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Abstract

OBJECTIVE:

Lymphoma is considered to be a kind of malignant tumour. Gene therapy and radiotherapy have been reported as treatment methods for head and neck lymphoma. This study aims to evaluate the efficacy and safety for the treatment of head and neck lymphoma by a combination of recombinant adenovirus p53 (rAd-p53) and radiotherapy.

METHODS:

A total of 156 patients with head and neck lymphoma were selected. All patients received an intratumor injection of rAd-p53 of four different doses, namely, 0, 1 $\times$ 10 ${}^{10}$ VP, 1 $\times$ 10 ${}^{11}$ VP and 1 $\times$ 10 ${}^{12}$ VP, once a week for 8 weeks, and radiotherapy was administered 3 days after the rAd-p53 injection using the same dosage and method. Four, eight and twelve weeks after treatment, tumor reduction and complete response (CR) rates, special laboratory examination and adverse reaction assessment were detected to evaluate the efficacy and safety of combined treatment with rAd-p53 injection and radiotherapy for head and neck lymphoma.

RESULTS:

At week 4, 8 and 12 of treatment with rAd-p53 at the 1 $\times$ 10 ${}^{10}$ VP, 1 $\times$ 10 ${}^{11}$ VP and 1 $\times$ 10 ${}^{12}$ VP doses, the average tumour reduction and CR rates were evidently elevated, the anti rAd-p53 antibody in the serum of patients was expressed positively, and the T cell subsets (CD3/CD4/CD8) increased and interleukin 2 receptor (IL-2R) level decreased markedly. Additionally, rAd-p53 was proven to be clinically safe in the treatment.

CONCLUSION:

Altogether, we conclude that rAd-p53 combined with radiotherapy improves the efficacy and safety in treating head and neck lymphoma, which has a broad scope in future clinical application.

Keywords

Head and neck lymphoma recombinant adenovirus p53 radiotherapy efficacy safety adverse reaction

1. Introduction

Lymphoma is a kind of malignant tumour progressively mutated from normal lymphoid cells and is systematically divided into two main subgroups as Hodgkin’s lymphoma (HL) or Hodgkin’s disease (HD) and non-Hodgkin’s lymphoma (NHL) [1]. The disease is one of the major causes for adenopathies of head and neck, which present in the form of adenopathy or inflammation, such as Waldeyer’s ring or salivary gland [2, 3]. Now, lymphoid neoplasms are the sixth most prevalent class of cancers across the world and the incidence has been predicted to rise over the next two decades [4]. NHL boasts of a high treatable rate, with evidence acknowledging complete recovery of some patients suffering from the disease [5]. Newly-diagnosed HL in the advanced stage has a higher remission rate at about 60% to 80% owing to the improved combined treatment with chemotherapy and radiotherapy [6]. However, more than 20% of patients with classic HL cannot be cured after treatment, and a large fraction of patients are extensively treated [7]. A preclinical study conducted by Bossi et al reported that re-expression of p53 might be a potential target in the treatment of cancer [8].

The wild-type human gene p53 (wt-p53) is located on chromosome 17p.13, which is a human tumour suppressor gene and acts as a main mediator of DNA repair, apoptosis, cell cycle arrest and tumour development [9, 10]. The mutated p53 protein is overexpressed in many different forms of human cancers, and improves metastasis, transformation and drug resistance of cancer cells by suppressing the wt-p53 and p53 families [11]. A previous study revealed that recombinant adenovirus p53 (rAd-p53) transfected with the wt-p53 gene has been adopted as a gene therapy, which makes radiotherapy and chemotherapy more effective, restrains tumour growth, and leads to apoptosis by promoting the expression of Bax, Fas, Bak and Puma [12]. Another previous study indicated that the combined treatment with rAd-p53 and other therapies, such as radiotherapy, resulted in better efficacy, for instance, intra-arterial infusion of chemotherapy combined with rAd-p53 has improved efficacy of patients with stage III oral cancer, as the survival rate increased greatly [13]. It was demonstrated that patients with locally advanced cervical cancer had a better efficacy when treated with rAd-p53 transfer and radiotherapy together than radiotherapy alone, since the former has a higher 5-year overall survival rate than the latter [14] However, due to the lack of knowledge regarding the effect of rAd-p53 combined with radiotherapy in treating head and neck lymphoma, this study was designed. Therefore, the present study determined to investigate the efficacy and safety of the combined treatment of rAd-p53 and radiotherapy against head and neck lymphoma.

2. Materials and methods

2.1 Ethical statement

This study was performed with approval of the Ethics Committee of Weifang People’s Hospital. All participants signed informal consent prior to the study.

2.2 Study subjects

Between January 2011 and January 2014, a total of 156 patients with head and neck lymphoma that underwent treatment in Weifang People’s Hospital were enrolled in the study. Among the 156 patients, there were 104 males and 52 females aging from 16 to 81 years with an average age of 45.4 $\pm$ 12.9 years. The differential diagnosis of malignant lymphoma (ML) for all patients was made by biopsy or postoperative pathological examination. According to the canceration derived from lymphocytes or tissue cells, 14 cases were classified as HD and 142 cases were NHL, including 56 cases of diffuse large B cell lymphoma (DLBLC), 32 cases of follicular lymphoma (FL) and 50 cases of other types. According to the World Health Organization (WHO) staging classification [15] of lymphoma, stage I had 56 patients, stage II had 32, stage III had 27, and stage IV had 41 patients, respectively. All selected patients had measurable lesions that were evident and suitable for clinical observation and medication, with Karnofsky $\geqslant$ 70 scores and normal cardiopulmonary functions. The exclusion criteria were as follows: (1) patients with uncontrollable infection; (2) patients who suffered from disease of hemorrhagic tendency; (3) patients with severe neurological disorder; (4) patients with twice the normal level of serum creatinine.

2.3 Treatment regimens

A total of 156 patients were grouped into 4 groups ( $n=$ 39) in accordance with different dosage of rAd-p53 injection: the 0, 1 $\times$ 10 ${}^{10}$ VP, 1 $\times$ 10 ${}^{11}$ VP and 1 $\times$ 10 ${}^{12}$ VP groups. Patients received rAd-p53 injection once a week, for 8 weeks consecutively and radiotherapy was administered 3 days after the injection. The same conventional radiotherapy regimen was administered to the four groups: 5 times a week with 2 Gy every time. Both the primary tumour and metastatic lymph node of neck were allowed to reach to 70 Gy/7 $\sim$ 8 w.

2.4 Efficacy evaluation

Four weeks, eight weeks and twelve weeks after treatment, computed tomography (CT) scan was performed to measure the tumour size by the two-dimensional method (tumour size $=$ maximum transverse diameter $\times$ maximum vertical diameter). The tumour reduction rates (%) at 4, 8 and 12 weeks were used to evaluate efficacy under the standard of Response Evaluation Criteria In Solid Tumour (RECIST) [16], which gave four parameters including complete response (CR), partial response (PR), stable disease (SD) and progressive disease (PD). The overall response rate (ORR) was the sum of CR and PR percentages.

Table 1
Baseline characteristics of patients with head and neck lymphoma in the four groups

Items	0	1 $\times$ 10 ${}^{10}$ VP	1 $\times$ 10 ${}^{11}$ VP	1 $\times$ 10 ${}^{12}$ VP	$p$
Case number	39	39	39	39
Gender (male/female)	27/12	26/13	25/14	26/13	0.973
Age (year)	43.3 $\pm$ 13.7	47.0 $\pm$ 10.7	45.8 $\pm$ 12.2	45.4 $\pm$ 14.7	0.645
Tumor size (cm ${}^{2}$ )	73.12 $\pm$ 12.39	79.23 $\pm$ 15.29	75.15 $\pm$ 21.34	77.10 $\pm$ 12.99	0.369
Tumour stage					0.782
I	16	13	13	14
II	7	8	8	11
III	4	10	7	6
IV	12	8	11	8
Tumor classification					0.960
HD	4	7	3	4
DLBCL	14	13	14	15
FL	9	8	7	8
Others	12	11	15	12
Tumor location					0.776
Neck	19	24	23	20
Nasal cavity	5	3	4	5
Nasopharynx	0	2	2	3
Others	15	10	10	11

Notes: HD, Hodgkin disease; DLBLC, diffuse large B cell lymphoma; FL, follicular lymphoma; NHL, non-Hodgkin lymphoma.

2.5 Routine clinical examination and special laboratory examination

Routine blood, urine and stool examinations were performed weekly, and blood chemical tests [creatinine (Cr), blood urea nitrogen (BUN), alanine transaminase (ALT), aspartate aminotransferase (AST), chest X-ray and electrocardiogram (ECG) were examined monthly. Especially, changes in body temperature were observed and monitored carefully, and the ephemeral self-limited fever after rAd-p53 injection was also under surveillance if occurred.

Anti-rAd-p53 antibody examination was conducted as follows: the collected whole blood from patients was centrifuged, and the supernatant serum was extracted as sample. Enzyme linked immunosorbent assay (ELISA) was employed to examine the anti specific rAd-p53 antibody purchased from Sibiono Co., Ltd. Shenzhen, China.

T cell subsets and interleukin 2 receptor (IL-2R) measurements were performed as follows: the cell percentages of T cell subsets (CD3, CD4 and CD8) were determined using flow cytometry (Becton, Dickinson and Company Bioscience, San Jose, CA, USA). The ELISA kit (Diaclone, Besancon, Cedex, France) was used to examine the IL-2R content.

2.6 Toxicity assessment

In every stage of treatment, toxicity and adverse reaction were evaluated and classified in accordance with the WHO classification [17], which listed four grades from Grade 0 to IV based on the changes in blood routine, amount of blood loss, gastrointestinal condition and allergy. Specific classification was as follows: Grade 0, patients with no blood loss, gastrointestinal adverse reaction or other adverse symptoms; Grade I, patients with petechiae, transient diarrhea, nausea, and mild infection; Grade II, patients with mild blood loss, oral erythema and ulcer, transient vomiting, and severe haematuria; Grade III, patients with apparent blood loss, oralulcer, vomiting, diarrhea, severe haematuria and dyspnea; Grade IV, severe blood loss, bloody diarrhea, unmanageable vomiting, allergy and major infection with hypotension.

2.7 Statistical analysis

All data were analysed using SPSS 21.0 (IBM Corp. Armonk, NY, USA) statistical software. Measurement data were presented as mean $\pm$ standard deviation. One-way analysis of variance (ANOVA) was employed for comparisons among three or more groups, whereas the least significant difference (LSD) was adopted for comparing between two groups. The enumeration data were shown in percentage and examined by $X^{2}$ , and a p value $<$ 0.05 was considered to be statistically significant.

Table 2
rAd-p53 combined with radiotherapy increases average tumour reduction rate

Items	0	1 $\times$ 10 ${}^{10}$ VP	1 $\times$ 10 ${}^{11}$ VP	1 $\times$ 10 ${}^{12}$ VP
Week 4 (%)	39.12 $\pm$ 13.53	69.41 $\pm$ 16.39*	70.99 $\pm$ 19.25*	72.12 $\pm$ 18.13*
Week 8 (%)	58.89 $\pm$ 10.68	87.38 $\pm$ 6.81*	89.10 $\pm$ 21.37*	90.15 $\pm$ 15.22*
Week 12 (%)	69.76 $\pm$ 19.30	89.47 $\pm$ 18.23*	90.84 $\pm$ 12.29*	92.29 $\pm$ 23.65*

Notes: *, $p<$ 0.05 vs. the 0 group.

Table 3

rAd-p53 combined with radiotherapy improves CR rate of patients with head and neck lymphoma

Items	0	1 $\times$ 10 ${}^{10}$ VP	1 $\times$ 10 ${}^{11}$ VP	1 $\times$ 10 ${}^{12}$ VP
Number of tumor lesion	39	39	39	39
Four weeks after treatment
CR $+$ PR (%)	13 (33.33%)	39 (100%)*	39 (100%)*	39 (100%)*
SD $+$ PD (%)	26 (66.67%)	0	0	0
CR (%)	0	3 (7.69%)*	5 (12.82%)*	8 (20.51%)*
Eight weeks after treatment
CR $+$ PR (%)	36 (92.31%)	39 (100%)*	39 (100%)*	39 (100%)*
SD $+$ PD (%)	3 (7.69%)	0	0	0
CR (%)	4 (10.26%)	29 (74.36%)*	31 (79.49%)*	33 (84.62%)*
Twelve weeks after treatment
CR $+$ PR (%)	39 (100%)	39 (100%)	39 (100%)	39 (100%)
CR (%)	5 (12.82%)	31 (79.49%)*	35 (89.74%)*	36 (92.31%)*

Notes: *, $p<$ 0.05 vs. the 0 group; CR, complete response; PR, partial response; SD, stable disease; PD, progressive disease.

3. Results

3.1 Baseline characteristics of patients with head and neck lymphoma

Initially, the baseline characteristics of patients with head and neck lymphoma included in this study were analyzed. Among these 156 patients, no significant differences were observed in parameters such as sex, age, tumour size, clinical stage, tumor classification and tumor location (all $p>$ 0.05) (Table 1).

3.2 rAd-p53 combined with radiotherapy increases average tumour reduction rate

Tumor reduction of patients was obviously observed in the four groups after treatment. On comparison with the average tumour reduction rate among groups at week 4, 8, and 12, it was observed that the tumor reduction rate in the 1 $\times$ 10 ${}^{10}$ VP, 1 $\times$ 10 ${}^{11}$ VP and 1 $\times$ 10 ${}^{12}$ VP groups were greater than those in the 0 group (all $p<$ 0.05), with no significant differences among the three groups (all $p<$ 0.05) (Table 2), which demonstrated that the efficacy in those three groups were superior compared to the 0 group. The results indicated that a combination of rAd-p53 with radiotherapy could increase the average tumor reduction rate.

Table 4
rAd-p53 combined with radiotherapy increases T cell subsets and decreases IL-2R levels

Item	0	1 $\times$ 10 ${}^{10}$ VP	1 $\times$ 10 ${}^{11}$ VP	1 $\times$ 10 ${}^{12}$ VP
Before treatment
CD3 (%)	46.25 $\pm$ 6.14	45.98 $\pm$ 9.16	44.82 $\pm$ 11.02	41.97 $\pm$ 14.74
CD4 (%)	25.88 $\pm$ 5.75	24.09 $\pm$ 4.99	23.15 $\pm$ 7.15	26.40 $\pm$ 6.98
CD8 (%)	15.67 $\pm$ 3.09	13.76 $\pm$ 4.81	15.10 $\pm$ 1.86	14.12 $\pm$ 3.00
IL-2R (pg/ml)	757.12 $\pm$ 101.89	746.57 $\pm$ 208.32	763.93 $\pm$ 156.83	764.83 $\pm$ 140.09
After treatment
CD3 (%)	50.31 $\pm$ 4.71#	61.02 $\pm$ 9.88*#	68.05 $\pm$ 5.93*#	64.82 $\pm$ 11.42*#
CD4 (%)	28.83 $\pm$ 4.08#	33.92 $\pm$ 8.60*#	42.35 $\pm$ 7.89*#	43.62 $\pm$ 6.22*#
CD8 (%)	19.23 $\pm$ 1.84#	34.82 $\pm$ 6.12*#	31.85 $\pm$ 9.35*#	32.86 $\pm$ 10.91*#
IL-2R (pg/ml)	418.24 $\pm$ 120.98#	332.74 $\pm$ 63.91*#	324.38 $\pm$ 98.53*#	301.87 $\pm$ 43.69*#

Notes: the normal values of CD3, CD4, CD8 and IL-2R (pg/ml): 60–82, 35–55, 20–36, 30–140; *, $p$ < 0.05 vs. the 0 group; #, $p<$ 0.05 vs. the values before treatment; IL-2R, interleukin 2 receptor.

Table 5

rAd-p53 is clinically safe in the treatment (cases)

Adverse reaction	0	1 $\times$ 10 ${}^{10}$ VP	1 $\times$ 10 ${}^{11}$ VP	1 $\times$ 10 ${}^{12}$ VP
Hematologic toxicity
Grade 0	23	20	24	24
Grade I	8	12	8	8
Grade II	5	1	4	3
Grade III	3	6	3	4
Hepatorenal impairment
Grade 0	32	33	33	30
Grade I	5	4	3	8
Grade II	2	2	3	1
Grade III	0	0	0	0
Non-hematologic toxicity
Grade 0	25	29	29	28
Grade I	9	6	5	8
Grade II	5	4	5	3
Grade III	0	0	0	0

3.3 rAd-p53 combined with radiotherapy improves CR rate

Subsequently, the clinical efficacy of rAd-p53 combined with radiotherapy in the treatment of malignant head and neck lymphoma was evaluated. The tumour of patients in the 1 $\times$ 10 ${}^{10}$ VP, 1 $\times$ 10 ${}^{11}$ VP and 1 $\times$ 10 ${}^{12}$ VP groups reduced evidently as the ORR (CR $+$ PR) reached 100% at 4, 8 and 12 weeks. On the 4 ${}^{\rm th}$ week, the ORR in the 0 group was 33.33%, with a significant difference in comparison to the other three groups (all $p<$ 0.05). On the 12 ${}^{\rm th}$ week, the CR rates in the 0, 1 $\times$ 10 ${}^{10}$ VP, 1 $\times$ 10 ${}^{11}$ VP and 1 $\times$ 10 ${}^{12}$ VP groups were 12.82%, 79.49%, 89.74% and 92.31%, respectively, indicating significant difference in CR rates between the 0 group and the other three groups at 8 and 12 weeks (all $p<$ 0.05), while no markedly difference in this indicator was detected among the other three groups (all $p>$ 0.05) (Table 3). It was proven that rAd-p53 combined with radiotherapy could improve CR rate.

3.4 rAd-p53 combined with radiotherapy increases T cell subsets and decreases IL-2R levels

Furthermore, Anti-rAd-p53 antibody examination and T cell subsets and interleukin 2 receptor (IL-2R) measurements were regularly performed using flow cytometry and ELISA.

Anti-rAd-p53 antibody of patients was detected to be negative using ELISA assay before treatment and no significant differences were observed among the 1 $\times$ 10 ${}^{10}$ VP, 1 $\times$ 10 ${}^{11}$ VP and 1 $\times$ 10 ${}^{12}$ VP groups. After 4 weeks of -rAd-p53 injection, the anti-rAd-p53 antibody of patients in the 1 $\times$ 10 ${}^{10}$ VP, 1 $\times$ 10 ${}^{11}$ VP and 1 $\times$ 10 ${}^{12}$ VP groups was found to be positively expressed, the content of which was elevated with the increased time of rAd-p53 injection, while 20.51% (8/39) of anti-rAd-p53 antibody of patients in the 0 group was expressed negatively.

The 1 $\times$ 10 ${}^{10}$ VP, 1 $\times$ 10 ${}^{11}$ VP and 1 $\times$ 10 ${}^{12}$ VP groups showed improved levels of T cell subsets (CD3/CD4/CD8) and IL-2R with reference to the normal values (Table 4), owing to elimination of tumor cells by rAd-p53 injection.

3.5 rAd-p53 is clinically safe in the treatment

The results of blood, urine and stool examinations of all patients were within the normal range before and after treatment. The Cr, BUN, ALT and AST values showed no evident increase according to the biochemical examination of blood. In the 1 $\times$ 10 ${}^{11}$ VP and 1 $\times$ 10 ${}^{12}$ VP groups, 7 patients experienced low-grade fever on the day they received rAd-p53 injection, with an incidence of 8.97%. It was self-limited fever, which disappeared with no special treatment after 2 $\sim$ 3 h, with no symptoms or local signs of upper respiratory tract infection. Therefore, the low-grade fever might be due to an immune response triggered by rAd-p53.

There were 63 patients who suffered from hematologic toxicity with decreases in haemoglobin, platelet and leukocyte, 24 patients who suffered from hepatorenal impairment, and 41 patients who suffered from non-hematologic toxicity including shivering, fever, elevated blood pressure and gastrointestinal reaction, but none experienced adverse reaction in Grade IV (Table 5). Moreover, no significant differences were observed for an adverse reaction in the four groups, which indicated that radiotherapy was attributed for the adverse reaction while rAd-p53 was clinically safe with no obvious adverse reaction.

4. Discussion

The incidence of head and neck lymphoma rose worldwide significantly since 2000, with nearly 3% increase rate annually, which represents a percentage faster than majority of cancers [18]. It has been reported that mutated p53 gene often encodes for higher level of heterogeneous mutated p53 proteins in numerous cancers, consequently which loses its potency, thereby making it less effective towards radiotherapy treatment due to the resistance to radiation in patients with mutated protein type, and thus the main task is to diminish this resistance by proposing new mechanisms [11, 19]. In the present study, we investigated the efficacy and safety of the combination of rAd-p53 and radiotherapy treatment for head and neck lymphoma and found that this combined therapy was clinically safe and effective in treating head and neck lymphoma.

Initially, it was observed that the average tumour reduction rates in the 1 $\times$ 10 ${}^{10}$ VP, 1 $\times$ 10 ${}^{11}$ VP and 1 $\times$ 10 ${}^{12}$ VP groups were greater than those in the 0 group at 4, 8, and 12 weeks, while the 1 $\times$ 10 ${}^{10}$ VP, 1 $\times$ 10 ${}^{11}$ VP and 1 $\times$ 10 ${}^{12}$ VP groups showed relatively higher CR rates at 12 weeks. rAd-p53 gene therapy for head and neck squamous cell carcinoma (HNSCC) has been approved by the State Food and Drug Administration of China [20]. Accumulating clinical studies of rAd-p53 gene therapy have targeted HNSCC, and rAd-p53 has been proven to be both safe and effective in treatment of HNSCC [21]. Consistently, rAd-p53 combined with radiotherapy was used to treat patients with a large intrathoracic malignant schwannoma, and the tumor shrank greatly as its diameter dwindled noticeably with no evident tumor cells after treatment [22]. A relevant study revealed that the foci of patients suffering from myoepithelial carcinoma in submandibular gland were relieved after receiving the same combination therapy, with no cancer progression in 5-year follow-up [23]. A part of the prevailing success was due to the p53 injection that greatly contributed to the inhibition of spontaneous tumorigenesis through regulating the metabolism and functioning as an anti-oxidant [24]. Brady et al. also found out that p53 is a crucial transcription factor for suppressing tumors [25]. Another reason for the welcoming results of this combined therapy was due to the immune response triggered by rAd-p53, as in a case of advanced nasopharyngeal carcinoma treated with the same therapy showed infiltration of lymphocytes after intratumoral administration of rAd-p53 [21]. It was also indicated that rAd-p53 combined with other treatments like chemotherapy or radiotherapy could result not only in better CR but also increased survival rate of patients with advanced oral cancer [13].

Additionally, the 1 $\times$ 10 ${}^{10}$ VP, 1 $\times$ 10 ${}^{11}$ VP and 1 $\times$ 10 ${}^{12}$ VP groups significantly increased T cell subsets (CD3/CD4/CD8) and decreased IL-2R level in comparison to the 0 group. One experiment showed that T cell subsets, as represented by the index of immunological aging, are important predictors for life span of mice with lymphoma and some other diseases [26]. Moreover, Dave et al. found out that T-cell-related genes predominantly exhibited good prognosis in follicular lymphoma (FL, a common type of NHL), while the accessory cell gene was expressed abnormally in FL with poor prognosis [27]. According to a previous study, high level of IL-2R is related to poor prognosis in FL with shorter event-free survival [28]. From the aforementioned, we inferred that rAd-p53 combined with radiotherapy increased T cell subsets and decreased IL-2R level, hence to provide good prognosis and better efficacy for head and neck lymphoma.

Consequently, no significant differences in adverse reaction in the 0, 1 $\times$ 10 ${}^{10}$ VP, 1 $\times$ 10 ${}^{11}$ VP and 1 $\times$ 10 ${}^{12}$ VP groups were observed, which indicated that radiotherapy were primarily responsible for any adverse reaction while rAd-p53 was approved to be clinically safe with no obvious adverse reaction. In line with our study, Liu et al. demonstrated that the mild or medium fever and flu-like symptoms of patients with gingival carcinoma and tongue cancer were recurrent and frequently observed in the experimental group, and were considered to be associated with application of rAd-p53 and the immune response caused by rAd-p53 injection [29]. Numerous studies focusing on rAd-p53 also showed no significant signs of adverse reaction, for instance, rAd-p53 therapy has been proven to be effective and safe for treating patients with a variety of malignant tumor, including oesophageal squamous cell carcinoma, and ovarian cancer [30, 31].

In summary, our trial proved that the combined treatment of rAd-p53 and radiotherapy can effectively reduce malignant head and neck lymphoma, thus introducing a potential and effective therapy for this disease. However, the present study was incomplete due to the limitation of sample size in the study. Moreover, the pathogenesis and tumorigenesis of cancers are abound and complex, which means that the mere gene therapy may have limited efficacy. Therefore, future clinical trial of combined treatment of rAd-p53 and radiotherapy for cancer is warranted.

Footnotes

Acknowledgments

We would like to give our sincere appreciation to the reviewers for their helpful comments on this article.

Conflict of interest

The authors have declared that no competing interests exist.

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Recombinant adenovirus p53 combined with radiotherapy improves efficacy and safety in the treatment of head and neck lymphoma

Abstract

OBJECTIVE:

METHODS:

RESULTS:

CONCLUSION:

Keywords

1. Introduction

2. Materials and methods

2.1 Ethical statement

2.2 Study subjects

2.3 Treatment regimens

2.4 Efficacy evaluation

Table 1 Baseline characteristics of patients with head and neck lymphoma in the four groups

2.6 Toxicity assessment

2.7 Statistical analysis

Table 2 rAd-p53 combined with radiotherapy increases average tumour reduction rate

3.1 Baseline characteristics of patients with head and neck lymphoma

3.2 rAd-p53 combined with radiotherapy increases average tumour reduction rate

Table 4 rAd-p53 combined with radiotherapy increases T cell subsets and decreases IL-2R levels

3.4 rAd-p53 combined with radiotherapy increases T cell subsets and decreases IL-2R levels

3.5 rAd-p53 is clinically safe in the treatment

4. Discussion

Footnotes

Acknowledgments

Conflict of interest

References

Table 1
Baseline characteristics of patients with head and neck lymphoma in the four groups

Table 2
rAd-p53 combined with radiotherapy increases average tumour reduction rate

Table 4
rAd-p53 combined with radiotherapy increases T cell subsets and decreases IL-2R levels