Effects of Focal Radiation on [18 F]-Fluoro-D-Glucose Positron Emission Tomography in the Brains of Miniature Pigs: Preliminary Findings on Local Metabolism.

OBJECTIVES: It would be a medically important advance if durable and focal neuromodulation of the brain could be delivered noninvasively and without ablation. This ongoing study seeks to elucidate the effects of precisely delivered ionizing radiation upon focal brain metabolism and the corresponding cellular integrity at that target. We hypothesize that focally delivered ionizing radiation to the brain can yield focal metabolic changes without lesioning the brain in the process. MATERIALS AND METHODS: We used stereotactic radiosurgery to deliver doses from 10 Gy to 120 Gy to the left primary motor cortex (M1) of Lee Sung miniature pigs (n = 8). One additional animal served as a nonirradiated control. We used positron emission tomography-computed tomography (PET-CT) to quantify radiation dose-dependent effects by calculating the ratio of standard uptake values (SUV) of 2-deoxy-2-[18 F]-fluoro-D-glucose (18 F-FDG) between the radiated (left) and irradiated (right) hemispheres across nine months. RESULTS: We found that the FDG-PET SUV ratio at the targeted M1 was significantly lowered from the pre-radiation baseline measurements for animals receiving 60 Gy or higher, with the effect persisting at nine months after radiosurgery. Only at 120 Gy was a lesion suggesting ablation visible at the M1 target. Animals treated at 60-100 Gy showed a reduced signal in the absence of an identifiable lesion, a result consistent with the occurrence of neuromodulation. CONCLUSION: Focal, noninvasive, and durable changes in brain activity can be induced without a magnetic resonance imaging (MRI)-visible lesion, a result that may be consistent with the occurrence of neuromodulation. This approach may provide new venues for the investigation of neuromodulatory treatments for disorders involving dysfunctional brain circuits. Postmortem pathological analysis is needed to elucidate whether there have been morphological changes not detected by MRI.

Intensity modulated radiotherapy for elderly bladder cancer patients.

BACKGROUND: To review our experience and evaluate treatment planning using intensity-modulated radiotherapy (IMRT) and helical tomotherapy (HT) for the treatment of elderly patients with bladder cancer. METHODS: From November 2006 through November 2009, we enrolled 19 elderly patients with histologically confirmed bladder cancer, 9 in the IMRT and 10 in the HT group. The patients received 64.8 Gy to the bladder with or without concurrent chemotherapy. Conventional 4-field "box" pelvic radiation therapy (2DRT) plans were generated for comparison. RESULTS: The median patient age was 80 years old (range, 65-90 years old). The median survival was 21 months (5 to 26 months). The actuarial 2-year overall survival (OS) for the IMRT vs. the HT group was 26.3% vs .37.5%, respectively; the corresponding values for disease-free survival were 58.3% vs. 83.3%, respectively; for locoregional progression-free survival (LRPFS), the values were 87.5% vs. 83.3%, respectively; and for metastases-free survival, the values were 66.7% vs. 60.0%, respectively. The 2-year OS rates for T1, 2 vs. T3, 4 were 66.7% vs. 35.4%, respectively (p = 0.046). The 2-year OS rate was poor for those whose RT completion time greater than 8 weeks when compared with the RT completed within 8 wks (37.9% vs. 0%, p = 0.004). CONCLUSION: IMRT and HT provide good LRPFS with tolerable toxicity for elderly patients with invasive bladder cancer. IMRT and HT dosimetry and organ sparing capability were superior to that of 2DRT, and HT provides better sparing ability than IMRT. The T category and the RT completion time influence OS rate.

Should helical tomotherapy replace brachytherapy for cervical cancer? Case report.

BACKGROUND: Stereotactic body radiation therapy (SBRT) administered via a helical tomotherapy (HT) system is an effective modality for treating lung cancer and metastatic liver tumors. Whether SBRT delivered via HT is a feasible alternative to brachytherapy in treatment of locally advanced cervical cancer in patients with unusual anatomic configurations of the uterus has never been studied. CASE PRESENTATION: A 46-year-old woman presented with an 8-month history of abnormal vaginal bleeding. Biopsy revealed squamous cell carcinoma of the cervix. Magnetic resonance imaging (MRI) showed a cervical tumor with direct invasion of the right parametrium, bilateral hydronephrosis, and multiple uterine myomas. International Federation of Gynecology and Obstetrics (FIGO) stage IIIB cervical cancer was diagnosed. Concurrent chemoradiation therapy (CCRT) followed by SBRT delivered via HT was administered instead of brachytherapy because of the presence of multiple uterine myomas with bleeding tendency. Total abdominal hysterectomy was performed after 6 weeks of treatment because of the presence of multiple uterine myomas. Neither pelvic MRI nor results of histopathologic examination at X-month follow-up showed evidence of tumor recurrence. Only grade 1 nausea and vomiting during treatment were noted. Lower gastrointestinal bleeding was noted at 14-month follow-up. No fistula formation and no evidence of haematological, gastrointestinal or genitourinary toxicities were noted on the most recent follow-up. CONCLUSIONS: CCRT followed by SBRT appears to be an effective and safe modality for treatment of cervical cancer. Larger-scale studies are warranted.

Comparison of coplanar and noncoplanar intensity-modulated radiation therapy and helical tomotherapy for hepatocellular carcinoma.

BACKGROUND: To compare the differences in dose-volume data among coplanar intensity modulated radiotherapy (IMRT), noncoplanar IMRT, and helical tomotherapy (HT) among patients with hepatocellular carcinoma (HCC) and portal vein thrombosis (PVT). METHODS: Nine patients with unresectable HCC and PVT underwent step and shoot coplanar IMRT with intent to deliver 46-54 Gy to the tumor and portal vein. The volume of liver received 30Gy was set to keep less than 30% of whole normal liver (V30<30%). The mean dose to at least one side of kidney was kept below 23 Gy, and 50 Gy as for stomach. The maximum dose was kept below 47 Gy for spinal cord. Several parameters including mean hepatic dose, percent volume of normal liver with radiation dose at X Gy (Vx), uniformity index, conformal index, and doses to organs at risk were evaluated from the dose-volume histogram. RESULTS: HT provided better uniformity for the planning-target volume dose coverage than both IMRT techniques. The noncoplanar IMRT technique reduces the V10 to normal liver with a statistically significant level as compared to HT. The constraints for the liver in the V30 for coplanar IMRT vs. noncoplanar IMRT vs. HT could be reconsidered as 21% vs. 17% vs. 17%, respectively. When delivering 50 Gy and 60-66 Gy to the tumor bed, the constraints of mean dose to the normal liver could be less than 20 Gy and 25 Gy, respectively. CONCLUSION: Noncoplanar IMRT and HT are potential techniques of radiation therapy for HCC patients with PVT. Constraints for the liver in IMRT and HT could be stricter than for 3DCRT.

Toxic risk of stereotactic body radiotherapy and concurrent helical tomotherapy followed by erlotinib for non-small-cell lung cancer treatment--case report.

BACKGROUND: Stereotactic body radiation therapy (SBRT) applied by helical tomotherapy (HT) is feasible for lung cancer in clinical. Using SBRT concurrently with erlotinib for non-small cell lung cancer (NSCLC) is not reported previously. CASE PRESENTATION: A 77-year-old man with stage III NSCLC, received erlotinib 150 mg/day, combined with image-guided SBRT via HT. A total tumor dose of 54 Gy/9 fractions was delivered to the tumor bed. The tumor responded dramatically and the combined regimen was well tolerated. After concurrent erlotinib-SBRT, erlotinib was continued as maintenance therapy. The patient developed dyspnea three months after the combined therapy and radiation pneumonitis with interstitial lung disease was suspected. CONCLUSIONS: Combination SBRT, HT, and erlotinib therapy provided effective anti-tumor results. Nonetheless, the potential risks of enhanced adverse effects between radiation and erlotinib should be monitored closely, especially when SBRT is part of the regimen.

Total marrow irradiation with helical tomotherapy for bone marrow transplantation of multiple myeloma: first experience in Asia.

Three Asian patients with plasma cell myeloma stage IIIa with IgG predominant were selected for autologous hematopoietic cell transplantation (HSCT). Total marrow irradiation (TMI) tomotherapy planned with melphalan 140 mg/m2 as a preconditioning regimen of HSCT. Two image sets of computed tomography (CT) were scanned with 2.5 mm and 5 mm for the upper and lower part of the plan, respectively. The junction was determined and marked at 15 cm above knee on both thighs for upper and lower part of the plan. The clinical target volume (CTV) included the entire skeletal system. The planning target volume (PTV) was generated with with 0.8 cm for CTV(extremities) and with 0.5 cm margin for all other bones of CTV. A total dose of 800 cGy (200 cGy/fraction) was delivered to the PTV. Update to presentation, all of three patients post transplant without evidence of active disease were noted. During TMI treatment, one with grade 1 vomiting, two with grade 1 nausea, one with grade 1 mucositis, and three with grade 1 anorexia were noted. Toxicity of treatment was scored according to the Common Terminology Criteria for Adverse Events v3.0 (CTCAE v3.0). The average for upper part versus lower part of PTV (Bone marrow) of CI and H-index were 1.5 and 1.4 versus 1.2 and 1.2, respectively. The dose reduction of TMI tomotherapy to various OARs of head, chest, and abdomen relative to TBI varied from 31% to 74%, 21% to 51%, and 46% to 63%, respectively. The maximum average value of registration for upper torso versus lower extremities in different translation directions were 5.1 mm versus 4.1 mm for pretreatment and 1.5 mm versus 0.7 mm for post-treatment, respectively. The average treatment time for the upper versus lower part in beam-on time, setup time, and MVCT registration time took roughly 49.9, 23.3, and 11.7 min versus 11.5, 10.0, and 7.3 min, respectively. The margin of PTV could be less than 1 cm under good fixation and close position confirmation with MVCT. Antiemetics should be prescribed in the whole course of TMI for emesis prevention. TMI technique replaced TBI technique with 8 Gy as conditioning regiment for multiple myeloma could be acceptable for the Asian and the outcomes were feasible for the Asian.

Toxicity risk of non-target organs at risk receiving low-dose radiation: case report.

The spine is the most common site for bone metastases. Radiation therapy is a common treatment for palliation of pain and for prevention or treatment of spinal cord compression. Helical tomotherapy (HT), a new image-guided intensity modulated radiotherapy (IMRT), delivers highly conformal dose distributions and provides an impressive ability to spare adjacent organs at risk, thus increasing the local control of spinal column metastases and decreasing the potential risk of critical organs under treatment. However, there are a lot of non-target organs at risk (OARs) occupied by low dose with underestimate in this modern rotational IMRT treatment. Herein, we report a case of a pathologic compression fracture of the T9 vertebra in a 55-year-old patient with cholangiocarcinoma. The patient underwent HT at a dose of 30 Gy/10 fractions delivered to T8-T10 for symptom relief. Two weeks after the radiotherapy had been completed, the first course of chemotherapy comprising gemcitabine, fluorouracil, and leucovorin was administered. After two weeks of chemotherapy, however, the patient developed progressive dyspnea. A computed tomography scan of the chest revealed an interstitial pattern with traction bronchiectasis, diffuse ground-glass opacities, and cystic change with fibrosis. Acute radiation pneumonitis was diagnosed. Oncologists should be alert to the potential risk of radiation toxicities caused by low dose off-targets and abscopal effects even with highly conformal radiotherapy.