Skip Navigation
Skip to contents

Cancer Res Treat : Cancer Research and Treatment

Search
Advanced Search
OPEN ACCESS
mobile search button mobile menu button

Articles

Page Path
HOME > Cancer Res Treat > Volume 51(2); 2019 > Article
Original Article Reduction of Target Volume and the Corresponding Dose for the Tumor Regression Field after Induction Chemotherapy in Locoregionally Advanced Nasopharyngeal Carcinoma
Lei Wang, MM1, Zheng Wu, MM2, Dehuan Xie, MM3, Ruifang Zeng, MM4, Wanqin Cheng, MM5, Jiang Hu, MM3, Shaomin Huang, PhD3, Shu Zhou, PhD3, Rui Zhong, MM3, Yong Su, MD, PhD3,
Cancer Research and Treatment : Official Journal of Korean Cancer Association 2019;51(2):685-695.
DOI: https://doi.org/10.4143/crt.2018.250
Published online: August 13, 2018

1Department of Radiation Oncology, National Cancer Center/Cancer Hospital & Shenzhen Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Shenzhen, China

2Department of Radiation Oncology, Hunan Cancer Hospital and The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, China

3Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Guangzhou, China

4Department of Radiotherapy, TCM-Integrated Cancer Center of Southern Medical University, Guangzhou, China

5Department of Oncology, Shunde Hospital, Southern Medical University, Foshan, China

Correspondence: Yong Su, MD, PhD Department of Radiation Oncology, Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, 651 Dong Feng Road East, Guangzhou 510060, China
Tel: 86-20-87343704 Fax: 86-20-87343295 E-mail: suyong@sysucc.org.cn
*Lei Wang and Zheng Wu contributed equally to this work.
• Received: April 26, 2018   • Accepted: August 8, 2018

Copyright © 2019 by the Korean Cancer Association

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

  • 8,790 Views
  • 250 Download
  • 26 Web of Science
  • 28 Crossref
  • 27 Scopus
prev next
Full Article

Download PDF Download PDF

  • 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.
  • Key words: Nasopharyngeal carcinoma, Induction chemotherapy, Intensity-modulated radiotherapy, Target volume, Dose distribution
The incidence of nasopharyngeal carcinoma (NPC) is high in south China and Southeast Asia [1]. Radiotherapy is the standard treatment modality, and a combination of radiotherapy and chemotherapy employed as the mainstay strategy [2]. Currently, induction chemotherapy (IC) combined with concurrent chemoradiotherapy is one of the most popular treatments for locoregionally advanced NPC, with confirmed therapeutic value. A phase III clinical trial [3] comparing the efficacy of IC plus concurrent chemoradiotherapy to that of chemoradiotherapy alone for treatment of locoregionally advanced NPC conducted by Sun et al. [3] showed that inclusion of IC significantly improves progression-free survival (PFS; 3-year PFS, 80% vs. 72%). The addition of IC effectively reduced distant metastasis, which could be transformed into overall survival (OS) benefit. In addition, multiple studies have reported a response rate of 73%-89% with significant tumor volume decreasing in NPC after IC [4-6], leading to challenge of target delineation for following radiotherapy.
Currently, accurate definition of the target volume of NPC after IC presents a major clinical challenge and remains a subject of extensive debate. According to Perez & Brady's Principles and Practice of Radiation Oncology, 6th edition [7], target volumes should be defined based on the extent of the tumor before IC. In 2009, the consensus [8] was that gross tumor volume (GTV) should be outlined based on the pre-IC tumor volume (cavity partially retracted) in locoregionally advanced head-and-neck cancer after IC and the irradiation dose should remain constant, regardless of whether or not the lesions achieve complete remission. However, evidencebased reports are lacking in the literature. According to the basic principles of radiobiology [7], the tumor control probability curve suggests that therapeutic radiation dose should be increased with a higher tumor burden to achieve radical treatment for clinically detectable tumors. Conversely, once gross tumor lesions transform into subclinical lesions that are undetectable with imaging methods after IC, the tumor burden decreases and the radiation dose may need to be altered accordingly. For other malignancies, such as lymphoma [9], small cell and non-small cell lung cancer [10,11], earlier studies have shown that reducing the dose of radiation therapy in the tumor regression areas after IC does not adversely affect efficacy. Furthermore, reduction of the radiation dose led to decreased toxicity, which improved the quality of life in patients.
In summary, for treatment of locoregionally advanced NPC, it is unreasonable to define the target volume after IC as the pre-IC volume, especially for cases showing significant tumor regression after IC. In the current study, methods for outlining the accurate target volume of NPC after IC and feasibility of appropriate reduction of the radiation dose in the tumor regression area were assessed, and follow-up analysis of patients conducted to determine long-term treatment efficacy and toxicity outcomes.
Patients were eligible if they had (1) biopsy-proven previously untreated World Health Organization type II or III NPC; (2) stage III–IVB according to the American Joint Committee on Staging of Cancer classification (AJCC 2009); (3) ages between 18 and 65 years; (4) absence of a second malignancy; (5) Karnofsky performance score ≥ 70; (6) adequate bone marrow reserve, liver function and renal function; and (7) adequate mental status to follow instructions.
1. Treatment

1) Patient evaluation

Before treatment, all patients underwent bone scan, chest X-ray, abdominal ultrasound and electrocardiography assessments. Clinical examination of the head and neck, magnetic resonance imaging (MRI) scan of the nasopharynx and neck and electronic nasopharyngoscopy were performed before IC and after two and four cycles of IC.

2) Chemotherapy

The regimen of IC is a combination of taxanes, cisplatin and fluorouracil (TPF), comprising intravenous infusion of docetaxel 50 mg/m2 on day 1, intravenous infusion of cisplatin 60 mg/m2 on day 1 and continuous intravenous infusion of 5-fluorouracil 500 mg/m2/day through days 1-5 for 120 hours, three-weekly, for four cycles. If tumor shrinkage achieved partial remission or above after two cycles of IC, patients continued IC to four cycles and were administered concurrent chemoradiation (CCRT); otherwise, patients received CCRT after two cycles of IC. Concurrent chemotherapy (CCT) consisted of cisplatin 30 mg/m2 intravenous infusion on day 1, weekly, for 4-6 cycles.

3) Radiotherapy and treatment planning

Prior to radiotherapy, all patients were immobilized with head-and-neck thermoplastic masks in a supine position, followed by computed tomography simulation using 3-mm slices including the head and neck within 1 to 2 weeks after IC. All patients received definitive intensity-modulated radiation therapy (IMRT) in 3 weeks after IC.
Target volumes and organs at risk (OAR) were determined according to the International Commission on Radiation Units and Measurements reports (ICRU) 50 and 62 as well as our institutional treatment protocol [12-14]. The gross tumor volume of nasopharynx (GTVnx)–pre and the gross tumor volume of cervical lymph node (GTVnd)–pre referred to the primary tumor (including retropharyngeal lymph node metastasis) and the neck lymph node metastasis before IC, respectively. The GTVnx-residual was defined as the residual primary tumor (including retropharyngeal lymph node metastasis) after IC, and the GTVnd-residual was defined as the residual GTVnd-pre after IC. The CTVnx1 and CTVnd1 were defined as GTVnx-residual and GTVnd-residual plus 1 cm margin and 0.5-1 cm margin, respectively. When the tumor debulked so much that the CTVnx1 and CTVnd1 were not able to encompass the region of GTVnx-pre and GTVndpre, respectively, the CTVnx1 and CTVnd1 should be modified to cover the region of GTVnx-pre and GTVnd-pre, respectively. CTV2 was defined as CTVnx1 and CTVnd1 plus a 5-mm margin together with the bilateral cervical selective lymph drainage areas. In cases where the primary tumor achieved complete remission after IC, the final site of tumor regression was contoured as GTVnx-residual. If the lymph node achieved complete remission after IC, the regressed lymph node and invaded structures were outlined as CTVnd1. Planning target volume (PTV) would encompass the corresponding GTVs and clinical target volumes (CTVs) with a 3-mm margin in all directions including anterior, posterior, superior, inferior, left and right. The GTVnx-pre and GTVnd-pre were the pre-IC target volumes with no prescribed dose, thus, the PTVs of GTVnx-residual, GTVndresidual, CTVnx1, CTVnd1, and CTV2 were designated PGTVnx-residual, PGTVnd-residual, PCTVnx1, PCTVnd1, and PCTV2, respectively, and prescribed radiation doses of 68 Gy, 62-66 Gy, 60 Gy, 60 Gy, and 50 Gy, respectively, in 30 fractions. All treatments were delivered once daily for 5 days per week. The names, definitions and prescribed doses of the target volumes are listed in the Table 1, and examples of target delineation are presented in Figs. 1 and 2. A standard constraint set conforming to the Radiation Therapy Oncology Group (RTOG) 0225 protocol [15] was applied for optimization and evaluation. The aim was to achieve 95% of any PTV at or above the prescription dose, at least 95% of any PTV at 95% of the prescription dose, and no more than 10% of PGTVnx-residual/PGTVnd-residual at or above 110% of the prescription dose.
2. Assessment and follow-up
Tumor response after two and four cycles of IC was evaluated according to the Response Evaluation Criteria in Solid Tumors (RECIST), and classified as complete response (CR), partial response (PR), stable disease (SD), or progressive disease (PD). We characterized chemotherapy-related and radiotherapy-related toxic effects according to the Common Terminology Criteria for Adverse Events ver. 3.0. All patients were assessed weekly during treatment and followed up every 3 months during the first 2 years, every 6 months during the subsequent 3 years, and yearly thereafter until death.
3. Endpoints
Our primary endpoints were locoregional relapse-free survival (LRFS) and patterns of locoregional failure, classified as “in-field” if 95% recurrent tumor volume was within the 95% isodose, “marginal” if 20%-95% recurrent tumor volume was within the 95% isodose or “out-of-field” if < 20% recurrent tumor volume was within the 95% isodose [16]. Our secondary endpoints were OS, distant metastasis-free survival (DMFS) and PFS.
4. Statistical analysis
The Statistical Package for Social Sciences, ver. 25.0 (SPSS, IBM Corp., Armonk, NY) was employed for statistical analysis. Patient characteristics were summarized using the descriptive statistics. The paired t test (two-sided test, α=0.05) was applied to compare tumor volumes before and after IC. Survival rates were computed using the Kaplan-Meier method.
5. Ethical statement
The study was approved by the Institutional Review Board of Sun Yan-Sen University Cancer Center and performed in accordance with the principles of the Declaration of Helsinki. Written informed consents were obtained.
From August 2009 to August 2013, 57 patients were reviewed. Patient and tumor characteristics are presented in Table 2.
1. Completion of treatment
Chemotherapy was administered to all patients. In total, 51/57 patients (89.5%) completed four cycles of IC, two of 57 patients (3.5%) underwent CCRT after two cycles of IC due to the incidence of herpes zoster and grade 3 thrombocytopenia, and four of 57 (7%) were evaluated as SD after two cycles of IC and underwent a third course while waiting for CCRT. Overall, 46 of 57 patients (80.7%) received more than four cycles of CCT. Reasons for CCT discontinuation included mucositis, grade 3 leukopenia and grade 4 thrombocytopenia. All patients completed definitive IMRT.
2. Acute toxicity
During IC, four of 57 patients (6.0%) developed grade 3 leukopenia, one of 57 (1.8%) developed grade 3 thrombocytopenia and one of 57 (1.8%) developed herpes zoster. CCRT induced several severe toxic effects, such as grade 3 mucositis (10.5%), grade 3 xerostomia (1.8%), grade 3 leukopenia (17.5%), grade 3 thrombocytopenia (1.8%), and grade 4 thrombocytopenia (1.8%).
3. Efficacy
The post-IC tumor volume was significantly decreased (p < 0.01), compared with the pre-IC tumor volume (Table 3). After completion of IC, CR was observed in 10.5% patients, PR in 82.5% patients, and SD in 7% patients.
Follow-up was updated in October 2017 at a median follow-up time of 68 months (range, 9 to 93 months). Overall, nine patients showed progression, including three with locoregional relapse alone, five with distant metastasis alone, and one with both locoregional relapse and distant metastasis. All locoregional recurrences occurred in the GTVnxresidual/GTVnd-residual region and were in-field, with no development of marginal or out-of-field recurrence (Table 4). Ten patients died during follow-up, specifically, three with locoregional relapse alone, four with distant metastasis alone, one with locoregional relapse and distant metastasis, one with pancreatic cancer, and one of unknown reason. The 5-year LRFS, DMFS, PFS, and OS rates were determined as 87.7%, 85.8%, 80.3%, and 82.2%, respectively. The Kaplan-Meier estimates of LRFS, DMFS, PFS and OS are shown in Fig. 3.
4. Late toxicity
Grade 4 late toxicity was not observed during follow-up. Overall, four of 57 patients (7.0%) developed temporal lobe injury (TLI) according to MRI findings, and two of these four patients presented clinical symptoms.
Previous focus on the role of chemotherapy in treatment of NPC has been to reduce distant metastasis and increase the OS rate. However, limited information is available on outlining of the radiotherapy target volume for optimizing the post-IC response in NPC. Conclusions are yet to be made on how to define the target tumor volume and the appropriate irradiation dose after IC. The conventional view [8] is that the tumor regression field after IC is still defined as GTV and treated with the radical irradiation dose used for gross tumor. However, according to the basic principles of radiobiology [7,17], only a high tumor burden requires the higher dose of radiation therapy.
To achieve good treatment effects, subclinical lesions in NPC are usually recommended 60 Gy of radiation [6,18]. However, for gross tumors that have shrunk to subclinical lesions after chemotherapy, administration of the same irradiation dose as that for the gross tumor appears unreasonable. Therefore, determination of the tumor regression area after chemotherapy as a CTV and provision of an equivalent corresponding radiation dose is important. This modification should provide two main benefits to patients: (1) the highdose irradiation area is reduced, potentially resulting in a significant decrease in toxicity to patients, and (2) in tumors adjacent to the OAR, such as brain stem or optic chiasm, the tumor size is reduced by IC and the distance between the GTV and critical tissues increased, so that radical treatment is possible for patients who have only been able to undergo palliative care in the past.
For other malignant tumors, outlining target volumes after IC to reduce treatment-related toxicity has been discussed and a consensus reached. In lymphoma radiotherapy, involved node radiation therapy and involved site radiation therapy are the newest irradiation concepts with smaller radiation volumes and lower toxicity than the original larger-field radiation therapy and the classical involved-field radiation therapy [9]. The concept of involved node radiation therapy developed by the European Organization for Research on Treatment of Cancer [19] is that GTV is the lymph node remnant alone and CTV only includes the tumors that achieve CR after chemotherapy without preventive irradiation to other regions. Both retrospective and prospective studies have demonstrated achievement of equivalent or enhanced survival rates compared with involved-field radiation therapy, suggesting that the target volume after IC can be effectively decreased in accordance with tumor debulking [20-22]. There were similar explorations of reducing target volumes and prescribed doses in the treatment of non-small cell lung cancer [23] and small cell lung cancer [10].
A few researchers have explored methods for outlining the target tumor volume after IC for NPC. Yu et al. [24] defined clinically detectable lesions after IC as GTV and prescribed a dose of 68 Gy, while 63 Gy was administered to the tumor shrinkage area after IC. The local control rate was 100% at the median follow-up time of 9 months. Among 24 patients, only one showed distant metastasis 15 months after the completion of treatment. Xue et al. [25] outlined GTV according to the clinically detectable tumor area after IC and prescribed a dose of 60 Gy in the tumor shrinkage and upper neck drainage areas. The local control rate at three years in 103 patients was 91.9%. These results collectively support the feasibility of reducing the radiation dose for the tumor regression area after IC without compromising the therapeutic effect. In a prospective randomized controlled trial by Yang et al. [26], a prescribed dose of 64 Gy was administered in the tumor regression area after IC. No significant differences in 3-year OS, PFS, LRFS, and DMFS were evident between the experimental and control groups (87% vs. 82.3%, 83.4% vs. 74.7%, 93.9% vs. 91.8%, and 88.6% vs. 81.3%, respectively). In addition, treatment toxicity was significantly reduced.
In our study, a dose of 60 Gy was prescribed for the tumor regression area. Long-term follow-up revealed 5-year OS, DMFS, LRFS, and PFS rates of 82.2%, 85.8%, 87.7%, and 80.3%, respectively, analogous to reports in the past. It should be noted that patients enrolled in the study had stage III-IVB disease, most with large primary tumors and extensive nodal involvement (stage N2-3). Only four cases showed locoregional relapse in 5 years. All local recurrences were determined as GTVnx-residual or GTVnd-residual and recurrences located in-field. No recurrence within CTVnx1, CTVnd1, or CTV2 was observed, either marginal or outof-field. These results confirmed the feasibility of outlining the target volume and altering the prescription dose accordingly for optimizing the effects of radiation therapy.
For NPC adjacent to brain stem, optic chiasm, optic nerve and other important OARs, IC could aid in increasing the distance between the tumor and organ, allowing the use of radiotherapy as radical treatment instead of palliative care. For the example of Fig. 2, the tumor invaded ethmoidal cellules and orbital apex, with the right optic nerve suspiciously invaded. If the target area was outlined according to the pre-IC tumor, the choice would be to either sacrifice the dose coverage of the tumor or optic nerve function. A radical treatment would be compromised, and visual impairment may occur after treatment. However, after four IC cycles, the tumor area had diminished and the GTV area decreased. The shrinkage area altered from GTVnx-pre to CTVnx1. Accordingly, the prescribed dose was decreased, which not only achieved the purpose of radicalizing the tumor but also protected the right optic nerve and optic chiasma. Notably, even at 70 months after treatment, no locoregional recurrences were observed, along with no right eye vision impairment or other long-term toxicities.
Thus, with the reduced irradiation volume and corresponding dose, side-effects are also significantly reduced. Previous reports demonstrated a high brain damage rate in T3/4 NPC patients after radiotherapy, which had a significant impact on their quality of life. Zhou et al. [27] retrospectively analyzed radiation-related temporal lobe damage in NPC patients caused by IMRT and two-dimensional radiotherapy. Among 305 patients with NPC receiving IMRT, 16% showed radiation-induced TLI after 5 years, of which 15.5% T3 and 52.6% T4 patients had TLI. Su et al. [28] additionally conducted a retrospective analysis of patients with NPC undergoing IMRT. Five-year median follow-up studies revealed a TLI incidence in 14/83 T3 patients (16.9%) and 26/49 T4 patients (53.1%). However, analysis of long-term outcomes in our study showed that only 4/57 patients (7.0%) developed temporal lobe injury, all of which were in the T4 category. In addition, only two out of four displayed clinical symptoms. The current study included 40.4% T3 and 45.6% T4 patients. Our data showed a significantly decreased incidence of temporal lobe injury, compared to previous findings.
While patients with NPC clearly achieved a lower incidence of toxicity and better outcomes in our study, a number of issues still require attention in clinical practice. (1) We need to establish the optimal number of IC cycles required to effectively reduce the irradiation dose of the tumor regression area in NPC. Currently, no relevant recommended standards are available. In our analysis, if CR/PR was observed after two cycles of chemotherapy, treatment with IC was continued in terms of better tumor debulking and normal tissue repair, which contributed to better target delineation, as this would aid in determining the existence of residual tumor cells in the retracted area. Even after exposure to a higher number of IC cycles, toxicities were tolerable in patients and the distant metastasis rate would decrease. (2) Accurate evaluation of the tumor shrinkage area after chemotherapy is the key in radiotherapy target outlining. A multidisciplinary approach was used in which an imaging physician with extensive experience in reading head and neck tumor images was consulted to determine the extent of tumor. In cases where it was difficult to determine tumor volume, suspicious residual tumor was treated with the radical radiation dose. (3) For patients who achieved CR after chemotherapy, not all regression fields were treated as subclinical lesions. Instead, the center of primary tumor that regressed at the last cycle of IC was treated with high-dose radiation (68 Gy). The efficacy of 60 Gy irradiation treatment for the whole regression field including the primary tumor site in CR patients after chemotherapy remains to be established. (4) The number of enrolled patients was small because the main treatment modality for locoregionally advanced NPC was CCRT at the beginning of our study, and the exploration of IC was rare with only a few patients underwent IC combined with CCRT rather than CCRT alone. Besides, the target delineation after IC was debated, thus, this contouring method was only applied in our team with strict inclusion criteria considering the intensity of the treatment.
Except for these limitations, this investigation is a novel attempt to reduce the irradiation dose in the tumor shrinkage area after IC in NPC therapy. The long-term follow-up results showed a good therapeutic effect and low incidence of toxicity, supporting the theory that defining clinically and radiologically detectable tumors after IC as GTV while defining regression regions as subclinical lesions, presenting a feasible method for outlining the target region for radiotherapy. However, the sample size in our study was relatively small. Prospective randomized controlled clinical studies are thus further warranted to confirm our findings.

Conflict of interest relevant to this article was not reported.

Acknowledgements
This work was supported by grants from the Planned Science and Technology Project of Guangdong Province (No.2010B080701016 and No. 2012B031800301).
Fig. 1.
(A) In MRI before IC, the primary tumor located in the bilateral roof and left wall of nasopharynx, spread to bilateral middle nasal turbinate and bilateral pterygopalatine fossa anteriorly (green arrow), laterally extended to left petrous apex, left carotid canal and posteriorly to left clivus (white arrow). (B) In MRI after IC, the tumor obviously regressed. Tumor enhancement signal could only be seen in anterior roof of nasopharynx, bilateral choanae and bilateral pterygopalatine fossa (green arrow in B), delineated as GTVnx-residual. Signal of skull base bone destruction became unapparent (white arrow in B). Left petrous apex, left carotid canal and left clivus partially recovered in the bone window of computed tomography scan (white arrow in C), delineated as CTVnx1 and prescribed 60 Gy. (D) Red line, purple line, and blue line indicate GTVnxresidual, CTVnx1, and CTV2, respectively. (E) Dose color wash (60 Gy). Yellow line, pink line, green line, light yellow line, blue line, and light blue line (arrow) indicate PGTVnx-residual, GTVnx-pre, PCTVnx1, PCTV2, brain stem, and optic chiasm, respectively. (F) DVH. Orange line, green line, blue line, and red line indicate PGTVnx-residual, PCTVnx1, brain stem, and optic chiasm, respectively. MRI, magnetic resonance imaging; IC, induction chemotherapy; GTVnx, gross tumor volume of nasopharynx; CTV, clinical target volume; PGTV, planning target volume of GTV; PCTV, planning target volume of CTV; DVH, dose volume histogram.
crt-2018-250f1.jpg
Fig. 2.
(A) In MRI before IC, the tumor invaded ethmoidal cellules and orbital apex, with the right optic nerve suspiciously invaded (white arrow). The patient suffered with inflammation after wadding for nasopharynx bleeding (red arrow in A). (B, C) The tumor volume was reduced and no tumor signal was founded in MRI after IC (white arrow in B) and computed tomography after IC (white arrow in C) in the same slice as A. (D) Therefore, the tumor regressed region was outlined as CTVnx1, prescribed 60 Gy (pink line, CTVnx1; blue line, CTV2 in D). (E) Dose color wash (60 Gy). Orange line and red line indicate PCTVnx1 and optic chiasm, respectively. (F) DVH. Green line, red line, and blue line, indicated PCTVnx1, right optic nerve, and optic chiasm, respectively. MRI, magnetic resonance imaging; IC, induction chemotherapy; CTV, clinical target volume; PCTV, planning target volume of CTV; DVH, dose volume histogram.
crt-2018-250f2.jpg
Fig. 3.
(A) Kaplan-Meier estimates of locoregional-free survival (5-year LRFS, 87.7%; 95% confidence interval [CI], 82.6 to 92.7). (B) Kaplan-Meier estimates of distant metastasis-free survival (5-year DMFS, 85.8%; 95% CI, 80.3 to 91.4). (C) KaplanMeier estimates of progression-free survival (5-year PFS, 80.3%; 95% CI, 73.0 to 87.6). (D) Kaplan-Meier estimates of overall survival (5-year OS, 82.2%; 95% CI, 75.9 to 88.5).
crt-2018-250f3.jpg
Table 1.
Definitions and prescribed dose of target volumes
Target volume Definition PTV Prescribed dose (Gy)
GTVnx-pre The primary tumor before IC (including retropharyngeal lymph node metastasis) - -
GTVnd-pre The neck lymph node metastasis before IC - -
GTVnx-residual The residual primary tumor after IC (including retropharyngeal lymph node metastasis) PGTVnx-residual 68
GTVnd-residual The residual GTVnd-pre after IC PGTVnd-residual 62-66
CTVnx1 GTVnx-residual plus 1 cm margin, covering the region of GTVnx-pre PCTVnx1 60
CTVnd1 GTVnd-residual plus 0.5-1 cm margin, covering the region of GTVnd-pre PCTVnd1 60
CTV2 CTVnx1 and CTVnd1 plus a 5 mm margin together with the bilateral cervical selective lymph drainage areas PCTV2 50

Illustrations: the GTVnx-pre and GTVnd-pre were the tumor volumes before induction chemotherapy (IC) with no prescribed dose for planning.

Table 2.
Characteristics of the 57 NPC patients
Characteristic No. of patients (%)
Age, median (range, yr) 44 (26-65)
Sex
 Male 47 (82.5)
 Female 10 (17.5)
Clinical stage
 III 26 (45.6)
 IV 31 (54.4)
T category
 T1 0
 T2 8 (14.0)
 T3 23 (40.4)
 T4 26 (45.6)
N category
 N0 0
 N1 15 (26.3)
 N2 36 (63.2)

NPC, nasopharyngeal carcinoma.

Table 3.
Comparison of tumor volume before and after IC
Target volume Pre-IC (cm3) Post-IC (cm3) p-value Tumor shrinkage (%)
GTVnx 63.7±45.6 21.8±23.7 < 0.01 66.5
GTVnd 21.7±21.8 7.5±9.4 < 0.01 68.0
GTV 85.4±51.0 29.3±26.6 < 0.01 67.2

IC, induction chemotherapy; GTV, gross tumor volume of nasopharynx (GTVnx)+gross tumor volume of cervical lymph node (GTVnd).

Table 4.
Clinical characteristics and patterns of locoregional failure of four patients
Patient No. T N AJCC IC CCT Tumor volume before IC (cm3)
 Tumor volume after IC (cm3)
 Failure site Patterns of failure TR (mo) Isodose level (Gy)
GTVnx -pre GTVnd -pre-L GTVnd -pre-R GTVnx-residual GTVnd-residual-L GTVnd-residual-R
1 4 2 IVA TPF*3 Cis*4 94.66 25.05 11.65 63.92 11.82 3.94 S. NP. In field 12 71
L. NC. 70
L. Level II LN 65
2 2 2 III TPF*3 Cis*3 38.51 37.45 4.49 6.96 1.50 3.80 L. Level II LN In field 15 63.5
3 3 2 III TPF*4 Cis*4 24.70 9.00 2.70 5.60 0.00 0.00 L. RPN In field 24 66.2
4 3 2 III TPF*3 Cis*4 23.58 0.98 46.61 10.77 0.00 26.18 R. Level II, III, IV LN In field 33 65

AJCC, American Joint Committee on Cancer; IC, induction chemotherapy; CCT, concurrent chemotherapy; GTVnx, gross tumor volume of nasopharynx; GTVnd, gross tumor volume of cervical lymph node; TR, time to relapse; TPF, a combination of taxanes, cisplatin and fluorouracil; Cis, cisplatin; S., superior; NP., nasopharynx; L., left; NC., nasal cavity; LN, lymph node; RPN, retropharyngeal lymph node; R., right.

  • 1. Razak AR, Siu LL, Liu FF, Ito E, O'Sullivan B, Chan K. Nasopharyngeal carcinoma: the next challenges. Eur J Cancer. 2010;46:1967–78. ArticlePubMed
  • 2. Pfister DG, Spencer S, Adelstein D, Adkins D, Brizel DM, Burtness BB, et al. NCCN clinical practice guidelines in oncology (NCCN Guidelines): head and neck cancers. Version 2.2016-October 11, 2016. Fort Washington, PA: National Comprehensive Cancer Network; 2016.
  • 3. Sun Y, Li WF, Chen NY, Zhang N, Hu GQ, Xie FY, et al. Induction chemotherapy plus concurrent chemoradiotherapy versus concurrent chemoradiotherapy alone in locoregionally advanced nasopharyngeal carcinoma: a phase 3, multicentre, randomised controlled trial. Lancet Oncol. 2016;17:1509–20. ArticlePubMed
  • 4. Hui EP, Ma BB, Leung SF, King AD, Mo F, Kam MK, et al. Randomized phase II trial of concurrent cisplatin-radiotherapy with or without neoadjuvant docetaxel and cisplatin in advanced nasopharyngeal carcinoma. J Clin Oncol. 2009;27:242–9. ArticlePubMed
  • 5. Fountzilas G, Ciuleanu E, Bobos M, Kalogera-Fountzila A, Eleftheraki AG, Karayannopoulou G, et al. Induction chemotherapy followed by concomitant radiotherapy and weekly cisplatin versus the same concomitant chemoradiotherapy in patients with nasopharyngeal carcinoma: a randomized phase II study conducted by the Hellenic Cooperative Oncology Group (HeCOG) with biomarker evaluation. Ann Oncol. 2012;23:427–35. ArticlePubMedPDF
  • 6. Ma J, Mai HQ, Hong MH, Min HQ, Mao ZD, Cui NJ, et al. Results of a prospective randomized trial comparing neoadjuvant chemotherapy plus radiotherapy with radiotherapy alone in patients with locoregionally advanced nasopharyngeal carcinoma. J Clin Oncol. 2001;19:1350–7. ArticlePubMed
  • 7. Halperin EC, Brady LW, Perez CA, Wazer DE. Perez and Brady’s principles and practice of radiation oncology. 6th ed. Philadelphia, PA: Lippincott Williams &Wilkins; 2013.
  • 8. Salama JK, Haddad RI, Kies MS, Busse PM, Dong L, Brizel DM, et al. Clinical practice guidance for radiotherapy planning after induction chemotherapy in locoregionally advanced head-and-neck cancer. Int J Radiat Oncol Biol Phys. 2009;75:725–33. ArticlePubMed
  • 9. Illidge T, Specht L, Yahalom J, Aleman B, Berthelsen AK, Constine L, et al. Modern radiation therapy for nodal non-Hodgkin lymphoma-target definition and dose guidelines from the International Lymphoma Radiation Oncology Group. Int J Radiat Oncol Biol Phys. 2014;89:49–58. ArticlePubMed
  • 10. Kalemkerian GP, Loo BW Jr, Akerley W, Attia A, Chow LQ, Decker R. NCCN clinical practice guidelines in oncology (NCCN guidelines): small cell lung cancer. Version 3.2017-February 23, 2017. Fort Washington, PA: National Comprehensive Cancer Network; 2017.
  • 11. De Ruysscher D, Faivre-Finn C, Nestle U, Hurkmans CW, Le Pechoux C, Price A, et al. European Organisation for Research and Treatment of Cancer recommendations for planning and delivery of high-dose, high-precision radiotherapy for lung cancer. J Clin Oncol. 2010;28:5301–10. ArticlePubMed
  • 12. Sun Y, Yu XL, Luo W, Lee AW, Wee JT, Lee N, et al. Recommendation for a contouring method and atlas of organs at risk in nasopharyngeal carcinoma patients receiving intensitymodulated radiotherapy. Radiother Oncol. 2014;110:390–7. ArticlePubMed
  • 13. Sun Y, Yu XL, Zhang GS, Liu YM, Tao CJ, Guo R, et al. Reduction of clinical target volume in patients with lateralized cancer of the nasopharynx and without contralateral lymph node metastasis receiving intensity-modulated radiotherapy. Head Neck. 2016;38 Suppl 1:E468–72. ArticlePubMed
  • 14. Xiao WW, Huang SM, Han F, Wu SX, Lu LX, Lin CG, et al. Local control, survival, and late toxicities of locally advanced nasopharyngeal carcinoma treated by simultaneous modulated accelerated radiotherapy combined with cisplatin concurrent chemotherapy: long-term results of a phase 2 study. Cancer. 2011;117:1874–83. ArticlePubMed
  • 15. RTOG Foundation. RTOG 0225 protocol information [Internet]. Rockville, MD: National Cancer Institute; 2008. [cited 2018 Jul 2]. Available from: https://www.rtog.org/ClinicalTrials/ProtocolTable/StudyDetails.aspx?study=0225
  • 16. Kong F, Ying H, Du C, Huang S, Zhou J, Chen J, et al. Patterns of local-regional failure after primary intensity modulated radiotherapy for nasopharyngeal carcinoma. Radiat Oncol. 2014;9:60.ArticlePubMedPMC
  • 17. Fletcher GH. Clinical dose response curves of human malignant epithelial tumours. Br J Radiol. 1973;46:151.Article
  • 18. Tang LQ, Chen DP, Guo L, Mo HY, Huang Y, Guo SS, et al. Concurrent chemoradiotherapy with nedaplatin versus cisplatin in stage II-IVB nasopharyngeal carcinoma: an openlabel, non-inferiority, randomised phase 3 trial. Lancet Oncol. 2018;19:461–73. ArticlePubMed
  • 19. Girinsky T, van der Maazen R, Specht L, Aleman B, Poortmans P, Lievens Y, et al. Involved-node radiotherapy (INRT) in patients with early Hodgkin lymphoma: concepts and guidelines. Radiother Oncol. 2006;79:270–7. ArticlePubMed
  • 20. Verhappen MH, Poortmans PM, Raaijmakers E, Raemaekers JM. Reduction of the treated volume to involved node radiation therapy as part of combined modality treatment for early stage aggressive non-Hodgkin's lymphoma. Radiother Oncol. 2013;109:133–9. ArticlePubMed
  • 21. Girinsky T, Specht L, Ghalibafian M, Edeline V, Bonniaud G, Van Der Maazen R, et al. The conundrum of Hodgkin lymphoma nodes: to be or not to be included in the involved node radiation fields. The EORTC-GELA lymphoma group guidelines. Radiother Oncol. 2008;88:202–10. ArticlePubMed
  • 22. Maraldo MV, Aznar MC, Vogelius IR, Petersen PM, Specht L. Involved node radiation therapy: an effective alternative in early-stage hodgkin lymphoma. Int J Radiat Oncol Biol Phys. 2013;85:1057–65. ArticlePubMed
  • 23. De Ruysscher D, Faivre-Finn C, Moeller D, Nestle U, Hurkmans CW, Le Pechoux C, et al. European Organization for Research and Treatment of Cancer (EORTC) recommendations for planning and delivery of high-dose, high precision radiotherapy for lung cancer. Radiother Oncol. 2017;124:1–10. ArticlePubMed
  • 24. Yu Z, Luo W, Zhou QC, Zhang QH, Kang DH, Liu MZ. Impact of changing gross tumor volume delineation of intensity-modulated radiotherapy on the dose distribution and clinical treatment outcome after induction chemotherapy for the primary locoregionally advanced nasopharyngeal carcinoma. Ai Zheng. 2009;28:1132–7. ArticlePubMed
  • 25. Xue F, Hu C, He X. Induction chemotherapy followed by intensity-modulated radiotherapy with reduced gross tumor volume delineation for stage T3-4 nasopharyngeal carcinoma. Onco Targets Ther. 2017;10:3329–36. ArticlePubMedPMC
  • 26. Yang H, Chen X, Lin S, Rong J, Yang M, Wen Q, et al. Treatment outcomes after reduction of the target volume of intensity-modulated radiotherapy following induction chemotherapy in patients with locoregionally advanced nasopharyngeal carcinoma: a prospective, multi-center, randomized clinical trial. Radiother Oncol. 2018;126:37–42. ArticlePubMed
  • 27. Zhou GQ, Yu XL, Chen M, Guo R, Lei Y, Sun Y, et al. Radiation-induced temporal lobe injury for nasopharyngeal carcinoma: a comparison of intensity-modulated radiotherapy and conventional two-dimensional radiotherapy. PLoS One. 2013;8:e67488ArticlePubMedPMC
  • 28. Su SF, Huang SM, Han F, Huang Y, Chen CY, Xiao WW, et al. Analysis of dosimetric factors associated with temporal lobe necrosis (TLN) in patients with nasopharyngeal carcinoma (NPC) after intensity modulated radiotherapy. Radiat Oncol. 2013;8:17.ArticlePubMedPMC

Figure & Data

REFERENCES

    Citations

    Citations to this article as recorded by  
    • Recurrent Patterns in Patients With Nasopharyngeal Caricinoma and Risks Leading to Inaccurate Delineation in Marginal Failure in the Era of Intensity‐Modulated Radiotherapy
      Shu Zhang, Ni Zeng, Jiangping Yang, Jiaqi Han, Jinlan He, Baofeng Duan, Xiaoqiang Chen, Xiaofang Gou, Fubin Zhu, Huizhen Liu, Ming Zeng, Di Yan, Nianyong Chen
      Head & Neck.2025; 47(3): 917.     CrossRef
    • Efficacy and Failure Patterns Following Target Volume and Dose Reduction After Neoadjuvant Therapy in Locoregionally Advanced Head and Neck Squamous Cell Carcinoma
      Xiong Zhou, Zheng Wu, Zichen Qiu, Minchuan Lin, Yalan Tao, Yong Su
      Head & Neck.2025; 47(4): 1247.     CrossRef
    • Comparison of TPF and PF induction chemotherapy combined with cisplatin concurrent chemoradiotherapy for locoregionally advanced nasopharyngeal carcinoma: A systematic review and meta-analysis
      Haiwen Li, Qibiao Wu, Haiqing Luo, Jiayuan Wu, Wenmei Su, Lili Yu
      Medicine.2025; 104(3): e41278.     CrossRef
    • Reduced‐volume radiotherapy versus conventional‐volume radiotherapy after induction chemotherapy in nasopharyngeal carcinoma: An open‐label, noninferiority, multicenter, randomized phase 3 trial
      Ling‐Long Tang, Lin Chen, Gui‐Qiong Xu, Ning Zhang, Cheng‐Long Huang, Wen‐Fei Li, Yan‐Ping Mao, Guan‐Qun Zhou, Feng Lei, Lu‐Si Chen, Shao Hui Huang, Lei Chen, Yu‐Pei Chen, Yuan Zhang, Xu Liu, Cheng Xu, Yin Zhao, Ji‐Bin Li, Na Liu, Fang‐Yun Xie, Rui Guo, Y
      CA: A Cancer Journal for Clinicians.2025;[Epub]     CrossRef
    • Post‐induction lymph node delineation in nasopharyngeal cancer: A single‐center experience
      Sezin Yuce Sari, Ecem Yigit, Gozde Yazici, Ibrahim Halil Gullu, Sercan Aksoy, Gokhan Ozyigit, Mustafa Cengiz
      Head & Neck.2023; 45(3): 612.     CrossRef
    • Tumor volume reduction after induction chemotherapy with gemcitabine plus cisplatin in nasopharyngeal carcinoma
      Qian Chen, Liangfang Shen, Shan Li
      European Archives of Oto-Rhino-Laryngology.2023; 280(5): 2497.     CrossRef
    • Characteristics of local extension based on tumor distribution in nasopharyngeal carcinoma and proposed clinical target volume delineation
      Zheng Wu, Bin Qi, Fei-Fei Lin, Lin Zhang, Qian He, Fei-Ping Li, Hui Wang, Ya-Qian Han, Wen-Jing Yin
      Radiotherapy and Oncology.2023; 183: 109595.     CrossRef
    • Optimizing induction chemotherapy regimens for radiotherapy in patients with locoregionally advanced nasopharyngeal carcinoma
      Ying Li, Jianping Bi, Guoliang Pi, Hanping He, Yanping Li, Dandan Zheng, Zecheng Wei, Guang Han
      Cancer Medicine.2023; 12(8): 9449.     CrossRef
    • Lessons and Opportunities for Biomarker-Driven Radiation Personalization in Head and Neck Cancer
      Elham Rahimy, Michael F. Gensheimer, Beth Beadle, Quynh-Thu Le
      Seminars in Radiation Oncology.2023; 33(3): 336.     CrossRef
    • Concurrent chemoradiotherapy with or without neoadjuvant chemotherapy in pediatric patients with stage III-IVa nasopharyngeal carcinoma: a real-world propensity score-matched cohort study
      Ya-Nan Jin, Zhao-Hui Ruan, Wan-Wei Cao, Lin Yang, Wei Yao, Xiao-Feng Pei, Wang-Jian Zhang, Tia Marks, Ji-Jin Yao, Liang-Ping Xia
      Journal of Cancer Research and Clinical Oncology.2023; 149(13): 11929.     CrossRef
    • Failure patterns of locoregional recurrence after reducing target volumes in patients with nasopharyngeal carcinoma receiving adaptive replanning during intensity-modulated radiotherapy: a single-center experience in China
      Xiate Zhou, Jian Zhu, Chao Zhou, Wei Wang, Weijun Ding, Meng Chen, Kuifei Chen, Shuling Li, Xiaofeng Chen, Haihua Yang
      Radiation Oncology.2023;[Epub]     CrossRef
    • Clinical target volume design of postoperative intensity-modulated radiotherapy for major salivary gland tumours according to surgical principles: an innovative method
      Shaowen Lyu, Zheng Wu, Dehuan Xie, Zhiqing Long, Rui Zhong, Wang Lei, Wanqin Cheng, Jiang Hu, Xuekui Liu, Chuanmiao Xie, Yong Su
      Journal of Cancer Research and Clinical Oncology.2022; 148(4): 921.     CrossRef
    • Local control and failure patterns after intensity modulated radiotherapy with reduced target volume delineation after induction chemotherapy for patients with T4 nasopharyngeal carcinoma
      Fang-Fang Kong, Meng-Shan Ni, Rui-Ping Zhai, Hong-Mei Ying, Chao-Su Hu
      Translational Oncology.2022; 16: 101324.     CrossRef
    • Tumor factors associated with in‐field failure for nasopharyngeal carcinoma after intensity‐modulated radiotherapy
      Xixi Liu, Bian Wu, Jing Huang, You Qin, Zhanjie Zhang, Liangliang Shi, Xiaohua Hong, Qian Ding, Gang Peng, Kunyu Yang
      Head & Neck.2022; 44(4): 876.     CrossRef
    • Gemcitabine Versus Docetaxel Plus Cisplatin as Induction Chemotherapy in Nasopharyngeal Carcinoma
      Qian Chen, Shan Li
      The Laryngoscope.2022; 132(12): 2379.     CrossRef
    • Individualized clinical target volume delineation and efficacy analysis in unilateral nasopharyngeal carcinoma treated with intensity-modulated radiotherapy (IMRT): 10-year summary
      De-Huan Xie, Zheng Wu, Wang-Zhong Li, Wan-Qin Cheng, Ya-Lan Tao, Lei Wang, Shao-Wen Lv, Fei-Fei Lin, Nian-Ji Cui, Chong Zhao, Jun Ma, Shao-Min Huang, Tai-Xiang Lu, Ya-Qian Han, Yong Su
      Journal of Cancer Research and Clinical Oncology.2022; 148(8): 1931.     CrossRef
    • Volumetric modulated arc therapy versus tomotherapy for late T-stage nasopharyngeal carcinoma
      Qian Chen, Lingwei Tang, Zhe Zhu, Liangfang Shen, Shan Li
      Frontiers in Oncology.2022;[Epub]     CrossRef
    • Is a high-risk clinical target volume required? Evaluation of the dosimetric feasibility based on T staging
      Xingxing Yuan, Chao Yan, Shiyi Peng, Zhiping Chen, Tianzhu Lu, Qiaoying Gong, Yang Qiu, Wenming Xiong, Fenghua Ao, Guoqing Li, Jingao Li, Ziwei Tu
      Frontiers in Oncology.2022;[Epub]     CrossRef
    • Long-term results of the phase II dose and volume de-escalation trial for locoregionally advanced nasopharyngeal carcinoma
      Fen Xue, Dan Ou, Xiaomin Ou, Xin Zhou, Chaosu Hu, Xiayun He
      Oral Oncology.2022; 134: 106139.     CrossRef
    • Is Surgery an Inevitable Treatment for Advanced Salivary Lymphoepithelial Carcinoma? Three Case Reports
      Shaowen Lv, Dehuan Xie, Zheng Wu, Lei Wang, Yong Su
      Ear, Nose & Throat Journal.2021; 100(9): NP402.     CrossRef
    • The change in tumor volume after induction chemotherapy with docetaxel plus cisplatin in 259 nasopharyngeal carcinoma patients
      Shan Li, Liangfang Shen
      European Archives of Oto-Rhino-Laryngology.2021; 278(8): 3027.     CrossRef
    • Extensive pelvic and abdominal lymphadenopathy with hepatosplenomegaly treated with radiotherapy—A case report
      Sahil Mittal, ShaikhA Hussain, RahulV. C Tiwari, AjithB Poovathingal, BPadma Priya, Rishabh Bhanot, Heena Tiwari
      Journal of Family Medicine and Primary Care.2020; 9(2): 1215.     CrossRef
    • Nutritional outcomes after radiotherapy target volume reduction for nasopharyngeal cancer: a Phase III trial
      Li Xiang, Jin-Feng Rong, Hao-Wen Pang, Huai-Lin He, Yue Chen, Jing-Bo Wu, Yong-Sheng Wang
      Future Oncology.2020; 16(9): 427.     CrossRef
    • Quality of Life, Toxicity and Unmet Needs in Nasopharyngeal Cancer Survivors
      Lachlan McDowell, June Corry, Jolie Ringash, Danny Rischin
      Frontiers in Oncology.2020;[Epub]     CrossRef
    • Impact of tumor volume enlargement after induction chemotherapy on subsequent radiotherapy in locally advanced nasopharyngeal carcinoma: A propensity‐score matching analysis
      Shan Li, Liangfang Shen
      Cancer Medicine.2020; 9(23): 8832.     CrossRef
    • Target delineation and dose prescription of adaptive replanning intensity‐modulated radiotherapy for nasopharyngeal carcinoma
      Dehuan Xie, Wanqin Cheng, Shaowen Lv, Rui Zhong, Lei Wang, Jiang Hu, Mingli Wang, Shaomin Huang, Yong Su, Yunfei Xia
      Cancer Communications.2019; 39(1): 1.     CrossRef
    • Cisplatin/docetaxel/fluorouracil

      Reactions Weekly.2019; 1753(1): 113.     CrossRef
    • Chemotherapy Potentially Facilitates the Occurrence of Radiation Encephalopathy in Patients With Nasopharyngeal Carcinoma Following Radiotherapy: A Multiparametric Magnetic Resonance Imaging Study
      Youming Zhang, Xiaoping Yi, Jianming Gao, Li Li, Lizhi Liu, Ting Qiu, Jinlei Zhang, Yuanchao Zhang, Weihua Liao
      Frontiers in Oncology.2019;[Epub]     CrossRef

    • PubReader PubReader
    • ePub LinkePub Link
    • Cite
      CITE
      export Copy Download
      Close
      Download Citation
      Download a citation file in RIS format that can be imported by all major citation management software, including EndNote, ProCite, RefWorks, and Reference Manager.
      Format:
      • RIS — For EndNote, ProCite, RefWorks, and most other reference management software
      • BibTeX — For JabRef, BibDesk, and other BibTeX-specific software
      Include:
      • Citation for the content below
      Reduction of Target Volume and the Corresponding Dose for the Tumor Regression Field after Induction Chemotherapy in Locoregionally Advanced Nasopharyngeal Carcinoma
      Cancer Res Treat. 2019;51(2):685-695.   Published online August 13, 2018
      DOI: https://doi.org/10.4143/crt.2018.250
      Close
    • XML DownloadXML Download
    • 0
    • 1
    • 2
    Reduction of Target Volume and the Corresponding Dose for the Tumor Regression Field after Induction Chemotherapy in Locoregionally Advanced Nasopharyngeal Carcinoma
    Image Image Image
    Fig. 1. (A) In MRI before IC, the primary tumor located in the bilateral roof and left wall of nasopharynx, spread to bilateral middle nasal turbinate and bilateral pterygopalatine fossa anteriorly (green arrow), laterally extended to left petrous apex, left carotid canal and posteriorly to left clivus (white arrow). (B) In MRI after IC, the tumor obviously regressed. Tumor enhancement signal could only be seen in anterior roof of nasopharynx, bilateral choanae and bilateral pterygopalatine fossa (green arrow in B), delineated as GTVnx-residual. Signal of skull base bone destruction became unapparent (white arrow in B). Left petrous apex, left carotid canal and left clivus partially recovered in the bone window of computed tomography scan (white arrow in C), delineated as CTVnx1 and prescribed 60 Gy. (D) Red line, purple line, and blue line indicate GTVnxresidual, CTVnx1, and CTV2, respectively. (E) Dose color wash (60 Gy). Yellow line, pink line, green line, light yellow line, blue line, and light blue line (arrow) indicate PGTVnx-residual, GTVnx-pre, PCTVnx1, PCTV2, brain stem, and optic chiasm, respectively. (F) DVH. Orange line, green line, blue line, and red line indicate PGTVnx-residual, PCTVnx1, brain stem, and optic chiasm, respectively. MRI, magnetic resonance imaging; IC, induction chemotherapy; GTVnx, gross tumor volume of nasopharynx; CTV, clinical target volume; PGTV, planning target volume of GTV; PCTV, planning target volume of CTV; DVH, dose volume histogram.
    Fig. 2. (A) In MRI before IC, the tumor invaded ethmoidal cellules and orbital apex, with the right optic nerve suspiciously invaded (white arrow). The patient suffered with inflammation after wadding for nasopharynx bleeding (red arrow in A). (B, C) The tumor volume was reduced and no tumor signal was founded in MRI after IC (white arrow in B) and computed tomography after IC (white arrow in C) in the same slice as A. (D) Therefore, the tumor regressed region was outlined as CTVnx1, prescribed 60 Gy (pink line, CTVnx1; blue line, CTV2 in D). (E) Dose color wash (60 Gy). Orange line and red line indicate PCTVnx1 and optic chiasm, respectively. (F) DVH. Green line, red line, and blue line, indicated PCTVnx1, right optic nerve, and optic chiasm, respectively. MRI, magnetic resonance imaging; IC, induction chemotherapy; CTV, clinical target volume; PCTV, planning target volume of CTV; DVH, dose volume histogram.
    Fig. 3. (A) Kaplan-Meier estimates of locoregional-free survival (5-year LRFS, 87.7%; 95% confidence interval [CI], 82.6 to 92.7). (B) Kaplan-Meier estimates of distant metastasis-free survival (5-year DMFS, 85.8%; 95% CI, 80.3 to 91.4). (C) KaplanMeier estimates of progression-free survival (5-year PFS, 80.3%; 95% CI, 73.0 to 87.6). (D) Kaplan-Meier estimates of overall survival (5-year OS, 82.2%; 95% CI, 75.9 to 88.5).

    Fig. 1.

    Fig. 2.

    Fig. 3.

    Reduction of Target Volume and the Corresponding Dose for the Tumor Regression Field after Induction Chemotherapy in Locoregionally Advanced Nasopharyngeal Carcinoma
    Target volume Definition PTV Prescribed dose (Gy)
    GTVnx-pre The primary tumor before IC (including retropharyngeal lymph node metastasis) - -
    GTVnd-pre The neck lymph node metastasis before IC - -
    GTVnx-residual The residual primary tumor after IC (including retropharyngeal lymph node metastasis) PGTVnx-residual 68
    GTVnd-residual The residual GTVnd-pre after IC PGTVnd-residual 62-66
    CTVnx1 GTVnx-residual plus 1 cm margin, covering the region of GTVnx-pre PCTVnx1 60
    CTVnd1 GTVnd-residual plus 0.5-1 cm margin, covering the region of GTVnd-pre PCTVnd1 60
    CTV2 CTVnx1 and CTVnd1 plus a 5 mm margin together with the bilateral cervical selective lymph drainage areas PCTV2 50
    Characteristic No. of patients (%)
    Age, median (range, yr) 44 (26-65)
    Sex
     Male 47 (82.5)
     Female 10 (17.5)
    Clinical stage
     III 26 (45.6)
     IV 31 (54.4)
    T category
     T1 0
     T2 8 (14.0)
     T3 23 (40.4)
     T4 26 (45.6)
    N category
     N0 0
     N1 15 (26.3)
     N2 36 (63.2)
    Target volume Pre-IC (cm3) Post-IC (cm3) p-value Tumor shrinkage (%)
    GTVnx 63.7±45.6 21.8±23.7 < 0.01 66.5
    GTVnd 21.7±21.8 7.5±9.4 < 0.01 68.0
    GTV 85.4±51.0 29.3±26.6 < 0.01 67.2
    Patient No. T N AJCC IC CCT Tumor volume before IC (cm3)
    		 Tumor volume after IC (cm3)
    		 Failure site Patterns of failure TR (mo) Isodose level (Gy)
    GTVnx -pre GTVnd -pre-L GTVnd -pre-R GTVnx-residual GTVnd-residual-L GTVnd-residual-R
    1 4 2 IVA TPF*3 Cis*4 94.66 25.05 11.65 63.92 11.82 3.94 S. NP. In field 12 71
    L. NC. 70
    L. Level II LN 65
    2 2 2 III TPF*3 Cis*3 38.51 37.45 4.49 6.96 1.50 3.80 L. Level II LN In field 15 63.5
    3 3 2 III TPF*4 Cis*4 24.70 9.00 2.70 5.60 0.00 0.00 L. RPN In field 24 66.2
    4 3 2 III TPF*3 Cis*4 23.58 0.98 46.61 10.77 0.00 26.18 R. Level II, III, IV LN In field 33 65
    Table 1. Definitions and prescribed dose of target volumes

    Illustrations: the GTVnx-pre and GTVnd-pre were the tumor volumes before induction chemotherapy (IC) with no prescribed dose for planning.

    Table 2. Characteristics of the 57 NPC patients

    NPC, nasopharyngeal carcinoma.

    Table 3. Comparison of tumor volume before and after IC

    IC, induction chemotherapy; GTV, gross tumor volume of nasopharynx (GTVnx)+gross tumor volume of cervical lymph node (GTVnd).

    Table 4. Clinical characteristics and patterns of locoregional failure of four patients

    AJCC, American Joint Committee on Cancer; IC, induction chemotherapy; CCT, concurrent chemotherapy; GTVnx, gross tumor volume of nasopharynx; GTVnd, gross tumor volume of cervical lymph node; TR, time to relapse; TPF, a combination of taxanes, cisplatin and fluorouracil; Cis, cisplatin; S., superior; NP., nasopharynx; L., left; NC., nasal cavity; LN, lymph node; RPN, retropharyngeal lymph node; R., right.

    Table 1.

    Table 2.

    Table 3.

    Table 4.

    Cancer Res Treat : Cancer Research and Treatment
    © Korean Cancer Association.
    Close layer
    TOP