World J Oncol

World Journal of Oncology, ISSN 1920-4531 print, 1920-454X online, Open Access

Article copyright, the authors; Journal compilation copyright, World J Oncol and Elmer Press Inc

Journal website http://www.wjon.org

Review

Volume 8, Number 1, February 2017, pages 1-6

Radiation-Induced Malignancies Making Radiotherapy a “Two-Edged Sword”: A Review of Literature

**Table 1.** RIM After Radiotherapy of Non-Oncological Diseases
Studies	Radiotherapy of non-oncological disease	Type of RIM	Comments
Ron et al [15, 16]	Tinea capitis - radiotherapy to scalp	CNS tumors like meningioma (most common), gliomas, nerve sheath tumor Head and neck malignancies and leukemia	Radiation doses of 1 - 2 Gy can significantly increase the risk of neural tumor
Smith and Doll [17]	Ankylosing spondylitis	Leukemia (most common)	About fivefold increase in deaths from leukemia and a 62% increase in deaths from cancers of sites that would have been in the radiation fields
Albright and Allday [18]	Acne vulgaris	Thyroid malignancies	Thyroid was not shielded during the treatment so received undetermined amount of radiation

Table 1. RIM After Radiotherapy of Non-Oncological Diseases

Studies

Radiotherapy of non-oncological disease

Type of RIM

Comments

Ron et al [15, 16]

Tinea capitis - radiotherapy to scalp

CNS tumors like meningioma (most common), gliomas, nerve sheath tumor
Head and neck malignancies and leukemia

Radiation doses of 1 - 2 Gy can significantly increase the risk of neural tumor

Smith and Doll [17]

Ankylosing spondylitis

Leukemia (most common)

About fivefold increase in deaths from leukemia and a 62% increase in deaths from cancers of sites that would have been in the radiation fields

Albright and Allday [18]

Acne vulgaris

Thyroid malignancies

Thyroid was not shielded during the treatment so received undetermined amount of radiation

**Table 2.** RIM After Radiotherapy for Breast Cancer
Studies	Site of radiation induced malignancy after radiotherapy for breast cancer	Comment
Deutsch et al [21]	Lung (ipsilateral and contralateral)	Higher dose of radiotherapy to lung in breast cancer patients of NSABP 04 in comparison to NSABP 06 trial was associated with increased incidence of subsequent RIM in both ipsilateral and contralateral lung.
Boice et al [22]	Contralateral breast	The average radiation dose to the contralateral breast in this study was 2.82 Gy and less than 3% of radiation-induced breast cancer could be attributed to previous radiotherapy.
Zablotska et al [23]	Esophagus (squamous cell carcinoma (SCC))	Increase the risk of SCC not adenocarcinoma. As upper and middle third esophagus (commonest site of SCC) not the lower third (commonest site of adenocarcinoma) comes in the radiation portal.
Kirova et al [24]	Sarcomas	Thirty-five out of 16,705 patients of breast cancer developed sarcomas (13 sarcomas were located in the breast, five in the chest wall, three in the sternum, two in the supraclavicular area, one in the scapula, and three in the axilla).

Table 2. RIM After Radiotherapy for Breast Cancer

Studies

Site of radiation induced malignancy after radiotherapy for breast cancer

Comment

Deutsch et al [21]

Lung (ipsilateral and contralateral)

Higher dose of radiotherapy to lung in breast cancer patients of NSABP 04 in comparison to NSABP 06 trial was associated with increased incidence of subsequent RIM in both ipsilateral and contralateral lung.

Boice et al [22]

Contralateral breast

The average radiation dose to the contralateral breast in this study was 2.82 Gy and less than 3% of radiation-induced breast cancer could be attributed to previous radiotherapy.

Zablotska et al [23]

Esophagus (squamous cell carcinoma (SCC))

Increase the risk of SCC not adenocarcinoma. As upper and middle third esophagus (commonest site of SCC) not the lower third (commonest site of adenocarcinoma) comes in the radiation portal.

Kirova et al [24]

Sarcomas

Thirty-five out of 16,705 patients of breast cancer developed sarcomas (13 sarcomas were located in the breast, five in the chest wall, three in the sternum, two in the supraclavicular area, one in the scapula, and three in the axilla).

**Table 3.** RIM After Pelvic or Genitourinary Irradiation
Studies	Primary malignancy	Increased risk of RIM
Chaturvedi et al [29]	Cervix	Colon, anus/rectum, bladder, ovary, and genital sites
PORTEC-1 trial [30]	Endometrium	Gastro-intestinal malignancy
Zelefsky et al [31]	Prostate	Skin, bladder and rectum
Van den Belt-Dusebout et al [32]	Testis	Stomach, pancreas, urinary bladder and kidney

Table 3. RIM After Pelvic or Genitourinary Irradiation

Studies

Primary malignancy

Increased risk of RIM

Chaturvedi et al [29]

Cervix

Colon, anus/rectum, bladder, ovary, and genital sites

PORTEC-1 trial [30]

Endometrium

Gastro-intestinal malignancy

Zelefsky et al [31]

Prostate

Skin, bladder and rectum

Van den Belt-Dusebout et al [32]

Testis

Stomach, pancreas, urinary bladder and kidney

**Table 4.** Risk of Development of RIM
Radiotherapy for primary disease	RIM	Relative risk of development of RIM
Breast [46]	Esophageal cancer	2.19 at 15+ years of radiotherapy
Lung cancer	1.62 at 10 - 14 years 1.49 at ≥ 15 years
Myeloid leukemia	2.99 at 1 - 5 years
Second breast cancer	1.34 at 5 - 10 years 1.26 at 15+ years
Prostate [47]	Rectal cancer	1.26 after EBRT 1.08 after brachytherapy 1.21 after EBRT and brachytherapy
Bladder cancer	Risk ratio of 1.5
Cervix [3]	Bladder carcinoma	4.5
Vaginal cancer	2.7
Non-Hodgkin’s lymphoma	2.5
Rectal cancer	1.8
Leukemia	2.0
Carcinoma stomach	2.1
Bone tumors	1.3
Uterine malignancy	1.3

Table 4. Risk of Development of RIM

Radiotherapy for primary disease

RIM

Relative risk of development of RIM

Breast [46]

Esophageal cancer

2.19 at 15+ years of radiotherapy

Lung cancer

1.62 at 10 - 14 years
1.49 at ≥ 15 years

Myeloid leukemia

2.99 at 1 - 5 years

Second breast cancer

1.34 at 5 - 10 years
1.26 at 15+ years

Prostate [47]

Rectal cancer

1.26 after EBRT
1.08 after brachytherapy
1.21 after EBRT and brachytherapy

Bladder cancer

Risk ratio of 1.5

Cervix [3]

Bladder carcinoma

4.5

Vaginal cancer

2.7

Non-Hodgkin’s lymphoma

2.5

Rectal cancer

1.8

Leukemia

2.0

Carcinoma stomach

2.1

Bone tumors

1.3

Uterine malignancy

1.3