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Target volume delineation for radical radiotherapy of early oesophageal carcinoma in elderly patients
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Target volume delineation for radical radiotherapy of early oesophageal carcinoma in elderly patients Délinéations du volume cible pour la radiothérapie radicale de cancer localisé de l’œsophage chez des patients âgés J. Su ∗ , S. Zhu , Z. Liu , Y. Zhao , C. Song Department of Radiation Oncology, Fourth Hospital of Hebei Medical University, Shijiazhuang 050011, China
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Article history: Received 22 January 2016 Received in revised form 22 July 2016 Accepted 3 August 2016 Keywords: Oesophageal neoplasm Radiotherapy Early stage Elderly patients Elective nodal prophylactic irradiation Involved-field irradiation Prognosis
a b s t r a c t Purpose. – To compare the prognosis of elderly patients with early oesophageal carcinoma between radical elective nodal prophylactic irradiation and involved-field irradiation and to estimate the failure modes and adverse effects, then to provide the patients the safe and individual therapeutic regimens. Material and methods. – The charts of 96 patients aged 65 and over with early stage oesophageal carcinoma receiving radical radiotherapy in our department were retrospectively analysed. Of all the patients, 49 received elective nodal prophylactic irradiation and the other 47 received involved-field irradiation. After completion of the whole treatment, we analysed short-term effects, tumour local control, overall survival of the patients, failure modes and adverse effects. Results. – The 1-, 3-, and 5-year local control rate in elective nodal irradiation and involved-field irradiation groups were 80.6%, 57.4%, 54.0% and 65.4%, 46.5%, 30.5% respectively, and the difference was statistically significant (2 = 4.478, P = 0.03). The differences of overall survival and progression-free survival were not significant (P > 0.05). The difference of 1-, 3-, and 5-years local regional failure rate was statistically significant between elective nodal prophylactic irradiation and involved-field irradiation groups, except for the overall failure and distant metastasis rates. The overall incidence of radiation-induced oesophagitis after elective nodal irradiation or involved-field irradiation was 79.6% and 59.6%, and the difference was statistically significant (2 = 4.559, P = 0.03). The difference of radiation pneumonitis between elective nodal prophylactic irradiation and involved-field irradiation was not significant (12.2% vs 14.9%; 2 = 0.144, P = 0.7). Conclusion. – For elderly patients with early stage oesophageal carcinoma receiving radical radiotherapy, although elective nodal prophylactic irradiation could increase the incidence of radiation-induced oesophagitis, patients could tolerate the treatment and benefit from local control. ´ e´ franc¸aise de radiotherapie ´ oncologique (SFRO). Published by Elsevier Masson SAS. All © 2016 Societ rights reserved.
r é s u m é Mots clés : Cancer de l’œsophage Radiothérapie Stade précoce Patients âgés Irradiation prophylactique ganglionnaire élective Irradiation des seuls territoires ganglionnaires initialement atteints Pronostic
Objectifs de l’étude. – Comparer chez des patients âgés le pronostic d’un cancer de l’œsophage localisé traité par irradiation prophylactique ganglionnaire élective radicale ou par irradiation des seuls territoires ganglionnaires initialement atteints et estimer les modes d’échec et les effets indésirables, puis de proposer aux patients des protocoles individualisés sûrs. Matériel et méthodes. – Les dossiers de 86 patients âgés de 65 ans et plus atteints d’un carcinome œsophagien localisé ayant rec¸u une radiothérapie radicale dans notre département ont été analysés. De tous les patients, 49 ont rec¸u une irradiation prophylactique ganglionnaire élective radicale, et les 47 autres une irradiation des seuls territoires ganglionnaires initialement atteints. Après l’achèvement de l’ensemble du traitement, l’objectif de l’étude était d’analyser l’effet à court terme du traitement, le contrôle local, la survie globale, les échecs et les effets indésirables.
∗ Corresponding author. E-mail address: [email protected] (J. Su). http://dx.doi.org/10.1016/j.canrad.2016.08.129 ´ e´ franc¸aise de radiotherapie ´ 1278-3218/© 2016 Societ oncologique (SFRO). Published by Elsevier Masson SAS. All rights reserved.
Please cite this article in press as: Su J, et al. Target volume delineation for radical radiotherapy of early oesophageal carcinoma in elderly patients. Cancer Radiother (2016), http://dx.doi.org/10.1016/j.canrad.2016.08.129
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Résultats. – Les taux de contrôle local 1, 3 et 5 ans dans les deux groupes étaient respectivement de 80,6 %, 57,4 %, 54,0 % et 65,4 %, 46,5 %, 30,5 %, et la différence était statistiquement significative (2 = 4,478, p = 0,03). Les différences de survie globale et de survie sans progression n’étaient pas significatives (p > 0,05). La différence à 1, 3 et 5 ans de taux d’échec locorégional était statistiquement significative entre les deux groupes ; à l’exception du taux d’échec global et de celui de dissémination métastatique à distance. Les incidences globales de l’œsophagite induite par la radiothérapie étaient respectivement de 79,6 % et 59,6 %, et la différence était statistiquement significative (2 = 4,559, p = 0,03). Il n’y avait pas de différence en termes de pneumopathie radique (12,2 % contre 14,9 % ; 2 = 0,144, p = 0,7). Conclusion. – Pour les patients âgés atteints d’un carcinome œsophagien localisé irradié radicalement, bien que l’irradiation prophylactique ganglionnaire élective radicale pourrait augmenter l’incidence d’œsophagite induite par la radiothérapie, les patients pouvaient tolérer le traitement et en bénéficier en termes de taux de contrôle local. ´ e´ franc¸aise de radiotherapie ´ oncologique (SFRO). Publie´ par Elsevier Masson SAS. Tous © 2016 Societ ´ ´ droits reserv es.
1. Introduction Although the development of radiotherapy of oesophageal carcinoma has led to significant increase in patient survival, regional failure is the main cause of failure after radiotherapy and there is still controversy in the design of radiation treatment plan, especially the target volume delineation for patients receiving radical radiotherapy. Our previous study showed that elective nodal prophylactic irradiation of early stage oesophageal carcinoma treated by radical irradiation could reduce locoregional failure and increase local control rate, then to improve the long-term survival [1]. However, elderly patients are special because they have poor general status, increased occurrence of chronic disease and overall decreased tolerance to high-intensity therapies. The median age at diagnosis of oesophageal carcinoma is 68 years old and there are 61% of patients over the age of 65, 33% over the age of 75 and 8% over the age of 85 [2]. In order to investigate if elderly patients can achieve good control and tolerate the side effects of the elective nodal prophylactic irradiation, we retrospectively analysed the clinical data of 96 elderly patients with early stage oesophageal carcinoma receiving radical radiotherapy and compared the locoregional control, overall survival, the failure modes and the side effects between the patients receiving elective nodal irradiation and involved-field irradiation. 2. Materials and methods 2.1. Patients From January 2006 to December 2011, 96 elderly patients with median age of 73 (range 65–82 years) with early stage oesophageal carcinoma (T1–3 N0–1 M0 ) received radical radiotherapy in our department. The Karnosky performance scores of all patients were greater than 70. All patients had histologically or cytologically confirmed oesophageal carcinoma. There were 90 squamous cell carcinomas and six non-squamous cell carcinomas. There were 60 male and 36 female patients. In all 96 cases, it included 20 cervical and upper thoracic segments oesophageal carcinoma, 54 middle thoracic segments oesophageal carcinoma and 22 lower thoracic segments oesophageal carcinoma. The patients’ general condition was evaluated according to the Eastern Cooperative Oncology Group (ECOG) performance status criteria and patients with performance status at least 4 were excluded from the study. Before treatment, all patients had undergone numerous examinations, including history and physical examination, computed tomography (CT) or magnetic resonance imaging (MRI) of the head, chest and upper abdomen, radionuclide bone scan or positron emission tomography (PET). According to the 6th edition of clinical
staging criteria of oesophageal carcinoma in 2002, 41 patients had clinical stage I and 55 stage II lesions. 2.2. Chemoradiotherapy All patients underwent 3-dimensional conformal radiotherapy or intensity-modulated radiation therapy delivered by 6 MV linear accelerators. Thirty-five elderly patients (out of 96) received 5-fluorouracil and cisplatin chemoradiotherapy, among which 12 patients received concurrent treatment consisting of two cycles during week one and six of radiotherapy, the other 23 received sequential treatment cycles of chemotherapy after radiotherapy. Among the 35 patients, 22 received two to four cycles of chemotherapy, the other 13 received six cycles. Statistical analysis of the clinical characteristics between two groups (elective nodal prophylactic or involved-field irradiation) showed that there was no significant difference except for the tumour site (Table 1). 2.3. Treatment plan and delivery According to the target volume delineation, 49 patients received elective nodal prophylactic irradiation (15 for 3-dimensional conformal radiotherapy and 34 for intensity-modulated radiation therapy), and 47 others received involved-field irradiation (16 for 3-dimensional conformal radiotherapy and 31 for intensitymodulated radiation therapy) (Table 1). Radiotherapy treatment planning was determined using 64 multidetector row spiral CT scanner. After administration of intravenous contrast agents, 3 mm CT images were obtained, including primary tumour, lymph node areas, lungs and upper abdomen. Lymph nodes with a diameter of 10 mm or more were considered to be pathological, as well as round, hypodense lymph nodes measuring more than 5 mm. All CT images were reviewed by two experienced radiologists, and the tumour volume was defined by an experienced radiation oncologist. 2.3.1. Target volume delineation/involved-field irradiation delineation The gross tumour volume (GTV) contained the primary oesophageal tumour. The clinical target volume (CTV) was obtained by adding a 0.5–1.0 cm margin in axial direction and a 1.5–2.0 cm margin in cranial–caudal direction to the primary tumour. The planning target volume (PTV) was generated by expanding the CTV with 0.5–0.8 cm margin. The gross tumour volume of lymph node (GTVnd ) included the pathologic lymph nodes. The clinical target volume of lymph node (CTVnd ) was obtained by adding a 0.5 cm margin around the pathologic lymph nodes. The planning target volume of lymph node (PTVnd ) was generated by
Please cite this article in press as: Su J, et al. Target volume delineation for radical radiotherapy of early oesophageal carcinoma in elderly patients. Cancer Radiother (2016), http://dx.doi.org/10.1016/j.canrad.2016.08.129
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Table 1 Radical radiotherapy of early oesophageal carcinoma in elderly patients: Comparison of clinical characteristics between two therapeutic regimens, elective nodal prophylactic irradiation and involved-field irradiation. Clinical characteristics Gender Male Female Performance status 0–1 ≥2 Tumour site Cervical and upper thoracic Middle thoracic Lower thoracic X ray based lesion length ≤4.5 cm >4.5 cm Diameter of the maximum level by CT ≤3.5 cm >3.5 cm Gross tumour volume ≤30 cm3 >30 cm3 T stage T1 + 2 T3 N stage N0 N1 TNM stage I II Chemotherapy No Yes Radiotherapy technique 3-dimensional conformal radiotherapy Intensity-modulated radiation therapy
Elective nodal prophylactic irradiation
Involved-field irradiation
34 15
26 21
19 30
20 27
15 27 7
5 27 15
26 23
20 27
33 16
34 13
41 8
39 8
32 17
26 21
32 17
32 15
23 26
18 29
31 18
30 17
15 34
16 31
expanding the CTVnd with 0.5–0.8 cm margin. At least 95% of the volume of PTV and PTVnd received 56–66 Gy (1.8–2.0 Gy/fraction, one fraction/day, five times a week). 2.3.2. Elective nodal prophylactic irradiation delineation The clinical target volume of elective nodal irradiation was defined as CTV1 , which contained the lymphatic drainage area according to the reference standards [3]. When the primary tumour was located at cervical or upper thoracic oesophagus, CTV1 contained bilateral supraclavicular, adjacent oesophagus, and regions 2, 4, 5 and 7. When the primary lesion was located at middle thoracic oesophagus, CTV1 contained lymphatic drainage area of adjacent oesophagus, regions 2, 4, 5 and 7. For the lower thoracic oesophageal carcinoma, CTV1 contained adjacent oesophagus, region 4, 5, and 7, left gastric and paracardial lymph drainage area. The planning target volume of elective nodal irradiation was defined as PTV1 , which was obtained by expanding the CTV1 with 0.5–1.0 cm margin. At least 95% of the volume of PTV1 received 46–52.2 Gy, and the prescribed dose of primary tumour and involved lymph nodes was boosted to 56–66 Gy in the late course (1.8–2.0 Gy/fraction, one fraction/day, five times a week). Organs at risk, such as lungs, heart and spinal cord, were contoured on CT images. Mean lung dose was less than 20 Gy, and V5 (the volume of both lungs receiving 5 Gy) was less than 55%, V20 less than 25%, V30 less than 18%. V30 of heart (the volume of heart receiving 30 Gy) was less than 50%, and V40 less than 30%. Dmax (the maximum dose) of spinal cord was less than 45 Gy. 2.4. Evaluation index after treatment After completion of whole treatment, the examinations described above were performed again in order to compare the
2
P value
2.026
0.2
0.142
0.7
7.871
0.02
1.061
0.3
0.284
0.6
0.008
0.9
1.001
0.3
0.083
0.8
0.732
0.4
0.003
0.9
0.129
0.7
size of primary tumour and nodes to analyse the patients’ therapy effects. Immediate effect was evaluated according to the World Health Organization (WHO) standard criteria [4]. Local control rate, overall survival rate and progression-free survival rate were estimated and compared between the elective nodal prophylactic irradiation and involved-field irradiation groups. Local failure included oesophageal or regional lymph node failure over 6 months after radiotherapy. Distant metastases included distant organ metastases or out-of-regional lymph node metastases. The overall failure included local regional failure and distance metastases. Acute adverse effects of radiation to lungs and oesophagus were graded according to the Radiation Therapy Oncology Group (RTOG). 2.5. Statistical analysis The statistics for local control, overall survival, progression-free survival, overall failure, local regional failure and distant metastases were estimated by Kaplan-Meier method, and the differences between the groups were tested by Log-rank method. The enumeration data were analysed by 2 method. 3. Results 3.1. Follow-up and overall treatment effects The median follow-up time was 38 months (range, 16.8–105 months). The follow-up rate was 97.9% (94/96). After completion of the treatment, 36 patients achieved complete response (21 in elective nodal prophylactic irradiation vs 15 in involved-field irradiation), and the other 60 patients achieved partial response (28 in elective nodal prophylactic irradiation vs 32
Please cite this article in press as: Su J, et al. Target volume delineation for radical radiotherapy of early oesophageal carcinoma in elderly patients. Cancer Radiother (2016), http://dx.doi.org/10.1016/j.canrad.2016.08.129
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80%
Table 2 Radical radiotherapy of early oesophageal carcinoma in elderly patients: comparison of therapeutic effects between two regimens, elective nodal prophylactic irradiation or involved-field irradiation.
Response rate
70% 60%
Elective nodal prophylactic irradiation (%)
50% 40% 30% 20% 10% 0% Complete response
Partial reponse
Fig. 1. Radical radiotherapy of early oesophageal carcinoma in elderly patients: comparison of short-term effects of elective nodal prophylactic or involved-field irradiation. White bars: elective nodal prophylactic irradiation group; black bars: involved-field irradiation group (2 = 1.226, P = 0.3).
Overall failure 1-yr 23.8 58.0 3-yr 63.0 5-yr Local regional failure 1-yr 19.4 3-yr 42.6 46.0 5-yr Distant metastases 1-yr 11.0 29.7 3-yr 43.8 5-yr
Involved-field irradiation (%)
2
P
2.329
0.1
4.478
0.03
0.156
0.7
44.7 64.2 76.5 34.6 53.5 69.5 24.0 36.5 36.5
in involved-field irradiation). The 1-, 3-, and 5-year local controls of all patients were 70.9%, 52.1% and 37.8%. For all patients, the 1-, 3-, and 5-year overall and progression-free survival rates were 69.3%, 37.6%, 29.8% and 70.9%, 52.1%, 37.8%, respectively.
(Table 2). For the elective nodal prophylactic irradiation group, four patients developed in-field failure, one was oesophageal failure and the other three were regional lymph nodes failure. For the involvedfield irradiation group, three patients developed out-of-field failure and two in-field failure.
3.2. Comparison of treatment effects between elective nodal prophylactic irradiation and involved-field irradiation groups
3.4. Adverse effects of radiotherapy
The difference of the immediate response rate between elective nodal prophylactic irradiation and involved-field irradiation group was not statistically significant (2 = 1.226, P = 0.3; Fig. 1). The 1-, 3, and 5-year local control in elective nodal prophylactic irradiation and involved-field irradiation groups were 80.6%, 57.4%, 54.0% and 65.4%, 46.5%, 30.5% respectively, and the difference was statistically significant (2 = 4.478, P = 0.03; Fig. 2). However, the differences of overall and progression-free survival rates were not significant (2 = 2.619, P = 0.1; 2 = 1.242, P = 0.3; Fig. 2B and C) between the two groups. In order to make sure if the other factors influence the results, we did further study. For patients with N0 stage, the 1-, 3-, and 5-year local control in elective nodal prophylactic irradiation and involved-field irradiation groups were 89.5%, 62.6%, 43.2% and 56.3%, 49.8%, 29.4% respectively, and the difference was statistically significant (P = 0.04). However, the difference of overall and progression-free survival rates between the two groups was not significant (P > 0.05). For patients with N1 stage, the difference of local control, overall and progression-free survival rates between elective nodal prophylactic irradiation and involved-field irradiation groups was not significant (P > 0.05). And for the tumour site, further stratification analysis showed that the difference of local control, overall and progression-free survival between elective nodal prophylactic irradiation and involved-field irradiation groups was not significant either (P > 0.05). 3.3. Analysis of failure modes After treatment, 59 patients developed failure, including 27 patients in elective nodal prophylactic irradiation group and 32 in involved-field irradiation group. In the elective nodal prophylactic irradiation group, 13 patients developed local regional failure, nine distant metastases and five both local failure and distant metastases. In the involved-field irradiation group, the number of patients developing local failure, metastases, or both of them was 18, five and nine respectively. The difference of 1-, 3-, and 5-years of local regional failure rate was statistically significant between elective nodal prophylactic irradiation and involved-field irradiation group except for the overall failure rate and distant metastasis rate
The overall incidence of radiation-induced acute oesophagitis in elective nodal prophylactic irradiation and involved-field irradiation were 79.6% and 59.6%, and the difference was statistically significant (2 = 4.559, P = 0.03). In the elective nodal prophylactic irradiation and involved-field irradiation groups, there were 25, 13 and 14, 13 patients developed grade 1 and 2 acute oesophagitis respectively. Although one patient in each group had grade 3 oesophagitis, the patients could tolerate further therapy and did not stop the treatment. No worse cases of oesophageal toxicity were seen. The difference of acute radiation pneumonitis between elective nodal prophylactic irradiation and involved-field irradiation was not significant (12.2% vs 14.9%; 2 = 0.144, P = 0.7). In elective nodal prophylactic irradiation and involved-field irradiation groups, there were three, three and two, five patients developed grade 1 and 2 pneumonitis respectively. No patients suffered from grade 3–4 pneumonitis. 4. Discussion Although some studies have demonstrated that patients with oesophageal carcinoma could achieve local control and survival benefits from three-field lymphadenectomy, there were still some early stage patients who cannot accept the radical resection because of old age and medical problems [5,6]. Moreover, some studies found that the 5-year survival rate was similar between patients with same stage oesophageal carcinoma receiving radical operation and radical radiotherapy [7–9]. Therefore, radical radiotherapy plays an important role in the management of patients with oesophageal carcinoma. Patients aged 65 and over are a special group because of the poor status and medical complications. In the past, elderly patients with oesophageal carcinoma only received palliative treatment in consideration of a short life expectancy, poor prognosis and comorbidities. With the lengthening of life expectancy, elderly patients with oesophageal carcinoma became an important group. Some studies have shown that for patients with oesophageal carcinoma receiving chemoradiotherapy, age was not a significant influence factor of prognosis and did not increase the frequency of
Please cite this article in press as: Su J, et al. Target volume delineation for radical radiotherapy of early oesophageal carcinoma in elderly patients. Cancer Radiother (2016), http://dx.doi.org/10.1016/j.canrad.2016.08.129
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Fig. 2. Radical radiotherapy of early oesophageal carcinoma in elderly patients: comparison of local control, overall and progression-free survival rates between elective nodal prophylactic and involved-field irradiation. A. The local control rate of elective nodal prophylactic irradiation was higher than that of involved-field irradiation (P = 0.03). B. and C. There was no significant difference of overall survival and progression-free survival between elective nodal prophylactic irradiation and involved-field irradiation (P > 0.05); blue line: elective nodal prophylactic irradiation group; green line: involved-field irradiation group.
adverse events [10,11]. Our previous study showed that patients with early stage oesophageal carcinoma receiving radical radiotherapy could achieve the benefits of local control and long-term survival from elective nodal prophylactic irradiation [1]. Zhang et al. reported that local control rate, 3-year survival rate, and recurrence and metastasis-free survival rate of patients in clinical stage II and III receiving extensive regional field irradiation were statistically higher than those of patients receiving conventional field irradiation [12]. In our study, all of 96 patients with oesophageal carcinoma were aged 65 or over and in clinical stage I and II. It was shown that the 1-, 3- and 5-year local control rate of elective nodal prophylactic irradiation group was statistically higher than that of involved-field irradiation group (Fig. 2A) and elective nodal prophylactic irradiation could reduce local regional failure significantly (P = 0.03). Although the differences of overall and progression-free survival rates between elective nodal prophylactic irradiation and involved-field irradiation were not statistically significant, the 1-, 3- and 5-year overall and progression-free survival rates of elective nodal prophylactic irradiation were higher than those of involved-field irradiation. All of these indicated that elective nodal prophylactic irradiation maybe could offer benefits to elderly patients with early stage oesophageal carcinoma.
Zhao et al. analysed the data from 53 patients with oesophageal squamous cell carcinoma who received 3-dimensional conformal radiotherapy and only the primary tumour and positive lymph nodes were irradiated [13]. The results indicated that the omission of elective nodal irradiation was not associated with significant failure in lymph node regions not included in the planning target volume. Local failure and distant metastases remained the predominant problems. In our study, for the elective nodal prophylactic irradiation group, four patients developed in-field failure, one was oesophageal failure and the other three were regional lymph nodes failure. For the involved-field irradiation group, three patients developed out-of-field failure and two in-field failure. The patients in this study were all 65 years old and over, therefore, the treatment tolerance was a crucial issue. Several studies showed that chemoradiotherapy was a tolerable treatment in elderly patients with oesophageal carcinoma, so the elderly patients should not be excluded from potentially curative treatment based on age alone [10,14,15]. In order to make sure whether elective nodal prophylactic irradiation would increase the incidence of radiation-induced adverse effects because of the larger volume of irradiation, we compared radiation-induced
Please cite this article in press as: Su J, et al. Target volume delineation for radical radiotherapy of early oesophageal carcinoma in elderly patients. Cancer Radiother (2016), http://dx.doi.org/10.1016/j.canrad.2016.08.129
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oesophagitis and pneumonitis between elective nodal prophylactic irradiation and involved-field irradiation groups. It showed that the overall incidence of radiation-induced oesophagitis in the elective nodal prophylactic irradiation group was significantly higher than that in the involved-field irradiation group (P = 0.03), but one patient in each group had grade 3 oesophagitis, and the other 38 and 27 patients developed grade 1 or 2 oesophagitis respectively. The difference of radiation pneumonitis between elective nodal prophylactic irradiation and involved-field irradiation was not significant. Patients could tolerate further therapy and did not stop the treatment. In conclusion, for elderly patients with early stage oesophageal carcinoma receiving radical radiation, although elective nodal prophylactic irradiation increased the incidence of radiation-induced oesophagitis, it could be tolerable and could reduce local regional failure and increase local control rate, as well as improve long-term survival. Disclosure of interest The authors declare that they have no competing interest. References [1] Zhu S, Dong H, Liu Z, Shen W, Li J, Su J, et al. Comparative study of different irradiation ranges in radical radiotherapy for early-stage esophageal cancer. Chin J Radiat Oncol 2015;24:615–8. [2] National Cancer Institute. SEER cancer statistics review 1975–2006. Bethesad, MD: National Cancer Institute; 2009 [database on the Internet, available from: http://seer.cancer.gov/csr/1975-2006/]. [3] Yin W, Yu Z, Xu G, Yimin H. Radiation oncology. 4th edition Beijing: Pecking Union Medical College Press; 2008. p. 546–7 [M].
[4] Tomatis L, Aitio A, Day N, Heseltine E, Kaldor J, Miller A, et al. Cancer: causes, occurrence and control. IARC Sci Publ 1990;100:1–352. [5] Nakagawa S, Kanda T, Kosugi S, Ohashi M, Suzuki T, Hatakeyama K. Recurrence pattern of squamous cell carcinoma of the thoracic esophagus after extended radical esophagectomy with three-field lymphadenectomy. J Am Coll Surg 2004;198:205–11. [6] Li H, Zhang Y, Cai H, Xiang J. Pattern of lymph node metastases in patients with squamous cell carcinoma of the thoracic esophagus who underwent three-field lymphadenectomy. Eur Surg Res 2007;39:1–6. [7] Sun XD, Yu JM, Fan XL, Ren RM, Li MH, Zhang GL. Randomized clinical study of surgery versus radiotherapy alone in the treatment of resectable esophageal cancer in the chest. Zhonghua Zhong Liu Za Zhi 2006;28:784–7. [8] Yamamoto S, Ishihara R, Motoori M, Kawaguchi Y, Uedo N, Takeuchi Y, et al. Comparison between definitive chemoradiotherapy and esophagectomy in patients with clinical stage I esophageal squamous cell carcinoma. Am J Gastroenterol 2011;106:1048–54. [9] Motoori M, Yano M, Ishihara R, Yamamoto S, Kawaguchi Y, Tanaka K, et al. Comparison between radical esophagectomy and definitive chemoradiotherapy in patients with clinical T1bN0M0 esophageal cancer. Ann Surg Oncol 2012;19:2135–41. [10] Tougeron D, Di Fiore F, Thureau S, Berbera N, Iwanicki-Caron I, Hamidou J, et al. Safety and outcome of definitive chemoradiotherapy in elderly patients with oesophageal cancer. Br J Cancer 2008;99:1586–92. [11] Uno T, Isobe K, Kawakami H, Ueno N, Kobayashi H, Shimada H, et al. Efficacy and toxicities of concurrent chemoradiation for elderly patients with esophageal cancer. Anticancer Res 2004;24:2483–6. [12] Zhang P, Xie CY, Wu SX. Concurrent chemoradiation with paclitaxel and platinum for locally advanced esophageal cancer. Chin J Oncol 2007;29: 773–7. [13] Zhao KL, Ma JB, Liu G, Wu KL, Shi XH, Jiang GL. Three-dimensional conformal radiation therapy for esophageal squamous cell carcinoma: is elective nodal irradiation necessary? Int J Radiat Oncol Biol Phys 2010;76:446–51. [14] Anderson SE, Minsky BD, Bains M, Hummer A, Kelsen D, Ilson DH. Combined modality chemoradiation in elderly oesophageal cancer patients. Br J Cancer 2007;96:1823–7. [15] Li X, Zhao LJ, Liu NB, Zhang WC, Pang QS, Wang P, et al. Feasibility and efficacy of concurrent chemoradiotherapy in elderly patients with esophageal squamous cell carcinoma: a respective study of 116 cases from a single institution. Asian Pac J Cancer Prev 2015;16:1463–9.
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Original article
Target volume delineation for radical radiotherapy of early oesophageal carcinoma in elderly patients Délinéations du volume cible pour la radiothérapie radicale de cancer localisé de l’œsophage chez des patients âgés J. Su ∗ , S. Zhu , Z. Liu , Y. Zhao , C. Song Department of Radiation Oncology, Fourth Hospital of Hebei Medical University, Shijiazhuang 050011, China
a r t i c l e
i n f o
Article history: Received 22 January 2016 Received in revised form 22 July 2016 Accepted 3 August 2016 Keywords: Oesophageal neoplasm Radiotherapy Early stage Elderly patients Elective nodal prophylactic irradiation Involved-field irradiation Prognosis
a b s t r a c t Purpose. – To compare the prognosis of elderly patients with early oesophageal carcinoma between radical elective nodal prophylactic irradiation and involved-field irradiation and to estimate the failure modes and adverse effects, then to provide the patients the safe and individual therapeutic regimens. Material and methods. – The charts of 96 patients aged 65 and over with early stage oesophageal carcinoma receiving radical radiotherapy in our department were retrospectively analysed. Of all the patients, 49 received elective nodal prophylactic irradiation and the other 47 received involved-field irradiation. After completion of the whole treatment, we analysed short-term effects, tumour local control, overall survival of the patients, failure modes and adverse effects. Results. – The 1-, 3-, and 5-year local control rate in elective nodal irradiation and involved-field irradiation groups were 80.6%, 57.4%, 54.0% and 65.4%, 46.5%, 30.5% respectively, and the difference was statistically significant (2 = 4.478, P = 0.03). The differences of overall survival and progression-free survival were not significant (P > 0.05). The difference of 1-, 3-, and 5-years local regional failure rate was statistically significant between elective nodal prophylactic irradiation and involved-field irradiation groups, except for the overall failure and distant metastasis rates. The overall incidence of radiation-induced oesophagitis after elective nodal irradiation or involved-field irradiation was 79.6% and 59.6%, and the difference was statistically significant (2 = 4.559, P = 0.03). The difference of radiation pneumonitis between elective nodal prophylactic irradiation and involved-field irradiation was not significant (12.2% vs 14.9%; 2 = 0.144, P = 0.7). Conclusion. – For elderly patients with early stage oesophageal carcinoma receiving radical radiotherapy, although elective nodal prophylactic irradiation could increase the incidence of radiation-induced oesophagitis, patients could tolerate the treatment and benefit from local control. ´ e´ franc¸aise de radiotherapie ´ oncologique (SFRO). Published by Elsevier Masson SAS. All © 2016 Societ rights reserved.
r é s u m é Mots clés : Cancer de l’œsophage Radiothérapie Stade précoce Patients âgés Irradiation prophylactique ganglionnaire élective Irradiation des seuls territoires ganglionnaires initialement atteints Pronostic
Objectifs de l’étude. – Comparer chez des patients âgés le pronostic d’un cancer de l’œsophage localisé traité par irradiation prophylactique ganglionnaire élective radicale ou par irradiation des seuls territoires ganglionnaires initialement atteints et estimer les modes d’échec et les effets indésirables, puis de proposer aux patients des protocoles individualisés sûrs. Matériel et méthodes. – Les dossiers de 86 patients âgés de 65 ans et plus atteints d’un carcinome œsophagien localisé ayant rec¸u une radiothérapie radicale dans notre département ont été analysés. De tous les patients, 49 ont rec¸u une irradiation prophylactique ganglionnaire élective radicale, et les 47 autres une irradiation des seuls territoires ganglionnaires initialement atteints. Après l’achèvement de l’ensemble du traitement, l’objectif de l’étude était d’analyser l’effet à court terme du traitement, le contrôle local, la survie globale, les échecs et les effets indésirables.
∗ Corresponding author. E-mail address: [email protected] (J. Su). http://dx.doi.org/10.1016/j.canrad.2016.08.129 ´ e´ franc¸aise de radiotherapie ´ 1278-3218/© 2016 Societ oncologique (SFRO). Published by Elsevier Masson SAS. All rights reserved.
Please cite this article in press as: Su J, et al. Target volume delineation for radical radiotherapy of early oesophageal carcinoma in elderly patients. Cancer Radiother (2016), http://dx.doi.org/10.1016/j.canrad.2016.08.129
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Résultats. – Les taux de contrôle local 1, 3 et 5 ans dans les deux groupes étaient respectivement de 80,6 %, 57,4 %, 54,0 % et 65,4 %, 46,5 %, 30,5 %, et la différence était statistiquement significative (2 = 4,478, p = 0,03). Les différences de survie globale et de survie sans progression n’étaient pas significatives (p > 0,05). La différence à 1, 3 et 5 ans de taux d’échec locorégional était statistiquement significative entre les deux groupes ; à l’exception du taux d’échec global et de celui de dissémination métastatique à distance. Les incidences globales de l’œsophagite induite par la radiothérapie étaient respectivement de 79,6 % et 59,6 %, et la différence était statistiquement significative (2 = 4,559, p = 0,03). Il n’y avait pas de différence en termes de pneumopathie radique (12,2 % contre 14,9 % ; 2 = 0,144, p = 0,7). Conclusion. – Pour les patients âgés atteints d’un carcinome œsophagien localisé irradié radicalement, bien que l’irradiation prophylactique ganglionnaire élective radicale pourrait augmenter l’incidence d’œsophagite induite par la radiothérapie, les patients pouvaient tolérer le traitement et en bénéficier en termes de taux de contrôle local. ´ e´ franc¸aise de radiotherapie ´ oncologique (SFRO). Publie´ par Elsevier Masson SAS. Tous © 2016 Societ ´ ´ droits reserv es.
1. Introduction Although the development of radiotherapy of oesophageal carcinoma has led to significant increase in patient survival, regional failure is the main cause of failure after radiotherapy and there is still controversy in the design of radiation treatment plan, especially the target volume delineation for patients receiving radical radiotherapy. Our previous study showed that elective nodal prophylactic irradiation of early stage oesophageal carcinoma treated by radical irradiation could reduce locoregional failure and increase local control rate, then to improve the long-term survival [1]. However, elderly patients are special because they have poor general status, increased occurrence of chronic disease and overall decreased tolerance to high-intensity therapies. The median age at diagnosis of oesophageal carcinoma is 68 years old and there are 61% of patients over the age of 65, 33% over the age of 75 and 8% over the age of 85 [2]. In order to investigate if elderly patients can achieve good control and tolerate the side effects of the elective nodal prophylactic irradiation, we retrospectively analysed the clinical data of 96 elderly patients with early stage oesophageal carcinoma receiving radical radiotherapy and compared the locoregional control, overall survival, the failure modes and the side effects between the patients receiving elective nodal irradiation and involved-field irradiation. 2. Materials and methods 2.1. Patients From January 2006 to December 2011, 96 elderly patients with median age of 73 (range 65–82 years) with early stage oesophageal carcinoma (T1–3 N0–1 M0 ) received radical radiotherapy in our department. The Karnosky performance scores of all patients were greater than 70. All patients had histologically or cytologically confirmed oesophageal carcinoma. There were 90 squamous cell carcinomas and six non-squamous cell carcinomas. There were 60 male and 36 female patients. In all 96 cases, it included 20 cervical and upper thoracic segments oesophageal carcinoma, 54 middle thoracic segments oesophageal carcinoma and 22 lower thoracic segments oesophageal carcinoma. The patients’ general condition was evaluated according to the Eastern Cooperative Oncology Group (ECOG) performance status criteria and patients with performance status at least 4 were excluded from the study. Before treatment, all patients had undergone numerous examinations, including history and physical examination, computed tomography (CT) or magnetic resonance imaging (MRI) of the head, chest and upper abdomen, radionuclide bone scan or positron emission tomography (PET). According to the 6th edition of clinical
staging criteria of oesophageal carcinoma in 2002, 41 patients had clinical stage I and 55 stage II lesions. 2.2. Chemoradiotherapy All patients underwent 3-dimensional conformal radiotherapy or intensity-modulated radiation therapy delivered by 6 MV linear accelerators. Thirty-five elderly patients (out of 96) received 5-fluorouracil and cisplatin chemoradiotherapy, among which 12 patients received concurrent treatment consisting of two cycles during week one and six of radiotherapy, the other 23 received sequential treatment cycles of chemotherapy after radiotherapy. Among the 35 patients, 22 received two to four cycles of chemotherapy, the other 13 received six cycles. Statistical analysis of the clinical characteristics between two groups (elective nodal prophylactic or involved-field irradiation) showed that there was no significant difference except for the tumour site (Table 1). 2.3. Treatment plan and delivery According to the target volume delineation, 49 patients received elective nodal prophylactic irradiation (15 for 3-dimensional conformal radiotherapy and 34 for intensity-modulated radiation therapy), and 47 others received involved-field irradiation (16 for 3-dimensional conformal radiotherapy and 31 for intensitymodulated radiation therapy) (Table 1). Radiotherapy treatment planning was determined using 64 multidetector row spiral CT scanner. After administration of intravenous contrast agents, 3 mm CT images were obtained, including primary tumour, lymph node areas, lungs and upper abdomen. Lymph nodes with a diameter of 10 mm or more were considered to be pathological, as well as round, hypodense lymph nodes measuring more than 5 mm. All CT images were reviewed by two experienced radiologists, and the tumour volume was defined by an experienced radiation oncologist. 2.3.1. Target volume delineation/involved-field irradiation delineation The gross tumour volume (GTV) contained the primary oesophageal tumour. The clinical target volume (CTV) was obtained by adding a 0.5–1.0 cm margin in axial direction and a 1.5–2.0 cm margin in cranial–caudal direction to the primary tumour. The planning target volume (PTV) was generated by expanding the CTV with 0.5–0.8 cm margin. The gross tumour volume of lymph node (GTVnd ) included the pathologic lymph nodes. The clinical target volume of lymph node (CTVnd ) was obtained by adding a 0.5 cm margin around the pathologic lymph nodes. The planning target volume of lymph node (PTVnd ) was generated by
Please cite this article in press as: Su J, et al. Target volume delineation for radical radiotherapy of early oesophageal carcinoma in elderly patients. Cancer Radiother (2016), http://dx.doi.org/10.1016/j.canrad.2016.08.129
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Table 1 Radical radiotherapy of early oesophageal carcinoma in elderly patients: Comparison of clinical characteristics between two therapeutic regimens, elective nodal prophylactic irradiation and involved-field irradiation. Clinical characteristics Gender Male Female Performance status 0–1 ≥2 Tumour site Cervical and upper thoracic Middle thoracic Lower thoracic X ray based lesion length ≤4.5 cm >4.5 cm Diameter of the maximum level by CT ≤3.5 cm >3.5 cm Gross tumour volume ≤30 cm3 >30 cm3 T stage T1 + 2 T3 N stage N0 N1 TNM stage I II Chemotherapy No Yes Radiotherapy technique 3-dimensional conformal radiotherapy Intensity-modulated radiation therapy
Elective nodal prophylactic irradiation
Involved-field irradiation
34 15
26 21
19 30
20 27
15 27 7
5 27 15
26 23
20 27
33 16
34 13
41 8
39 8
32 17
26 21
32 17
32 15
23 26
18 29
31 18
30 17
15 34
16 31
expanding the CTVnd with 0.5–0.8 cm margin. At least 95% of the volume of PTV and PTVnd received 56–66 Gy (1.8–2.0 Gy/fraction, one fraction/day, five times a week). 2.3.2. Elective nodal prophylactic irradiation delineation The clinical target volume of elective nodal irradiation was defined as CTV1 , which contained the lymphatic drainage area according to the reference standards [3]. When the primary tumour was located at cervical or upper thoracic oesophagus, CTV1 contained bilateral supraclavicular, adjacent oesophagus, and regions 2, 4, 5 and 7. When the primary lesion was located at middle thoracic oesophagus, CTV1 contained lymphatic drainage area of adjacent oesophagus, regions 2, 4, 5 and 7. For the lower thoracic oesophageal carcinoma, CTV1 contained adjacent oesophagus, region 4, 5, and 7, left gastric and paracardial lymph drainage area. The planning target volume of elective nodal irradiation was defined as PTV1 , which was obtained by expanding the CTV1 with 0.5–1.0 cm margin. At least 95% of the volume of PTV1 received 46–52.2 Gy, and the prescribed dose of primary tumour and involved lymph nodes was boosted to 56–66 Gy in the late course (1.8–2.0 Gy/fraction, one fraction/day, five times a week). Organs at risk, such as lungs, heart and spinal cord, were contoured on CT images. Mean lung dose was less than 20 Gy, and V5 (the volume of both lungs receiving 5 Gy) was less than 55%, V20 less than 25%, V30 less than 18%. V30 of heart (the volume of heart receiving 30 Gy) was less than 50%, and V40 less than 30%. Dmax (the maximum dose) of spinal cord was less than 45 Gy. 2.4. Evaluation index after treatment After completion of whole treatment, the examinations described above were performed again in order to compare the
2
P value
2.026
0.2
0.142
0.7
7.871
0.02
1.061
0.3
0.284
0.6
0.008
0.9
1.001
0.3
0.083
0.8
0.732
0.4
0.003
0.9
0.129
0.7
size of primary tumour and nodes to analyse the patients’ therapy effects. Immediate effect was evaluated according to the World Health Organization (WHO) standard criteria [4]. Local control rate, overall survival rate and progression-free survival rate were estimated and compared between the elective nodal prophylactic irradiation and involved-field irradiation groups. Local failure included oesophageal or regional lymph node failure over 6 months after radiotherapy. Distant metastases included distant organ metastases or out-of-regional lymph node metastases. The overall failure included local regional failure and distance metastases. Acute adverse effects of radiation to lungs and oesophagus were graded according to the Radiation Therapy Oncology Group (RTOG). 2.5. Statistical analysis The statistics for local control, overall survival, progression-free survival, overall failure, local regional failure and distant metastases were estimated by Kaplan-Meier method, and the differences between the groups were tested by Log-rank method. The enumeration data were analysed by 2 method. 3. Results 3.1. Follow-up and overall treatment effects The median follow-up time was 38 months (range, 16.8–105 months). The follow-up rate was 97.9% (94/96). After completion of the treatment, 36 patients achieved complete response (21 in elective nodal prophylactic irradiation vs 15 in involved-field irradiation), and the other 60 patients achieved partial response (28 in elective nodal prophylactic irradiation vs 32
Please cite this article in press as: Su J, et al. Target volume delineation for radical radiotherapy of early oesophageal carcinoma in elderly patients. Cancer Radiother (2016), http://dx.doi.org/10.1016/j.canrad.2016.08.129
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80%
Table 2 Radical radiotherapy of early oesophageal carcinoma in elderly patients: comparison of therapeutic effects between two regimens, elective nodal prophylactic irradiation or involved-field irradiation.
Response rate
70% 60%
Elective nodal prophylactic irradiation (%)
50% 40% 30% 20% 10% 0% Complete response
Partial reponse
Fig. 1. Radical radiotherapy of early oesophageal carcinoma in elderly patients: comparison of short-term effects of elective nodal prophylactic or involved-field irradiation. White bars: elective nodal prophylactic irradiation group; black bars: involved-field irradiation group (2 = 1.226, P = 0.3).
Overall failure 1-yr 23.8 58.0 3-yr 63.0 5-yr Local regional failure 1-yr 19.4 3-yr 42.6 46.0 5-yr Distant metastases 1-yr 11.0 29.7 3-yr 43.8 5-yr
Involved-field irradiation (%)
2
P
2.329
0.1
4.478
0.03
0.156
0.7
44.7 64.2 76.5 34.6 53.5 69.5 24.0 36.5 36.5
in involved-field irradiation). The 1-, 3-, and 5-year local controls of all patients were 70.9%, 52.1% and 37.8%. For all patients, the 1-, 3-, and 5-year overall and progression-free survival rates were 69.3%, 37.6%, 29.8% and 70.9%, 52.1%, 37.8%, respectively.
(Table 2). For the elective nodal prophylactic irradiation group, four patients developed in-field failure, one was oesophageal failure and the other three were regional lymph nodes failure. For the involvedfield irradiation group, three patients developed out-of-field failure and two in-field failure.
3.2. Comparison of treatment effects between elective nodal prophylactic irradiation and involved-field irradiation groups
3.4. Adverse effects of radiotherapy
The difference of the immediate response rate between elective nodal prophylactic irradiation and involved-field irradiation group was not statistically significant (2 = 1.226, P = 0.3; Fig. 1). The 1-, 3, and 5-year local control in elective nodal prophylactic irradiation and involved-field irradiation groups were 80.6%, 57.4%, 54.0% and 65.4%, 46.5%, 30.5% respectively, and the difference was statistically significant (2 = 4.478, P = 0.03; Fig. 2). However, the differences of overall and progression-free survival rates were not significant (2 = 2.619, P = 0.1; 2 = 1.242, P = 0.3; Fig. 2B and C) between the two groups. In order to make sure if the other factors influence the results, we did further study. For patients with N0 stage, the 1-, 3-, and 5-year local control in elective nodal prophylactic irradiation and involved-field irradiation groups were 89.5%, 62.6%, 43.2% and 56.3%, 49.8%, 29.4% respectively, and the difference was statistically significant (P = 0.04). However, the difference of overall and progression-free survival rates between the two groups was not significant (P > 0.05). For patients with N1 stage, the difference of local control, overall and progression-free survival rates between elective nodal prophylactic irradiation and involved-field irradiation groups was not significant (P > 0.05). And for the tumour site, further stratification analysis showed that the difference of local control, overall and progression-free survival between elective nodal prophylactic irradiation and involved-field irradiation groups was not significant either (P > 0.05). 3.3. Analysis of failure modes After treatment, 59 patients developed failure, including 27 patients in elective nodal prophylactic irradiation group and 32 in involved-field irradiation group. In the elective nodal prophylactic irradiation group, 13 patients developed local regional failure, nine distant metastases and five both local failure and distant metastases. In the involved-field irradiation group, the number of patients developing local failure, metastases, or both of them was 18, five and nine respectively. The difference of 1-, 3-, and 5-years of local regional failure rate was statistically significant between elective nodal prophylactic irradiation and involved-field irradiation group except for the overall failure rate and distant metastasis rate
The overall incidence of radiation-induced acute oesophagitis in elective nodal prophylactic irradiation and involved-field irradiation were 79.6% and 59.6%, and the difference was statistically significant (2 = 4.559, P = 0.03). In the elective nodal prophylactic irradiation and involved-field irradiation groups, there were 25, 13 and 14, 13 patients developed grade 1 and 2 acute oesophagitis respectively. Although one patient in each group had grade 3 oesophagitis, the patients could tolerate further therapy and did not stop the treatment. No worse cases of oesophageal toxicity were seen. The difference of acute radiation pneumonitis between elective nodal prophylactic irradiation and involved-field irradiation was not significant (12.2% vs 14.9%; 2 = 0.144, P = 0.7). In elective nodal prophylactic irradiation and involved-field irradiation groups, there were three, three and two, five patients developed grade 1 and 2 pneumonitis respectively. No patients suffered from grade 3–4 pneumonitis. 4. Discussion Although some studies have demonstrated that patients with oesophageal carcinoma could achieve local control and survival benefits from three-field lymphadenectomy, there were still some early stage patients who cannot accept the radical resection because of old age and medical problems [5,6]. Moreover, some studies found that the 5-year survival rate was similar between patients with same stage oesophageal carcinoma receiving radical operation and radical radiotherapy [7–9]. Therefore, radical radiotherapy plays an important role in the management of patients with oesophageal carcinoma. Patients aged 65 and over are a special group because of the poor status and medical complications. In the past, elderly patients with oesophageal carcinoma only received palliative treatment in consideration of a short life expectancy, poor prognosis and comorbidities. With the lengthening of life expectancy, elderly patients with oesophageal carcinoma became an important group. Some studies have shown that for patients with oesophageal carcinoma receiving chemoradiotherapy, age was not a significant influence factor of prognosis and did not increase the frequency of
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Fig. 2. Radical radiotherapy of early oesophageal carcinoma in elderly patients: comparison of local control, overall and progression-free survival rates between elective nodal prophylactic and involved-field irradiation. A. The local control rate of elective nodal prophylactic irradiation was higher than that of involved-field irradiation (P = 0.03). B. and C. There was no significant difference of overall survival and progression-free survival between elective nodal prophylactic irradiation and involved-field irradiation (P > 0.05); blue line: elective nodal prophylactic irradiation group; green line: involved-field irradiation group.
adverse events [10,11]. Our previous study showed that patients with early stage oesophageal carcinoma receiving radical radiotherapy could achieve the benefits of local control and long-term survival from elective nodal prophylactic irradiation [1]. Zhang et al. reported that local control rate, 3-year survival rate, and recurrence and metastasis-free survival rate of patients in clinical stage II and III receiving extensive regional field irradiation were statistically higher than those of patients receiving conventional field irradiation [12]. In our study, all of 96 patients with oesophageal carcinoma were aged 65 or over and in clinical stage I and II. It was shown that the 1-, 3- and 5-year local control rate of elective nodal prophylactic irradiation group was statistically higher than that of involved-field irradiation group (Fig. 2A) and elective nodal prophylactic irradiation could reduce local regional failure significantly (P = 0.03). Although the differences of overall and progression-free survival rates between elective nodal prophylactic irradiation and involved-field irradiation were not statistically significant, the 1-, 3- and 5-year overall and progression-free survival rates of elective nodal prophylactic irradiation were higher than those of involved-field irradiation. All of these indicated that elective nodal prophylactic irradiation maybe could offer benefits to elderly patients with early stage oesophageal carcinoma.
Zhao et al. analysed the data from 53 patients with oesophageal squamous cell carcinoma who received 3-dimensional conformal radiotherapy and only the primary tumour and positive lymph nodes were irradiated [13]. The results indicated that the omission of elective nodal irradiation was not associated with significant failure in lymph node regions not included in the planning target volume. Local failure and distant metastases remained the predominant problems. In our study, for the elective nodal prophylactic irradiation group, four patients developed in-field failure, one was oesophageal failure and the other three were regional lymph nodes failure. For the involved-field irradiation group, three patients developed out-of-field failure and two in-field failure. The patients in this study were all 65 years old and over, therefore, the treatment tolerance was a crucial issue. Several studies showed that chemoradiotherapy was a tolerable treatment in elderly patients with oesophageal carcinoma, so the elderly patients should not be excluded from potentially curative treatment based on age alone [10,14,15]. In order to make sure whether elective nodal prophylactic irradiation would increase the incidence of radiation-induced adverse effects because of the larger volume of irradiation, we compared radiation-induced
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oesophagitis and pneumonitis between elective nodal prophylactic irradiation and involved-field irradiation groups. It showed that the overall incidence of radiation-induced oesophagitis in the elective nodal prophylactic irradiation group was significantly higher than that in the involved-field irradiation group (P = 0.03), but one patient in each group had grade 3 oesophagitis, and the other 38 and 27 patients developed grade 1 or 2 oesophagitis respectively. The difference of radiation pneumonitis between elective nodal prophylactic irradiation and involved-field irradiation was not significant. Patients could tolerate further therapy and did not stop the treatment. In conclusion, for elderly patients with early stage oesophageal carcinoma receiving radical radiation, although elective nodal prophylactic irradiation increased the incidence of radiation-induced oesophagitis, it could be tolerable and could reduce local regional failure and increase local control rate, as well as improve long-term survival. Disclosure of interest The authors declare that they have no competing interest. References [1] Zhu S, Dong H, Liu Z, Shen W, Li J, Su J, et al. Comparative study of different irradiation ranges in radical radiotherapy for early-stage esophageal cancer. Chin J Radiat Oncol 2015;24:615–8. [2] National Cancer Institute. SEER cancer statistics review 1975–2006. Bethesad, MD: National Cancer Institute; 2009 [database on the Internet, available from: http://seer.cancer.gov/csr/1975-2006/]. [3] Yin W, Yu Z, Xu G, Yimin H. Radiation oncology. 4th edition Beijing: Pecking Union Medical College Press; 2008. p. 546–7 [M].
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Please cite this article in press as: Su J, et al. Target volume delineation for radical radiotherapy of early oesophageal carcinoma in elderly patients. Cancer Radiother (2016), http://dx.doi.org/10.1016/j.canrad.2016.08.129