The Impact of Dose Rate on the Tumor Microenvironment Using Flattening-filter-free Beams.

AIMS: Recently, dose delivery technology has rapidly evolved with flattening filter-free beams (FFF), and the biological effects of high dose rates are a matter of interest. We hypothesized that FFF beams at different dose rates obtained with modern linear accelerators have different effects on the TME. MATERIALS AND METHODS: The B16-F10 melanoma syngeneic tumor model was established, and mice were randomized to 2 different doses (2 Gy and 10 Gy) and 3 different dose rates (1 Gy/min, 6 Gy/min, and 14 Gy/min) along with the control group. Euthanasia was performed on the seventh day after RT, and intracardiac blood was collected for a comet assay. Tumors were harvested and examined histomorphologically and immunohistochemically. Statistical analyses were performed using SPSS software version 23 (SPSS Inc., Chicago, IL, USA). RESULTS: The daily growth rate was uniform, and no difference was observed between tumor volumes across all three dose rates for each dose. Deoxyribonucleic acid (DNA) damage in blood mononuclear cells was not affected by dose or dose rate. In the TME histomorphological examination, the number of mitosis is less in the 10 Gy arm, whereas the pleomorphism score was greater. Nevertheless, varying dose rates had no effect on the number of mitosis or the pleomorphism score. The severity of the inflammation, cell densities in the TME, and expression of immunohistochemical markers were comparable across all doses and dose rates. CONCLUSION: In our study involving the B16-F10 syngeneic tumor model, varying dose rates obtained with FFF beams had no effect on tumor volume, blood mononuclear cell DNA damage, or TME parameters. However, in order to fully understand the biological impacts of novel techniques, our study should be validated with alternative preclinical setups.

Metastasis-directed radiotherapy for non-small cell lung cancer failured under TKI: A case report and literature review.

Although tyrosine kinase inhibitors (TKI) have revolutionized the treatment of anaplastic lymphoma kinase rearranged non-small cell lung cancer (ALKr-NSCLC), radiotherapy (RT) still plays an essential role for treatment of both intracranial and extracranial metastases, particularly for patients experienced a TKI-failure. We reported the case of a 38-year-old woman with metastatic ALKr-NSCLC who received whole-brain radiotherapy (RT) for multiple brain metastases (BMs), initially. After RT, alectinib was initiated and the patient had a good clinico-radiological response in both intracranial and extracranial regions. However, intracranial progression was developed and, stereotactic radiosurgery (SRS) was applied to the four progressed BMs. Two months after SRS, all BMs disappeared. While patient was using alectinib, a recurrent lung lesion, a hilar lymph node and bone metastasis were detected. Stereotactic body radiotherapy (SBRT) was applied to all metastatic sites and, alectinib was continued again. Three months after SBRT, a complete response was obtained. She has been alive with the initial systemic therapy agent for more than 4years without evidence of neither disease nor toxicity. SRS/SBRT may eradicate the TKI-resistant tumoral clones and it may prevent switching the systemic therapy, even if there is a failure.

Hyaluronic acid spacer in focal prostate reirradiation: A single centre experience.

PURPOSE: The optimal management of locally recurrent prostate cancer after curative radiotherapy is still unknown. In this study, we evaluated the preliminary results of reirradiation using stereotactic body radiotherapy for locally recurrent prostate cancer after initial definitive local radiotherapy. MATERIALS AND METHODS: Between April 2016 and February 2019, 11 patients with recurrent disease at the previously irradiated prostate were treated. Local recurrence was detected by radiological with or without functional imaging modalities including prostate multiparametric/pelvic MRI or positron-emission tomography-computerised tomography with (68Ga)-labelled prostate-specific membrane antigen performed after rising prostate specific antigen serum level during follow-up. All patients received stereotactic body radiotherapy to the recurrent nodule to a total dose of 30Gy in five fractions. Hyaluronic acid spacer was injected between prostate and rectum in seven patients to decrease the rectal dose. Acute toxicity was evaluated by using Common Terminology Criteria for Adverse Events version 4.0, and late toxicity was evaluated by using Radiation Therapy Oncology Group/European Organisation for Research and Treatment of Cancer late radiation morbidity scoring schema. RESULTS: At the diagnosis, the median age was 64 years, and the mean prostate specific antigen serum concentration was 17.7ng/mL. The median interval time between local recurrence and initial definitive radiotherapy was 63 months. Mean prostate specific antigen concentration nadir value during follow-up was 0.43ng/mL. With a median follow up of 19 months, three patients developed either local or distant relapse. One patient had grade 3 acute rectal toxicity, and one patient had grade 2 late urinary toxicity. We did not observe any acute or late toxicity due to hyaluronic acid spacer injection. CONCLUSION: Reirradiation after local recurrence following initial definitive radiotherapy together with hyaluronic acid spacer use seems to be effective and safe.

Hypofractionated radiotherapy for non-metastatic bone and soft tissue sarcomas.

PURPOSE: To evaluate the efficacy and toxicity of hypofractionated radiotherapy in non-metastatic soft tissue and bone sarcomas. PATIENTS AND METHODS: Thirty patients underwent hypofractionated radiotherapy between 2007 and 2015. Overall, 17 patients underwent primary hypofractionated radiotherapy, nine underwent hypofractionated radiotherapy for reirradiation, and four received a boost dose via hypofractionated radiotherapy after external beam radiotherapy. Most common disease sites were head and neck and retroperitoneum. Hypofractionated radiotherapy was administered with a definitive, adjuvant, or neoadjuvant intent. RESULTS: Median age was 37 years (range: 11-82 years). Median hypofractionated radiotherapy dose was 35Gy (range: 20-50Gy) in three to five fractions. Median follow-up was 21 months (range: 1-108 months). One- and 2-year overall survival rate was 75% and 52%, respectively. One- and 2-year local recurrence-free survival rate was 59% and 48%, with local recurrence rates of 16% and 33% in 1 and 2 years, respectively. Univariate analysis revealed tumour size (P=0.04), hypofractionated radiotherapy intent (P=0.016) and reirradiation (P=0.001) as prognostic factors for local recurrence-free survival. Severe late toxicity was observed in one patient as grade 3 trismus. CONCLUSION: Hypofractionated radiotherapy as the primary treatment or for reirradiation has been shown to be safe in the treatment of bone and soft tissue sarcomas. It can provide relatively good local control and survival rates.

Robotic Stereotactic Body Radiation Therapy in Patients With Recurrent or Metastatic Abdominopelvic Tumors: A Single Institute Experience.

BACKGROUND: The aim of this study was to evaluate the efficacy and toxicity of robotic CyberKnife (Accuray Incorporated, Sunnyvale, California)-based stereotactic body radiation therapy (SBRT) in patients with recurrent or metastatic abdominopelvic tumors. METHODS AND MATERIALS: A total of 69 patients treated between May 2008 and January 2011 were evaluated retrospectively. Indication for SBRT was persistent disease in 3 (4%) patients, local recurrence in 29 (42%) patients, regional recurrence in 13 (19%) patients, and oligometastatic disease in 24 (35%) patients. Forty-two (61%) patients were previously irradiated to the same region and 27 (39%) patients were treated for the first time. The median age was 59 years (range, 24-86 years). There were 31 (45%) male and 38 (55%) female patients. The median total dose was 30 Gy (range, 15-60 Gy) delivered with a median 3 fractions (range, 2-5 fractions). The tumor response to treatment was assessed by computed tomography, magnetic resonance imaging, or positron emission tomography. RESULTS: At the 12-month (range, 2-44 months) median follow-up, local control was 65% and median overall survival (OS) was 20 months. A larger gross tumor volume (≥ 67 cm(3)) was significantly correlated with worse 1-year OS (81% vs 48%, P = .03). The patients with local recurrence occurring <11 months had a significantly shorter 1-year local control rate than patients with ≥ 11 months (31% vs 91%, P < .001). Grade 3-4 acute and late toxicities were seen in 7% and 15% of patients, respectively. The patients with previous radiotherapy history had significantly higher rate of acute toxicity (19% vs 0%, P = .019). Late toxicity was significantly higher in pelvic tumors than in abdominal tumors (3% vs 28%, P = .004). CONCLUSION: The SBRT seems to be feasible and resulted in good treatment outcomes in patients with recurrent or metastatic abdominopelvic tumors.

Robotic stereotactic radiosurgery in patients with unresectable glomus jugulare tumors.

We evaluated the treatment results of robotic stereotactic radiosurgery (SRS) in our patients with unresectable glomus jugulare tumors (GJTs). The medical charts of fourteen patients with GJT, who were treated with robotic SRS, were retrospectively evaluated. The gross tumor volume was described as the clinical target volume. The median dose to the tumor was 25 Gy in median 5 fractions. The dose was normalized to 80% isodose line. All patients were evaluated for tumor growth and clinical outcome every 6 months in the first 2 years and then annually. Median follow-up was 39 months (range, 7-60 months). Lesions were stable in 8 patients, and tumor regression was observed in 6 patients. We did not observe any treatment related toxicity in our patients. In conclusion, according to our early experience, robotic SRS seems to be successful treatment option in the management of unresectable GJTs.

Malignant pleural mesothelioma with brain metastasis.

Malignant pleural mesothelioma (MPM) is a rare neoplasm associated with poor prognosis. Local disease progression is the major cause of death rather than distant metastasis. Intracranial metastases are seen very rarely. Herein, we report a case of MPM with brain metastasis treated with cranial irradiation.