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Purpose: To compare the incidence of xerostomia in nasopharyngeal carcinoma (NPC) patients treated with superficial parotid lobe-sparing intensity-modulated radiation therapy (SPLS-IMRT) and conventional IMRT (C-IMRT)., Methods: Patients with histologically confirmed NPC who met the eligibility criteria were randomly assigned to receive either SPLS-IMRT or C-IMRT. The primary endpoint was the incidence of xerostomia at 12 months post-IMRT. The secondary endpoints included the xerostomia questionnaire (XQ) score, unstimulated salivary flow rate (USFR), stimulated salivary flow rate (SSFR), and survival outcomes., Results: Ninety patients were enrolled. Eighty-two patients were included for xerostomia analysis (42 in the SPLS-IMRT group and 40 in the C-IMRT group). At 12 months post-IMRT, the incidence of xerostomia in the SPLS-IMRT group was significantly lower than that in the C-IMRT group (83.4% vs 95.0%; P = 0.007), especially the grade 3 xerostomia (0% vs 12.5%; P < 0.001). The median change in XQ score was similar between the two groups (11.9 points vs 14.1 points; P = 0.194). There was a significantly higher median fractional USFR (0.67 vs 0.35; P = 0.024) and SSFR (0.66 vs 0.32; P = 0.021) in the SPLS-IMRT group than the C-IMRT group. The 3-year LRRFS, DMFS, and OS in the SPLS-IMRT and C-IMRT groups were 92.5% vs 90.9%, 83.8% vs 81.7%, and 88.9% vs 88.2% (all P > 0.05)., Conclusion: SPLS-IMRT significantly reduced the incidence of xerostomia at 12 months post-IMRT in NPC by recovering parotid gland function earlier than C-IMRT, without compromising survivals. Phase III clinical trials are warranted. (ClinicalTrials.gov, number NCT05020067)., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Purpose: This study was aimed to investigate long-term survivals and toxicities of early-stage nasopharyngeal carcinoma (NPC) in endemic area, evaluating the role of chemotherapy in stage II patients., Materials and Methods: Totally 187 patients with newly diagnosed NPC and restaged American Joint Committee on Cancer/International Union Against Cancer 8th T1-2N0-1M0 were retrospectively recruited. All received intensity-modulated radiotherapy (IMRT)±chemotherapy (CT) from 2001 to 2010., Results: With 15.7-year median follow-up, 10-year locoregional recurrence-free survival, distant metastasis-free survival (DMFS), disease-specific survival (DSS), and overall survival (OS) were 93.3%, 93.5%, 92.9% and 88.2%, respectively. Multivariable analyses showed cervical lymph nodes positive and pre-treatment prognostic nutritional index ≥ 52.0 could independently predict DMFS (p=0.036 and p=0.011), DSS (p=0.014 and p=0.026), and OS (p=0.002 and p < 0.001); Charlson comorbidity index < 3 points could predict DSS (p=0.011); age > 45 years (p=0.002) and pre-treatment lactate dehydrogenase ≥ 240 U/L (p < 0.001) predicted OS. No grade 4 late toxicity happened; grade 3 late toxicities included subcutaneous fibrosis (4.3%), deafness or otitis (4.8%), skin dystrophy (2.1%), and xerostomia (1.1%). No differences on survivals were shown between IMRT+CT vs. IMRT alone in stage II patients, even in T2N1M0 (p > 0.05). Unsurprising, patients in IMRT+CT had more acute gastrointestinal reaction, myelosuppression, mucositis, late ear toxicity, and cranial nerve injury (all p < 0.05) than IMRT alone group., Conclusion: Superior tumor control and satisfying long-term outcomes could be achieved with IMRT in early-stage NPC with mild late toxicities. As CT would bring more toxicities, it should be carefully performed to stage II patients.

Purpose: Current guideline recommends a uniform method of delineation of subclinical disease within the primary clinical target volume (CTVp) for all stages of nasopharyngeal carcinoma (NPC). We performed a prospective observational study to investigate the outcomes with a reduced CTVp and radiation dose for early-stage NPC., Methods and Materials: Patients with newly diagnosed, biopsy-proven World Health Organization type II-III and American Joint Committee on Cancer/Union for International Cancer Control sixth edition stage T1-2N0-1 disease were enrolled. All patients were treated with intensity modulated radiation therapy alone. We categorized CTVp into CTVp1 (high risk) and CTVp2 (low risk). CTVp1 comprised of gross tumor (on magnetic resonance imaging or contrast-enhanced computed tomography) plus a 5-mm margin (3-mm posteriorly) and was prescribed to 60 Gy in 30 fractions (fr). CTVp2 was generated from CTVp1 plus a 5-mm margin (3 mm posteriorly), excluding the maxillary and cavernous sinuses, and was prescribed to 54 Gy in 30 fr. The prescribed doses to the primary and nodal gross tumor volume (GTVp and GTVn) were 68 Gy in 30 fr and 60 to 66 Gy in 30 fr, respectively. Primary endpoint was local recurrence-free survival. This study was registered in ClinicalTrials.gov, number NCT03839602., Results: From May 2001 to August 2006, 103 patients were recruited and completed IMRT. With a median follow-up of 15.2 years (range, 2.1-18.1 years), only 1 patient had local failure. Ten-year local recurrence-free survival, regional recurrence-free survival, distant metastasis-free survival, and overall survival were 90.3%, 88.3%, 90.3%, and 91.2%, respectively. Among late IMRT-related adverse events, we recorded 2 patients with G1 cranial nerve injury, 3 patients with G3 hearing loss, and 3 patients with G3 subcutaneous fibrosis. No patients had temporal lobe necrosis, brain stem injury, or trismus., Conclusions: Decreased CTV margins and radiation doses can achieve long-term tumor control with mild late toxicities for patients with early-stage NPC., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Purpose: This study aims to investigate the feasibility of contouring target volume according to residual tumor and decreasing the dose to the tumor regression field after induction chemotherapy (IC) in locoregionally advanced nasopharyngeal carcinoma (NPC)., Materials and Methods: From August 2009 to August 2013, patients with stage III-IVB NPC were treated with IC and concurrent chemoradiotherapy. Gross tumor volume of nasopharynx (GTVnx)-residual and gross tumor volume of cervical lymph node (GTVnd)-residual were contoured according to post-IC residual primary tumor and any N+ disease, respectively. The tumor regression field was included in CTVnx1/CTVnd1 and prescribed a dose of 60 Gy. Outcomes and toxicities of all patients were evaluated., Results: A total of 57 patients were enrolled. At a median follow-up of 68 months, three cases displayed locoregional recurrence and one case showed both distant metastasis and locoregional recurrence. All locoregional recurrences were in the GTVnx-residual/GTVnd-residual and in-field. The 5-year overall, locoregional relapse-free, distant metastasis-free, and progression-free survival rates were 82.2%, 87.7%, 85.8% and 80.3%, respectively., Conclusion: After IC, contouring of GTVnx-residual/GTVnd-residual as residual tumor volume and distribution 60 Gy ofradiation dose to the tumorregression field may be feasible and need further investigation.

Introduction: To evaluate the prognostic value of gross tumor volume (TV) in patients with locally recurrent, nonmetastatic nasopharyngeal carcinoma., Methods: Between 2001 and 2012, 291 consecutive patients with locally recurrent, nonmetastatic nasopharyngeal carcinoma underwent salvage IMRT were retrospectively reviewed. The correlations between TV and recurrent T classification were analyzed. Survival analyses were performed. Receiver operating characteristic (ROC) curves were calculated to identify cut-off point of TV. The Akaike information criterion and Harrell's concordance index (c-index) were utilized to test the prognostic value., Results: The median TV significantly increased with advancing recurrent T classification (P<0.001). The 5-year overall survival rate was 33.2% for the entire cohort. On multivariate analysis, TV was an independent negative prognostic factor for distant metastasis-free survival (hazard ratio =1.013, P =0.003), overall survival (hazard ratio = 1.015, P<0.001) and toxicity-related death (hazard ratio = 1.014, P<0.001). The 5-year overall survival rates were 63.1% and 20.8% for patients with a TV < 22 cm3 and TV ≥22 cm3, respectively (P < 0.001). In patient with TV <22 cm3, locoregional failure is the leading cause of death. In patients with TV≥22 cm3, distant metastasis rate is higher and occurred within short term after local recurrence; meanwhile, radiation-induced injuries became more common and led to half of deaths in this group. The Akaike information criterion and c-index analyses indicated that the predictive ability of recurrent T classification improved when combined with TV., Conclusions: Our data suggests TV is a significant prognostic factor for predicting the distant metastasis, overall survival and toxicity-related death of patients with locally recurrent, nonmetastatic nasopharyngeal carcinoma after salvage IMRT. TV should be considered when designing personalized salvage treatments for these patients. For patients with bulky local recurrent tumor, radiation may need to be de-emphasized in favor of systemic treatment or best supportive care.

Objectives: The utility of [18F]fluorodeoxyglucose (FDG) positron emission tomography (PET) in the prediction of distant metastasis after definitive treatment for non-disseminated NPC patients is not clear. We prospectively investigated the prognostic significance of (18)F-FDG PET-CT performed before treatment for the distant metastasis-free survival (DMFS) of NPC patients treated with intensity-modulated radiotherapy (IMRT) ± chemotherapy., Materials and Methods: The results of PET-CT scans performed at initial diagnosis were recorded and analyzed prospectively. Patients then received standard treatment per protocol independent of the PET-CT result. IMRT was administered to the nasopharynx and neck. Early stage patients received IMRT alone, whereas loco-regionally advanced patients received concurrent chemoradiation. Patient outcomes were evaluated., Results: One hundred and seventy-nine patients were analyzable. DM occurred in 33 patients and the 3-year DMFS rate of the whole cohort was 84.1%. The cut-off of the SUVmax at the primary site (SUVmax-P) for DMFS was 10.22 by ROC curve. The 3-year DMFS rates of the higher and lower SUVmax-P groups (SUVmax-P⩽or>10.22) were 93.2% and 75.1%, respectively, with an 18.1% difference (P=0.003). Multivariate analysis indicated that SUVmax-P was a risk factor independently associated with DMFS (HR, 2.672; 95%CI, 1.236-5.776; P=0.012) and OS (HR, 2.417; 95%CI, 1.313-4.448; P=0.005). Subgroup analysis indicated that the 5-year DMFS and OS in loco-regionally advanced patients with SUVmax-P⩽10.22 were similar to those of early stage patients, whereas those of loco-regionally advanced patients with SUVmax-P>10.22 patients predicted worse outcome., Conclusion: SUVmax-P is a useful biomarker to predict distant metastasis of NPC patients treated with IMRT. Combining SUVmax-P with tumor overall stage, a more precise picture could be obtained to predict treatment outcome., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Temporal lobe injury (TLI) is a debilitating complication after radiotherapy for nasopharyngeal carcinoma (NPC), especially in patients who suffer treatment relapses and receive re-irradiation. We explored the clinical characteristics and prognostic factors of TLI in locally recurrent NPC (rNPC) patients after re-irradiation using intensity modulated radiotherapy (IMRT). A total of 454 temporal lobes (TLs) from 227 locally rNPC patients were reviewed. The clinical characteristics of TLI were analyzed. In the two radiotherapy courses, the equivalent dose in 2 Gy per fraction (EQD2) for the TLs was recalculated to facilitate comparison of the individual data. The median follow-up time was 31 (range, 3-127) months. After re-irradiation using IMRT, 31.3 % (71/227) of patients developed TLI. The median latency of TLI was 15 (range, 4-100) months. Univariate and multivariate analysis showed that the interval time (IT) between the two courses of radiotherapy and the summation of the maximum doses of the two radiotherapy courses (EQD2 - ∑max) were independent factors influencing TLI. The 5-year incidence of TLI for an IT ≤26 or >26 months was 35.9 and 53.7 % respectively (p = 0.024). The median maximum doses delivered to the injured TLs were significantly higher than was the case for the uninjured TLs after two courses of radiotherapy (135.3 and 129.8 Gy, respectively: p < 0.001). The incidence of TLI with an EQD2 - ∑max < 125 Gy was <5 %, and with an EQD2 - ∑max <145 Gy it was <50 %. A treatment mode limiting EQD2 - ∑max <125 Gy with a >2-year interval was found to be relatively safe.

Background: The two-dimensional phantom dose verification (2D-PDV) using hybrid plan and planar dose measurement has been widely used for IMRT treatment QA. Due to the lack of information about the correlations between the verification results and the anatomical structure of patients, it is inadequate in clinical evaluation. A three-dimensional anatomical dose verification (3D-ADV) method was used in this study to evaluate the IMRT/VMAT treatment delivery for nasopharyngeal carcinoma and comparison with 2D-PDV was analyzed., Methods: Twenty nasopharyngeal carcinoma (NPC) patients treated with IMRT/VMAT were recruited in the study. A 2D ion-chamber array was used for the 2D-PDV in both single-gantry-angle composite (SGAC) and multi-gantry-angle composite (MGAC) verifications. Differences in the gamma pass rate between the 2 verification methods were assessed. Based on measurement of irradiation dose fluence, the 3D dose distribution was reconstructed for 3D-ADV in the above cases. The reconstructed dose homogeneity index (HI), conformity index (CI) of the planning target volume (PTV) were calculated. Gamma pass rate and deviations in the dose-volume histogram (DVH) of each PTV and organ at risk (OAR) were analyzed., Results: In 2D-PDV, the gamma pass rate (3%, 3 mm) of SGAC (99.55% ± 0.83%) was significantly higher than that of MGAC (92.41% ± 7.19%). In 3D-ADV, the gamma pass rates (3%, 3 mm) were 99.75% ± 0.21% in global, 83.82% ± 16.98% to 93.71% ± 6.22% in the PTVs and 45.12% ± 32.78% to 98.08% ± 2.29% in the OARs. The maximum HI increment in PTVnx was 19.34%, while the maximum CI decrement in PTV1 and PTV2 were -32.45% and -6.93%, respectively. Deviations in dose volume of PTVs were all within ±5%. D2% of the brainstem, spinal cord, left/right optic nerves, and the mean doses to the left/right parotid glands maximally increased by 3.5%, 6.03%, 31.13%/26.90% and 4.78%/4.54%, respectively., Conclusion: The 2D-PDV and global gamma pass rate might be insufficient to provide an accurate assessment for the complex NPC IMRT operation. In contrast, the 3D-ADV is superior in clinic-related quality assurance offering evaluation of organ specific pass rate and dose-volume deviations.

Background and Purpose: To evaluate the long-term survival outcomes and toxicity of NPC patients treated with intensity-modulated radiotherapy (IMRT)., Materials and Methods: From May 2001 to October 2008, 868 non-metastatic NPC patients treated by IMRT were analyzed retrospectively. The Radiation Therapy Oncology Group (RTOG) criteria were used to assess toxicity., Results: With a median follow-up of 50 months (range, 5-115 months), the 5-year estimated disease specific survival (DSS), local recurrence-free survival (LRFS), regional recurrence-free survival (RRFS) and distant metastasis-free survival (DMFS) were 84.7%, 91.8%, 96.4% and 84.6%, respectively. Of the 868 patients, 186 (21.3%) developed failure after treatment. Distant metastasis was the major failure pattern after treatment. The 5-year OS rate in patients with stage I, II, III, and IVa-b were 100.0%, 94.3%, 83.6%, and 70.5%, respectively. The 5-year LRFS rate in patients with stage T1, T2, T3, and T4 disease were 100.0%, 96.0%, 90.4%, and 83.3%, respectively (χ(2) = 26.32, P<0.001). The 5-year DMFS for N0, N1, N2, and N3 patients were 96.1%, 85.6%, 73.7%, and 62.1%, respectively (χ(2) = 65.54, P<0.001). Concurrent chemotherapy failed to improve survival rates for patients with advanced locoregional disease. The most common acute toxicities were mainly in grade 1 or 2. Compared with IMRT alone, IMRT plus concurrent chemotherapy increased the severity of acute toxicities. The incidence of brain radiation damage was relatively high (5.5%, 48/868 cases), and was not observed in patients with stage T1-2., Conclusion: IMRT for NPC yielded excellent survival outcomes, and distant metastasis was the most commonly seen failure pattern after treatment. The role of concurrent chemotherapy for advanced locoregional stage NPC patients needs to be further investigated. Treatment-related toxicities were well tolerable. However, the incidence of brain radiation damage was relatively high, especially for patients with advanced T-stage., (Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.)