Proton and Radiation Therapy Center

Website: Proton and Radiation Therapy Center

Chang Gung Memorial Hospital Proton and Radiation Therapy Center is the largest proton therapy center of Southeast Asia and is also the first proton therapy center in Taiwan. The Proton and Radiation Therapy Center establishment is a milestone in Taiwan cancer treatment. The main team members include radiation oncologists, medical physicists, medical radiotherapists, nurses, maintenance engineers and system operators, nutritionists, social workers and so on. The Center provides the most advanced radiotherapy, friendly medical environment and a full range of professional medical care services for cancer patients in Taiwan and all around the world. The Center has the most advanced radiotherapy equipment, including four proton therapy rooms and ten new linear accelerator treatment rooms, which are expected to serve about 3,000 patients with linear accelerators radiotherapy and 1,500 patients with proton-treatment per year. 


Service Items

Photon Therapy

True Beam
RapidArc
Novalis
Image-guided Radiotherapy
Respiratory Gating Radiotherapy
Deep inspiration breath hold radiotherapy)
Intra-operative Radiotherapy (Intrabeam)
Intensity Modulated Radiotherapy
Brachytherapy

Proton Therapy

Pencil Beam Scanning
Wobbling

The characteristic of Proton Therapy

Proton therapy is currently the most expensive and advanced medical facility in the world. There are 36 proton centers and more than 90,000 cases in the world till late 2012, and the facility and patient number are still booming. Comparing to the X-ray, the proton passes through tissues with lower entrance dose, but releases large amounts of energy when it reaches the desired depth of treatment (the Bragg peak), and deposits no dose to the normal tissues behind tumor. Therefore, proton therapy not only attacks tumor precisely but lowers the dose of normal tissue and rate of complication. The proton therapy is shown a better choice in some specific type of tumor. With proton therapy, for example, the cure rate of skull base tumor, liver cancer, and early lung cancer are higher and the complication rate of pediatric tumor and head and neck cancer are lower.

 


The potential benefits of proton therapy

  • Lower radiation dose of normal tissue
  • Fewer treatment-related complication and improving the life quality
  • Lower risk of subsequent tumor caused by the radiation
  • Higher cure rate by increasing the dose to tumor


Varian TrueBEAM Radiotherapy Linear Accelerator

The Varian TrueBEAM Radiotherapy Linear Accelerator provides not only 6MV and 10MV high-energy photon beams at a traditional dose rate (600 MU/min), but also special high intensity modes in 6MV and 10 MV-FFF (Flattening Filter Free). The maximum output dose can reach 2400 MU per minute, which is four times the normal mode of 600 MU per minute, thus dramatically decreasing treatment time for patients. Furthermore, the accuracy in mechanical movements and beam control of TrueBEAM is also the most advanced among all accelerator equipment. This device uses an all- digital method to combine radiotherapy and image-guided positioning to provide the best quality of radiotherapy to patients with the simplest operations. Due to the high dose rate, the radiation shielding plan has to be carefully re-evaluated for the operation venue in order to ensure protection from radiation for both staff and patients. At the same time, the high- precision mechanical apparatus and high-accuracy digital control system require a more comprehensive verification procedure to ensure the high quality of the equipment.

For quality verification, according to the standard operating procedure for testing received by medical physicists, the verification includes the complete testing of the following: mechanical movement accuracy of each component, energy of the output beam, validity of dose distribution, and effectiveness of each operative function. Overall, the mechanical movement accuracy of TrueBEAM is < 1 mm and the beam energy accuracy is < 0.5%. The level of accuracy is sufficient for executing stereotactic radiotherapy, stereotactic radiosurgery (SRT/SRS) or even stereotactic body radiotherapy (SBRT), which requires the highest accuracy.


Image Guided Radiation Therapy (IGRT)

Traditionally, physicians need to increase the safety margin around the tumor for conventional radiation therapy to ensure that the radiation remains within the tumor area; thus, we cannot effectively spare normal tissue organ. These limitations were mainly due to patient setup uncertainties and internal organ motion. Image-guided radiation therapy (IGRT) provides high-resolution, two-dimensional imaging and three- dimensional volumetric images prior to treatment to pinpoint bony landmarks or internal markers to ensure treatment accuracy and that the same position is targeted in every treatment session. Furthermore, it minimizes the deviation of internal organ motion or patient setup uncertainties, as well as decreases the irradiation to normal organs.

Through more precise targeting of the beam to tumors, doses to the tumors can be increased and the non-target volumes can be reduced. Higher radiation doses in tumors have been shown to enhance tumor control and better spare non-target regions, reducing the possibility of side effects after radiotherapy.

The On-Board Imager® kV imaging system with cone-beam CT and imaging fusion technique provides more precise localization information and better treatment quality and accuracy. Due to the need of x-ray imaging and patient positioning correction before each treatment for image guided radiotherapy, it takes about four to five minutes more than the conventional radiation therapy treatment time.


Respiratory Gating Radiotherapy

The respiratory gating radiotherapy technique is especially useful for tumors that move, such as those in lung and liver cancer. CGMH introduces the Real-time Position Management TM (RPM) respiratory gating system, which gates the beam delivery during treatment to account for organ motion. Information about tumor movement can be realized by using an infrared camera to detect the patient breathing in and out during treatment; then the respiratory gating signal can trigger the LINAC accelerator x-ray beam to treat the tumor within the gated phase to assure the accuracy of treatment position. A non-invasive marker box is placed on the patient’s body and the infrared system tracks the chest wall’s movement during the CT imaging. The big bore CT simulator with four-dimensional CT capability provides the correlation of respiratory phase and tumor location with a dynamic time frame. During the treatment, the radiation beam is gated to when the target falls within the treatment field while avoiding critical organs. In this case, we can treat patients with high accuracy while minimizing treatment errors, and the patient can breathe normally and remain comfortable and with high compliance during the treatment. This technique takes about five to ten minutes more than regular treatment time.


Deep inspiration breath hold radiotherapy (DIBH)

The deep inspiration breath-hold technique (DIBH) can be applied to patients with breast or lung cancer as one of the respiratory gating techniques. The main purposes are expanding the lung volume and increasing the distance of the heart to the treatment region, as well as to minimize overall organ motion. The patient needs to be able to control himself or herself during the deep inspiration breath-hold, based on the visualization goggle display.


Intraoperative radiation therapy (IORT) in treating early breast cancer

Intraoperative radiation therapy (IORT) delivers a single, high dose of radiation therapy to a tumor bed during surgery. The rationale behind using IORT is delivering the radiation precisely to the targeted area with minimal exposure to the surrounding normal tissues, which are displaced or shielded during the IORT. Comparing to the conventional postoperative whole breast irradiation, IORT can lower the dose to the skin, heart and lung and thus reduces the complication rate without compromising the cosmetic outcome. It can also replace routine postoperative radiation therapy which would generally take 5-7 weeks. It is a much more convenient treatment option to the patients, and also prevents the local recurrence when patient cannot tolerate the long treatment course.

Two large-scale studies, TARGIT-A and ELIOT trials (more than 3000 and 2000 patients, respectively), were published. The phase 3, prospective TARGIT-A trial showed by adopting INTRABEAM system, The 4-year risk for local recurrence was 1.2% for INTRABEAM versus 0.95% for conventional treatment. Moderate to serious complication were much the same between groups (3.3% vs. 3.9%, respectively). There are no statistic difference between groups. ELIOT trial revealed the risk for 3-year local recurrence in IORT group was 2.3%.

The Linkou CGMH introduced the first INTRABEAM system in Taiwan and got certificated by the Ministry of Health and Welfare in 2012. During the operation, after the tumor is resected, we put the INTRABEAM sphere system to the postoperative cavity and applying the radiation therapy. The therapy takes about 20 minutes, and after the radiotherapy, the surgeon will close the wound. Therefore, we can largely reduce the radiation therapy course. However, there are some exceptions. When the pathologic examination showed residual tumor on the surgical margin, the operation should be arranged again and followed by postoperative radiation therapy for 5 weeks. Also, when pathologic examination revealed infiltrating lobular carcinoma or diffuse lymphovascular infiltration, the patient will still need additional radiation therapy for 5 weeks.

Dr. Ji-Hong HONG

Specialty:
Gynecologic tumors, Prostate cancer, Genitourinary tumors, Gastrointestinal tumors

Dr. Joseph Tung-Chieh CHANG

Specialty:
Proton Therapy. Head and Neck Cancer. Nasopharyngeal cancer Radiotherapy, Breast cancer, Hepatoma, GI cancer, Health related Quality of life research, Patient Decision Making Sharing and Coaching

Dr. Ngan-Ming TSANG

Specialty:
Head and neck cancer, Nasopharyngeal carcinoma, Thyroid cancer, Digestive system cancer, Liver cancer, Colorectal cancer

Dr. Chen-Kan TSENG

Specialty:
Radiotherapy for adult CNS tumor, esophageal cancer, sarcoma, and the pediatric cancers, radiosurgery

Dr. Chun-Chieh WANG

Specialty:
Proton and Photon radiotherapy for brain, lung and Gyn cancers. Combining RT with immunotherapy.

Dr. Ping-Ching PAI

Specialty:
Breast cancer, esophageal cancer, brain tumor, chest tumor

Dr. Chien-Yu LIN

Specialty:
Radiotherapy for Head and Neck Cancer, Nasopharyngeal Cancer

Dr. Kang-Hsing FAN

Specialty:
Proton therapy, radiotherapy for prostate cancer and genitourinary tract cancer, radiotherapy for head and neck cancer

Dr. Bing-Shen HUANG

Specialty:
Liver and upper GI cancers, Nasopharyneal cancer and head and neck cancers

Dr. Tsung-Min HUNG

Specialty:
Esophageal cancer, Nasopharyneal carcinoma, Head and neck cancers

 

Beam Delivery System

The proton therapy machine has two different treatment techniques to meet the individual needs of tumor treatment, Pencil Beam Scanning and Wobbling. The principle of Wobbling involves sending a narrow proton beam through a magnetic field of the X- and Y-axes and deflectors while it expands with a rotation of a specific radius into a broader beam with a wider range. When it passes through the ridge filter, the vertical axis expands into SOBP, passes through the compensator and collimator, and then conforms before reaching the body. Another method that can reduce unnecessary normal tissue dose involves using layer stacking and a multileaf collimator (MLC) that can adjust the field size. This way, the dose distribution can be done as shown in the figure below. The figure clearly shows that the orange block, which represents normal tissue, receives a much smaller dose. This advanced technology is being used by our Proton Therapy Center. Since the energy output of the cyclotron is fixed (230MeV), by using the energy selection system (ESS), the energy level that reaches the treatment site can be adjusted. Different energy levels can penetrate different depths. Therefore, by using adjustment mechanisms, the tumor is divided into different layers of the same width. Treatment starts from the deepest layer and gradually moves upwards, while the use of the multileaf collimator follows the 3D shape of the tumor.

 

The principle of Pencil Beam Scanning involves sending a narrow proton beam through a magnetic field of the X- and Y-axes and distributing it directly in the field by scanning. This technique controls the weighted dose of each point in the field to achieve "Intensity Modulated Proton Therapy (IMPT)". This advanced technology is currently in the Proton Therapy Optimization Plan and is essentially the direction of the future of proton therapy.


Patient Position System 

Digital Imaging Positioning System: To ensure the positional accuracy of proton therapy, every treatment room is equipped with a digital imaging guiding system, which acquires images through three different methods: digital radiography, fluoroscopy and computed tomography.

A. Digital radiography can acquire two orthogonal two-dimensional images to match the treatment site. 

B. Fluoroscopy can view lesion displacement caused by a variety of reasons, such as breathing, and adjust treatment to such breathing with the aid of proton therapy equipment.

C. Computed tomography is used to compare its image with the simulated image from the computer treatment plan system to ensure the accuracy of the treatment site.


X-ray Imaging Positioning System


Digital Radiography


Robotic Couch

After the Digital Imaging Positioning System determines the correct patient position on the couch, this information is immediately sent to the robotic couch for a 6-dimensional shift. The robotic couch is a specialized couch developed by combining an industrial computer-controlled robotic arm and a radiotherapy couch. The robotic couch has a total of six drive motors, which enable it to move along six axes and rotate with an accuracy of 0.01 mm. Not only can it measure the weight of a patient (maximum user weight 200 kg), but it can also compensate for inclinations due to weight. It is the most advanced and accurate couch among radiotherapy equipment today.

Comparison between proton therapy and other radiotherapies

  Proton therapy RapidArc Cyberknife Tomotherapy Gamma Knife

Treatment sites

Whole Body Whole Body Whole Body Whole Body Head only (<3cm)
Beam Proton Beam X-Ray X-Ray X-Ray Gamma-Ray
Low dose bath area Limited Moderate Moderate Moderate Moderate
Radiation dose to nearby normal tissue Limited Fair Fair Fair Fair
Image-Guided Radiation Therapy Yes Yes Yes Yes No
Fractionation Yes Yes Yes Yes No
Treatment time for each fraction 20~60 mins <5 mins 20 mins-2 hours <30 minutes 20 ~60 mins
Pros Reduce radiation dose exposure to normal tissue in order to reduce  treatment-related toxicities Rapidly deliver 360 degree volumetric Modulated Arc Therapy (VMAT) and reduce the discomfort of long treatment time. Use x-ray images to correct setup or positioning errors during the treatment Use tomography (CT) for setup localization before treatment High fixation and treatment accuracy
Cons Expensive Due to the complexity of the plan, it takes more time for treatment planning. Repeated x-ray imaging further increases the treatment time and radiation dose Not able to instantly correct the treatment error caused by displacement of localization Only can treat small head lesions. Treatment time will be increased as radioactive sources decay.

 

A lot of curable cancer could achieve high curative and low complication rate when using proton beam therapy combining with surgical treatment or chemotherapy. As shown in the figure, the radiation dose was represented by different colors. Areas covered by red color are low dose area, and areas covered by blue color representing the high ones. In addition to irradiating cancer cells, proton beam therapy could avoid scattered radiation dose affecting the surrounding normal tissues. Therefore, the figure of proton beam therapy clearly shows the surrounding normal tissues receive scanty or no radiation dose. Aside from improving life quality during and after radiotherapy, using the proton beam therapy could also lower the risk of secondary cancer occurring in the previously normal tissues caused by radiotherapy.


Brain tumor

Lowering the radiation dose to normal brain tissues could further minimize the damage to brain tissue. This would reduce the impact on memory and endocrine function. Thereby, the quality of life is less affected after treatment.

  • Indication: (1) Resected tumor with positive margin    (2) Inoperable tumor with indication of radiosurgery, such as larger arteriovenous malformation, acoustic neuroma, pituitary adenoma and etc…


Head and neck cancer

When the proton beam therapy is utilized in treating the cancer in nasopharynx or oral cavity, radiation dose in oral cavity, hypopharynx and esophagus could be lowered or reduced to no dose. In this way, damage to the oral mucosa and throat was cut down, which could reduce the complication of pain, dry mouth, taste change and lowering the need of nasogastric tube insertion. For other head and neck cancer, the possibilities of dry mouth, mucositis, sore throat, hearing impairment, trismus, neck fibrosis and swallowing difficulties are lower in patient using proton beam therapy than ones using photon therapy, and therefore improving patients’ quality of life.


Esophageal cancer

Reducing the irradiation dose to the heart and lung could minimize the impact on cardiopulmonary function. It would therefore lower the complication rate of surgical treatment after concurrent chemotherapy and radiotherapy.



Lung cancer

Reducing the irradiation dose to the heart, normal lung and esophagus could minimize the impact on cardiopulmonary function and lung fibrosis. It also reduced the pain while swallowing. By using proton beam therapy, complications caused by conventional concurrent chemotherapy and radiotherapy, such as esophagitis, heart burning sensation, pneumonia, and shortness of breath are lowered.

Indication: Stage I to III esophageal cancer

Contraindication: infiltrative tumor, multiple distant metastases (more than 3 sites)


Breast cancer

Common complications such as mild skin redness, swelling and eruption still occur in patients receiving proton beam therapy. The benefit of using proton beam therapy lies in reducing the radiation dose of heart, lung and contralateral breast. Using proton beam thereby reduce the risk of myocardial infarction, pulmonary function decline and secondary cancer in contralateral breast. Recent researches have shown that left breast cancer patients treated by conventional radiotherapy have higher risk of myocardial infarction as long-term complication. Therefore, the proton therapy could reduce the risk of myocardial infarction significantly.

  • Indication: (1) Internal or lower chest wall tumor    (2) Higher radiation dose of heart in conventional radiotherapy    (3) Bilateral reconstructed breast with permanent implantation    (4) Internal mammary lymph node metastasis    (5) Poor cardiopulmonary function    (6) Young age patient with intention to reduce lung and contralateral breast radiation dose
  • Contraindication: distant metastasis


Liver tumor

Proton beam therapy could achieve high radiation dose in liver tumor, and therefore reach a good local control. It also minimizes the influence of liver function and lower side effect in gastro-intestinal tract, such as nausea and vomiting. Patients who receive proton beam therapy would have lower rate of liver dysfunction, ascites and death.

  • Indication: (1) Patient that is inoperable or unwilling to receive surgical resection    (2) Tumor less than 5 cm: Tumor control rate is around 90~95%    (3) Tumor  from 5~10cm: Tumor control rate is around 85%    (4) Tumor larger than 10 cm: Tumor control rate is around 45%    (5) Tumor recurrence after previous surgical resection or failed to treat the tumor with radiofrequency ablation and trans-arterial chemo-embolization (6) Unable to control the lesion with surgical or other intervention    (7) Residual solitary tumor after small other small lesion being controlled.
  • Contraindication: (1) Infiltrative tumor    (2) Multiple large tumor    (3) Distant metastasis    (4) For tumor that is close to gastro-intestinal tract, further evaluation is needed


Pancreatic cancer

By using proton beam therapy, radiation dose to liver, kidney and gastro-intestinal tract could be lowered, and therefore the influences on organ function are reduced. The benefits of using proton beam therapy in pancreatic cancer result in the reduction of complication such as nausea, vomiting, poor appetite or body weight loss. The better quality of life helps those patients more tolerable to the concurrent chemotherapy, which is almost the standard treatment in most patients. The higher completion rate of the chemotherapy results in elevation in overall survival. This is especially important in cancers with very poor prognosis such as pancreatic cancer.

  • Indication: (1) Inoperable tumor without distant metastasis    (2)  High risk of recurrence after surgical treatment    (3) Concurrent chemo-radiotherapy to increase the possibility of complete resection before surgical treatment
  • Contraindication: (1) Extensive lymph node metastasis    (2) Distant metastasis


Gynecology tumor

Proton beam therapy would result in lower scattering radiation dose to small intestine, colon and ovary, which lower the complication of diarrhea. Endocrine function decline would also be less affected.


Pediatric tumor

Children are more sensitive to the effects of radiation because they are still in the process of body growing and development. Proton beam therapy could significantly reduce the moderate and low scattering dose, and therefore reduce the influence on children growth and development. Furthermore, it also reduces the risk of secondary tumor. Take pediatric brain tumor for example, the benefit of proton beam therapy is that normal tissues behind the tumor have no radiation dose at all. In this circumstances, risks of secondary tumor and mental and development disorder are lowered.

The necessary evil when killing tumor

High-energy X ray produced by linear accelerator could be said as the standard modality of radiotherapy. The high penetrating ability of high-energy X-ray would even penetrate through the human body. Therefore, normal tissues in front of the tumor would receive higher radiation dose, and the tissue behind still receive residual dose. Take a 3-cm tumor for example, the X-ray would release its energy in its way through the tumor, but the damaged area would exceed 3 cm. Therefore, normal tissues are affected.

During the war between radiation and tumor cell, some of the cancer cells are perished, but some are merely injured. However, those injured cells could be repaired and grow again under sufficient time, energy and nutrient. To totally eradicate cancer cells, adequate radiation dose is needed. However, when we try to concentrate the radiation dose to the tumor, the price is that normal tissue prior to the tumor cell would receive radiation dose higher than tumor cell itself. Meanwhile, the X-ray keep on going after passing through the tumor area, and therefore causing dose accumulation in normal tissue behind the tumor. The resulting damage may cause secondary cancer or other disorder day after day.

The radiation dose to normal tissues is the necessary evil of conventional radiotherapy. To avoid complication from scattering radiation, conventional radiotherapy utilizes the photon beam from different angle, intending to even the dose that scattered to surrounding normal tissues.

Complications of conventional radiotherapy (Photon beam therapy)

(1) Acute complication: Usually occur during radiotherapy. Complications mostly occur as acute inflammation and mucosa damage. They would occur within weeks and resolve few weeks after completing radiotherapy.

(2) Chronic / late complication: Usually occur months or years after radiotherapy. Most late complications occur as chronic inflammation, fibrosis and vascular disorder, and mostly they would not resolve.

The quality and quantity of complication vary according to the radiation dose, body part and personal body nature. Some have no complication and some have severe complication. There is no universal condition of complication severity. Moreover, complication does not correlate to the cure rate. A fully cured patient may have severe complication or have little complication.


What are the common complications?

Due to the tumor destruction and inflammatory reaction, patients would have general reactions as mild local swelling, malaise and poor appetite in initial days of radiotherapy. The resting specific complication varies according to the tumor location, including nausea, vomiting, oral pain, taste change, dysphagia, voice change, body weight loss, diarrhea, hair loss, skin scaling… etc. Especially in head and neck, abdominal and large area irradiation, more severe reaction may occur. Long term complication may occur as dry mouth, trismus and swelling difficulties in head and neck cancer; lung fibrosis and difficulties in breathing in lung; liver function decline and gastro-intestinal ulcer…etc in abdominal and pelvic irradiation.

Since the start of the proton center on 2015/11/04, a total of 590 patients complete proton therapy. Liver tumors are the largest number disease with nearly one-third of the tumors (as shown below). The other major tumors complete treatment including (by order): Brain tumors, lung tumors, head and neck tumors, pancreatic tumors and breast tumors.

A total of 112 liver cancer patients have received and completed the proton therapy. Prospective observation the 112 patients treatment outcome, the first year local control rate is as high as 95% with nearly no local tumor recurrence. The first year overall survival rate is as high as 90%. In the proton provide very precise treatment to the liver tumor as Figure 2 and the patient's local tumor has very good control. However, the live cancer is multiple focal occurrence. Although the local control rate is as high as 95%, there are still 60% of patients who have new tumors in the liver absence exposure of proton therapy. The proton therapy is not only treatment for liver cancer, and we also provide multimodality treatment by teamwork with other specialist Doctor for liver cancer patients to improve the treatment outcome.

The left picture shows the proton therapy pre-treatment plan. The right picture is the image four months after the end of treatment. By comparison between the two pictures, the proton treatment is quite accurate.

Chang-Gung Memorial Hospital provides Faster and Finer Pencil-beam Scanning Treatment than MD Anderson Cancer Center

Papers from recent 3 years

  1. S. Y. Lin, C. S. Tsai, Y. C. Chang, K. K. Ng, T. C. Chang, W. H. Kao and J. H. Hong* The role of pretreatment FDG-PET in managing cervical cancer patients with enlarged pelvic lymph node(s) shown on MRI: a phase III randomized trial with long-term follow-up. Int. J. Radiat. Oncol. Biol. Phys. 2015, Jul, 92:577-585 (SCI)
  2. Chiang CH, Wu CC, Lee LY, Li YC, Liu HP, Hsu CW, Lu YC, Chang JT*, Cheng AJ*. (2016, 9) Proteomics Analysis Reveals Involvement of Krt17 in Areca Nut-Induced Oral Carcinogenesis. J Proteome Res. 15(9):2981-97. doi: 10.1021/acs.jproteome.6b00138. Epub 2016 Aug 4. (共同指導作者)
  3. Huang BS, Chen WY, Hsieh CE, Lin CY, Lee LY, Fang KH, Tsang NM, Kang CJ, Wang HM, Chang JT*. (2016, 9) Outcomes and prognostic factors for surgery followed by modern radiation therapy in parotid gland carcinomas. Jpn J Clin Oncol. 46(9):832-8. doi: 10.1093/jjco/hyw067. Epub 2016 Jun 17.
  4.  Li YC, Chang JT, Chiu C, Lu YC, Li YL, Chiang CH, You GR, Lee LY, Cheng AJ*. (2016, 5) Areca nut contributes to oral malignancy through facilitating the conversion of cancer stem cells. Mol Carcinog. 55(5):1012-23. doi: 10.1002/mc.22344. Epub 2015 Jun 18. (共同第一作者)
  5.  Wang HM, Lin CY, Hsieh CH, Hsu CL, Fan KH, Chang JT, Huang SF, Kang CJ, Liao CT, Ng SH, Yen TC. (2016, 4) Induction chemotherapy with dose-modified docetaxel, cisplatin, and 5-fluorouracil in Asian patients with borderline resectable or unresectable head and neck cancer. J Formos Med Assoc. 2016 Apr 25. pii: S0929-6646(16)30015-8. doi: 10.1016/j.jfma.2016.03.005. [Epub ahead of print]
  6.  Adel M, Tsao CK, Wei FC, Chien HT, Lai CH, Liao CT, Wang HM, Fan KH, Kang CJ, Chang JT, Huang SF. (2016, 4) Preoperative SCC Antigen, CRP Serum Levels, and Lymph Node Density in Oral Squamous Cell Carcinoma. Medicine (Baltimore). 2016 Apr;95(14):e3149.doi: 10.1097/MD.0000000000003149.
  7. Lu YC, Chang JT, Chan EC, Chao YK, Yeh TS, Chen JS, Cheng AJ*. (2016, 3) miR-196, an emerging cancer biomarker for digestive tract cancers. J Cancer. 7(6):650-5. doi: 10.7150/jca.13460. eCollection 2016. (共同第一作者)
  8. Hsieh CE, Lin CY, Lee LY, Yang LY, Wang CC, Wang HM, Chang JT, Fan KH, Liao CT, Yen TC, Fang KH, Tsang YM*. (2016, 3) Adding concurrent chemotherapy to postoperative radiotherapy improves locoregional control but Not overall survival in patients with salivary gland adenoid cystic carcinoma-a propensity score matched study. Radiat Oncol. 2016 Mar 22;11(1):47. doi: 10.1186/s13014-016-0617-7.
  9. Chen SH, Wang HM, Lin CY, Chang JT, Hsieh CH, Liao CT, Kang CJ, Yang LY, Yen TC. (2016, 2) RGD-K5 PET/CT in patients with advanced head and neck cancer treated with concurrent chemoradiotherapy: Results from a pilot study. Eur J Nucl Med Mol Imaging. 2016 Feb 27. [Epub ahead of print]
  10. Ng SH, Liao CT, Lin CY, Chan SC, Lin YC, Yen TC, Chang JT, Ko SF, Fan KH, Wang HM, Yang LY, Wang JJ. (2016, 2) Dynamic contrast-enhanced MRI, diffusion-weighted MRI and 18F-FDG PET/CT for the prediction of survival in oropharyngeal or hypopharyngeal squamous cell carcinoma treated with chemoradiation. Eur Radiol. 2016 Feb 24. [Epub ahead of print]
  11. Tsang NM, Pai PC*, Chuang CC, Chuang WC, Tseng CK, Chang KP, Yen TC, Lin J, Chang JT. (2016, 1) Overweight and obesity predict better overall survival rates in cancer patients with distant metastases. Cancer Med. 2016 Jan 26. doi: 10.1002/cam4.634. [Epub ahead of print]
  12. Wang HM, Cheng NM, Lee LY, Fang YH, Chang JT, Tsan DL, Ng SH, Liao CT, Yang LY, Yen TC. (2016, 2) Heterogeneity of (18) F-FDG PET combined with expression of EGFR may improve the prognostic stratification of advanced oropharyngeal carcinoma. Int J Cancer. 138(3):731-8. doi: 10.1002/ijc.29811. Epub 2015 Sep 1.
  13. 12. Lee LA, Huang CG, Tsao KC, Liao CT, Kang CJ, Chang KP, Huang SF, Chen IH, Fang TJ, Li HY, Yang SL, Lee LY, Hsueh C, Lin CY, Fan KH, Chang TC, Wang HM, Ng SH, Yen TC. (2015, 11) Human Papillomavirus Infections are Common and Predict Mortality in a Retrospective Cohort Study of Taiwanese Patients With Oral Cavity Cancer. Medicine (Baltimore). 94(47):e2069. doi: 10.1097/MD.0000000000002069.
  14. Liao CT, Fan KH, Kang CJ, Lin CY, Chang JT, Tsang NM, Huang BS, Chao YK, Lee LY, Hsueh C, Wang HM, Liau CT, Hsu CL, Hsieh CH, Ng SH, Lin CH, Tsao CK, Fang TJ, Huang SF, Chang KP, Yen TC. (2015, 9) Clinical Outcomes of Patients with Resected Oral Cavity Cancer and Simultaneous Second Primary Malignancies. PLoS One. 10(9): e0136918.
  15. Lee LY, Chen YJ, Lu YC, Liao CT, Chen IH, Chang JT*, Huang YC, Chen WH, Huang CC, Tsai CY, Cheng AJ*. (2015, 9) Fascin is a circulating tumor marker for head and neck cancer as determined by a proteomic analysis of interstitial fluid from the tumor microenvironment. Clin Chem Lab Med. 2015 Mar 10. Clin Chem Lab Med. 53(10):1631-41. doi: 10.1515/cclm-2014-1016.
  16.  Hsu YP, Hsieh CH, Chien HT, Lai CH, Tsao CK, Liao CT, Kang CJ, Wang HM, Chang JT, Huang SF. (2015, 8) Serum markers of CYFRA 21-1 and C-reactive proteins in oral squamous cell carcinoma. World J Surg Oncol. 21;13:253. doi: 10.1186/s12957-015-0656-9.
  17. Chen SC*, Lai YH, Huang BS, Lin CY, Fan KH, Chang JT. (2015, 6) Changes and predictors of radiation-induced oral mucositis in patients with oral cavity cancer during active treatment. Eur J Oncol Nurs. 19(3):214-9.
  18. Cheng NM*, Fang YH, Lee LY, Chang JT, Tsan DL, Ng SH, Wang HM, Liao CT, Yang LY, Hsu CH, Yen TC. (2015, 3) Zone-size nonuniformity of 18F-FDG PET regional textural features predicts survival in patients with oropharyngeal cancer. Eur J Nucl Med Mol Imaging. 42(3):419-28.
  19. Lu YC, Chang JT, Huang YC, Huang CC, Chen WH, Lee LY, Huang BS, Chen YJ, Li HF, Cheng AJ*. (2015, 2) Combined determination of circulating miR-196a and miR-196b levels produces high sensitivity and specificity for early detection of oral cancer. Clin Biochem. 48(3):115-21. (共同第一作者)
  20. Huang SF, Chang JT, Liao CT, Kang CJ, Lin CY, Fan KH, Wang HM, Chen IH. (2015, 1) The role of elective neck dissection in early stage buccal cancer. Laryngoscope. 125(1):128-33.
  21. Lapke N, Lu YJ, Liao CT, Lee LY, Lin CY, Wang HM, Ng SH, Chen SJ, Yen TC. (2016, 06) Missense mutations in the TP53 DNA-binding domain predict outcomes in patients with advanced oral cavity squamous cell carcinoma. Oncotarget. 2016 Jun 8. doi: 10.18632/oncotarget.9925. [Epub ahead of print]
  22. Chiang CH, Wu CC, Lee LY, Li YC, Liu HP, Hsu CW, Lu YC, Chang JT*, Cheng AJ*. (2016, 9) Proteomics Analysis Reveals Involvement of Krt17 in Areca Nut-Induced Oral Carcinogenesis. J Proteome Res. 15(9):2981-97. doi: 10.1021/acs.jproteome.6b00138. Epub 2016 Aug 4.
  23.  Huang BS, Chen WY, Hsieh CE, Lin CY, Lee LY, Fang KH, Tsang NM, Kang CJ, Wang HM, Chang JT*. (2016, 9) Outcomes and prognostic factors for surgery followed by modern radiation therapy in parotid gland carcinomas. Jpn J Clin Oncol. 46(9):832-8. doi: 10.1093/jjco/hyw067. Epub 2016 Jun 17.
  24. Chang C, Lin WN, Hsin LJ, Lee LA, Lin CY, Li HY, Liao CT, Fang TJ. (2016, 4) Reliability of office-based narrow-band imaging-guided flexible laryngoscopic tissue samplings. Laryngoscope. 2016 Apr 23. doi: 10.1002/lary.26016. [Epub ahead of print]
  25. Wang HM, Lin CY, Hsieh CH, Hsu CL, Fan KH, Chang JT, Huang SF, Kang CJ, Liao CT, Ng SH, Yen TC. (2016, 4) Induction chemotherapy with dose-modified docetaxel, cisplatin, and 5-fluorouracil in Asian patients with borderline resectable or unresectable head and neck cancer. J Formos Med Assoc. 2016 Apr 25. pii: S0929-6646(16)30015-8. doi: 10.1016/j.jfma.2016.03.005. [Epub ahead of print]
  26. Hsieh CE, Lin CY*, Lee LY, Yang LY, Wang CC, Wang HM, Chang JT, Fan KH, Liao CT, Yen TC, Fang KH, Tsang YM*. (2016, 3) Adding concurrent chemotherapy to postoperative radiotherapy improves locoregional control but Not overall survival in patients with salivary gland adenoid cystic carcinoma-a propensity score matched study. Radiat Oncol. 2016 Mar 22;11(1):47. doi: 10.1186/s13014-016-0617-7.(共同責任作者)
  27. Adel M, Liao CT, Lee LY, Hsueh C, Lin CY, Fan KH, Wang HM, Ng SH, Lin CH, Tsao CK, Huang SF, Kang CJ, Fang KH, Wang YC, Chang KP, Fang TJ, Yang LY, Yen TC. (2016, 3) Incidence and Outcomes of Patients With Oral Cavity Squamous Cell Carcinoma and Fourth Primary Tumors: A Long-term Follow-up Study in a Betel Quid Chewing Endemic Area. Medicine (Baltimore). 95(12):e2950. doi: 10.1097/MD.0000000000002950.
  28. Chen SH, Wang HM, Lin CY, Chang JT, Hsieh CH, Liao CT, Kang CJ, Yang LY, Yen TC. (2016, 2) RGD-K5 PET/CT in patients with advanced head and neck cancer treated with concurrent chemoradiotherapy: Results from a pilot study. Eur J Nucl Med Mol Imaging. 2016 Feb 27. [Epub ahead of print]
  29. Liao CT, Kang CJ, Lee LY, Hsueh C, Lin CY, Fan KH, Wang HM, Ng SH, Lin CH, Tsao CK, Fang TJ, Huang SF, Chang KP, Chang YL, Yang LY, Yen TC. (2016, 2) Association between multidisciplinary team care approach and survival rates in patients with oral cavity squamous cell carcinoma. Head Neck. 2016 Feb 18. doi: 10.1002/hed.24276. [Epub ahead of print]
  30. Liao CT, Chen SJ, Lee LY, Hsueh C, Yang LY, Lin CY, Fan KH, Wang HM, Ng SH, Lin CH, Tsao CK, Chen IH, Chang KP, Huang SF, Kang CJ, Chen HC, Yen TC. (2016, 2) An Ultra-Deep Targeted Sequencing Gene Panel Improves the Prognostic Stratification of Patients With Advanced Oral Cavity Squamous Cell Carcinoma. Medicine (Baltimore). 2016 Feb;95(8):e2751. doi: 10.1097/MD.0000000000002751.
  31. Ng SH, Liao CT, Lin CY, Chan SC, Lin YC, Yen TC, Chang JT, Ko SF, Fan KH, Wang HM, Yang LY, Wang JJ. (2016, 2) Dynamic contrast-enhanced MRI, diffusion-weighted MRI and 18F-FDG PET/CT for the prediction of survival in oropharyngeal or hypopharyngeal squamous cell carcinoma treated with chemoradiation. Eur Radiol. 2016 Feb 24. [Epub ahead of print]
  32. Chin SC, Lin CY, Huang BS, Tsang NM, Fan KH, Ku YK, Hsu CL, Chan SC, Huang SF, Li CH, Tseng HJ, Liao CT, Liu HL, Sung K. (2016, 2) Pretreatment Dynamic Contrast-Enhanced MRI Improves Prediction of Early Distant Metastases in Patients With Nasopharyngeal Carcinoma. Medicine (Baltimore). 95(6):e2567. doi: 10.1097/MD.0000000000002567.
  33. Lee LA, Huang CG, Tsao KC, Liao CT, Kang CJ, Chang KP, Huang SF, Chen IH, Fang TJ, Li HY, Yang SL, Lee LY, Hsueh C, Lin CY, Fan KH, Chang TC, Wang HM, Ng SH, Yen TC. (2015, 11) Human Papillomavirus Infections are Common and Predict Mortality in a Retrospective Cohort Study of Taiwanese Patients With Oral Cavity Cancer. Medicine (Baltimore). 94(47):e2069. doi: 10.1097/MD.0000000000002069.
  34. Liao CT, Fan KH, Kang CJ, Lin CY, Chang JT, Tsang NM, Huang BS, Chao YK, Lee LY, Hsueh C, Wang HM, Liau CT, Hsu CL, Hsieh CH, Ng SH, Lin CH, Tsao CK, Fang TJ, Huang SF, Chang KP, Yen TC. (2015, 9) Clinical Outcomes of Patients with Resected Oral Cavity Cancer and Simultaneous Second Primary Malignancies. PLoS One. 10(9): e0136918.
  35. Chen SC*, Lai YH, Huang BS, Lin CY, Fan KH, Chang JT. (2015, 6) Changes and predictors of radiation-induced oral mucositis in patients with oral cavity cancer during active treatment. Eur J Oncol Nurs. 19(3):214-9.
  36. Kang CJ, Lin CY, Yang LY, Ho TY, Lee LY, Fan KH, Wang HM, Huang SF, Chang KP, Fang KH, Ng SH, Liao CT*, Yen TC*. (2015, 1) Positive Clinical Impact of an Additional PET/CT Scan Before Adjuvant Radiotherapy or Concurrent Chemoradiotherapy in Patients with Advanced Oral Cavity Squamous Cell Carcinoma. J Nucl Med. 56(1):22-30.(共同第一作者)
  37. Huang SF, Tung-Chieh Chang J, Liao CT, Kang CJ, Lin CY, Fan KH, Wang HM, Chen IH. (2015, 1) The role of elective neck dissection in early stage buccal cancer. Laryngoscope. 125(1):128-33.
  38. Lin, S. Y., Tsai, C. S., Chang, Y. C., Ng, K. K., Chang, T. C., Kao, W. H., Lai, C. H., Hong, J. H. The Role of Pretreatment FDG-PET in Treating Cervical Cancer Patients With Enlarged Pelvic Lymph Node(s) Shown on MRI: A Phase 3 Randomized Trial With Long-Term Follow-Up. International Journal of Radiation Oncology Biology Physics 2015; 92(3): 577-585 (SCI)
  39. Kao, W. H., Shen, Y. L., Hong, J. H. What are the Potential Benefits of Using Proton Therapy in Taiwanese Cancer Patients? Biomedical Journal 2015; (ahead of print)
  40. Hsieh CE, Lin CY, Lee LY et al. Adding concurrent chemotherapy to postoperative radiotherapy improves locoregional control but Not overall survival in patients with salivary gland adenoid cystic carcinoma—a propensity score matched study. Radiation Oncology 2016; 11: 1-10.
  41. Huang BS, Chen WY, Hsieh CE et al. Outcomes and prognostic factors for surgery followed by modern radiation therapy in parotid gland carcinomas. Japanese Journal of Clinical Oncology 2016; 46: 832-838.
  42.  Hsieh CE, Lin CY, Lee LY et al. Postoperative Radiotherapy with or without Concurrent Chemotherapy for Salivary Gland Carcinomas. Therapeut Radiol Oncol 2015; 22(2): 89-101

Q:  How the radiotherapy (including proton therapy) kill cancer?

It was well known by doctors that X-ray could penetrate our body since 1890s. Because of this property, X-ray is widely used to exam different part of human body like chest, teeth or bone. Besides, a high energy X-ray (thousand times to diagnostic X-ray) could treat cancer or benign tumor.

Radiotherapy kills cancer by using high energy X-ray or particles which has high penetrating power to give tumor irradiation. This kind of treatment could kill cancer or suppress benign tumor growing.

This high energy radiation is made from special machines, like X-ray from linear accelerator, proton beam from cyclotron/synchrotron or from radioactive isotopes which would release gamma ray.

The mechanism for radiotherapy to treat cancer is that tumor cell have worse ability to repair after radiation damage and normal tissue have better ability for recovering. This difference was used to by radiation oncologist to treat disease. To avoid severe acute toxicities and late complications, we use fractionated treatment clinically, which could achieve tumor control and make normal tissue damage as low as possible. According to cancer type, disease severity and different treatment modalities, radiotherapy take minutes to hour every day from Monday to Friday and would cost 1 week to 2 months long.

There are also risks to take radiotherapy. High energy radiation would kill cancer but also damage normal tissue near cancer cell and thus complications (ex. Swallowing difficulty after radiotherapy to oropharyngeal cancer) occur. So radiation oncologist need evaluate the patient comprehensively before radiotherapy.


Q:  What the timing for Proton Therapy?

Radiotherapy (including Proton Therapy) usually combine with operation to cure cancer. Before operation, radiotherapy could reduce the tumor size and make operation easier. On the other hand, it is used to treat residual cancer cells after operation in order to prevent disease recurrence. However, radiotherapy could also be used for primary treatment to avoid operation and preserve organ function. Photon radiotherapy is generally used for cancer treatment and proton therapy is a new treatment having ability to reduce side effects even increase probability of tumor control.


Q:  What the process of proton therapy?

In our Proton and Radiotherapy Center, there have 4 treatment room in operation. You can make an appointment by telephone or from our web site. Please prepare the complete medical records, which would help radiation oncologist to evaluate your disease correctly and design a proper treatment plan. The contents of medical record needed is listed in following question. After you decide to take proton therapy, there had two nurses responsible for questions about proton therapy during the treatment process. All your problem could be solved by our doctor or professional nurses.

All the patients would receive comprehensive evaluation of their disease. The radiation oncologist would make a treatment plan according to each patient’s disease condition and tumor shape. This plan need a customized cast and simulation with computer tomography(CT) and would be calculated by computer. The time need for a plan is about 2 to 3 weeks and patient would start treatment after the plan finished.

The customized cast is needed to make sure your position is just like the simulation day. Some patient would need magnetic resonance imaging(MRI) exam to clearly define tumor region. Radiation oncologist would define treatment field (including tumor location and organ having to be spare) according to different kinds of image and the medical physicists would make a treatment plan base these terms. The final would be confirmed by the doctors before treatment.

The treatment would take 1 to 8 weeks, five days a week from Monday to Friday based on disease complexity. You would spend 30-60 minutes a day. If children patient needing sedation, there have to cost more time to do the treatment. The proton therapy is painless and feeless, and would not cause radiation residue after treatment.


Q:  Is proton therapy suitable for my disease? What kinds of cancer could managed with proton therapy?

In order to build a reasonable understanding about proton therapy, we should know that there also have limitations of proton therapy. Proton therapy is not suitable for all patients. It is kind of radiotherapy, and is suitable for different kinds tumor from whole body. Disease which could be treated by current photon radiotherapy can also executed by proton therapy. However, it can’t replace the role of chemotherapy, target therapy or most operations. For patient who is with disseminated disease or have multiple metastasis, the effects on overall survival is little even proton therapy could reach good local disease control, and thus these kind of patients would not be suggested to receive proton therapy.


Q:  What is the indications of Proton Stereotactic Radiosurgery?

Proton stereotactic radiosurgery is suit for patients with following conditions:
1. Intracranial tumors or vascular lesion, which is from 3~10 centimeter and the number of tumor/lesion is less than three.
2. Residual tumor after operation or recurrent tumor after treatment
3. Patient who is inoperable.


Q:  What information should I prepare before the clinic for proton therapy consultation?

Patient came for proton therapy consultation should prepare following information including:
1. Pathology reports
2. Previous radiation therapy and medical treatment record
3. Medical records and images like sonography, X-rays, computer tomography(CT), Magnetic Resonance Imaging(MRI) and positron emission tomography (PET).


Q:  How could I contact Chang-Gung Hospital to take evaluation of proton therapy?

If you want to know whether proton therapy is suitable to treat your disease, you may contact us for a professional evaluation. The contact information is following:
International Medical Center: +886-3-3184301
Tel: +886-3-3281200 ext. 5477
Email: wecare@chang-gung.comisc@cgmh.org.tw