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Treatment on Nasopharyngeal Carcinoma (NPC)

2019-08-26 11:46

Treatment on Nasopharyngeal Carcinoma (NPC) by Gamma System + Conventional Radiation Therapy

Huiyan Duan, Huanghua Luo, Wenfei Chen, Guangyi Kuang, Xianzhao Chen

Gamma Knife Treateatment Research Center, Hainan People抯 Hospital

[Outline] Objective: To discuss the feasibility of using conventinal radiation therapy as supplementary treatment to gamma system treatment, and the way to reduce post-radiation syndrome and improve life quality of patients. Method: Supplementary conventional radiation therapy was given one week after gamma system treatment using 45Gy dose to 75 patients, result shows the effectiveness in tumor control accounts for 100% in a for Phase I-II tumor (3-18-month), 86% control rate for Phase III tumor. The life quality improves significantly and syndrome dramatically decreases.

[Key words] NPC, Gamma system, Supplementary radiation therapy

There have been many disputes regarding clinic application of Gamma system on NPC treatment. Since 2000, the Gamma system Treatment Center of Hainan People抯 Hospital has treated 75 NPC cases using complex treatment and achieved successful results. Below is the clinical information of the 75 cases: Male: 55 cases, female: 20 cases, age ranging from 26-78, average age 52. Among which 3 cases of familial concurrence. The early symptom appears mostly as neck tumor, found in 70%-80% of diagnosed patients, which is due to the rich lymphatic vessels in nasopharynx. The other common symptoms are blood streak, nasal or auditory symptoms. The course of diseases ranges from 15 days to 6 months. There might be family history for NPC. 2 patients are cousins and 8 cases lose their hearings and suffer damage to pharyngeal accessory nerve. Tumor size ranges from 2.0 cm to 7.0 cm. 49 cases are Phase I-II, 26 cases are Phase III-IV. Mehtods: 1. Adaptive diseases: UICC/AJCA 1997, TNH, NPC Classified Phase I- III, T4, without metastasis to body parts below neck after Ultrasonic B Scanning, BCT and Chest Radiography. ? Best adaptive diseases Phase I-IIab, relatively adaptive diseases Phase III. The IVa patient is strictly excluded. ? Senior patients that could not undergo complete radiation therapy are excluded. ? Relapse after radiation also excluded. 2. Installation of the Stereotactic Frame. To ensure that the complete image of rhinopharyngeal cavity, ethmoidal sinus and upper neck lymph on the CT scan, the Stereotactic Localization Frame need to be relocated. The base circle need to be put at the surface level of the neck and move forward to maximally, with the X axis close to the head skin, the internal frame the surface level and the Z axis lean to the tumor area. 3. CT 3mm, without space in between, with increased density scan, which could clearly show the tumor shape and lymph distribution.

Table 1. UICC/AJCA 1997, TNH, NPC Classification Standards

Phase I

T1 NO MO

Phase II a

T2 N MO

Phase II b

T1

T2a

T2b

N

NI

NO- NI

MO

MO

MO

Phase III

T1

T2a T2b

T3

N2

N2

NO-N2

MO

MO

MO

Phase IV a

T4

NO-N2

MO

Phase IV b

AnyT N3 MO

Phase IV c

AnyT AnyT MI

4.Treatment Plan: after outlining the tumor, the target area for Phase I-IIab: CTV>GTV0.5; target area for Phase III-IVa: CTV>GTV1.0, edge dose 18-20Gy, center dose 45-50 Gy. 40% same dose curve, target number: 4-16. The dose absorbed by pons is controlled under 12 Gy, the dose of neck lymphatic node depends on the result of Ultrasonic B scan and CT. If a single node is conglutinated with neck artery, it could be included in the target area, whereas the weigh of the target is lowered 30%. According to the treatment plan, rotating gamma ray treatment is used. During the treatment, 15 mg of hormone is used to prevent acute radiation syndrome.

Supplementary Radiation Therapy: 1 week after the gamma system treatment, radiation therapy is used as supplementary treatment. According the dose of gamma system treatment, rhinopharyngeal area is treated with 16 Gy at Phase I-IIab, 18-20Gy at Phase III-IVa. Treatment to neck depends on lymphatic node metastasis: 6000cGy dose radiation treatment is for patients with lymphatic node metastasis, normal treatment is provided to patients without node metastasis; 5 periods of radiation therapy are provided to patients at Phase III-IVa. Result: 1-18months after the therapy, upon nasopharyngeal inspection, CT and MRI scan, neck Ultrasonic B scan, in 99.8% of the cases, tumor shrinks significantly or disappears, in 2 cases of Phase IVa, metastasis appears, one of which the patient dies in 12 months. The rate of radiation syndrome for complex treatment is much lower than that of single therapy.

Table 2. Syndrome after the complex treatment in 1-18 months for 75 cases
 
3 months
6 months
12 months
%
Radiation-related brain disease
0
0
0
0
Tympanitis
0
2
3
3.2
Stiff faces
0
0
0
0
Mouth opening damage
0
0
0
2.1
Skin damage
0
0
0
0
Hear loss
6
0
0
0
Hypothyroid pituitary
0
0
0
0
Blood system
0
0
0
0
Immune system
0
0
0
0
Oral cavity mucous membrane complication
45
0
0
4.8
Radioactive tooth
0
0
1
1
Nervous damage
0
0
0
0
Radioactive brain spinal desease
0
0
0
0
Acute parotitis complication
3 (0.5-2)
0
0
3.2
Table 3: 318 months visit to 49 cases of Phase I-IIab after complex treatment
 
Cases
3 months
6 months
12 months
18 months
Image inspection
49
Shrinking of tumor, rhinitis
Tumor and lymphatic node disappears
Clean nasopharyngeal cavity, neck lymphatic structure unclear 
Clean nasopharyngeal cavity and symmetric tissue
Pathologic
25
Phlogistic putrescence C
Necrotic cells
Metabolized tissue C
Normal tissue
Digital endoscopy
49
Radioactive blood shortage, tumor changed or disappear
Radiation area paleness, a little pus
Radiation area Tissue sheet putrescence
Normal Tissues
 
Table 4 26 cases of follow-up (318months) on treatment of SRS+SRT
Months
Cases
Imaging
Pathologic
Digital endoscopy
Part Recrudescence
Distant Metastasis
Death
3
26
Tumor lymphatic node Shrink Obviously
Phlogistic Necrotic cells
Blood 杝hortage Changed in the irradiation area
Nil
One case of  distance osseous metastasis
Nil
6
26
Tumor and lymphatic node disappears
Necrotic cells
Radiation area paleness, a little pus
Nil
One case of encephalic, jaw, liver & osseous metastasis
Nil
12
26
Clean nasopharyngeal cavity, neck lymphatic structure unclear
Metabolized epidermis Cell
Radiation area Tissue sheet putrescence, change
Nil
Nil
1 case
18
26
Clean nasopharyngeal cavity and symmetric tissue
Normal tissue & mucous membrane
Tissues structure normal
Nil
Nil
Nil
 

Discussion:

Nasopharyngeal cancer (NPC) was once called 揋uangdong Cancer� in the area with high disease incidence like Guangdong, Hainan, Fujian, Taiwan, Hongkong, etc . According to the Stat. & investigation, the incidence of the disease in Guangdong and Hainan are 210,000 and 100,000 respectively, and the death rate 149,000 & 100,000. Esp. the incidence is even higher in Zhaoqing in middle Guangdong, Foshan in west Guangdong and Guangzhou area. The incidence in Sihui of Zhaoping for male is 14.9/100,000, for female is 12.11/100,000; Zhongshan city male 21.73/102,000, female 8.66/100,000; Hongkong male 24.3/100,000, female 10.2/100,000; Hainan male 23.5/100,000, female 9.81/100,000, and Taiwan male 7.7/100,000, female 2.33/100,000. In China, the incidence of nasopharyngeal cancer (NPC) decreases gradually from the Southern area to the Northern. The NPC has apparent race gender, the yellow-colored people are liable to take the disease (Chinese, Malay, Indonesian, Thai, Vietnamese & Filipino). There are slim chances for the white people to take the disease, the incidence for American is 0.63/100,000, of which the immigrated Chinese is 7 times higher of that of the locals.

Nosogenesis: 1. 3.4 Ruo Bing Bi of burning firewood ash is a carcinogen. 2. Smoking. 3. Food with nitrosamine. 4. Local environment & microelement: the Se content in the hair & blood of the NPC patients is lower. 5. Descendiblity. 6. EB virus: the IgA-VcA positive rate in the patients� serum is 41 times of that of the healthy. 7. The HLA: because human HLA is the gene element situated at the sixth pair of chromosome, in research, it抯 found that the disease incidence of the people with special HLA genotype (A2/B64, A33/B58) is 23 times higher than that of the normal people, and the gene location which increases the incidence of the disease is probably at MHC, central of Chass I gene & end of Chass III. Presently it has been found that the several Microsatallite earmarking locations in these genes are connected with the increase of the incidence of the NPC.

Pathologic Characteristic: The NPC is a malignant tumor occurring at the epidermis tissue of the nasopharynx, including the covered epidermis of the nasopharynx mucous membrane & the hidden sockets. Classified by Pathologic Histology, by differentiation degree, there are: High Differentiation, Low Differentiation and Non Differentiation. By Tissue Structure: 1. Squama Cancer. 2. Adenocarcinoma, Vesicle-shape nucleus Cancer. 3. Non Differentiation cancer. Clinical Representation: ? Neck Tumor, 70%-80% of the patients had neck tumors when identifying the diagnosis, this is because there are rich Lymph tracts, it is easy for the cancer to transfer from these lymph to the neck lymphatic node or other parts of the body such as the bones, the lungs and the liver. ? The nasal mucus or phlegm with blood threads; the canker & bleeding on the surface of the nasopharyngeal tumor will result in nasal mucus or phlegm cancer, esp. the phlegm with blood thread from the nasal sides. It is rare that the heavy bleeding is from the front nostril. ? The Nasal symptoms: including the snuffle, pus nasal mucus, effluvial secretion, etc. The causes: nasopharyngeal tumor clogs up the nostril and the nasal cavity, or the canker of the tumor. ? The ear symptoms: mainly caused by damage of the functions of the ear & pharynx canal. The ear & pharynx canal can balance the pressure in the eardrum cavities. For example, you will feel a stuffed/stuffy ear when you are climbing or flying, you will feel suddenly relieved if you open the ear & pharynx canal by swallowing the sputa, thus to balance the pressure in the eardrum cavity. This helps to explain why ear stuff, tinnitus, eardrum fluid accumulation, auditory obstruction etc. result from nasopharyngeal tumor impinging the pharynx canal. ? Headache: nasopharynx is at the central of the encephalon, apart from nasal antrum & skull cavity. When nasopharyngeal cancer is impinging nasal antrum, encephalon or skull cavity, the headache occurs, and the headache is unilateral. ? Symptoms of the encephalon nerves: nasopharynx is at the central of the encephalon, separated from the skull cavity by the firm skull. There are passage for vascular nerves around the nasopharynx, headache & functional obstruction will occur when nasopharyngeal cancer is impinging into the skull cavity along these passages. For example: numb face will occur when trigeminal is being attacked. Eyeball moving malfunction, difficult swallowing & hoarse voice will result from pneumogastric nerve malfunction.

Clinical Inspection: 1. Head & neck inspection: to inspect if there is any NPC expansion outwards for nasal cavity, oral cavity, earlap passage, tympanum, eye socket & soft palate; to inspect if there is eyesight decline, ablepsia & systemic lymphatic node. 2. CT inspection to know the location of the tumor inside nasopharynx cavity, whether the cavities are symmetric or distorted; whether the eye sockets became shallow or obstructed. 3. B-type Ultrasonic Inspection, it is easy & suitable for diagnosis & treatment of the NPC in the right, it is mainly used for inspections for liver, neck, peritoneum, etc., to find out whether there is any neck, liver metastasis. 4. Radioactive nucleus os imaging diagnosis: its accuracy rate for os metastasis positive is 30% higher than that of X Ray, and we can find out the focus 3-6 months earlier by using the above method.

Treatment:

Therapies have been applied for the NPC and the curative effect has been proved positively. The survival rate in I-IV phase is 45-50%, of which the recrudescence rate for 15 years is 35-40%. Fatality was mainly caused by systemic metastasis. But the side effects & sequela after the radioactive treatment will affect the life quality of the patient, thus decreasing the natural immunity affecting existent time.

Common post-radiation reactions:

1. The systemic radiation reactions: fatigue, dizzy, dyspeptic, nausea, vomit, ageusic, insomnia or lethargy.

2. Mucoumembranous reactions: after 40Gy Radiation, mucous membrane oedema or increasing blood effusion may occur at the mucous membrane inside the oral pharynx, nasopharynx, nasal cavity & nasal sinus. There will be dot & sheet white membrane or sheet membrane. There will be pain in pharynx & larynx, difficult in taking food and snuffle nose in the process of radiation.

3. Fluid gland reactions: apparent decrease in saliva, and the patient will feel thirsty & difficult in taking food.

4. Reaction for skin and endermic tissue: There will be red speckles, pigmentation, hair falling off & dry desquamation in the radiation area. If there is a fast radiation, oedema will occur, if the radiation continues, blisters will occur and the blister will melt into chronic desquamation, fluid effusion & putrescence.

5. The terminal stage reactions for the radioactive treatment: There will be skin & endermic tissue atrophy, thinner skin and pigment fading in the face.

6. Difficult in opening the mouth: in different degrees.

7. Radioactive decayed tooth and radioactive lower jaw putrescence.

8. Radioactive tympanitis

9. Radioactive encephalopathy & spinal cord damage/damnification.

Aiming at the above treatment complication, the experts have been exploring researching & summarizing approaches of more effective, from the early X-Ray treatment instrument, CO distance treatment instrument, & CS central instrument to the presently wide-spread linear accelerator. But they are restricted by problems of energy output, depth dose, half field, dose curve etc, this is why there is multi-leaves instruments other instruments, etc. Gamma system meets all the above requirements/projects, with accurate three-dimensional Localization Frame, it can guide the heavy dose radiation to the target at one time, protecting & reducing the radioactive damage/damnification to the normal important nervous tissue around the target.

The advantage for NPC treatment of Gamma system + normal Radioactive therapy: 1. Can give sufficient dose at one time to cause ischemic putrescence of the tumor in a short term, even the tumor containing anaerobic cells will also die under the above circumstance. The therapy time will be reduced as it is unnecessary to repeat the therapies. 2. Not under the control of the 4 splitting periods. 3. Little side effect (bigger dose rate ratio of focus to surface, smaller penumbra), avoid the damage/damnification for the nerve & tissue skin caused by the long term radioactive therapy. 4. The flexible dose curve can achieve the effect of bigger central dose, smaller edge dose & small field radioactive therapy. By 40% dose curve, it can get 18Gy within 2cm of tumor. As the Gamma system is not effective to the transferred cancer cells, thus, for a better all-round curative effect, we now combine Gamma system with linear accelerator to learn from others's strong points to offset its� weakness, it has undoubtedly broken a new approach for NPC treatment.

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Treatment on Nasopharyngeal Carcinoma (NPC)
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