Dosimetric comparison of intensity modulated radiotherapy and intensity modulated proton therapy in the treatment of recurrent nasopharyngeal carcinoma.

BACKGROUND AND PURPOSE: To compare the dosimetric performance of Intensity Modulated Proton Therapy (IMPT) and Intensity Modulated Radiotherapy (IMRT) in terms of target volume coverage and sparing of neurological organs-at-risk (OARs) in salvaging recurrent nasopharyngeal carcinoma (rNPC). The maximum dose to the internal carotid artery (ICA) and nasopharyngeal (NP) mucosa, which are associated with potential carotid blowout and massive epistaxis, were also evaluated. MATERIALS AND METHODS: IMRT and IMPT treatment plans were created for twenty patients with locally advanced rNPC. Planning Target Volume (PTV) was used to account for the setup and spatial error/uncertainty in the IMRT planning. Robust optimization on Clinical Target Volume (CTV) coverage with consideration of range and setup uncertainty was employed to produce two IMPT plans with 3-field and 4-field arrangements. The planning objective was to deliver 60 Gy to the PTV (IMRT) and CTV (IMPT) without exceeding the maximum lifetime cumulative Biologically Effective Dose (BED) of the neurological OARs (applied to the Planning organs-at-risk volume). The target dose coverage as well as the maximum dose to the neurological OARs, ICA, and NP mucosa were compared. RESULTS: Compared with IMRT, 3-field IMPT achieved better coverage to GTV V100% (83.3% vs. 73.2%, P <0.01) and CTV V100% (80.5% vs. 72.4%, P <0.01), and lower maximum dose to the critical OARs including the spinal cord (19.2 Gy vs. 22.3 Gy, P <0.01), brainstem (30.0 Gy vs. 32.3 Gy, P <0.01) and optic chiasm (6.6 Gy vs. 9.8 Gy, P <0.01). The additional beam with the 4-fields IMPT plans further improved the target coverage from the 3-field IMPT (CTV V98%: 85.3% vs. 82.4%, P <0.01) with similar OAR sparing. However, the target dose was highly non-uniform with both IMPT plans, leading to a significantly higher maximum dose to the ICA (∼68 Gy vs. 62.6 Gy, P <0.01) and NP mucosa (∼72 Gy vs. 62.8 Gy, P <0.01) than IMRT. CONCLUSION: IMPT demonstrated some dosimetric advantage over IMRT in treating rNPC. However, IMPT could also result in very high dose hot spots in the target volume. Careful consideration of the ICA and NP mucosal complications is recommended when applying IMPT on rNPC patients.

Automatic segmentation for adaptive planning in nasopharyngeal carcinoma IMRT: Time, geometrical, and dosimetric analysis.

The aim of this study was to quantify the geometrical differences between manual contours and autocontours, the dosimetric impacts, and the time gain of using autosegmentation in adaptive nasopharyngeal carcinoma (NPC) intensity-modulated radiotherapy (IMRT) for a commercial system. A total of 20 consecutive Stages I to III NPC patients who had undergone adaptive radiation therapy (ART) re planning for IMRT treatment were retrospectively studied. Manually delineated organs at risks (OARs) on the replanning computed tomography (CT) were compared with the autocontours generated by VelocityAI using deformable registration from the original planning CT. Dice similarity coefficients and distance-to-agreements (DTAs) were used to quantify their geometric differences. IMRT test plans were generated with the assistance of RapidPlan based on the autocontours of OARs and manually segmented target volumes. The dose distributions were applied on the manually delineated OARs, their dose volume histograms and dose constraints compliances were analyzed. Times spent on target, OAR contouring, and IMRT replanning were recorded, and the total time of replanning using manual contouring and autocontouring were compared. The averaged mean DTA of all structures included in the study were less than 2 mm, and 90% of the patients fulfilled the mean distance agreement tolerance recommended by AAPM 132.1 The averaged maximum DTA for brainstem, cord, optic chiasm, and optic nerves were all less than 4 mm, whereas temporal lobes and parotids have larger average maximum DTA of 4.7 mm and 6.8 mm, respectively. It was found that large contour discrepancies in temporal lobes and parotids were often associated with large magnitude of deformation (warp distance) in image registrations. The resultant maximum dose of manually segmented brainstem, cord, and temporal lobe and the median dose of manually segmented parotids were found to be statistically higher than those to their autocontoured counter parts in test plans. Dose constraints of the manually segmented OARs in test plans were only met in 15% of the cases. The average time of manual contouring and autocontouring were 108 and 10 minutes, respectively (p < 0.001). More than 30% of the total replanning time would be spent in manual OAR contouring. Manual OAR delineation takes up a significant portion of time spent in ART replanning and OAR autocontouring could considerably enhance ART workflow efficiency. Geometrical discrepancies between auto- and manual contours in head and neck OARs were comparable to typical interobserver variation suggested in various literatures; however, some of the corresponding dosimetric differences were substantial, making it essential to carefully review the autocontours.

Potential improvement of tumor control probability by induction chemotherapy for advanced nasopharyngeal carcinoma.

PURPOSE: To assess the reduction of tumor bulk and improvement of tumor control probability (TCP) by using induction chemotherapy for advanced nasopharyngeal carcinoma (NPC). MATERIALS AND METHODS: From February to December 2005, 20 patients with Stage III-IVB NPC were treated with induction-concurrent chemotherapy and intensity-modulated radiotherapy with accelerated fractionation. Combination of cisplatin and 5-fluorouracil was used in the induction phase and single agent Cisplatin in the concurrent phase. All patients were irradiated at 2Gy per fraction, 6 daily fractions per week, to a total dose of 70Gy. RESULTS: Nineteen (95%) patients completed all 3 cycles of induction chemotherapy and 90% had 2 cycles of concurrent chemotherapy. Induction chemotherapy achieved significant down-staging of T-category in 35% of patients (p=0.016) and reduction of gross tumor volume (GTV_P) from 55.6 to 22.9cc (mean 61.4%, p<0.001). Although the mean radiation dose did not show any substantial change, the volume within GTV_P that failed to reach 70Gy was reduced from 10.2% to 3.8% (p=0.017). The estimated local TCP increased from 0.83 to 0.89 (p=0.002). CONCLUSIONS: Induction chemotherapy using cisplatin-5-fluorouracil could significantly reduce tumor bulk leading to potential improvement in tumor control.

Reirradiation with intensity-modulated radiotherapy for locally recurrent T3 to T4 nasopharyngeal carcinoma.

BACKGROUND: The purpose of this study was to assess the efficacy and toxicities of reirradiation using intensity-modulated radiotherapy (IMRT) in patients with locally advanced recurrent nasopharyngeal carcinoma (NPC). METHODS: Thirty-eight patients with consecutive rT3 to rT4 NPC treated between 2005 and 2013 were retrospectively analyzed. RESULTS: The 3-year overall survival (OS), progression-free survival (PFS), and local control rate were 47.2%, 17.5%, and 44.3%, respectively. Gross target volume (GTV) D95 , GTV D50 , and age were all important prognostic factors for OS and PFS, but only GTV D95 was an important determinant for local control. A total of 73.7% patients experienced ≥1 grade 3 late toxicities and 3 patients died of massive epistaxis. Temporal lobe necrosis (TLN) developed sooner with a higher total biological equivalent dose. CONCLUSION: Adequate tumor dose coverage was important for treating rT3 to rT4 NPC. Although late complications were common, treatment-related mortality was solely vascular in nature. Dose constraints of neurologic structures for reirradiation should be revised with the latest information on late toxicities. © 2016 Wiley Periodicals, Inc. Head Neck 39: 533-540, 2017.

The impact of dosimetric inadequacy on treatment outcome of nasopharyngeal carcinoma with IMRT.

BACKGROUND AND PURPOSE: This study aims to address the relationship between tumor size and dosimetric inadequacy in treating nasopharyngeal carcinoma (NPC), and how it subsequently affects the local control. MATERIAL AND METHODS: 444 NPC patients treated with IMRT from 2005 to 2010 were included in the study. The planning aim was to deliver at least 66.5 Gy (i.e. 95% of 70 Gy) to 95% of the primary gross tumor volume (GTV_P) while keeping all the critical neurological organs at risk (OAR) within dose tolerance. Treatment outcome were analyzed according to T stage, GTV_P volume and the degree of under-dosing. RESULTS: Disease outcome was related to T stage, GTV_P volume and the degree of under-dosing. The 5-year local failure free survival (LFFS), disease free survival (DFS) and overall survival (OS) for T4 disease were 74%, 50.4% and 63.6% respectively. 48 cm(3) was identified as the critical cut-off GTV_P volume, the large volume group (GTV_P ≥ 48 cm(3)) had lower 5-year DFS (50.4% vs. 76.6%) and OS (65.2% vs. 86.3%, p < 0.001). Most T4 diseases (and some T3) were under-dosed (<66.5 Gy) and an under-dosed GTV_P volume of 3.4 cm(3) was found to be prognostically important. Multivariate analyses showed that the effect of GTV_P volume on LFFR and DFS was outweighed by the degree of under-dosing. CONCLUSIONS: Treatment outcome of locally advanced NPC was significantly affected by the volume of under-dosed (<66.5 Gy) GTV_P due to the neighboring neurological structures. A new set of OAR dose constraint and specification is proposed.

Evolution of treatment for nasopharyngeal cancer--success and setback in the intensity-modulated radiotherapy era.

BACKGROUND AND PURPOSE: To assess the therapeutic gains and setbacks as we evolved from the 2-dimensional radiotherapy (2DRT) to conformal 3-dimensional (3DRT) and to intensity-modulated (IMRT) era. MATERIALS AND METHODS: 1593 consecutive patients from 1994 to 2010 were retrospectively analyzed. Evolving changes in the different era included advances in staging investigation, radiotherapy technique, dose escalation, and use of chemotherapy. RESULTS: The 3DRT era achieved significant improvement in local failure-free rate (L-FFR), disease-specific survival (DSS) and overall survival (OS). Neurological damage and bone/soft tissue necrosis were significantly reduced. However, the improvement in distant failure-free rate (D-FFR) was insignificant, and more hearing impairment occurred due to chemotherapy. Significantly higher D-FFR was achieved in the IMRT era, but L-FFR did not show further improvement. 5-Year DSS increased from 78% in the 2DRT, to 81% in the 3DRT, and 85% in the IMRT era, while the corresponding neurological toxicity rate decreased from 7.4% to 3.5% and 1.8%. CONCLUSIONS: Significant improvement in survival and reduction of serious toxicity was achieved as we evolved from 2DRT to 3DRT and IMRT era; the therapeutic ratio for all T-categories improved with more conformal techniques. Improvements in tumor control were attributed not only to advances in RT technique, but also to better imaging and increasing use of potent chemotherapy. However, it should also be noted that hearing impairment significantly increased due to chemotherapy, L-FFR reached a plateau in the 3DRT era, and it is worrisome that the result for T4 remained unsatisfactory. Besides exploring for more potent chemotherapy and innovative methods, the guideline on dose constraint should be re-visited to optimize the therapeutic ratio.

RapidArc radiotherapy planning for prostate cancer: single-arc and double-arc techniques vs. intensity-modulated radiotherapy.

RapidArc is a novel technique using arc radiotherapy aiming to achieve intensity-modulated radiotherapy (IMRT)-quality radiotherapy plans with shorter treatment time. This study compared the dosimetric quality and treatment efficiency of single-arc (SA) vs. double-arc (DA) and IMRT in the treatment of prostate cancer. Fourteen patients were included in the analysis. The planning target volume (PTV), which contained the prostate gland and proximal seminal vesicles, received 76 Gy in 38 fractions. Seven-field IMRT, SA, and DA plans were generated for each patient. Dosimetric quality in terms of the minimum PTV dose, PTV hotspot, inhomogeneity, and conformity index; and sparing of rectum, bladder, and femoral heads as measured by V70, V-40, and V20 (% of volume receiving >70 Gy, 40 Gy, and 20 Gy, respectively), treatment efficiency as assessed by monitor units (MU) and treatment time were compared. All plan objectives were met satisfactorily by all techniques. DA achieved the best dosimetric quality with the highest minimum PTV dose, lowest hotspot, and the best homogeneity and conformity. It was also more efficient than IMRT. SA achieved the highest treatment efficiency with the lowest MU and shortest treatment time. The mean treatment time for a 2-Gy fraction was 4.80 min, 2.78 min, and 1.30 min for IMRT, DA, and SA, respectively. However, SA also resulted in the highest rectal dose. DA could improve target volume coverage and reduce treatment time and MU while maintaining equivalent normal tissue sparing when compared with IMRT. SA achieved the greatest treatment efficiency but with the highest rectal dose, which was nonetheless within tolerable limits. For busy units with high patient throughput, SA could be an acceptable option.

Clinical outcomes and patterns of failure after intensity-modulated radiotherapy for nasopharyngeal carcinoma.

PURPOSE: To study and report the clinical outcomes and patterns of failure after intensity-modulated radiotherapy (IMRT) for nasopharyngeal carcinoma (NPC). METHODS AND MATERIALS: The treatment outcomes of NPC patients treated with IMRT at Pamela Youde Nethersole Eastern Hospital between 2005 and 2007 were reviewed. The location and extent of locoregional failures were transferred to the pretreatment planning computed tomography for dosimetry analysis. Statistical analyses were performed on dose coverage and locoregional failures. RESULTS: A total of 193 NPC patients were analyzed; 93% had Stage III/IV disease. Median follow-up was 30 months. Overall disease failure (at any site) developed in 35 patients. Among these, there were 23 distant metastases, 16 local failures, and 9 regional failures. Four of the locoregional failures were marginal. Dose conformity with IMRT was excellent. Patients with at least 66.5 Gy to their target volumes had significantly less locoregional failure. The 2-year local progression-free, regional progression-free, distant metastasis-free, and overall survival rates were 95%, 96%, 90%, and 92%, respectively. CONCLUSIONS: Intensity-modulated radiotherapy provides excellent locoregional control for NPC. Distant metastasis remains the most difficult challenge, and more effective systemic agents should be explored for patients presenting with advanced locoregional diseases.

Results of excision of cerebral radionecrosis: experience in patients treated with radiation therapy for nasopharyngeal carcinoma.

OBJECT: In theory, the purpose of the treatment of cerebral radionecrosis (CRN), a nonneoplastic condition, is to minimize loss of brain function by preventing the progression and reversing some of the processes of CRN. In a practical sense, factors for achieving this purpose may include the following: removal of a CRN lesion that is causing mass effect, control of brain edema, prevention of recurrence of CRN lesions, minimization of adverse effects from treatments, and achievement of reasonably long and good-quality survivals. Based on these practical issues, the authors performed a retrospective study to evaluate the results of excision for the treatment of CRN. METHODS: The authors retrospectively reviewed the results of excision of CRN lesions in a group of patients with temporal lobe CRN due to radiotherapy for nasopharyngeal carcinoma. Patients who had undergone surgery at the authors' institution between January 1998 and November 2008 were analyzed. Surgical results were evaluated by assessing postoperative resolution of brain edema, recurrence of temporal lobe CRN, surgery-related complications, and postoperative functional status and survival. RESULTS: Twenty-four patients were included (age range 39-69 years; in 23 patients nasopharyngeal carcinoma was in remission). All patients underwent craniotomy for excision of the contrast-enhancing region. The indications for operation were temporal lobe CRN lesions with a mass-occupying effect beyond the temporal lobe. There were 32 craniotomies in all (mean postoperative follow-up 40 months). It was found that brain edema resolved rapidly postoperatively. The recurrence and reoperation rates were 6.3 and 3.1%, respectively. There were no surgery-related deaths. The median survival was 72 months, and 67% of the patients had a Karnofsky Performance Scale score of > or = 70% at the time of their last follow-up. CONCLUSIONS: In a specific group of patients with CRN of the temporal lobe in whom the CRN lesions were causing a mass-occupying effect beyond the temporal lobe, excision of the contrast-enhancing region was safe and could achieve prompt resolution of brain edema and a low incidence of recurrence of CRN.

Effectiveness of brachytherapy and fractionated stereotactic radiotherapy boost for persistent nasopharyngeal carcinoma.

BACKGROUND: Nasopharyngeal carcinoma (NPC) with local persistence after primary radiotherapy carries a high risk of treatment failure. We compared the effectiveness of brachytherapy and a fractionated stereotactic radiotherapy (SRT) boost in improving tumor control. METHODS: We retrospectively reviewed the records of 755 patients with NPC treated from 1994 to 2001. Fifty-two patients (7%) had persistent local disease, but seven of them were unsuitable for radiotherapy boost. Overall, 24 patients received brachytherapy boost at a median dose of 20 Gy, and 21 patients received an SRT boost at a median dose of 15 Gy. RESULTS: Despite the radiotherapy boost, the overall 3-year local failure-free control rate was still significantly lower for patients with persistent disease than for the rest (71% vs 86%, p < .01). Only the SRT subgroup achieved a local failure-free control rate close to that of the complete responders (82% vs 86%, p = .71). CONCLUSIONS: SRT boost is more effective in reverting the poor prognostic influence of local persistent disease.