Update report of nasopharyngeal carcinoma treated with reduced-volume intensity-modulated radiation therapy and hypothesis of the optimal margin

doi:10.1016/j.radonc.2014.01.011

Radiotherapy and Oncology

Volume 110, Issue 3, March 2014, Pages 385-389

https://doi.org/10.1016/j.radonc.2014.01.011 Get rights and content

Abstract

Background and purpose

To establish the minimally required margins in different directions measured from GTV in the definitive treatment of nasopharyngeal carcinoma (NPC) using IMRT based on the 5-year results.

Methods and materials

Between November 2003 and May 2007, 414 patients with non-metastatic NPC were treated with IMRT according to our institutional protocol. Treatment outcomes at 5 years were analyzed. Distances from GTV-T to CTV2 (i.e., CTV 59.4 Gy) in 6 directions (anterior, posterior, superior, inferior, and bilateral) were measured and analyzed.

Results

The 5-year estimated overall survival (OS), disease free survival (DFS), local control (LC) were 80%, 77% and 95%, respectively. For the margins measured from GTV-T to CTV2, margins used with T4 disease were significantly and uniformly smaller than the whole group in all the 6 directions (P = 0.000, 0.000, 0.000, 0.000 and 0.046, respectively). However, no increase of local recurrence was associated to this limited margins used.

Conclusions

Our 5-years’ experience showed a very high LC rate. The strategy we used for CTV delineation was safe and reliable. Determined CTV through GTV expansion to a minimally required margin, using GTV + margin (used in our T4 patients) + the whole nasopharyngeal mucosa, especially for the patients with early T disease, might be feasible.

Section snippets

Patients and pretreatment evaluation

Between November 2003 and May 2007, a total of 414 histologically diagnosed non-metastatic NPC patients treated primarily with IMRT according to an IRB-approved institutional treatment protocol¹¹ at the Cancer Hospital of Fujian Medical University were enrolled in this study, including 312 male and 102 female patients, with a median age of 45 years old (range 11–86). Pretreatment evaluation consisted of a complete history and physical examination, flexible fiberoptic endoscopic examination,

Treatment outcome

The median follow-up time for the entire group of patients was 60 months (range, 5–92 months). All patients were able to complete the whole course of irradiation without treatment interruption because of acute toxicities. Two patients died of nasopharyngeal ulceration (i.e., grade V toxicities). Five and 1 patients developed grade III and IV hearing impairment, respectively. No xerostomia over grade III was observed.

At the time of their last follow-up, a total of 95 patients (22.9%) had treatment

Discussion

Although Radiation Therapy Oncology Group (RTOG) 0225 and 0615 have provided a practical reference for the delineation of CTVs for NPC [2], [3], the rationale for the definition of CTV delineation at the level of the nasopharynx for the primary disease has not been optimized. We have previously demonstrated that definitive treatment using a reduced volume for CTV produced an acceptable outcome of 3 years [11]. This update demonstrated that IMRT treated with reduced CTV maintained an excellent

Conclusions

Our 5-years’ experience of using a reduce-volume technique during IMRT treatment for NPC showed a very high local control rate, the strategy we delineated the target was safe and reliable. Defining CTV using GTV + margin + the whole nasopharyngeal mucosa, especially for the patients with early T disease is feasible. We suggested that it can be determined by the margins of T4 patients as follows: CTV = GTV + margins (anteriorly 7, posteriorly 3.3, laterally 7.5, superiorly 9.7, inferiorly 14.3) + whole

Conflict of interest statement

The authors declare that they have no competing interests.

Acknowledgments

This work was sponsored by Key Clinical Specialty Discipline Construction Program of Fujian, People’s Republic of China.

References (23)

N. Lee et al.
Intensity-modulated radiotherapy in the treatment of nasopharyngeal carcinoma. An update of the UCSF experience
Int J Radiat Oncol Biol Phys
(2002)
M.K. Kam et al.
Treatment of nasopharyngeal carcinoma with intensity-modulated radiotherapy. The Hong Kong experience
Int J Radiat Oncol Biol Phys
(2004)
S.L. Wolden et al.
Intensity-modulated radiation therapy (IMRT) for nasopharynx cancer. Update of the Memorial Sloan–Kettering experience
Int J Radiat Oncol Biol Phys
(2006)
I.W. Tham et al.
Treatment of nasopharyngeal carcinoma using intensity-modulated radiotherapy. The National Cancer Centre Singapore experience
Int J Radiat Oncol Biol Phys
(2009)
S. Lin et al.
Nasopharyngeal carcinoma treated with reduced-volume intensity-modulated radiation therapy: report on the 3-year outcome of a prospective series
Int J Radiat Oncol Biol Phys
(2009)
J.D. Cox et al.
Toxicity criteria of the Radiation Therapy Oncology Group (RTOG) and the European Organization for Research and Treatment of Cancer (EORTC)
Int J Radiat Oncol Biol Phys
(1995)
S.Z. Lai et al.
How does intensity-modulated radiotherapy versus conventional two-dimensional radiotherapy influence the treatment results in nasopharyngeal carcinoma patients?
Int J Radiat Oncol Biol Phys
(2011)
T. Wang et al.
Intensity-modulated radiation therapy for nasopharyngeal carcinoma: a review
J Radiat Oncol
(2012)
Radiation therapy oncology group protocol 02-25. Available at: http://www.rtog.org/ members/protocols/0225/0225.pdf...
Radiation therapy oncology group protocol 06-15. Available at: http://www.rtog.org/ members/protocols/0615/0615.pdf...

D.L. Kwong et al.

Intensity-modulated radiotherapy for early-stage nasopharyngeal carcinoma. A prospective study on disease control and preservation of salivary function

Cancer

(2004)

Cited by (116)

Selectively sparing of the supraclavicular area during intensity-modulated radiotherapy in nasopharyngeal carcinoma: A double-center observation study
2024, Radiotherapy and Oncology
This study was aimed at evaluating the feasibility of sparing the supraclavicular area, namely levels IVb and Vc, during intensity-modulated radiotherapy (IMRT) in nasopharyngeal carcinoma (NPC) patients with N1-2 disease[except N1 disease with purely restropharyngeal lymph nodes(RPN) involvement], and providing a basis for the revision of International Guideline for the delineation of the clinical target volume (CTV).
Patients with NPC (stage T_anyN_1-2M₀) diagnosed pathologically in Fujian Cancer Hospital (Center 1, Only Lin SJ‘s attending group) from January 2014 to March 2018 and Jiangxi Cancer Hospital(Center 2) from January 2014 to December 2015 were included. According to our principle, the supraclavicular area (levels IVb and Vc) were excluded from the CTVnd. Survival outcomes focused on regional recurrence-free survival (RRFS) and recurrence rates of levels IVb and Vc were analysed.
A total of 672 eligible patients were recruited (Center 1, n = 362; Center 2, n = 310). There was no significant difference in 5-year RRFS (97.33 % vs. 97.24 %, p = 0.980), overall survival (OS) (89.14 % vs. 88.56 %, p = 0.327), local recurrence-free survival (LRFS) (94.90 % vs. 95.30 %, p = 0.593) and distant metastasis-free survival (DMFS) (89.38 % vs. 86.60 %, p = 0.130) between Center 1 and Center 2. Twenty patients developed regional failure (median: 36 months), among them, only one case (0.15 %) was recorded as levels IVb and Vc recurrence.
Omitting the supraclavicular area (levels IVb and Vc) during IMRT should be safe and feasible for N1-2 disease (except N1 disease with purely RPN involvement). Well-designed multicenter prospective trials should be conducted to confirm our findings.
Significance of radiologic extranodal extension in locoregionally advanced nasopharyngeal carcinoma with lymph node metastasis: a comprehensive nomogram
2024, Brazilian Journal of Otorhinolaryngology
We aimed to assess the significance of rENE and creat a predictive tool (nomogram) for estimating Overall Survival (OS) in locoregionally advanced Nasopharyngeal Carcinoma (NPC) patients with Lymph Node Metastasis (LNM) based on their clinical characteristics and Radiologic Extranodal Extension (rENE).
Five hundred and sixty-nine NPC patients with LNM were randomly divided into training and validation groups. Significant factors were identified using univariate and multivariate analyses in the training cohort. Then, the nomogram based on the screening results was established to predict the Overall Survival (OS). Calibration curves and the Concordance index (C-index) gauged predictive accuracy and discrimination. Receiver Operating Characteristic (ROC) analysis assessed risk stratification, and clinical utility was measured using Decision Curve Analysis (DCA). The nomogram's performance was validated for discrimination and calibration in an independent validation cohort.
A total of 360 (63.2%) patients were present with radiologic extranodal extension at initial diagnosis. Patients with rENE had significantly lower OS than other patients. Multivariate analysis identified the five factors, including rENE, for the nomogram model. The C-index was 0.75 (0.71–0.78) in the training cohort and 0.76 (0.69–0.83) in the validation cohort. Notably, the nomogram outperformed the 8th TNM staging system, as evident from the higher AUC values (0.77 vs. 0.60 for 2 year and 0.75 vs. 0.65 for 3 year) and well-calibrated calibration curves. Decision curve analysis indicated improved Net Benefit (NB) with the nomogram for predicting OS. The log-rank test confirmed significant survival distinctions between risk groups in both training and validation cohorts.
We demonstrated the prognostic value of rENE in nasopharyngeal carcinoma and developed a nomogram based on rENE and other factors to provide individual prediction of OS for locoregionally advanced nasopharyngeal carcinoma with lymph node metastasis.
III.
The role of radiologic extranodal extension in predicting prognosis and chemotherapy benefit for T1-2 N1 nasopharyngeal carcinoma: A multicenter retrospective study
2023, Radiotherapy and Oncology
This multicenter retrospective study aimed to investigated the prognostic value of unequivocal radiologic extranodal extension (rENE) and the efficacy of chemotherapy for stage T1-2 N1 nasopharyngeal carcinoma (NPC) in the IMRT era.
We included 1,082 patients treated in 2005–2017 from three centers. rENE was recorded as G1 (coalescent nodal mass comprising ≥ 2 inseparable nodes) or G2 (invading beyond perinodal fat to frankly infiltrate adjacent structures). Multivariable analysis (MVA) evaluated the prognostic value of rENE. The value of chemotherapy was assessed in rENE-positive (rENE + ) and rENE-negative (rENE − ) subset separately.
Centers 1, 2, and 3 had 139/515 (27.0 %), 100/365 (27.4 %), and 43/202 (21.3 %) cN + patients with rENE, respectively. Compared to rENE−, rENE + patients had a worse distant metastasis-free survival (DMFS) and overall survival (OS) (all p < 0.001). MVA confirmed the prognostic of both G1-rENE and G2-rENE for distant metastasis [G1: hazard ratio (HR): 2.933, G2: HR: 6.942, all p < 0.001] and death (G1: HR: 1.587, p = 0.040; G2: HR: 6.162, p < 0.001). There was no significant difference for DMFS and OS between chemo-radiotherapy and radiotherapy alone in rENE + and rENE − groups (all p > 0.1). However, rENE + patients with a cumulative cisplatin/nedaplatin dose (CCND) of > 160 mg/m² had an improved DMFS (p = 0.033) but no OS (p = 0.197).
Unequivocal rENE is prognostic in patients with T1-2 N1 NPC. Addition of chemotherapy to radiotherapy did not affect DMFS and OS in rENE − patients. Chemotherapy with a CCND of > 160 mg/m² improved DMFS in rENE + patients.
Diffusion-Weighted Magnetic Resonance Imaging-Guided Dose Painting in Patients With Locoregionally Advanced Nasopharyngeal Carcinoma Treated With Induction Chemotherapy Plus Concurrent Chemoradiotherapy: A Randomized, Controlled Clinical Trial
2022, International Journal of Radiation Oncology Biology Physics
Citation Excerpt :
Additionally, no toxicities led to treatment discontinuation during chemoradiotherapy. Our results showed that the DWI-guided DP-IMRT regimen did not increase acute toxicities compared with conventional MRI-based IMRT in patients with NPC, as reported by Lin et al16 and Lee et al.22 The toxicity profile of this study was also similar to our previous study which applied PET/CT-guided DP-IMRT.34 In our present study, a single (0.8%) patient with primary tumor invasion to the ipsilateral parotid gland and metastatic lymph node invasion to the contralateral parotid gland in the conventional MRI-based IMRT group had grade 3 dry mouth.
We hypothesized that diffusion-weighted magnetic resonance imaging (DWI)–guided dose-painting intensity modulated radiation therapy (DP-IMRT) is associated with improved local tumor control and survival in locoregionally advanced nasopharyngeal carcinoma (NPC). The purpose of this randomized study was to compare the efficacy and toxicity of DWI-guided DP-IMRT to conventional magnetic resonance imaging (MRI)-based IMRT in locoregional advanced NPC.
A total of 260 patients with stage III-IVa NPC disease were randomly assigned in a 1:1 ratio to receive induction chemotherapy followed by chemoradiotherapy by DWI-guided DP-IMRT (group A, n = 130) or conventional MRI-based IMRT (group B, n = 130) in this prospective clinical trial. In group A, subvolume GTVnx-_DWI (gross tumor volume of nasopharynx in DWI) was defined as the areas within the GTV_nx (gross tumor volume of nasopharynx) with an apparent diffusion coefficient (ADC) below the mean ADC (ADC < mean) according to MRI before induction chemotherapy. The dose to GTVnx-_DWI was escalated to 75.2 Gy/32 fx in patients with T1-2 disease and to 77.55 Gy/33 fx in those with T3-4 disease in 2.35 Gy per fraction. In group B, planning gross tumor volume of nasopharynx was irradiated at 70.4 to 72.6 Gy/32 to 33 fx in 2.2 Gy per fraction. This trial is registered with chictr.org.cn (ChiCTR1800015779).
A total of 260 patients were included in the trial (130 patients in group A and 130 in group B). Complete response rates after chemoradiotherapy were 99.2% (129 of 130) and 93.8% (122 of 130) in groups A and B, respectively (P = .042). At a median follow-up of 25 months, DWI-guided DP-IMRT was associated with improved 2-year disease-free survival (DFS; 93.6% [95% confidence interval {CI}, 88.1%-99.1%] vs 87.5% [95% CI, 81.4%-93.6%], P = .015), local recurrence-free survival (100% [95% CI, not applicable {NA}] vs 91.3% [95% CI, 85.4%-97.2%]), locoregional recurrence-free survival (LRRFS; 95.8% [95% CI, NA] vs 91.3% [95% CI, 85.4%-97.2%]), distant metastasis-free survival (DMFS; 97.8% [95% CI, NA] vs 90.9% [95% CI, 85.8%-96.0%]), and overall survival (100% [95% CI, NA] vs 94.5% [95% CI, 89.2%-99.8%]). Zero and 3 patients had local-only recurrences in group A and B, respectively. The most common site of first failure in each arm was distant organ failure. No statistically significant differences in acute and late toxic effects were observed. Multivariate analyses showed that DP (DWI-guided DP-IMRT vs conventional MRI-based IMRT without DP) was associated with DFS, local recurrence-free survival, LRRFS, and distant metastasis-free survival. Epstein-Barr virus DNA level was associated with DFS and LRRFS.
DWI-guided DP-IMRT plus chemotherapy is associated with a disease-free survival benefit compared with conventional MRI-based IMRT among patients with locoregionally advanced NPC without increasing acute toxic effects.
Level Ib sparing intensity-modulated radiation therapy in selected nasopharyngeal carcinoma patients based on the International Guideline
2022, Radiotherapy and Oncology
To investigate the feasibility of level Ib sparing in selected nasopharyngeal carcinoma (NPC) patients during intensity-modulated radiation therapy (IMRT) based on the International Guideline.
Patients with histologically-proven NPC who received definitive IMRT at our group were candidates for this analysis. Other eligibility criteria for analysis were designed according to the recommendation of International Guideline for selective coverage of level Ib. Survival outcomes focused on regional recurrence-free survival (RRFS) and level Ib recurrence rate were analyzed.
A total of 450 patients were included, 60 of them received level Ib-covering IMRT due to the first three principles of the International Guideline according to our protocol. Of note, patients with level Ib involvement would receive ultrasound guided puncture, only those with positive pathological results would undergo level Ib-covering IMRT. For the remaining 390 patients who only fulfilled the last two criteria and/or level Ib involvement with negative pathological results, level Ib-sparing IMRT was delivered, with a median follow-up time of 112 months (range 6 to 194 months), reported 5- and 10-year RRFS were 95.4% and 92.9%, respectively. Twenty-two patients occurred regional recurrence at censorship (median 44.5 months), only 4(4/390, 1.03%) were recorded as level Ib recurrence.
Level Ib-sparing IMRT should be safe and feasible for patients who only had level II involvement with ECE, and/or had a MAD of greater than 2 cm in level II, and/or level Ib involvement with negative pathological results. Further well-designed multi-center prospective trials should be conducted.
Risk-adapted locoregional radiotherapy strategies based on a prognostic nomogram for de novo metastatic nasopharyngeal carcinoma patients treated with chemoimmunotherapy
2024, Scientific Reports

View all citing articles on Scopus

View full text

Radiotherapy of NPCUpdate report of nasopharyngeal carcinoma treated with reduced-volume intensity-modulated radiation therapy and hypothesis of the optimal margin

Abstract

Background and purpose

Methods and materials

Results

Conclusions

Section snippets

Patients and pretreatment evaluation

Treatment outcome

Discussion

Conclusions

Conflict of interest statement

Acknowledgments

Int J Radiat Oncol Biol Phys

Int J Radiat Oncol Biol Phys

Int J Radiat Oncol Biol Phys

Int J Radiat Oncol Biol Phys

Int J Radiat Oncol Biol Phys

Int J Radiat Oncol Biol Phys

Int J Radiat Oncol Biol Phys

Intensity-modulated radiation therapy for nasopharyngeal carcinoma: a review

J Radiat Oncol

Intensity-modulated radiotherapy for early-stage nasopharyngeal carcinoma. A prospective study on disease control and preservation of salivary function

Cancer

Radiotherapy of NPC
Update report of nasopharyngeal carcinoma treated with reduced-volume intensity-modulated radiation therapy and hypothesis of the optimal margin