcome and toxicities of patients with RSTS treated with neo-adjuvant external beam radiation (EBRT) therapy using IMRT. This is a retrospective study of 21 patients treated with preoperative IMRT for primary or recurrent RSTS between 2005 and 2011. Overall survival (OS) and local recurrence free survival (LRFS) were computed using the Kaplan-Meier method (log-rank test). Acute and chronic toxicities were assessed using the CTCAE v. 3 criteria. The actuarial 2 and 3-year OS was 66% for both and the 5-year OS was 51%. As for LRFS it was 57% at 2 and 3-year and 51% for the 5-year LRFS. Factors predictive for local control were microscopically negative margins (p = 0.022), a median tumor diameter <15 cm (p = 0.007) and pathology of liposarcoma (p = 0.021). Furthermore, patients treated for recurrent disease fared worse (p = 0.04) in local control than patients treated for primary disease. As for OS, patients treated for Grade 1 histology had a better outcome (p 5 0.05). EBRT was generally well tolerated. Acute gastrointestinal (GI) Grade 1 or 2 toxicities occurred in 33% of patients and one patient had unexplained post-radiation Grade 2 fever that resolved after tumor resection. As for chronic toxicities 24% of our patients presented Grade 1 GI toxicity and one patient presented Grade 3 small bowel stenosis not clearly due to radiation toxicity. Despite the location and volume of the tumors treated, preoperative IMRT was very well tolerated in our patients with retroperitoneal sarcoma. Unfortunately local recurrences remain common and dose escalation is to be considered.