Malignant mucosal melanoma treated with carbon ion radiotherapy with concurrent chemotherapy: Prognostic value of pretreatment apparent diffusion coefficient (ADC)

doi:10.1016/j.radonc.2010.09.017

Radiotherapy and Oncology

Volume 98, Issue 1, January 2011, Pages 68-73

https://doi.org/10.1016/j.radonc.2010.09.017 Get rights and content

Abstract

Background and purpose

To evaluate the potential of apparent diffusion coefficient (ADC) value before carbon ion radiotherapy (C-ion RT) for malignant mucosal melanoma (MMM) to predict prognosis.

Materials and methods

We recruited 37 patients with MMM in the head and neck treated by C-ion RT with concomitant chemotherapy. Univariate and multivariate analyses of minimum ADC, mean ADC, tumor volume, age, PS, and gender were performed to identify prognostic factors.

Results

The 3-year local control rate, distant metastasis-free survival rate and overall survival rate of all patients were 81.1%, 37.6% and 65.3%, respectively, with a median follow-up period of 19.0 months. In univariate analyses, lower minimum ADC (⩽0.6380 × 10⁻³ mm²/s) and lower mean ADC (⩽1.1523 × 10⁻³ mm²/s) were unfavorable prognostic factors for distant metastasis (p = 0.029 and p = 0.014, respectively), and lower minimum ADC was an unfavorable prognostic factor for overall survival (p = 0.019). However, there was no significant prognostic factor of local control including ADC value. In multivariate analyses, only minimum ADC was selected as a prognostic factor of distant metastasis-free survival and overall survival (p = 0.015 and p = 0.006, respectively).

Conclusion

Minimum ADC can be a prognostic factor of MMM in the head and neck after C-ion RT.

Section snippets

Patient selection and characteristics

Consecutive patients with MMM were recruited from the phase II study of C-ion RT with concomitant chemotherapy for MMM in the head and neck. Before treatment in our institution, all patients underwent whole body computed tomography (CT) and ¹¹[C]-methionine positron emission tomography (PET) to rule out metastasis and magnetic resonance imaging (MRI) in the primary region to confirm the spread of the tumor. The patients’ medical records as well as their CT, MRI and PET data were reviewed

Results

From April 2006 to March 2009, we treated 46 patients with MMM in the head and neck using C-ion RT with concomitant DAV therapy. However, in nine patients, the tumors were too small to be detected on an ADC map. Therefore, 37 patients (19 males, 18 females; median age, 65 years; range, 33–80 years) were enrolled in the present study. Dose distribution, MR images and endoscopic images before and at 6 months and 2 years after C-ion RT in a typical patient who had no recurrence and no severe adverse

Discussion

This survey revealed that minimum ADC was a significant prognostic factor of distant-free survival and overall survival of MMM after C-ion RT with concomitant DAV therapy.

DWI is used for evaluation of tumors at both intracranial and extracranial sites. The technique has been used for differentiating a tumor from nontumorous tissue, for assessment of treatment response and for prediction of treatment outcome [6], [22], [23], [24]. Previous reports on DWI of rats have been used to validate DWI

Conflicts of interest notification

There is no conflict of interest in relation to the present study.

Acknowledgement

This study was partially supported by funding from the Japan Radiological Society.

References (31)

A.M. Herneth et al.
Apparent diffusion coefficient: a quantitative parameter for in vivo tumor characterization
Eur J Radiol
(2003)
L. Lemaire et al.
Assessment of induced rat mammary tumour response to chemotherapy using the apparent diffusion coefficient of tissue water as determined by diffusion-weighted ¹H NMR spectroscopy in vivo
MAGMA
(1999)
A. Dzik Jurasz et al.
Diffusion MRI for prediction of response of rectal cancer to chemoradiation
Lancet
(2002)
H. Wada et al.
A multi-institutional retrospective analysis of external radiotherapy for mucosal melanoma of the head and neck in Northern Japan
Int J Radiat Oncol Biol Phys
(2004)
J.P. Pignon et al.
Chemotherapy added to locoregional treatment for head and neck squamous-cell carcinoma: three meta-analyses of updated individual data. MACH-NC collaborative group. Meta-analysis of chemotherapy on head and neck cancer
Lancet
(2000)
T. Kanai et al.
Biophysical characteristics of HIMAC clinical irradiation system for heavy-ion radiation therapy
Int J Radiat Oncol Biol Phys
(1999)
Y. Liu et al.
Diffusion-weighted imaging in predicting and monitoring the response of uterine cervical cancer to combined chemoradiation
Clin Radiol
(2009)
A.F. DeVries et al.
Tumor microcirculation and diffusion predict therapy outcome for primary rectal carcinoma
Int J Radiat Oncol Biol Phys
(2003)
J.A. Brunberg et al.
In vivo MR determination of water diffusion coefficients and diffusion anisotropy: correlation with structural alteration in gliomas of the cerebral hemispheres
AJNR Am J Neuroradiol
(1995)
Y. Roth et al.
High-b-value diffusion-weighted MR imaging for pretreatment prediction and early monitoring of tumor response to therapy in mice
Radiology
(2004)

K.M. Gauvain et al.

Evaluating pediatric brain tumor cellularity with diffusion-tensor imaging

AJR Am J Roentgenol

(2001)

Y. Kurihara et al.

Coil sensitivity encoding in MR imaging: advantages and disadvantages in clinical practice

AJR Am J Roentgenol

(2002)

R. Bammer et al.

Improved diffusion-weighted single-shot echo-planar imaging (EPI) in stroke using sensitivity encoding (SENSE)

Magn Reson Med

(2001)

A.C. Guo et al.

Lymphomas and high-grade astrocytomas: comparison of water diffusibility and histologic characteristics

Radiology

(2002)

D.M. Koh et al.

Predicting response of colorectal hepatic metastasis: value of pretreatment apparent diffusion coefficients

(2007)

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Carbon ion radiotherapyMalignant mucosal melanoma treated with carbon ion radiotherapy with concurrent chemotherapy: Prognostic value of pretreatment apparent diffusion coefficient (ADC)

Abstract

Background and purpose

Materials and methods

Results

Conclusion

Section snippets

Patient selection and characteristics

Results

Discussion

Conflicts of interest notification

Acknowledgement

Eur J Radiol

MAGMA

Lancet

Int J Radiat Oncol Biol Phys

Lancet

Int J Radiat Oncol Biol Phys

Clin Radiol

Int J Radiat Oncol Biol Phys

In vivo MR determination of water diffusion coefficients and diffusion anisotropy: correlation with structural alteration in gliomas of the cerebral hemispheres

AJNR Am J Neuroradiol

High-b-value diffusion-weighted MR imaging for pretreatment prediction and early monitoring of tumor response to therapy in mice

Radiology

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AJR Am J Roentgenol

Coil sensitivity encoding in MR imaging: advantages and disadvantages in clinical practice

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Improved diffusion-weighted single-shot echo-planar imaging (EPI) in stroke using sensitivity encoding (SENSE)

Magn Reson Med

Lymphomas and high-grade astrocytomas: comparison of water diffusibility and histologic characteristics

Radiology

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Carbon ion radiotherapy
Malignant mucosal melanoma treated with carbon ion radiotherapy with concurrent chemotherapy: Prognostic value of pretreatment apparent diffusion coefficient (ADC)