Le-Jung Wu

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 CTVextremities 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 PTVBone 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.

Concurrent image-guided intensity modulated radiotherapy and chemotherapy following neoadjuvant chemotherapy for locally advanced nasopharyngeal carcinoma.

BackgroundTo evaluate the experience of induction chemotherapy followed by concurrent chemoradiationwith helical tomotherapy (HT) for nasopharyngeal carcinoma (NPC).MethodsBetween August 2006 and December 2009, 28 patients with pathological proven nonmetastatic NPC were enrolled. All patients were staged as IIB-IVB. Patients were first treated with 2 to 3 cycles of induction chemotherapy with EP-HDFL (Epirubicin, Cisplatin, 5-FU, and Leucovorin). After induction chemotherapy, weekly based PFL was administered concurrent with HT. Radiation consisted of 70 Gy to the planning target volumes of the primary tumor plus any positive nodal disease using 2 Gy per fraction.ResultsAfter completion of induction chemotherapy, the response rates for primary and nodal disease were 96.4% and 80.8%, respectively. With a median follow-up after 33 months (Range, 13-53 months), there have been 2 primary and 1 nodal relapse after completion of radiotherapy. The estimated 3-year progression-free rates for local, regional, locoregional and distant metastasis survival rate were 92.4%, 95.7%, 88.4%, and 78.0%, respectively. The estimated 3-year overall survival was 83.5%. Acute grade 3, 4 toxicities for xerostomia and dermatitis were only 3.6% and 10.7%, respectively.ConclusionHT for locoregionally advanced NPC is feasible and effective in regard to locoregional control with high compliance, even after neoadjuvant chemotherapy. None of out-field or marginal failure noted in the current study confirms the potential benefits of treating NPC patients by image-guided radiation modality. A long-term follow-up study is needed to confirm these preliminary findings.

Image-guided intensity modulated radiotherapy with helical tomotherapy for postoperative treatment of high-risk oral cavity cancer

BackgroundThe aim of this study was to assess the treatment results and toxicity profiles of helical tomotherapy (HT) for postoperative high-risk oral cavity cancer.MethodsFrom December 6, 2006 through October 9, 2009, 19 postoperative high-risk oral cavity cancer patients were enrolled. All of the patients received HT with (84%) or without (16%) chemotherapy.ResultsThe median follow-up time was 17 months. The 2-year overall survival, disease-free survival, locoregional control, and distant metastasis-free rates were 94%, 84%, 92%, and 94%, respectively. The package of overall treatment time > 13 wk, the interval between surgery and radiation ≤ 6 wk, and the overall treatment time of radiation ≤ 7 wk was 21%, 84%, and 79%, respectively. The percentage of grade 3 mucositis, dermatitis, and leucopenia was 42%, 5% and 5%, respectively.ConclusionsHT achieved encouraging clinical outcomes for postoperative high-risk oral cavity cancer patients with high compliance. A long-term follow-up study is needed to confirm these preliminary findings.

Concurrent Chemoradiotherapy With Helical Tomotherapy for Oropharyngeal Cancer: A Preliminary Result

PURPOSE To review the experience with and evaluate the treatment plan for helical tomotherapy for the treatment of oropharyngeal cancer. METHODS AND MATERIALS Between November 1, 2006 and January 31, 2009, 10 histologically confirmed oropharyngeal cancer patients were enrolled. All patients received definitive concurrent chemoradiation with helical tomotherapy. The prescription dose to the gross tumor planning target volume, the high-risk subclinical area, and the low-risk subclinical area was 70 Gy, 63 Gy, and 56 Gy, respectively. During radiotherapy, all patients were treated with cisplatin, 30 mg/m(2), plus 5-fluorouracil (425 mg/m(2))/leucovorin (30 mg/m(2)) intravenously weekly. Toxicity of treatment was scored according to the Common Terminology Criteria for Adverse Events, version 3.0. Several parameters, including maximal or median dose to critical organs, uniformity index, and conformal index, were evaluated from dose-volume histograms. RESULTS The mean survival was 18 months (range, 7-22 months). The actuarial overall survival, disease-free survival, locoregional control, and distant metastasis-free rates at 18 months were 67%, 70%, 80%, and 100%, respectively. The average for uniformity index and conformal index was 1.05 and 1.26, respectively. The mean of median dose for right side and left side parotid glands was 23.5 and 23.9 Gy, respectively. No Grade 3 toxicity for dermatitis and body weight loss and only one instance of Grade 3 mucositis were noted. CONCLUSION Helical tomotherapy achieved encouraging clinical outcomes in patients with oropharyngeal carcinoma. Treatment toxicity was acceptable, even in the setting of concurrent chemotherapy. Long-term follow-up is needed to confirm these preliminary findings.

Abdominal irradiation modulates 5-Fluorouracil pharmacokinetics

BackgroundConcurrent chemoradiation with 5-fluorouracil (5-FU) is widely accepted for treatment of abdominal malignancy. Nonetheless, the interactions between radiation and 5-FU remain unclear. We evaluated the influence of abdominal irradiation on the pharmacokinetics of 5-FU in rats.MethodsThe radiation dose distributions of cholangiocarcinoma patients were determined for the low dose areas, which are generously deposited around the intrahepatic target volume. Then, corresponding single-fraction radiation was delivered to the whole abdomen of Sprague-Dawley rats from a linear accelerator after computerized tomography-based planning. 5-FU at 100 mg/kg was intravenously infused 24 hours after radiation. A high-performance liquid chromatography system equipped with a UV detector was used to measure 5-FU in the blood. Ultrafiltration was used to measure protein-unbound 5-FU.ResultsRadiation at 2 Gy, simulating the daily human treatment dose, reduced the area under the plasma concentration vs. time curve (AUC) of 5-FU by 31.7% compared to non-irradiated controls. This was accompanied by a reduction in mean residence time and incremental total plasma clearance values, and volume of distribution at steady state. Intriguingly, low dose radiation at 0.5 Gy, representing a dose deposited in the generous, off-target area in clinical practice, resulted in a similar pharmacokinetic profile, with a 21.4% reduction in the AUC. This effect was independent of protein binding capacity.ConclusionsAbdominal irradiation appears to significantly modulate the systemic pharmacokinetics of 5-FU at both the dose level for target treatment and off-target areas. This unexpected and unwanted influence is worthy of further investigation and might need to be considered in clinical practice.

Left-Sided Whole Breast Irradiation with Hybrid-IMRT and Helical Tomotherapy Dosimetric Comparison

Purpose. Limited-tomotherapy and hybrid-IMRT treatment techniques were compared for reductions in ipsilateral and contralateral lung, heart, and contralateral breast radiation doses. Methods and Materials. Thirty consecutively treated left-sided early-stage breast cancer patients were scheduled for lTomo and hIMRT. For the hIMRT plan conventional tangential-field and four-field IMRT plans were combined with different weightings in the prescribed dose. For the lTomo plan a geometrically limited arc was designed for the beamlet entrance. A D p of 50.4 Gy in 28 fractions was used for the PTV. The dose coverage, homogeneity index, conformity index of the target, and the dose volumes of critical structures were compared. Results. Both modalities presented similar target coverage. The homogeneity and conformity were improved for lTomo with P < 0.001 and P = 0.006, respectively. In the lTomo plan a concave dose distribution was generated with significant dose reductions in both high and low dose regions for ipsilateral lung and heart (P < 0.001). Conclusions. lTomo plan can have similar dose coverage and better homogeneity and conformity to the target. By properly designing the directionally and completely blocked structure, lTomo plan was developed successfully in reducing doses to the healthy tissues for early-stage left-sided breast cancer radiotherapy.

Clinical effectiveness, toxicity, and failure patterns of helical tomotherapy for postoperative oral cavity cancer patients

Background The outcome of postoperative high- and intermediate-risk oral cavity cancer (OCC) patients receiving helical tomotherapy (HT) remains limited. Materials and methods Between November 2006 and November 2012, 53 postoperative high- and intermediate-risk OCC patients treated with HT were enrolled. Results The 4-year locoregional, local, and regional control rates were 66%, 76.4%, and 94.3%, respectively. The 4-year locoregional control rates of oral tongue and buccal mucosa cancer were 88.3% and 37.1%, respectively (P=0.012). Eleven (20.8%) patients experienced locoregional failure. In-field failure occurred in six of 53 (11.3%) in the primary area and three of 53 (5.7%) in the regional lymph-node area. No marginal failure was noted. Two of 53 (3.8%) experienced out-of-field failure. The rates of grade 3 dermatitis, mucositis, and dysphagia were 11%, 34%, and 13%, respectively. No grade 3 xerostomia was noted. Grade 2 xerostomia was 33% at month 6 and declined to 0 at month 48. A rate of 56% of grade 2 trismus at month 6 was noted, and declined to around 30% after 2 years. No grade 3 trismus was noted after 2 years. Conclusion HT as a postoperative modality provided satisfying results, especially for xerostomia and trismus, and was impressive in high- and intermediate-risk OCC patients receiving postoperative HT.

Esophageal Metal Stents with Concurrent Chemoradiation Therapy for Locally Advanced Esophageal Cancer: Safe or Not?

BACKGROUND The purpose of this study was to review the risks and benefits of concurrent chemoradiation therapy (CCRT) with esophageal self-expandable metal stents (SEMS) for the treatment of locally advanced esophageal cancer. MATERIALS AND METHODS Between January 2014 and December 2016, the data from 46 locally advanced esophageal cancer patients who received CCRT at our institution were retrospectively reviewed. Eight patients who received CCRT concomitant with SEMS placement (SEMS plus CCRT group) and thirty-eight patients who received CCRT without SEMS placement (CCRT group) were identified. The risk of developing esophageal fistula and the overall survival of the two groups were analyzed. RESULTS The rate of esophageal fistula formation during or after CCRT was 87.5% in the SEMS plus CCRT group and 2.6% in the CCRT group. The median doses of radiotherapy in the SEMS plus CCRT group and the CCRT group were 47.5 Gy and 50 Gy, respectively. SEMS combined with CCRT was associated with a greater risk of esophageal fistula formation than CCRT alone (hazard ratio [HR], 72.30; 95% confidence interval [CI], 8.62-606.12; p < .001). The median overall survival times in the SEMS plus CCRT and CCRT groups were 6 months and 16 months, respectively. Overall survival was significantly worse in the SEMS plus CCRT group than in the CCRT group (HR, 5.72; 95% CI, 2.15-15.21; p < .001). CONCLUSION CCRT concomitant with SEMS for locally advanced esophageal cancer results in earlier life-threatening morbidity and a higher mortality rate than treatment with CCRT alone. Further prospective and randomized studies are warranted to confirm these observations. IMPLICATIONS FOR PRACTICE Patients treated with SEMS placement followed by CCRT had higher risk of esophageal fistula formation and inferior overall survival rate compared with patients treated with CCRT alone. SEMS placement should be performed cautiously in patients who are scheduled to receive CCRT with curative intent.

Preliminary Results of Helical Tomotherapy for Non-metastatic Prostate Cancer

Purpose: We report the results of non-metastatic prostate cancer patients treated by helical tomotherapy (HT) in a single institution. Materials and Methods: From December 2006 to June 2013, eighty-five prostate cancer patients receiving image-guided radiation therapy (IGRT) with HT were enrolled in this study. Mega-voltage computed tomography was performed to minimize geographic miss and setup error. The Phoenix definition was used to define biochemical failure. Toxicities were recorded based on Common Terminology Criteria for Adverse Events, version 4.0. Results: The median follow-up interval was 41 months (range, 8-96 months). The median radiation dose delivered was 76 Gy to the whole prostate. Fifty-four percent of patients were in the high-risk category. The 4-year biochemical control rate was 93.3%. All of the patients attributed to the low- and intermediate-risk groups had good biochemical control (n=39). For high-risk group, only 13% (6/46) patients had biochemical failure, and 2 of them also developed bony metastases. During treatment, only 4.7% and 9.4% of the patients experienced grade 2 acute gastrointestinal and genitourinary toxicities, respectively. No grade 3 or 4 acute toxicity was observed. The cumulative incidence of late toxicities of grade 2 or above hemorrhagic proctitis, hemorrhagic cystitis and urethral stricture were 8.2%, 4.7% and 4.7%, respectively. Conclusion: For prostate cancer patients, IGRT with HT results an excellent biochemical control in our limited follow-up period. The treatment-related toxicities were acceptable.

Helical Tomotherapy Reduces Pain Efficiently for Circuited Pleural Metastasis of Nasopharyngeal Carcinoma-A Case Report

Nasopharyngeal carcinoma (NPC) with pleural circulative metastasis is difficult to treat due to the cylinder shape and close critical organs. Helical tomotherapy (HT) is a new type of CT-based rotational intensity modulated radiotherapy with highly conformal dose distributions and critical organs sparing. HT could be helpful in this kind of difficult situation.A 38-year-old male Asian nasopharyngeal carcinoma patient with pleural and liver metastasis was treated. Thirty-six Gy was delivered to bilateral pleural and mediastinum metastatic sites with HT. After HT treatment, pain was controlled by narcotics successfully. Pain scale decreased from 10 to 0. Tumor volume decreased from 629 ml to 158 ml. HT reduced V20 by more than 50% for each lung and reduced the mean lung dose by 22.2% and 33.8% in the right lung and left lung when compared with the IMRT technique, respectively.For palliative treatment, HT provides impressive ability for irregularly shaped metastatic sites and reduces painful sensation successfully.[Therapeut Radiol Oncol 2011; 18(4): 341-345]