Xiao Wu Deng

Local control, survival, and late toxicities of locally advanced nasopharyngeal carcinoma treated by simultaneous modulated accelerated radiotherapy combined with cisplatin concurrent chemotherapy

The aim of this phase 2 study was to determine the long‐term local control, survival, and late toxicities among patients with locally advanced nasopharyngeal carcinoma (NPC) treated with intensity‐modulated radiotherapy (IMRT) with the simultaneous modulated accelerated radiation therapy (SMART) boost technique and concurrent chemotherapy.

Initial experience using intensity-modulated radiotherapy for recurrent nasopharyngeal carcinoma

PURPOSE To report our initial experience on the feasibility, toxicity, and tumor control using intensity-modulated radiotherapy (IMRT) for retreatment of recurrent nasopharyngeal carcinoma (NPC). METHODS AND MATERIALS A total of 49 patients with locoregional recurrent carcinoma in the nasopharynx were treated with IMRT between January 2001 and February 2002 at the Sun Yat-Sen University Cancer Center, Guangzhou, China. The average time to the nasopharyngeal recurrence was 30.2 months after initial conventional RT. The median isocenter dose to the nasopharynx was 70 Gy (range 60.9-78.0) for the initial conventional RT. All patients were restaged at the time of recurrence according to the 1992 Fuzhou, China staging system on NPC. The number of patients with Stage I, II, III and IV disease was 4, 9, 10, and 26, respectively. T1, T2, T3, and T4 disease was found in 4, 9, 11, and 25 patients, respectively. N0, N1, N2, and N3 disease was found in 46, 2, 0, and 1 patient, respectively. Invasion of the nasal cavity, maxillary sinus, ethmoid sinus, sphenoid sinus, and cavernous sinus and erosion of the base of the skull was found in 8, 1, 3, 8, 15, and 20 patients, respectively. The gross tumor volume (GTV) was contoured according to the International Commission on Radiation Units and Measurements (ICRU) Report 62 guidelines. The critical structures were contoured, and the doses to critical structures were constrained according to ICRU 50 guidelines. The GTV in the nasopharynx and positive lymph nodes in the neck received a prescription dose of 68-70 Gy and 60 Gy, respectively. All patients received full-course IMRT. Three patients who had positive lymph nodes were treated with five to six courses of chemotherapy (cisplatin + 5-fluorouracil) after IMRT. RESULTS The treatment plans showed that the percentage of GTV receiving 95% of the prescribed dose (V(95-GTV)) was 98.5%, and the dose encompassing 95% of GTV (D(95-GTV)) was 68.1 Gy in the nasopharynx. The mean dose to the GTV was 71.4 Gy. The average doses of the surrounding critical structures were much lower than the tolerable thresholds. At a median follow-up of 9 months (range 3-13), the locoregional control rate was 100%. Three cases (6.1%) of locoregional residual disease were seen at the completion of IMRT, but had achieved a complete response at follow-up. Three patients developed metastases at a distant site: two in the bone and one in the liver and lung at 13 months follow-up. Acute toxicity (skin, mucosa, and xerostomia) was acceptable according to the Radiation Therapy Oncology Group criteria. Tumor necrosis was seen toward the end of IMRT in 14 patients (28.6%). CONCLUSION The improvement in tumor target coverage and significant sparing of adjacent critical structures allow the feasibility of IMRT as a retreatment option for recurrent NPC after initial conventional RT. This is the first large series using IMRT to reirradiate local recurrent NPC after initial RT failed. The treatment-related toxicity profile was acceptable. The initial tumor response/local control was also very encouraging. In contrast to primary NPC, recurrent NPC reirradiated with high-dose IMRT led to the shedding of tumor necrotic tissue toward the end of RT. More patients and longer term follow-up are warranted to evaluate late toxicity and treatment outcome.

Results of a phase 2 study examining the effects of omitting elective neck irradiation to nodal levels IV and Vb in patients with N 0-1 nasopharyngeal carcinoma

PURPOSE To evaluate the patterns of nodal failure and toxicity in clinically negative necks of N0-1 nasopharyngeal carcinoma (NPC) patients who were treated with intensity modulated radiation therapy (IMRT) but did not receive elective neck irradiation (ENI) to level IV and Vb nodes. METHODS AND MATERIALS We conducted a phase 2 prospective study in N0-1 NPC patients treated with IMRT. ENI included the retropharyngeal nodes and levels II to Va but omitted levels IV and Vb in clinically negative necks. Patterns of nodal failure, regional control (RC), and late toxicity were evaluated. RESULTS Between 2001 and 2008, a total of 212 patients (128 N0 and 84 N1) were enrolled in the study. Seven patients (4 in-field and 3 out-of-field) developed nodal failure. One patient (0.5%) developed nodal failure at level Vb, but no patients developed nodal failure at level IV. The 5-year RC rates of the entire group, N0 patients and N1 patients were 95.6%, 98.2%, and 91.3%, respectively. Fifteen patients (7.1%) developed distant metastases. The 5-year distant failure-free survival (DFFS) and overall survival (OS) rates were 91.4% and 89.8%, respectively. The rates of grade 2 or greater skin dystrophy, subcutaneous fibrosis and xerostomia were 6.2%, 16.6%, and 17.9%, respectively. CONCLUSIONS The rate of out-of-field nodal failure when omitting ENI to levels IV and Vb in clinically negative necks of patients with N0-1 NPC was extremely low; therefore, a further phase 3 study is warranted.

A real-time in vivo dosimetric verification method for high-dose rate intracavitary brachytherapy of nasopharyngeal carcinoma.

PURPOSE A real-time in vivo dosimetric verification method using metal-oxide-semiconductor field effect transistor (MOSFET) dosimeters has been developed for patient dosimetry in high-dose rate (HDR) intracavitary brachytherapy of nasopharyngeal carcinoma (NPC). METHODS The necessary calibration and correction factors for MOSFET measurements in (192)Iridium source were determined in a water phantom. With the detector placed inside a custom-made nasopharyngeal applicator, the actual dose delivered to the tumor was measured in vivo and compared to the calculated values using a commercial brachytherapy planning system. RESULTS Five MOSFETs were independently calibrated with the HDR source, yielding calibration factors of 0.48 ± 0.007 cGy∕mV. The maximum sensitivity variation was no more than 7% in the clinically relevant distance range of 1-5 cm from the source. A total of 70 in vivo measurements in 11 NPC patients demonstrated good agreement with the treatment planning. The mean differences between the planned and the actually delivered dose within a single treatment fraction were -0.1% ± 3.8% and -0.1% ± 3.7%, respectively, for right and left side assessments. The maximum dose deviation was less than 8.5%. CONCLUSIONS In vivo measurement using the real-time MOSFET dosimetry system is possible to evaluate the actual dose to the tumor received by the patient during a treatment fraction and thus can offer another line of security to detect and prevent large errors.

Effect of total dose and fraction size on survival of patients with locally recurrent nasopharyngeal carcinoma treated with intensity-modulated radiotherapy: a phase 2, single-center, randomized controlled trial.

The optimal model of total dose and fraction size for patients with locally recurrent nasopharyngeal carcinoma treated with intensity‐modulated radiotherapy (IMRT) remains unclear. The authors designed a randomized phase 2 clinical trial to investigate the efficacy of 2 different models, with the objective of determining an optimal model.

Retrospective analysis of 234 nasopharyngeal carcinoma patients with distant metastasis at initial diagnosis: therapeutic approaches and prognostic factors.

Purpose The purpose of this retrospective study was to identify the independent prognostic factors and optimize the treatment for nasopharyngeal carcinoma (NPC) patients with distant metastasis at initial diagnosis. Methods A total of 234 patients referred between January 2001 and December 2010 were retrospectively analyzed. Among the 234 patients, 94 patients received chemotherapy alone (CT), and 140 patients received chemoradiotherapy (CRT). Clinical features, laboratory parameters and treatment modality were examined with univariate and multivariate analyses. Results The median overall survival (OS) time was 22 months (range, 2-125 months), and the 1-year, 2-year, 3-year overall survival rates were 82.2%, 51.3% and 34.1%. The overall response and disease control rates of metastatic lesions after chemotherapy were 56.0% and 89.8%. The factors associated with poor response were karnofsky performance score (KPS) <80, liver metastasis, lactate dehydrogenase (LDH)>245 IU/L, and number of chemotherapy cycles <4. The 3-year OS of patients receiving CRT was higher than those receiving CT alone (48.2% vs. 12.4%, p<0.001). Subgroup analysis showed that significantly improved survival was also achieved by radiotherapy of the primary tumor in patients who achieved complete remission (CR)/partial remission (PR) or stable disease (SD) of metastatic lesions after chemotherapy. Significant independent prognostic factors of OS were KPS, liver metastasis, levels of LDH, and multiple metastases. Treatment modality, response to chemotherapy and chemotherapy cycles were also associated with OS. Conclusion A combination of radiotherapy and chemotherapy seems to have survival benefits for selected patients with distant metastases at initial diagnosis. Clinical and laboratory characteristics can help to guide treatment selection. Prospective randomized studies are needed to confirm the result.

Effect of total dose and fraction size on survival of patients with locally recurrent nasopharyngeal carcinoma treated with intensity-modulated radiotherapy

The optimal model of total dose and fraction size for patients with locally recurrent nasopharyngeal carcinoma treated with intensity‐modulated radiotherapy (IMRT) remains unclear. The authors designed a randomized phase 2 clinical trial to investigate the efficacy of 2 different models, with the objective of determining an optimal model.

Dosimetric Analysis of Respiratory-Gated Radiotherapy for Hepatocellular Carcinoma

The purpose of this study was to define individualized internal target volume (ITV) for hepatocellular carcinoma (HCC) using 4D computed tomography (4DCT), and to determine the geometric and dosimetric benefits of respiratory gating. Gross tumor volumes (GTVs) were contoured on 10 respiratory phases of 4DCT images for 12 patients with HCC. Three treatment plans were prepared using different planning target volumes (PTVs): (1) PTV(3D), derived from a single helical clinical target volume (CTV) plus conventional margins; (2) PTV(10 phases), derived from ITV(10 phases), which encompassed all 10 CTVs plus an isotropic margin of 0.8 cm; (3) PTV(gating), derived from ITV(gating), which encompassed three CTVs within gating-window at end-expiration plus an isotropic margin of 0.8 cm. The PTV(3D) was the largest volume for all patients. The ITV-based plans and gating plans spared more normal tissues than 3D plans, especially the liver. Without increasing normal tissue complication probability of the 3D plans, the ITV-based plans allowed for increasing the calculated dose from 50.8 Gy to 54.7 Gy on average, and the gating plans could further escalate the dose to 58.5 Gy. Compared with ITV-based plans, the dosimetric gains with gating plan strongly correlated with GTV mobility in the craniocaudal direction. The ITV-based plans can ensure target coverage with less irradiation of normal tissues compared with 3D plans. Respiratory-gated radiotherapy can further reduce the target volumes to spare more surrounding tissues and allow dose escalation, especially for patients with tumor mobility >1 cm.

Phase II trial of recombinant human endostatin in combination with concurrent chemoradiotherapy in patients with stage III non-small-cell lung cancer

PURPOSE The objective of this study was to evaluate the efficacy and safety of Endostar combined with concurrent chemoradiotherapy (CCRT) in patients with stage III non-small-cell lung cancer (NSCLC). METHODS Patients with unresectable stage III NSCLC were treated with Endostar (7.5mg/m(2)/d) for 7days at weeks 1, 3, 5, and 7, while two cycles of docetaxel (65mg/m(2)) and cisplatin (65mg/m(2)) were administered on days 8 and 36, with concurrent thoracic radiation to a dose of 60-66Gy. Primary end points were short-term efficacy and treatment-related toxicity. RESULTS Fifty patients were enrolled into the study, and 48 were assessable. Of the 48 patients, 83% had stage IIIB and 65% had N3 disease. Median follow-up was 25.0months. Overall response rate was 77%. The estimated median progression-free survival (PFS) was 9.9months, and the estimated median overall survival (OS) was 24.0months. The 1-, 2-, and 3-year local control rates were 75%, 67%, and 51%, PFS rates were 48%, 27%, and 16%, and OS rates were 81%, 50%, and 30%, respectively. All toxicities were tolerable with proper treatment. CONCLUSIONS The combination of Endostar with CCRT for locally advanced NSCLC patients was feasible and showed promising survival and local control rates.

Normal Tissue Complication Probability Model for Radiation-induced Temporal Lobe Injury after Intensity-modulated Radiation Therapy for Nasopharyngeal Carcinoma

PURPOSE To identify predictors for the development of temporal lobe injury (TLI) after intensity-modulated radiation therapy (IMRT) for nasopharyngeal carcinoma. MATERIALS AND METHODS Data in 351 patients with nasopharyngeal carcinoma treated with IMRT were reviewed retrospectively according to institutional ethics committee approval. Clinical factors associated with TLI were analyzed. Dose-volume histograms for 550 evaluable temporal lobes were analyzed, and the predictive value of therapy-associated and patient-associated factors for the occurrence of TLI was evaluated. Survival curves were depicted by using the Kaplan-Meier method and compared by using the log-rank test. Logistic regression analysis was used for multivariate analyses. RESULTS Median follow-up was 76 months (range, 6-100 months). Twenty-nine of 351 patients (8.3%) developed TLI; 21 patients had unilateral TLI, and eight had bilateral TLI. Median latency from IMRT until first TLI was 33 months (range, 12-83 months) among patients with TLI. The actuarial TLI-free survival rates were 94.4% and 91.3% at 3 and 5 years after radiation therapy, respectively. Logistic regression analysis demonstrated that dose delivered to a 1-cm(3) volume of the temporal lobe (D1cc) was the only independent predictor for TLI. The biologically equivalent tolerance doses at 2 Gy for a 5% and 50% probability of developing TLI were 62.83-Gy equivalents (95% confidence interval: 59.68, 65.97) and 77.58-Gy equivalents (95% confidence interval: 74.85, 80.32), respectively. CONCLUSION D1cc is predictive for radiation-induced TLI, suggesting that delivery of a high dose of radiation to a small volume of the temporal lobe is unsafe. A D1cc of 62.83 Gy by using a correction formula for varying fraction size may be the dose tolerance of the temporal lobe.