JOURNAL READING

Feasibility and efficiency of concurrent chemoradiotherapy for nasopharyngeal carcinoma patients

Advicer :
Dr. Ariman Syukri, Sp.THT-KL
Dr. Asmawati, Sp.THT-KL
Dr. Harianto, Sp.THT-KL
By :
Galuh Tiara Akbar, S.Ked
Muhammad Maliki S.Ked
Nur Islah Agusti S.Ked
Ranti Purnama Sari S.Ked
Sepnita Usman S.Ked
Trigen Rahmat Yulis S.Ked

BACKGROUND

Nasopharyngeal carcinoma (NPC) is distinct from other malignancies in the head

and neck with respect to its epidemiology, pathology, clinical presentation and
response to treatment.

This neoplasm has a notable ethnic and geographic distribution with a high
prevalence in Southeast Asian and North African
populations

It is relatively frequent in Tunisia with incidence rates of 3.4/ 100.000 population in

males and 1.6/ 100.000 population in females

NPC is highly radiosensitive. Although early-stage NPC is highly radiocurable,

the cure rate with RT alone for loco regionally advanced NPC is low.

Because NPC is a chemosensitive tumor, CT added to RT in various manners

should be a method to improve survival rates

The predominant finding of these studies is a survival advantage associated with

the use of CCRTwith or without adjuvant CT (ACT) over RT alone

The aim of this retrospective study is to evaluate the feasibility and

efficiency of CCRT in loco regionally advanced NPC patients.

PATIENTS AND METHODS

Patient characteristics
A total of 33 patients with a histologically confirmed diagnosis of nonmetastatic NPC were treated with CCRT at Salah Azaiz Institute between
January 2004 and December 2006.

The patient age at presentation ranged from 11 to 66 years (median, 41). Of

the 33 patients, 25 were males and 8 were females.

The initial staging evaluation included a complete history and physical

examination, endoscopy and biopsy, complete blood count determination,
liver and renal function tests, chest X-ray, abdominal ultrasonography, CTscan of the nasopharynx and neck region, and bone scintigraphy.

Patients underwent clinically staging according to the 2002 TNM staging

system

T3-T4 locally advanced tumors and N2-N3 nodal status rates were 67 and 46%,
respectively

All 33 patients had the undifferentiated (WHO Type III) variant of NPC

Treatment plan:

All patients were treated with a radical intent using a combination of

CT and RT.

They received conventional 2D RT using a telecobalt unitwith bilateral

parallel opposing fields to the primary tumor and upper neck, and a
single anterior field to the lower neck with a central shield

After 42-44Gy, the primary tumor was boostedusing bilaterally

opposed reduced portals and the posterior cervical lymphatic chains
were treated with appropriate electrons (6-9 MeV)

The total dose planned was 70-74 Gy to the primary tumour and the involved
lymph nodesin daily fractions of 2 Gy, 5 d/wk.

Patients received IV cisplatin at 40 mg/m2 weekly during the entire duration of

a 7 weeks course of external RT.

The complete blood picture and biochemistry were checked weekly before CT
was administered

The number of cycles of cisplatin that could be given depending on

the patients tolerance.

Patient evaluation and follow-up

Acute RT-related toxicities were documented

according to the Radiation Therapy Oncology Group
guideline and CT-related toxicities by the WHO
criteria

At each follow-up visit, a complete physical examination

(including endoscopy if required) was performed

A post-therapy CT scan or MRI of head and neck was

obtained for all patients at 3 months after treatment.

Statistical methods:

Study endpoints include acute toxicities, overall survival

(OS), disease-free survival (DFS), loco-regional relapse-free
survival (LRRFS) and metastasis relapse-free survival
(MRFS).

All survivals were calculated from the date of histologically

confirmed diagnosis to the date of the observed endpoints
or to the date of the last follow-up

Survival endpoints were analyzed using the Kaplan-Meier

method. Univariateanalyse was performed for evaluation of
the prognostic factors.

The Log-rank test was used to compare the curves

and p-values < 0.05 were considered to be
statistically significant.

RESULTS
Toxicity :

:
Events and survival
After a median follow-up of 58 months (range, 3-94

months)

6 patients (18%) developed loco-regional relapse associated

with distant metastasis in 4 cases (12%)
6 patients (18%) developed distant metastases alone

Overall survival (OS) 70%

Disease-free survival (DFS) 63%
Loco-regional relapse-free survival (LRRFS) 80%
Metastasis relapse-free survival (MRFS) 68%

Overall survival

Disease-free survival (DFS)

Loco-regional relapse-free survival (LRRFS)

Metastasis relapse-free survival (MRFS)

Prognostic factors:
The age >40 years, Stage T4, Stage N3, and cycles of CT 5 had a
statistically significant pejorative impact on OS

Stage T4 had a statistically significant influence on

LRRFS, Stage N3 had a statistically significant influence on MRFS

Patients who received more than 5 cycles of cisplatin had significantly

better DF Sand MRFS than those who received less than or equal to 5
cycles of CT

DISCUSSION
NPC is highly radiosensitive and chemosensitive, and an excellent disease
control can be achieved using combined modality chemoradiation even in
patients with locally advanced disease.

Asian countries where NPC is prevalent, the treatment efficacy of CCRT

with or without ACT was confirmed in many clinical studies

Conclude that CCRT with or without ACT is also applicable to patients in

endemic areas and should be standard of practice in locally advanced
disease

analysis demonstrated that CT led to asignificant benefit in overall

survival (OS) and progression-free survival (PFS)

The effect was most significant for the concurrent group.

At present, concurrent CT during the course of RT should be

considered the standard of care.

Weekly (30-40 mg/m2) as well as 3-weekly (100 mg/m2) cisplatinbased regimens are accepted as standard practice.

Toxic effects are considerable with the 3-weekly schedule as revealed

by the Intergroup study

In terms of toxicity and compliance to CT, the systemic and local

toxicities were generally acceptable, 60% of patients completed at least
5 cycles of concurrent cisplatin, and only 44% completed the planned 6
cycles of concurrent cisplatin during RT

Had found weekly scheduling practical and feasible for CCRT in

NPC, resulting in decreased interruptions in radiation treatment
and minimal acute toxic events without compromising local control

No fatal toxicity related to planed treatment was observed.

A possible explanation for this may be the fact CCRT for these
patients with such high-risk disease may not be enough to
improve their outcome significantly

This will thus warrant further exploration of NACT or ACT as an

additional treatment modality of this subset of patients.

The fact that these were retrospective analyses, the causal

relationship between cycles of cisplatin and improvement in OS is
not clearly defined.

These results should at least enable us to advise our patients that

compliance to CT during CCRT may influence prognosis.

They found that IMRT without concurrent CT provides good

treatment outcome with acceptable toxicityand without significant
difference in patients treated with CT

The practice of CCRT in stage II disease is acceptable as long as a

balance is taken with the associated short and long-term toxicities of
concurrent CT

Concurrent chemotherapy failed to improve survival rates for patients

with advanced locoregional disease and increased the severity of acute
toxicities

CONCLUSION
Our study confirms that weekly cisplatin concurrent
with RT for locally advanced nasopharyngeal cancers
was found tolerable with a high efficiency and
provides further evidence on the prognostic
significance of CT dosing during the concurrent
phase with RT.

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