Radiation induced malignancy28/3/2014

Dr shada wadi-Ramah

Biomedical physicsDepartment

King Faisal specialist Hospital

Linear accelerator - electron and X-ray beams

Rush University Medical Center, Chicago, IL

Courtesy Of Dr. Shada Ramahi, KHCC

Simulator

Rush University Medical Center, Chicago, IL

Courtesy Of Dr. Shada Ramahi, KHCC

Co60 machine - ray beam

Radiation Induced Second Malignancy Following Treatment for

Breast Cancer

Case Presentation

Belal El Hawwari 2006

• One of the most significant effects of radiation therapy on normal tissues is mutagenesis, which is the basis for radiation-induced malignancies. Radiation-induced malignancies are late complications arising after radiotherapy, increasing in frequency among survivors of both pediatric and adult cancers.

• Individuals exposed to atomic bombs were of the general population at Hiroshima and Nagasaki. Long-term follow up of atomic bomb survivors has shown that tumor development was increased in this population compared to non-irradiated individuals.

Methods and material:

• Most radiation-induced second malignancies arise as tumors arising in the irradiated region, or encompassed within the radiotherapy field (“in-field” tumors), however there is evidence that the effects of radiotherapy on non-targeted tissues can influence cell and tissue function in diverse ways.

• We investigated the clinical records of 232 military patients who had received RT for the treatment of cancer at Albashier hospital between 1999 and 2012.

Result

• There were 4 patients with a second malignancies developing in the irradiated field, consisting of 2 patients with breast cancer, 1 case with carcinoma and 1 case with sarcoma. The pathological diagnosis was Invasive ductal carcinoma in breast patients, small cell carcinoma and lymphangiosarcoma in the carcinoma and sarcoma patient respectively. Two of the patients died of the second malignancies, while the remaining 2 patients are still living at the time of writing, with neither recurrence of the second tumor nor relapse of the primary tumor. The median interval between the RT and the diagnosis of the second malignancies was 7 years (range, 3 to 13years.

Case

• 66 yr female

• June’04- severe cough which resolved after 2-3/52 without medication

• Sept/Oct’04- right upper chest abn feeling with resolution

• Dec ‘04- cough and CXR January’05 RUZ Abn with widened mediastinum

• CT chest/abdo- RUZ lesion with mediastinal Lymphadenopathy

Case contd

• CT guided biopsy- small cell carcinoma

• PMHx-

• 1985- R infiltrating ductal adenocarcinoma LIQ breast, 35x25x25mm, extending macro to within 0.4cm from skin surface, micro extending into adipose tissue w/ early invasion of muscle and perineural invasion.

• Treated with WLE, CMF chemotx and 50Gy in 25# to breast, axilla, internal mammary.

Case contd

• PMHx contd-

• osteopaenia/OA, appendicectomy, tonsillectomy,hysterectomy and R salpingectomy for cysts in 1982, menopause during chemo at age 45.

• Non smoker

• IMPRESSION- Radiation induced small cell ca

• Staging- PET- inrc uptake RUL with evidence of nodal disease. Consistent with stage IIIA.

Case contd

Mx-

• Carboplatin and Etoposide with post chemo radiotx of 45 Gy in 25# to mediastinum.

• Decision for Radiotx and field made after thorough review of imaging and previous radiotx fields. Acceptance of some overlap in treatment of lung lesion and small overlap in skin overlying central chest.

Radiation Induced Malignancies following breast radiotx

• British Journal of Cancer 2004-

• retospective study using Thames Cancer Registry database from 1960-2000. Compared incidence of 2nd primary cancers in women who received radiotx with those who did not receive radiotx (pts who received chemotx were excluded)

• 62,782 women in total (33,763 received post op radiotx)

Rad induced 2nd malignancy contd

• 5217 2nd primary tumours detected.

• 2857 at one of primary sites of interest of study (lung, colon, oesophagus,thyroid, mal melanoma, myeloid leukaemia, breast)

• elevated RR in lung ca at >10 yrs of 1.49-1.62 (95% CI 1.05-2.54)

• elevated RR myeloid leukaemia at 1-5 yrs 2.99 (95% CI 1.13-9.33)

• elevated RR in oesophageal ca at >15 yrs of 2.19 (95%CI 1.10-4.62)

Rad induced 2nd Malignancy contd

• Elevated RR in Breast ca in both grps yet at >5 yrs excess in RT group with RR 1.34 (95% CI 1.10-1.63)

• no sig differences b/w groups for colon, thyroid, malignant melanoma

• They concluded that benefits of radiotx still outweigh risks in appropriate pts, yet aim should be to minimise radiation dose to surrounding tissues or volume of exposed tissues

• Also, other factors may contribute such as genetic predisposition, e’ment exposures, reproductive factors, incr medical surveillance.

Proposed Pathogenesis

• International Journal of Cancer 2003

• study performed at Center for Radiological Research in NYC

• used immortalised human breast epithelial cell line (MCF 10F) in combination with oestrogen and radiation as model- step wise neoplastic transformation of cell line

• identified 3 regions on chromosone 11- high incidence of loss of heterozygosity/microsatellite instability- potential role for carcinogenesis.

Proposed Pathogenesis contd

• Same centre published another study using same cell line in Carcinogenesis 2001

• high rate of allele imbalance at regions on chromosome 6 and 17- suggests presence and inactivation of one or more tumour suppressor genes in these regions.

Impact of 3D- CRT and IMRT

• May, 2003 International Journal of Radiation Oncology, Biology, Physics (Center for Radiological Reasearch, NY)

• some animal and human data suggest decrease in 2nd malignancies at higher doses due to cell killing

• excess sarcomas in heavily irradiated in- field tissues and incidence of carcinomas, s’times in sites remote from tx fields

• 3D-CRT- incr. in dose to target tissue with reduction of normal tissue receiving dose compared to prior conventional radiotx

IMRT contd

• Paper suggests, move to IMRT involves more fields and as a consequence a greater volume of normal tissue is exposed to lower doses.

• Potential for increase in no of 2nd malignancies.

• They predict increase of 0.75% for patients surviving >10 yrs.

Conclusions

• Radiation Induced Second Malignancies are a real risk, yet low risk

• Risk should not interfere with decision to treat with radiotx in appropriate patients, yet care should be taken to reduce radiation exposure to normal tissues.

• Risk likened to risk of operative death

• Inclusion in differential in those patients who have been treated with radiotx many years prior with new second malignancy

Conclusion contd

• Future studies are required to determine risk and occurrence in patients treated with more recent practices

• IMRT may potentially increase risk