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SECONDARY MALIGNANCIES AFTER LYMPHOMA TREATED BY RADIOTHERAPY-CASE REPORT
Alper ?elik,Suat Kutun,Turgay Fen,Gülay Bilir
Marmara Medical Journal , 2006,
Abstract: We hereby describe a case of Hodgkin lymphoma treated with radiotherapy to head and neck region, who further developed lung and multiple skin cancers. A 50-year-old male patient with stage IA Hodgkin lymphoma was treated with radiotherapy to mantle zone. Six years later we detected basal cell carcinoma on his nose, invasive epidermoid carcinoma on his right ear, and in-situ epidermoid carcinoma on left infraorbital area. After surgical removal, radiotherapy was applied to right auricular area and left infraorbital area due to close lateral margin and the patient’s refusal for re-excision. One year later he admitted with dyspnea. We detected a mass involving the upper and middle zones of his right lung, and bronchoscopic biopsy revealed epidermoid carcinoma. Vena cava superior syndrome was established, and he was re-treated with radiotherapy and medical treatment. His medical condition deteriorated, and 15 days later he died.
Radio-induced malignancies after breast cancer postoperative radiotherapy in patients with Li-Fraumeni syndrome
Steve Heymann, Suzette Delaloge, Arslane Rahal, Olivier Caron, Thierry Frebourg, Lise Barreau, Corinne Pachet, Marie-Christine Mathieu, Hugo Marsiglia, Céline Bourgier
Radiation Oncology , 2010, DOI: 10.1186/1748-717x-5-104
Abstract: We reviewed a cohort of patients with germ-line p53 mutations who had been treated for breast cancer as the first tumor event. We assessed their outcome and the incidence of secondary radio-induced malignancies.Among 47 documented Li-Fraumeni families treated from 1997 to 2007 at the Institut Gustave Roussy, 8 patients had been diagnosed with breast cancer as the first tumor event. Three patients had undergone conservative breast surgery followed by postoperative radiotherapy and five patients had undergone a mastectomy (3 with postoperative radiotherapy). Thus, 6/8 patients had received postoperative radiotherapy. Median follow-up was 6 years. Median age at the diagnosis of the primary breast cancer was 30 years. The histological characteristics were as follows: intraductal carcinoma in situ (n = 3), invasive ductal carcinoma (n = 4) and a phyllodes tumor (n = 1). Among the 6 patients who had received adjuvant radiotherapy, the following events had occurred: 3 ipsilateral breast recurrences, 3 contralateral breast cancers, 2 radio-induced cancers, and 3 new primaries (1 of which was an in-field thyroid cancer with atypical histology). In contrast, only one event had occurred (a contralateral breast cancer) among patients who had not received radiation therapy.These observations could argue in favor of bilateral mastectomy and the avoidance of radiotherapy.Li-Fraumeni syndrome (LFS) is a rare disorder that considerably increases the risk of developing several types of cancer, particularly in children and young adults. The first observations were described by Li and Fraumeni in 1969 [1]. LFS is inherited in an autosomal dominant pattern with the frequent occurrence of soft tissue/bone sarcoma, breast cancer, leukemia, brain tumors and other cancers (melanoma, colon cancer, pancreatic cancer, adrenocortical carcinoma) [1,2]. Since then, several reports of affected families have contributed to a more precise definition of the Li Fraumeni syndrome [3].Germ-line TP53 gen
Dosimetric risk estimates of radiation-induced malignancies after intensity modulated radiotherapy  [cached]
Patil Vijay,Kapoor Rakesh,Chakraborty Santam,Ghoshal Sushmita
Journal of Cancer Research and Therapeutics , 2010,
Abstract: Context: The increasing popularity of intensity-modulated radiotherapy (IMRT) stems from its ability to generate a more conformal plan than hitherto possible with conventional planning. As a result, IMRT is in widespread use across diverse indications. However, the inherent nature of IMRT delivery makes it monitor unit inefficient and leads to increased normal tissue integral dose. This in turn may result in an increased risk of radiation-induced second malignancies. Aim: To calculate the risk of second malignancy post-IMRT. Settings and Design: Observational study in a tertiary care institute. Materials and Methods: Eighteen previously untreated patients with head and neck cancers (n = 10) and prostate cancer (n = 8) were selected. In these patients, selected infield organs around the planning target volume were contoured, viz. brain and thyroid in patients with head and neck cancer and bladder, rectum and small intestine in patients with carcinoma prostate. The estimates of radiation-induced malignancies in these organs and the whole of the body were derived using the concept of Organ Equivalent Dose. Statistical Analysis Used: Descriptive statistics (SPSS version 12). Results: The modal estimated incidence of radiation-induced malignancies was 129.87, 1.4, 0.10, 3.42, 7.789 and 129.85 per 10,000 person-years for the brain, thyroid, bladder, rectum, small intestine and whole body respectively. Conclusions: The estimated risk of radiation-induced malignancies in the thyroid and rectum was similar to the available literature, while the risk for bladder carcinomas was lower than that reported. However, the calculated risk of radiation-induced tumors of the brain was more than that reported with conventional radiation therapy. We propose that estimation of the risk of radiation-induced malignancies should be a part of the plan evaluation process and special care should be taken before using this modality in young patients with benign tumors in the head and neck region.
Integral Dose and Radiation-Induced Secondary Malignancies: Comparison between Stereotactic Body Radiation Therapy and Three-Dimensional Conformal Radiotherapy  [PDF]
Marco D'Arienzo,Stefano G. Masciullo,Vitaliana de Sanctis,Mattia F. Osti,Laura Chiacchiararelli,Riccardo M. Enrici
International Journal of Environmental Research and Public Health , 2012, DOI: 10.3390/ijerph9114223
Abstract: The aim of the present paper is to compare the integral dose received by non-tumor tissue (NTID) in stereotactic body radiation therapy (SBRT) with modified LINAC with that received by three-dimensional conformal radiotherapy (3D-CRT), estimating possible correlations between NTID and radiation-induced secondary malignancy risk. Eight patients with intrathoracic lesions were treated with SBRT, 23 Gy × 1 fraction. All patients were then replanned for 3D-CRT, maintaining the same target coverage and applying a dose scheme of 2 Gy × 32 fractions. The dose equivalence between the different treatment modalities was achieved assuming α/β = 10Gy for tumor tissue and imposing the same biological effective dose (BED) on the target (BED = 76Gy 10). Total NTIDs for both techniques was calculated considering α/β = 3Gy for healthy tissue. Excess absolute cancer risk (EAR) was calculated for various organs using a mechanistic model that includes fractionation effects. A paired two-tailed Student t-test was performed to determine statistically significant differences between the data ( p ≤ 0.05). Our study indicates that despite the fact that for all patients integral dose is higher for SBRT treatments than 3D-CRT ( p = 0.002), secondary cancer risk associated to SBRT patients is significantly smaller than that calculated for 3D-CRT ( p = 0.001). This suggests that integral dose is not a good estimator for quantifying cancer induction. Indeed, for the model and parameters used, hypofractionated radiotherapy has the potential for secondary cancer reduction. The development of reliable secondary cancer risk models seems to be a key issue in fractionated radiotherapy. Further assessments of integral doses received with 3D-CRT and other special techniques are also strongly encouraged.
Secondary hematological malignancies following breast cancer treatment
Soley Bayraktar,Maricer P. Escalon
Oncology Reviews , 2011, DOI: 10.4081/48
Abstract: Breast cancer (BC) incidence has increased among women in most Western countries. Concurrently, the survival time of BC patients has increased with 5-year survival rates reaching 80–90%. Secondary hematological malignancies (SHM) following BC treatment are an issue of concern to clinicians and also to patients and their families. However, therapy-induced leukemia after BC is an underemphasized clinical problem. In this review,we will focus on the incidences and patterns of occurrence ofSHM in patients with BC. We will address risk factors for the development of SHM and we will explore how secondary hematological malignancies impact the survival of BC patients.
Modeling of Radiation Pneumonitis after Lung Stereotactic Body Radiotherapy: A Bayesian Network Approach  [PDF]
Sangkyu Lee,Norma Ybarra,Krishinima Jeyaseelan,Sergio Faria,Neil Kopek,Pascale Brisebois,Toni Vu,Edith Filion,Marie-Pierre Campeau,Louise Lambert,Pierre Del Vecchio,Diane Trudel,Nidale El-Sokhn,Michael Roach,Clifford Robinson,Issam El Naqa
Physics , 2015,
Abstract: Background and Purpose: Stereotactic body radiotherapy (SBRT) for lung cancer accompanies a non-negligible risk of radiation pneumonitis (RP). This study presents a Bayesian network (BN) model that connects biological, dosimetric, and clinical RP risk factors. Material and Methods: 43 non-small-cell lung cancer patients treated with SBRT with 5 fractions or less were studied. Candidate RP risk factors included dose-volume parameters, previously reported clinical RP factors, 6 protein biomarkers at baseline and 6 weeks post-treatment. A BN ensemble model was built from a subset of the variables in a training cohort (N=32), and further tested in an independent validation cohort (N=11). Results: Key factors identified in the BN ensemble for predicting RP risk were ipsilateral V5, lung volume receiving more than 105% of prescription, and decrease in angiotensin converting enzyme (ACE) from baseline to 6 weeks. External validation of the BN ensemble model yielded an area under the curve of 0.8. Conclusions: The BN model identified potential key players in SBRT-induced RP such as high dose spillage in lung and changes in ACE expression levels. Predictive potential of the model is promising due to its probabilistic characteristics.
Region of Treatment in Radiotherapy and Second Malignancies in Breast Cancer Patients  [PDF]
Wei Zhang, Aldo Becciolini, Annibale Biggeri, Paolo Pacini, Colin R. Muirhead
Journal of Cancer Therapy (JCT) , 2012, DOI: 10.4236/jct.2012.325096
Abstract: A cohort study was conducted based on clinical records for 5248 women treated for breast cancer in Florence (Italy), with continuous follow up from 1965 to 1994. The subjects were categorised into groups such as no radiation treatment; breast dose only; and radiation doses in one, two, three or four of the following fields: namely internal mammary chain, supraclavicular nodes, axillary lymph nodes and chest wall. The Cox proportional hazards model for ungrouped survival data was used to estimate the relative risk for second cancer after radiotherapy delivered to different regions. The relative risk for all second cancers combined was statistically significantly raised if the internal mammary chain and supraclavicular nodes were irradiated. However, we found that the relative risk of the second malignancies could be reduced if all the locoregional lymph nodes (the internal mammary chain, supraclacicular nodes, axillary nodes) and chest wall are irradiated at the same time. If this finding can be verified by other large cohort studies or randomized clinical trials, it may have implications in clinical practice when deciding upon the targeted areas for radiotherapy; partial radiation treatment of the locoregional lymph nodes could raise the risk of second malignancies and should ideally be avoided.
Study protocol of the German "Registry for the Detection of Late Sequelae after Radiotherapy in Childhood and Adolescence" (RiSK)
Tobias Bolling, Andreas Schuck, Hildegard Pape, Christian Rube, Barbara Pollinger, Beate Timmermann, Rolf D Kortmann, Karin Dieckmann, Normann Willich
Radiation Oncology , 2008, DOI: 10.1186/1748-717x-3-10
Abstract: Radiation parameters including detailed organ doses as well as toxicity evaluations are collected prospectively from centres all over Germany. Standardized documentation forms are used. These forms are given in an English and German version as additional files to this publication. Documentation is planned for all children who receive radiotherapy in one of the therapy trials of the "German Society of Paediatric Oncology and Haematology (GPOH)". The study started in a pilot phase in June 2001 in few centres. Since 2004 documentation has been performed all over Germany and is still on-going.To our knowledge, "RiSK" is the only multi-centre study that evaluates radiation associated side effects prospectively with detailed information about organ dose levels. With ongoing recruitment and prolongation of follow-up powerful data will be obtained in a few years. A broad use and international cooperation are welcome.Radiotherapy is of fundamental importance in paediatric oncology. Individual decisions for the use of ionizing radiation always have to consider the potential benefit and possible side effects. Whereas the benefit is no matter of major discussions, the risk for potential side effects like secondary malignancies and non-cancer health effects cannot be quantified based on sufficient data. Especially, there is a lack of information regarding dose-effect relationships of ionizing radiation. This is of special importance when ionizing radiation is used in childhood and adolescence due to potential higher vulnerability of growing tissue and longer expected life span [1-3]. For radiotherapy, late effects after treatment in childhood and adolescence have mainly been characterized retrospectively with small patient numbers [4-7]. Many of these analyses are limited due to little information about organ dose levels and older radiation techniques in some cases. Recently, the characterization of late effects after cancer therapy in childhood including chemotherapy, surgery a
Can the risk of secondary cancer induction after breast conserving therapy be reduced using intraoperative radiotherapy (IORT) with low-energy x-rays?
Muhammad Aziz, Frank Schneider, Sven Clausen, Elena Blank, Carsten Herskind, Muhammad Afzal, Frederik Wenz
Radiation Oncology , 2011, DOI: 10.1186/1748-717x-6-174
Abstract: Computer-tomography scans of an anthropomorphic phantom were acquired with an INTRABEAM IORT applicator (diameter 4 cm) in the outer quadrant of the breast and transferred via DICOM to the treatment planning system. Ipsilateral breast, contralateral breast, ipsilateral lung, contralateral lung, spine and heart were contoured. An INTRABEAM source (50 kV) was defined with the tip of the drift tube at the center of the spherical applicator. A dose of 20 Gy at 0 mm depth from the applicator surface was prescribed for IORT and 34 Gy (5 days × 2 × 3.4 Gy) at 10 mm depth for APBI. For EBRT a total dose of 50 Gy in 2 Gy fractions was planned using two tangential fields with wedges. The mean and maximal doses, DVHs and volumes receiving more than 0.1 Gy and 4 Gy of organs at risk (OAR) were calculated and compared. The life time risk for secondary cancers was estimated according to NCRP report 116.IORT delivered the lowest maximal doses to contralateral breast (< 0.3 Gy), ipsilateral (1.8 Gy) and contralateral lung (< 0.3 Gy), heart (1 Gy) and spine (< 0.3 Gy). In comparison, maximal doses for APBI were 2-5 times higher. EBRT delivered a maximal dose of 10.4 Gy to the contralateral breast and 53 Gy to the ipsilateral lung. OAR volumes receiving more than 4 Gy were 0% for IORT, < 2% for APBI and up to 10% for EBRT (ipsilateral lung). The estimated risk for secondary cancer in the respective OAR is considerably lower after IORT and/or APBI as compared to EBRT.The calculations for maximal doses and volumes of OAR suggest that the risk of secondary cancer induction after IORT is lower than compared to APBI and EBRT.The breast is the most common site of cancer in women and with the wide-spread use of mammography more than two-thirds of breast cancers are diagnosed at an early stage [1,2]. Early stage breast cancer carries a better prognosis, with outcomes having improved dramatically over the last two decades with a 25% reduction of breast cancer mortality [3]. Breast-conserving
Intensity modulated radiotherapy for sinonasal malignancies with a focus on optic pathway preservation
Chi Alexander,Nguyen Nam P,Tse William,Sobremonte Gill
Journal of Hematology & Oncology , 2013, DOI: 10.1186/1756-8722-6-4
Abstract: Purpose To assess if intensity-modulated radiotherapy (IMRT) can possibly lead to improved local control and lower incidence of vision impairment/blindness in comparison to non-IMRT techniques when treating sinonasal malignancies; what is the most optimal dose constraints for the optic pathway; and the impact of different IMRT strategies on optic pathway sparing in this setting. Methods and materials A literature search in the PubMed databases was conducted in July, 2012. Results Clinical studies on IMRT and 2D/3D (2 dimensional/3 dimensional) RT for sinonasal malignancies suggest improved local control and lower incidence of severe vision impairment with IMRT in comparison to non-IMRT techniques. As observed in the non-IMRT studies, blindness due to disease progression may occur despite a lack of severe toxicity possibly due to the difficulty of controlling locally very advanced disease with a dose ≤ 70 Gy. Concurrent chemotherapy’s influence on the the risk of severe optic toxicity after radiotherapy is unclear. A maximum dose of ≤ 54 Gy with conventional fractionation to the optic pathway may decrease the risk of blindness. Increased magnitude of intensity modulation through increasing the number of segments, beams, and using a combination of coplanar and non-coplanar arrangements may help increase dose conformality and optic pathway sparing when IMRT is used. Conclusion IMRT optimized with appropriate strategies may be the treatment of choice for the most optimal local control and optic pathway sparing when treating sinonasal malignancy.
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