Nasopharyngeal carcinoma (NPC) is a malignancy with an unusually variable incidence rate across the world. NPC has by far the highest incidence in southern China in the provinces of Guandong (formerly Kwantung, which is why NPC is sometimes called Kwantung tumour), Guang Xi and Fujian, and in Hong Kong. It has the lowest incidence of all pharyngeal cancers (naso, oro and hypo) in NorthAmerica and Europe, with only a relatively small number of cases seen annually within individual cancer centres.

Pathogenesis of NPC: A multi-step model

Previous epidemiologic studies have correlated NPC with three major well-defined etiologic factors: a genetically determined susceptibility in some individuals, an early-age exposure to chemical carcinogens, particularly of Cantonese salted fish, and an association with a latent Epstein-Barr virus (EBV) infection.3–5 In areas with a high incidence, NPC clustering in families suggests that both ethnic/geography and genetics may influence disease risk.
Unique interaction of environmental and genetic factors and latent EBV infection provides a progression model from normal nasopharyngeal epithelium to pre-invasive lesions and to invasive cancer, which is accompanied by accumulation of specific genetic and epigenetic changes. Identifying the critical genetic changes in the progression of this cancer has allowed the delineation of the possible sequence of events and a multi-step model for the pathogenesis and development of NPC (Fig 1). Progress in the elucidation of the molecular genetic changes that lead to the development of this cancer is likely to bring novel diagnostic and therapeutic procedures into routine clinical practice.

Treatment
NPC is one of the most technically difficult sites within the head and neck region to treat with radiotherapy because of the close proximity to the primary site of radiation sensitive structures such as the eyes and spinal cord. Also, when irradiating the neck nodes either prophylactically or because of the presence of regional disease, the skin surface anatomy relative to the nodal locations is far from simple geometry. This has led to the proposal of many different types of field arrangements, treatment phases with or without coning down field sizes and organ shielding techniques. These range from the use of orthovoltage X-rays to telecobalt to photons from linear accelerators with or without the use of electron beams and with different time–dose fractionation schedules. Chemotherapy is also an integral part of treatment protocols and, with the advent of high dose rate (HDR) remote afterloading machines, such as the microSelectron-HDR with its small 192Iridium source, the use of HDR brachytherapy for residual or recurrent disease is more often used today than in the past. Low dose rate (LDR) brachytherapy using a moulage technique has been in regular use in France for many years, formerly with radium but now using 192Iridium or 125Iodine.
NPC treatment in the new century will also, no doubt, see the routine use of intensity modulated radiation therapy (IMRT) and photodynamic therapy (PDT). Perhaps though, we have almost reached the final level of technological advances in radiation oncology, both for treatment delivery and treatment planning. However, there are a lot of fields waiting for us to explore, especially PDT and other new therapies.
It is an opportune time to review the treatments and outcomes of NPC over the last 100 years.

Historical era (1896–1950)

First successful X-ray therapy relief of pain: NPC (1896)
Ro¨entgen discovered X-rays on 8 November 1895. However, the first proven successful X-ray therapy of histologically verified cancer was not until June 1899, reported at the Swedish Society of Medicine meeting in December 1899. The first claim for treatment success was at a meeting of the Society of Physicians of Hamburg, Germany on 3 February 1896 and concerned treatment of an 89-year-old patient with NPC, the outcome of which is relief of pain.
Radiotherapy not considered for NPC (1900–1920)
X-ray therapy in the first decade of the 20th century was typically described in the 545 page textbook of 1907 by Mihran Kassabian, Director of the Roentgen Ray Laboratory of the Philadelphia Hospital, and the 1115 page textbook of 1910 by Sinclair Tousey, Consulting Surgeon to St. Bartholomew’s Clinic, New York. They considered X-rays to have therapeutic value only for cancers of the breast, sternum, oesophagus, larynx, stomach and bowels, and uterus. No text in the USA during this period mentioned NPC and nor did any European standard textbook. Neither was NPC mentioned as a site suitable for treatment using radium.
Radium brachytherapy (1921–1950)
It was not until the 1920s that NPC was considered to be practicable for radiation treatment, in part because, prior to this decade, X-ray tubes could seldom operate at 200 kV or above and consequently had extremely poor depth dose characteristics. With radium sources it was a different matter and in the early 1920s Georges Richard and Jean Pierquin at the Institut du Radium (now the Institut Curie), Paris first employed an intracavitary method using a cork containing a tube of radium for the treatment of primary NPC. This cork was held in the nasopharynx by retaining strings in the same manner as a posterior nasal pack for epistaxis.
Brachytherapy is regularly used for cases with small primary T1–T2, N0–N3 tumours of thickness below 10 mm, with radium now replaced by remote afterloading 192Iridium. It is combined with external radiotherapy to total doses in the range 76–84 Gy and also with chemotherapy. Brachytherapy for NPC continues into the 21st century. Today, CT and MRI are used for planning and moulage applicators are made individually.
X-ray therapy and teleradium (1921–1950)
Treatment techniques using several small fields, 200 kV X-rays or short source skin disease teleradium were common throughout the 1930s and 1940s with the Coutard, Paris method being the delivery over a 6–8 week period and the Radiumhemmet, Stockholm method delivering two 2-week external courses with an intracavitary radium application between the courses. In 1931 the Radiumhemmet results were quoted as a 5-year survival rate of 11.4% in 70 cases..

Transitional era (1951–1970)

This period saw the widespread introduction of 60Cobalt teletherapy, which marked the real start of megavoltage radiotherapy. Earlier, a very few van de Graaf machines operating at 2 MV had been installed in radiotherapy departments and by 1970 linear accelerators had begun to be installed in several major centres throughout the world. However, these had not yet begun to generally replace the use of 60Cobalt teletherapy in the industrialized world. It must be remarked that, even at the start of the 21st century, telecobalt still has a role to play in developing countries where the infrastructure for maintenance of the technologically more complicated linear accelerators is virtually non-existent. This is seen in the current market for refurbished telecobalt machines.
Elective neck irradiation
Douglas Quick of Memorial Hospital, New York was, in the 1920s, one of the first to suggest that radiotherapy could be used electively for possible subclinical disease, particularly for cancers of the buccal cavity and the lip. However, the external beam radiation machines then available were not able to deliver an adequate dose distribution to the lymph nodes of the neck; only relatively small sized fields were initially available and the depth dose characteristics were not optimal.
After telecobalt machines were available, several treatment planning schemes were proposed to prophylactically irradiate the neck nodes, and data on the frequency of particular nodal involvement was also reported.
Radiation field arrangements
As with the field arrangements for elective neck irradiation, many different variants of field arrangements, including shielding to minimize dose to the eyes and spinal cord, have been proposed.
Brachytherapy
By the 1950s and 1960s it had been realized that NPC, either primary, recurrent or residual disease, could be treated by intracavitary or interstitial brachytherapy. It was really only in Paris that the moulage method pioneered by Richard and Pierquin in the 1920s continued to be routinely used, although patient numbers were small. For example, Mazeron reported in 1987 that, for the years 1961–1975, a total of only 33 previously untreated NPC cases were treated by a combination of external beam therapy and intracavitary brachytherapy with 192Iridium wires.
Overall survival is 13 of 31 (42%), which although 31 is only a small number is an improvement. Nevertheless, 11 of 13 patients have been continuously disease free, although 13 of the 31 patients have died with active disease.
The cylinder was designed to fill the nasopharyngeal lumen, but in practice the source tended to rest on the superior surface of the soft palate and was therefore unsatisfactory.
Interstitial brachytherapy as a treatment for NPC did not start until after 1970 and although 222Radon seeds were temporarily implanted in many different cancer sites they were never implanted in the nasopharynx. For this brachytherapy method implants were permanent, using 198Gold or 125Iodine. However, this was not performed until the modern era.

Modern era (1971–)

Brachytherapy for primary, residual and recurrent NPC
Brachytherapy is a special radiotherapy technique that delivers dose at a short distance with a rapid dose fall-off. Brachytherapy is a useful addition to external beam irradiation in the treatment of patients with head and neck cancer. The advantage of limiting the high dose region to the tumour bearing area owing to the rapid dose fall-off is of particular interest because of the proximity of critical dose limiting structures to the nasopharynx.
This is especially true when treating recurrent or residual NPC because the region will already have received a high dose from the initial treatment using external beam radiotherapy.
Brachytherapy can be given as an interstitial implant or intracavitary treatment. A retrospective series seems to suggest that interstitial implant is better than intracavitary radiotherapy owing to certainty of dose delivery and higher tissue dose. However, only a prospective randomized trial can properly answer the question of whether interstitial implant is better than intracavitary treatment.
It is still controversial as to whether brachytherapy should routinely be given as part of initial therapy. It is favoured in studies by Teo et al, Wang, Levendag et al and Chang et al. An alternative method is to give brachytherapy only when residual or recurrent disease is documented or strongly suspected.

Intensity modulated radiotherapy (IMRT)
It is always the goal in radiotherapy to spare normal tissue from radiation as much as possible while maintaining high dose to target. Intensity modulated radiotherapy (IMRT) is advanced conformal radiotherapy which has potential to fulfill such goal.
In the 1990s IMRT has been delivered using one of the following three techniques: (a) manually cut partial transmission blocks; (b) computer controlled auto-sequencing static multileaf collimator (MLC); and (c) Peacock system using a dynamic multivane intensity-modulating collimator (MIMiC). A forward 3D treatment planning system was used for the first two methods and an inverse treatment planning system was used for the third method.
IMRT is like treating the tumor with multiple pencil beams with different intensities coming in multiple directions so that a defined dose can be given to a limited area and a sharp dose fall off can be achieved at the interface between tumor and the normal tissues. Such fine-tuned treatment is technically feasible recently with the advancement in computer for the dose computation, and with the improvement in radiotherapy machine hardware to execute the complex treatment. With the availability of IMRT and better planning systems to avoid normal structures, many of the severe complications may now be avoidable.
One definite advantage of IMRT is the ability to avoid the spinal cord and parotid gland. Accuracy is greatly improved by these modern technologies. With the advances in computing power, comparison of plans is easier than in the past when using only dose-volume histograms.
Early studies comparing IMRT plans with conventional treatment technique had shown encouraging dosimetric results, substantiating the theoretical advantage of inverse-planning IMRT in the management of NPC. It was shown that target coverage of the primary tumor was maintained and nodal coverage was improved, as compared with conventional beam arrangements. IMRT also resolves the problem of dose uncertainty at the junction between the primary tumor and neck lymphatic target volumes, as it enables the primary tumor and the upper neck nodes to be treated in one volume throughout. However, in order to maximize the benefit to be gained, 3D conformal radiotherapy and IMRT should be adopted throughout the treatment, and negative results have been reported for 3D conformal boost.
Stereotactic radiosurgery
Stereotactic radiosurgery is another modern development and is given in a single large fraction. Fractionated stereotactic radiotherapy has also been reported for use in NPC. This can be used as a boost for bulky disease, or treatment of residual or recurrent disease.
Molecular markers for prediction of radiation response
Another development in the modern era is the use of molecular markers to predict treatment response and outcome. Among them p53, proliferating cell nuclear antigen (PCNA), Ki-67, c-erbB2 and angiogenesis factors have been tested. The clinical response rate of primary tumour was 85.1% (40 of 47 cases) in positive p53 immunostaining and 95.2% (20 of 21 cases) in those with no immunostaining.

Chemotherapy

The Role of Chemotherapy in NPC
Radiotherapy has been the mainstay treatment for NPC and leads to high 5-year overall and disease-free survival rates in early-stage disease. However, there are significant rates of local failure and distant metastases subsequent to radiotherapy in the advanced stage of disease at which most NPC patients present. Local recurrence at the periphery of the irradiated area receiving an insufficient RT dose due to its proximity to critical organs and a high propensity for distant metastasis have been the two major causes of treatment failure. For patients with advanced local tumor and early nodal disease (T3-4N0-1), the pattern of failure is mainly in the nasopharynx. For patients with early local tumor and advanced nodal disease (T1-2N2-3), the pattern of failure is mainly nodal and distant failure. For patients with advanced local tumor and advanced nodal disease (T3-4N2-3), the pattern of failure includes local, nodal, and distant failure. Together with the advances in radiotherapy and combination chemotherapy, allowed the adoption of different strategies to deal with the different patterns of failure.
Chemotherapy was first used in the 1970s as a component for the primary curative treatment. A combined approach with chemotherapy, nasopharyngectomy (in selected cases), reduced cumulative external radiotherapy dose and brachytherapy or stereotactic radiotherapy boost may become potential areas for further research.
The addition of chemotherapy to RT for patients with advanced disease has been studied extensively during the last 2 decades. These results have indicated the followings: (i) in comparison with treatment with RT alone, concurrent chemoradiotherapy with or without adjuvant chemotherapy showed a significant survival benefit in two randomized studies; (ii) sequential (neoadjuvant and/or adjuvant) chemotherapy with RT failed to achieve survival advantage in seven randomized studies, although some showed a longer relapse-free survival when neoadjuvant chemotherapy was used.
Even in patients who failed ERT, or those with systemic metastasis, high response rates are reported with the use of chemotherapy, with many patients alive and well more than 2 years after chemotherapy. This review will only discuss its use in NPC.
The disease is highly sensitive to platinum-based chemotherapy and hence efforts have been made to improve treatment results by integrating radiotherapy with some form of chemotherapy as primary treatment. At the same time, refinements in radiation treatment, including altered fractionation and more precise delivery of a high dose to the tumor target by intensity-modulated radiotherapy (IMRT), also have been reported to improve treatment results. With the recently reported excellent local control from various series using IMRT throughout the primary course, it is not necessary to increase the prescribed dose to above the conventional tumoricidal dose level of 66 to 70 Gy. Chemotherapy has also been combined with altered fractionation and IMRT. The evidence on the various chemotherapy-radiotherapy sequencing approaches is presented in the following sections, and an optimum treatment policy and the directions for future research are discussed.
Adjuvant chemotherapy
To date, only two randomized studies of adjuvant chemotherapy have been reported. Both the study by Rossi et al and Chi et al reported a significant rate of patient noncompliance to adjuvant chemotherapy, and this is consistent with our own experience. In our randomized study comparing radiation with neoadjuvant and adjuvant chemotherapy versus radiation therapy alone, only 55% of patients completed the planned adjuvant chemotherapy due to poor tolerance. The main limiting toxicity was oral and oropharyngeal mucositis with exacerbations during the chemotherapy causing difficulty in feeding and swallowing. It thus appears that after radical radiotherapy for NPC that delivers a significant dose to the oral and oropharyngeal mucosa, patients’ tolerance of chemotherapy is poor. Hence, at present, the use of adjuvant therapy after radiotherapy alone is not recommended.
Neoadjuvant chemotherapy
There have been four randomized studies on the use of neoadjuvant chemotherapy, two of which showed positive results. However, none of the studies demonstrated a significant overall survival benefit. Thus, at this time the only “absolute” indication for this treatment approach is, in our opinion, in patients with very bulky intracranial NPC extending to such close proximity to the optic chiasma and/or the brainstem that even with IMRT adequate dose-sparing to within radiation tolerance of these important neural organs is not possible. In such cases, neoadjuvant chemotherapy may help to shrink the tumor away from the critical structures and provide a wider safety margin around the gross tumor volume. In recent years, improved local control in NPC has been reported with IMRT. The true value of neoadjuvant chemotherapy in NPC now needs to be redefined by randomized studies in which IMRT replaces conventionally fractionated two-dimensional radiotherapy in both the control and the experimental arms. In addition, the neoadjuvant approach provides a unique opportunity to test the efficacy of innovative agents and combinations (such as gemcitabine and taxanes) in treatment-naive patients.
Recently, activity has been reported for the use of the epidermal growth factor receptor (EGFR)-targeting agent cetuximab (C225) in heavily pretreated metastatic NPC.
Concurrent chemoradiation The Meta-analysis of Chemotherapy in Head and Neck Cancer (MACH-NC) concluded that the addition of chemotherapy to locoregional treatment yielded a pooled hazard ratio of death of 0.9 (95% confidence interval, 0.85 to 0.94; P <0.0001), with significant benefit from concurrent chemoradiation but no significant benefit from adjuvant or neoadjuvant chemotherapy. It thus appears that the concurrent use of chemotherapy and radiotherapy is the only way of sequencing the two modalities that consistently improves survival in head and neck cancers.
The evidence that concurrent chemoradiation with adjuvant chemotherapy produces survival advantage over radiotherapy alone in NPC has been provided by the Intergroup Study. Hence, in the United States, such a combined modality treatment has become standard treatment for the advanced stage (III and IV) NPC. Cisplatin 100 mg/m2 every 3 weeks × 3 is given concurrently with radiotherapy followed by adjuvant cisplatin 80 mg/m2 on day 1 and 5-fluouracil (5FU) 1 g/m2 on days 1 to 4 × 3.
It appears that one can confidently apply concurrent cisplatin-radiation with/without adjuvant chemotherapy using cisplatin and 5FU as standard treatment for locoregionally advanced NPC.
Neoadjuvant chemotherapy followed by concurrent chemoradiation Since the use of both neoadjuvant chemotherapy and concurrent chemoradiation has been shown consistently to improve progression-free and/or overall survival in advanced NPC, the development of sequential neoadjuvant chemotherapy and concurrent chemoradiation would seem a logical strategy in an attempt to summate the benefit from both approaches. In addition, when concurrent chemoradiation, rather than radiotherapy alone, is used as the mainstay treatment, neoadjuvant chemotherapy is better tolerated by patients than adjuvant chemotherapy for reasons discussed earlier. This strategy has been tested in two phase II studies. All three studies demonstrated that neoadjuvant chemotherapy using infusional ECF (epirubicin, cisplatin, 5FU), paclitaxel 70 mg/m2 weekly, and carboplatin area under the curve 6 (AUC6) every 3 weeks, or PFL-IFN (cisplatin, 5FU, leucovoin, interferon α2b) followed by concurrent chemotherapy-radiotherapy were well tolerated. The 4-year progression-free and overall survival rates were 81% and 90%, respectively. The strategy of neoadjuvant chemotherapy followed by concurrent chemoradiation should be further studied in a prospective randomized fashion against concurrent chemoradiation alone.
Intra-arterial (i.a.) Chemotherapy
Anti-cancer therapy is potentially toxic to both neoplastic and normal tissues. So the therapeutic efficacy of anti-tumour treatment depends on the relative selectivity of a treatment modality for the tumour in preference to the normal tissues. For surgery this therapeutic selectivity, which is based on anatomic discrimination, becomes ineffective when an adequate tumor resection requires removal of normal tissues whose function is indispensable or irreplaceable.
For chemotherapy and radiotherapy the therapeutic selectivity is based on physiologic and biochemical features that are more prevalent in rapidly dividing cancer cells than in normal cells. The goal of intra-arterial (i.a.) administration of chemotoxic drugs or radionuclides is to add anatomic selectivity to the inherent physiologic selectivity of anti-neoplastic agents.
Initially i.a. mono-chemotherapy is given with palliative intent [Sullivan and Daly, 1961]. In the 1970s and 1980s various treatment schedules based on the combination of multi-drug chemotherapy regimens and radiotherapy have been developed and used either as a sequential or as a concomitant (i.e. concurrent or simultaneous) treatment with curative intent.
Intra-arterial chemotherapy alone is still employed as palliative treatment of NPC. If curative treatment is planned, i.a. chemotherapy must be part of a multi-modality treatment. It can be combined with concurrent radiotherapy or used as an induction therapy with subsequent surgery. In the beginning of the 1990s, the group of Robbins successfully initiated an organ preservation protocol to reduce dysfunction related to major oncological surgery. The treatment consisted of repetitive superselective i.a. infusions of supradose cisplatin with simultaneous i.v. thiosulfate rescue and concomitant radiotherapy. With this protocol a 60-70% 2-year overall survival with an acceptable morbidity was obtained for advanced disease, which meant a renaissance of the i.a. chemotherapy for NPC. However, repeated i.a catheter interventions carry the risk of dislodging arteriosclerotic plaques and a substantial amount of the supradose cisplatin still reaches the systemic circulation, urging the use of a thiosulfate rescue. Regional chemotherapy by intra-arterial infusion of platinum derivatives has been shown to play a promising role in the multimodality management of advanced squamous cell carcinoma (SCC) of head and neck (H&N).
To evaluate the efficacy of a novel method of superselective intra-arterial infusion via the temporal artery for the treatment of stage III, IV NPC, we determined the clinical outcome of daily concurrent radiotherapy and chemotherapy with cisplatin (C) or docetaxel plus cisplatin (DC) utilizing this novel method. Sixty-six patients with stage III, IV oral cancer underwent preoperative chemoradiotherapy using superselective intra-arterial infusion via the superficial temporal artery. Catheters of varying curvature were prepared by modifying angiographic catheters measuring 1.35 mm in diameter. The catheter was inserted into the feeding artery of the tumor using guide wire via the superficial temporal artery. Radiotherapy (total dose: 40 Gy), and superselective intra-arterial infusion chemotherapy using C (total dose of C: 100 mg/m2/4 weeks) or DC (total dose of D: 60 mg/m2/4 weeks, total dose of C: 100 mg/m2/4 weeks) were concurrently performed daily, followed by surgery. Intra-arterial infusion was successful in 57 patients, and unsuccessful in the remaining 9 due to arterial anomalies. Of the 30 patients who received C, the clinical effects were complete response (CR) in 8 patients (CR rate: 26.7%) and partial response (PR) in 22, and the pathological effects following tumor resection were grade III (only non-viable tumor cells present) in 11 patients (36.7%) and grade IIB (few viable tumor cells remaining) in 19 (63.3%) according to the Shimosato-Oboshi classification. Of the 27 patients who received DC, the clinical were CR in 21 patients (CR rate: 77.8 %) and PR in 6, and the pathological effects were grade III in 24 (88.9 %), and grade IIB in 3 (11.1%). The 3-year cumulative survival rates were 66.7% for C and 85.2% for DC. Chemoradiotherapy using the novel method of intra-arterial infusion with DC promises to be the strategy of choice for treatment of head and neck cancer.

Photodynamic therapy (PDT)

In Guangdong and Hong Kong where nasopharyngeal carcinoma (NPC) is endemic, radiotherapy has been the primary treatment of choice. Adequate or effective treatments are not always available for most recurrent or residual nasopharyngeal cancers (NPC). Photodynamic therapy (PDT) is a promising new modality in the treatment of cancer. PDT using hematoporphyrin derivative (HpD) was evaluated for its effectiveness in treating patients, who conventionally failed, with curative or palliative intent.
Photodynamic therapy (PDT) is a relatively new method for treatment of cancer. It can be used for superficial tumors by application of a cream and for larger tumors and tumors in difficult – to – reach areas after an intravenous injection of a drug. In all treatment situations the tumor must be illuminated by light to a specific dose and with a wavelength purposed for the drug. This treatment can be used after failure of ionizing radiation. The treatment can be repeated many times, but usually one treatment is satisfactory. The intravenous drugs used for PDT are retained in tumor tissue longer than in normal surrounding tissue, with a few exceptions. These drugs are also mediators of energy in the form of visible light. When a tumor loaded with a sensitizer is irradiated with light with the appropriate wavelength the energy is transported to oxygen which in turn is activated from it’s normal triplet state to singlet oxygen – a highly toxic agent. Singlet oxygen will kill any cell (usually a tumor cell) in its proximity.
Twelve patients (three females and nine males) with ages ranging from 33 to 65 years in our hospital were treated with an infusion of hematoporphyrin derivative (5 mg/kg) 48-72 h before exposure to 200 J/cm2 light (wavelength, 630 nm) delivered from a gold vapor laser. All 12 patients showed a dramatic response as judged by computed tomography or magnetic resonance imaging at 6 months post-PDT. Of the eight patients in whom cure was aimed for, three remained disease-free at 9-12 months after a single treatment. Three of the remaining four patients achieved useful palliation. Skin hypersensitivity occurred in two patients and was the only significant complication encountered. This experience indicates that PDT can be an encouraging palliative or definitive management for recurrent superficial NPC.
There was another study, thirteen patients were treated from March 1994 to November 1998. PDT was given to eradicate tumor cells, debulk tumor mass for other treatment options, and to resolve obstruction. Long-term tumor control could be achieved in 6 patients with localized lesions at T1-T2 stages. The mean disease free survival time was 25.8 months (range 5-61 months). For tumors beyond T2 stage (7 cases), PDT in combination with chemotherapy, laser surgery or radiotherapy induced complete response in 1 out of 5 patients (survival time = 40 months) and partial response in the rest (survival time = 16-37 months). In two patients who refused or were in tolerable to further treatment, PDT yielded useful palliative results (i.e. resolve nasal obstruction and epistaxis). On an overall basis, the average survival time for these patients with relatively advanced diseases was 24.7 months (range 9-40 months). It demonstrated that HpD-PDT could effectively control locally recurrent or residual NPC at T1-T2 stages and offered good palliation for more advances. Combined PDT and chemotherapy seemed to prolong survival time for a period longer than 2 years in T3-T4 tumors.
Treatment of recurrent nasopharyngeal is a challenge. Re-treatment with external radiation alone is possible but can cause severe side effects such as necrosis of the skull base. We prefer to use photodynamic therapy together with external radiation and chemotherapy or brachytherapy for recurrent or residual nasopharyngeal cancer. We have tumor free five-year follow-ups for two patients treated with PDT and a few additional patients have been followed for 1 to 4 years without a second recurrence.

Outlook

There have been dramatic advances in the understanding of genetic changes in NPC, allowing the description of a multistep model for the pathogenesis of this disease. In the future, early diagnosis, adequate radiation dose to the primary with boost to bulky disease, and regular follow-up with biopsy of any suspicious residual or recurrent disease, are likely to become key issues to improve outcome. Also, apart from direct/indirect nasopharyngoscopy, the role of follow-up CT needs to be studied for early detection of residual or recurrent disease. More clinical trials on chemo-radiation are also required, in order to study optimum doses and agents.
The Future of Photodynamic Therapy: Photodynamic therapy will likely be used in the treatment of more other cancers and diseases in the future. New photosensitizing agents (such as temoporfin) that may be able to treat tumors that are deeper under the skin are now being investigated. Researchers are also looking at different types of lasers and other light sources. Some newer agents may respond to small doses of radiation as well as to light. This could allow doctors to use smaller amounts of radiation than the doses used in conventional radiation therapy, which could lead to fewer side effects. Another exciting area of research is in the use of photodynamic therapy as an adjuvant (addition) to current therapy to make it more effective.
In addition, three important clues arose from this survey which should influence the future direction of clinical trials for nasopharyngeal cancer: (i) this intensive approach seems more important for patients in the advanced stage disease than for those who have intermediate stage disease; (ii) a less toxic approach using adjunctive chemotherapy combined with RT aiming at improvement of LRC (locoregional control rate) should be tested for patients with intermediate stage disease; and (iii) different treatment approaches in order to improve LRC should be planned for patients with keratinizing disease considering their remarkably poor LRC.

Standard treatment options
——Recommended By Fuda Cancer Hospital Guangzhou

Stage I Nasopharyngeal Cancer (NPC):

High-dose radiation therapy to the primary tumor site and prophylactic radiation therapy to the nodal drainage.
PDT
Stage II Nasopharyngeal Cancer
Chemoradiotherapy.
High-dose radiation therapy to the primary tumor site and prophylactic radiation therapy to the nodal drainage.
PDT
Stage III Nasopharyngeal Cancer
Chemoradiotherapy.
High-dose or superfractionated radiation therapy to the primary tumor site and bilateral neck nodes that are clinically positive.
PDT
Brachytherapy
Intra-arterial (i.a.) Chemotherapy
Neck dissection may be indicated for persistent or recurrent nodes if the primary tumor site is controlled.
Stage IV Nasopharyngeal Cancer
Chemoradiotherapy.
High-dose or superfractionated radiation therapy to the primary tumor site and bilateral lymph nodes that are clinically positive.
PDT
Brachytherapy
Neck dissection should be reserved for persistent or recurrent nodes.
Chemotherapy for patients with stage IVC disease.
Intra-arterial (i.a.) Chemotherapy
Recurrent Nasopharyngeal Cancer
PDT
Brachytherapy
Intra-arterial (i.a.) Chemotherapy
Selected patients may be re-treated with moderate-dose external-beam radiation therapy using limited ports and an intracavitary or interstitial irradiation boost to the site of recurrence.
In highly selected patients, surgical resection of recurrent lesions may be considered.
If a patient has metastatic disease or local recurrence that is no longer amenable to surgery or radiation, PDT, Brachytherapy and other microinvasional therapies should be considered.

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Complete surgical excision represents the most effective therapy for most solid tumors. However, the primary tumors in only about or even less than 30 percent of patients with cancer can be curatively resected by operation. Most of solid cancers can’t be cured by resection due to advanced disease in the organ, poor cardiac, renal function and/or poor pulmonary function. How to treat called unresectable cancer? Proper strategy are application of new high-technical, especially minimally invasive modalities, combination of high-technical modalities and traditional modalities (operation, radiation and chemotherapy), and integration of traditional Chinese medicine and western medicine. For this purpose, Microinvasional Treatment Center was found in our hospital, we introduced a lot of new high-tech microinvasional therapies for cancer treatment, including Chemical-ablation (alcohol, acetic acid), Cryoablation, Thermablation (Radiofrequency, Laser, microwave, ultrasound), Vascular intervention: Transarterial chemoembolization (TACE) [lipiodol, chemo-drugs, yttrium-90 microspheres (SIR-Spheres((R)), 131lipiodol) and Transarterial chemoinfusion, Photodynamic therapy, Antiangiogenic therapy (like thalidomide), Biologic therapy: Dendritic cell vaccine, LAK/Interleukin-2, CD3AK, Tumor-infiltrating, Lymphocyte (TIL), cytokine-activated killer (CIK), Monoclone antibody: Herceptin, Gefitinib, Erlotinib, Cetuximab (EGFR-TKIs), Gene therapy: Gendicine(R)? ( (P53), and so on. They may offer an option for treating cancers that are considered inoperable or that do not respond to standard treatments. Liver Cancer Information Center
A new or recurrent diagnosis of Liver Cancer often results in fear and confusion for patients and their family members. Understanding treatment options, accessing new and innovative therapies through clinical trials, as well as understanding the role of supportive care and complementary and alternative medicine are essential. Cancer screening, genetic testing and prevention are equally relevant to all individuals, especially those related to someone diagnosed with cancer.
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A new or recurrent diagnosis of Breast Cancer often results in fear and confusion for patients and their family members. Understanding treatment options, accessing new and innovative therapies through clinical trials, as well as understanding the role of supportive care and complementary and alternative medicine are essential. Cancer screening, genetic testing and prevention are equally relevant to all individuals, especially those related to someone diagnosed with cancer.
Our mission is to empower patients with current information on all aspects of the management of Breast Cancer in order to provide support and hope, as well as to facilitate informed decisions.
If you want to know more about Breast Cancer, please visit our website: www.fubig.com. It provides important background information about cancer, diagnosis, and treatment options. The amount of information that you need to understand can seem overwhelming at first. Brain Cancer Information Center
Current therapy for brain glioma centers on surgical resection with adjuvant radio- or chemotherapy. Despite refinements in these techniques, tumor recurrence is common, and the prognosis for patients with malignant glioma remains poor. The median survival time in patients with malignant glioma is limited to little more 12 months with tumor progression usually occurring at the margins of the former resection cavity. Taking recurrence patterns into account,patients might benefit from more aggressive local therapy.
Since 1996 we have started the trial of combination therapy consisted of surgical resection and following local infusion of Serratia Marcescens Vaccine (SMV) in tumor bed for malignant brain glioma and obtained better efficacy, compared with that of control group who received resection alone.
Now we offer a paper, which describes the final data of the trial, by Prof Wu, a famous specialis of brain surgery, as fellow.

Clinical trial of local immunotherapy into the tumor bed for prevention of recurrence of brain glioma.
Nianceng WU, Tianlu Wang. Fuda Cancer Hospital Guangzhou, Guangzhou 510300, Guangdong, China

附/Appendix:

抗　癌 中 成 药 举 例
Traditional Chinese Drugs Approved by SDA in China for Treatment of Cancer