Radiotherapy For Hodgkin Lymphoma Research Articles

Reduction in late mortality among 5-year survivors of childhood cancer: A report from the Childhood Cancer Survivor Study (CCSS).

LBA2 Background: Over the past four decades, treatment of many childhood cancers has been modified with the aim of achieving high survival rates while reducing the risk of life-threatening late-effects, and promoting risk-based follow-up care of survivors. Methods: Late mortality was evaluated in 34,033 5-year survivors (diagnosed < 21 years of age from 1970-1999, median follow-up 21 years, range 5-38) using cumulative incidence and Poisson regression models adjusted for demographic and disease factors to calculate relative risk (RR) and 95% confidence intervals (CI). Mortality due to non-recurrence/non-external (NR/NE) causes, which includes deaths that reflect late-effects of cancer therapy, was evaluated. Results: 1,622 (41%) of the 3,958 deaths were attributable to NR/NE causes, including 751 subsequent neoplasm (SN), 243 cardiac, and 136 pulmonary deaths. Changes in therapy by decade included reduced rates of: cranial radiotherapy (RT) for acute lymphoblastic leukemia (ALL, 86%, 54%, 22%), RT for Wilms tumor (WT, 77%, 54%, 49%) and RT for Hodgkin lymphoma (HL, 96%, 88%, 77%). Reductions in 15 year cumulative NR/NE mortality were observed across treatment eras for ALL (p < .001), HL (p = .005), and WT (p = .005). Cardiac deaths decreased in ALL (p = .002), HL (p = .06), and WT (p = .04), and SN deaths decreased in WT (p < .001). Year of diagnosis (adjusted for age, sex, diagnosis, follow-up time) was significantly associated with a reduced risk of all-cause mortality (RR = 0.85, CI 0.83-0.87), NR/NE death (RR = 0.87, CI 0.84-0.91), death from SN (RR = 0.84, CI 0.80-0.89), cardiac death (RR = 0.78, CI 0.69-0.87) and pulmonary death (RR = 0.79, CI 0.68-0.91). Conclusions: The CCSS cohort provides evidence that the strategy of modifying therapy to reduce the occurrence of late-effects, and promotion of early detection, is successfully translating into a significant reduction in observed late mortality. [Table: see text]

Simple Method to Estimate Mean Heart Dose From Hodgkin Lymphoma Radiation Therapy According to Simulation X-Rays

To describe a new method to estimate the mean heart dose for Hodgkin lymphoma patients treated several decades ago, using delineation of the heart on radiation therapy simulation X-rays. Mean heart dose is an important predictor for late cardiovascular complications after Hodgkin lymphoma (HL) treatment. For patients treated before the era of computed tomography (CT)-based radiotherapy planning, retrospective estimation of radiation dose to the heart can be labor intensive. Patients for whom cardiac radiation doses had previously been estimated by reconstruction of individual treatments on representative CT data sets were selected at random from a case-control study of 5-year Hodgkin lymphoma survivors (n=289). For 42 patients, cardiac contours were outlined on each patient's simulation X-ray by 4 different raters, and the mean heart dose was estimated as the percentage of the cardiac contour within the radiation field multiplied by the prescribed mediastinal dose and divided by a correction factor obtained by comparison with individual CT-based dosimetry. According to the simulation X-ray method, the medians of the mean heart doses obtained from the cardiac contours outlined by the 4 raters were 30 Gy, 30 Gy, 31 Gy, and 31 Gy, respectively, following prescribed mediastinal doses of 25-42 Gy. The absolute-agreement intraclass correlation coefficient was 0.93 (95% confidence interval 0.85-0.97), indicating excellent agreement. Mean heart dose was 30.4 Gy with the simulation X-ray method, versus 30.2 Gy with the representative CT-based dosimetry, and the between-method absolute-agreement intraclass correlation coefficient was 0.87 (95% confidence interval 0.80-0.95), indicating good agreement between the two methods. Estimating mean heart dose from radiation therapy simulation X-rays is reproducible and fast, takes individual anatomy into account, and yields results comparable to the labor-intensive representative CT-based method. This simpler method may produce a meaningful measure of mean heart dose for use in studies of late cardiac complications.

Calculation of Organs Doses and Secondary Cancer Risk during Mantle Field Radiotherapy for Hodgkin’s Lymphoma

Occurrence of radiation-induced secondary cancer risk following mantle field radiotherapy for Hodgkin's lymphoma (HL) patients with long survival demands well-established radiotherapy strategy. Organs doses and resulted secondary cancer risk due to out-of field photons were calculated during mantle field radiotherapy for Hl patient. The male and female mathematical phantom of the Oak Ridge National Laboratory (ORNL) and validated 6MV photon beam of a Varian 2300 C/D were modeled by MCNPX 2.4.0 MC code. Using suitable lungs and thyroid shields for AP and PA fields, the organ specific absorbed doses, effective dose, and secondary cancer risk were calculated following to mantle field radiotherapy for HL. Among the out-of-field organs, the nose, eyes, head and neck's skins and sinuses have the higher received doses. The total effective doses and secondary cancer risk for a male and female were estimated to be 199, 234 mSv and 1.72, 1.87 respectively. During mantle field radiotherapy for Hodgkin's lymphoma, accurately estimations of organs dose near to the field's edge and suitable shielding of critical in-field organs are crucial factor to establish an optimal treatment plan.

A new method to estimate doses to the normal tissues after past extended and involved field radiotherapy for Hodgkin lymphoma

IntroductionReconstruction of radiotherapy (RT) performed decades ago is challenging, but is necessary to address dose–response questions from epidemiological data and may be relevant in re-irradiation scenarios. Here, a novel method to reconstruct extended and involved field RT for patients with Hodgkin lymphoma was used. Materials and methodsFor 46 model patients, 29 organs at risk (OARs) were contoured and seven treatment fields reconstructed (mantle, mediastinal, right/left neck, right/left axillary, and spleen field). Extended and involved field RT were simulated by generating RT plans by superpositions of the seven individual fields. The mean (standard deviation) of the 46 individual mean organ doses were extracted as percent of prescribed dose for each field superposition. ResultsThe estimated mean doses to the OARs from 17 field combinations were presented. The inter-patient variability was found to be a larger contributor to the uncertainty than the field simulation process. The inter-patient variability depended on the OAR and primarily affected the estimates for OARs located at the edge of the RT field. ConclusionsDose estimates for 29 OARs were reported from extended and involved field RT. These estimates could be employed when individual reconstruction is not feasible and estimated doses from past treatments are needed.

Hodgkin Lymphoma With Bulky Mediastinal Disease: A Comparison of AP/PA, IMRT, and Volumetric Arc Plans

There is growing concern about the late effects of radiation therapy for Hodgkin Lymphoma (HL). To date, no studies have compared radiation therapy for HL patients with bulky mediastinal disease based on dose to Organs At Risk (OAR). Compared to traditional approaches, the involved node radiation therapy (INRT) approach allows for smaller volumes and improved dose distribution. However, while OAR receive less high dose exposure, a larger volume receives a lower, potentially more mutagenic, dose.

Breathing Adapted Radiation Therapy in Hodgkin Lymphoma: Do We Need the Staging PET/CT in Deep Inspiration Breath Hold?

was confirmed by PET (60%) or gallium (40%) in all patients. The median dose of consolidation RT was 24 Gy (range, 18-36 Gy). Four patients developed recurrent HL, two of which were in-field recurrences. Five and 10-year relapse-free survival were 95% (95% CI 0.87-0.98) and 93% (CI 0.82-0.97), respectively. Five and 10-year overall survival were both 98% (CI 0.92-0.99). The most common late effect was hypothyroidism which developed in 18 patients (20%). Seven secondary malignancies were diagnosed (2 basal cell carcinomas, 2 non-Hodgkin lymphomas, colon cancer, acute myelogenous leukemia, and small cell lung cancer). Only the lung cancer was within the RT field, diagnosed in an active smoker 13 years after treatment. One patient developed mild diastolic dysfunction; no other cardiac complications were diagnosed. Conclusions: Lower doses of RT may be sufficient when combined with >4 cycles of ABVD for UF HL. This strategy may decrease the risk of long-term complications. The standard approach of 4 cycles of ABVD and 30 Gy of RT should be compared to 6 cycles of ABVD and 20 Gy of RT. Author Disclosure: J. Torok: None. L.R. Prosnitz: None. M. Palta: None. Y. Wu: None. A. Beaven: None. L. Diehl: None. C.R. Kelsey: None.

Prospective phase II trial of image-guided radiotherapy in Hodgkin lymphoma: Benefit of deep inspiration breath-hold

Background. Long-term Hodgkin lymphoma (HL) survivors have an increased risk of late cardiac morbidity and secondary lung cancer after chemotherapy and mediastinal radiotherapy. In this prospective study we investigate whether radiotherapy with deep inspiration breath-hold (DIBH) can reduce radiation doses to the lungs, heart, and cardiac structures without compromising the target dose.Patients and methods. Twenty-two patients (14 female, 8 male), median age 30 years (18–65 years), with supra-diaphragmatic HL were enrolled and had a thoracic PET/CT with DIBH in addition to staging FDG-PET/CT in free breathing (FB) and a planning CT in both FB and DIBH. For each patient an involved-node radiotherapy plan was done for both DIBH and FB, and the doses to the lungs, heart, and female breasts were recorded prospectively. Mean doses to the heart valves and coronary arteries were recorded retrospectively. Patients were treated with the technique yielding the lowest doses to normal structures.Results. Nineteen patients were treated with DIBH and three with FB. DIBH reduced the mean estimated lung dose by 2.0 Gy (median: 8.5 Gy vs. 7.2 Gy) (p < 0.01) and the mean heart dose by 1.4 Gy (6.0 Gy vs. 3.9 Gy) (p < 0.01) compared to FB. The lung and heart V20Gy were reduced with a median of 5.3% and 6.3%. Mean doses to the female breasts were equal with FB and DIBH.Conclusion. DIBH can significantly decrease the estimated mean doses to the heart and lungs without lowering the dose to the target in radiotherapy for patients with mediastinal HL.

Implementation of contemporary radiation therapy planning concepts for pediatric Hodgkin lymphoma: Guidelines from the International Lymphoma Radiation Oncology Group

The optimal management of children with Hodgkin lymphoma (HL) should limit the risk of treatment-related toxicity without compromising disease control. Consequently, increasing effort is being directed to retaining the demonstrated efficacy of radiation therapy (RT) in maximizing the cure of HL while reducing the radiation exposure of normal tissues. Historically, guidelines for RT volume definition used in pediatric HL trials have referenced 2-dimensional imaging and bony landmarks to define classical involved field RT. With recognition of the efficacy of chemotherapy, the data on the adverse late effects of radiation, and the evolution of advanced imaging techniques that reveal the location of both tumor and normal tissues, it is necessary that radiation techniques for children and adolescents be refined. The concepts described by the International Commission on Radiation Units provide a common approach for field definition using 3-dimensional computed tomographic--based RT planning and volumetric image guidance. Here we describe the application of these concepts in the planning of RT for pediatric HL. This will be increasingly important as current and upcoming pediatric HL trials will employ these concepts to deliver RT.

Guidelines for the first line management of classical Hodgkin lymphoma

The guideline group was selected to be representative of UK-based medical experts and patients’ representatives. MEDLINE and EMBASE were searched systematically for publications in English from January 1990 to June 2013 using the key words Hodgkin, Lymphoma, Treatment, Chemotherapy and Radiotherapy. References from relevant publications were also searched. The writing group produced the draft guideline, which was subsequently revised by consensus by members of the Haemato-Oncology Task Force of the British Committee for Standards in Haematology (BCSH). The guideline was then reviewed by a sounding board of approximately 50 UK haematologists and the BCSH and comments incorporated where appropriate. The ‘GRADE’ system was used to quote levels and grades of evidence, details of which can be found in Appendix I. The objective of this guideline is to provide healthcare professionals with clear guidance on the management of patients with classical Hodgkin Lymphoma (HL). The guidance may not be appropriate for all patients with HL and in all cases individual patient circumstances may dictate an alternative approach.

Radiation therapy for Hodgkin lymphoma

The long-term cardiac complications of radio(chemo)therapy for Hodgkin lymphoma include coronary artery disease, cardiac arrhythmias, valvular disease, pericardial disease, cardiomyopathy and heart failure. The extent of myocardial damage after radiotherapy is dependent on the dose, the volume and the technique of chest irradiation. Also, patient-specific factors, such as the age of the patient at the time of treatment and the presence of classical cardiac risk factors are supposed to be important. The relative risk of cardiovascular events is estimated to be 2 to 7 times higher than the general population. The patient’s clinical picture can vary from asymptomatic to an acute presentation of end-stage coronary artery or valvular disease.

10 Year Experience of a National Breast Screening Programme Following Radiotherapy for Hodgkin Lymphoma in South East Wales

In 2003, the UK Department of Health initiated a recall and breast screening programme for women who received radiotherapy as treatment for HL. Velindre Cancer Centre in SE Wales (population 1.5 million) identified 300 female HL patients treated with RT through a case record search. Of these 100 had received RT to the mediastinum and/or axilla at age < 36 years. 7 patients had already died (3 lymphoma, 1 breast cancer, 1 treatment toxicity, 2 unknown). 83 patients treated with RT between 1968 – 2003 were traced and contacted. 3 patients were alive with breast cancer, and 1 with breast and thyroid cancer. Since 2003, a further 8 have died (5 lymphoma, 3 breast cancer, 2 brain metastases unknown primary, 1 lung cancer, 1 AML and 3 other/unknown). 2 breast cancers have been detected, 1 at the initial recall and 1 on the annual screening programme. The national programme for HL breast screening in Wales is provided by 3 regional centres and at-risk patients are registered on a database at time of RT. Screening starts 8 years after RT or at the age of 25yrs following a consultation with an oncologist for informed consent. Annual MRI is used for patients < 30yrs, and mammography ± MRI between 30 – 50yrs. HL patients are screened in 2 dedicated sessions at the Breast Test Wales (BTW) National Screening Centre in Cardiff, while MRI scans are performed at local hospitals. Standard 3-yearly screening is performed after the age of 50. Results are reviewed at an annual meeting, and a user survey has been very positive, with women finding screening reassuring. 40 patients currently have annual screening, 17 of these with MRI. 1 patient chose to have bilateral mastectomies. 18 patients are in standard 3 yearly screening, and 12 patients have not yet commenced screening. Numbers of patients at risk will fall with evolving treatment strategies, and the risk of breast cancer for treated patients may fall with smaller fields and lower doses. A treatment-risk adapted approach to screening combined with newer low dose mammographic techniques may improve outcomes and cost effectiveness of the programme.

Histologic subtypes of breast cancer following radiotherapy for Hodgkin lymphoma.

The purpose of the study was to determine whether breast cancers (BCs) that develop in women previously irradiated for Hodgkin lymphoma (HL) are biologically similar to sporadic BC. We retrospectively reviewed the charts of patients who developed BC after radiotherapy (RT) for HL. Tumors were classified as ductal carcinoma in situ (DCIS) or invasive carcinoma. Invasive carcinomas were further characterized according to the subtype: hormone receptor (HR)+/human epidermal growth factor receptor 2 (HER2)-, HR+/HER2+, HR-/HER2+, and HR-/HER2-. BCs after HL were compared with four age-matched sporadic, non-breast cancer (BRCA) I or II mutated BCs. One hundred forty-seven HL patients who were treated with RT between 1966 and 1999 and subsequently developed BCs were identified. Of these, 65 patients with 71 BCs had complete pathologic information. The median age at HL diagnosis was 23 (range, 10-48). The median age at BC diagnosis was 44 (range, 28-66). The median time to developing BC was 20 years. Twenty cancers (28%) were DCIS and 51 (72%) were invasive. Of the 51 invasive cancers, 24 (47%) were HR+/HER2-, 2 (4%) were HR+/HER2+, 5 (10%) were HR-/HER2+, and 20 (39%) were HR-/HER2-. There were no differences in BC histologic subtype according to the age at which patients were exposed to RT, the use of chemotherapy for HL treatment, or the time from RT exposure to the development of BC. In a 4 : 1 age-matched comparison to sporadic BCs, BCs after HL were more likely to be HR-/HER2- (39% versus 14%) and less likely to be HR+/HER2- (47% versus 61%) or HR+/HER2+ (4% versus 14%) (P = 0.0003). BCs arising in previously irradiated breast tissue were more likely to be triple negative compared with age-matched sporadic invasive cancers and less likely to be HR positive. Further studies will be important to determine the molecular pathways of carcinogenesis in breast tissue that is exposed to RT.

OC-0086: Coronary dosimetry based on heart CT angiographies for Hodgkin lymphoma radiation therapy

OC-0086: Coronary dosimetry based on heart CT angiographies for Hodgkin lymphoma radiation therapy

Pulmonary damage in Hodgkin's lymphoma patients treated with sequential chemo-radiotherapy: Predictors of radiation-induced lung injury

Background. Our aim was to define predictors of late radiation-induced lung injury (RILI) in Hodgkin's lymphoma (HL) survivors treated with bleomycin-containing chemotherapy and radiotherapy. Material and methods. Eighty consecutive patients treated with chemotherapy and subsequent supradiaphragmatic radiation therapy for HL were retrospectively reviewed for symptoms and/or radiological signs of RILI. Median patient age was 26 years (range 14–55). Left, right, and total lung dosimetric parameters along with clinical, disease, and treatment-related characteristics were analyzed. Multivariate logistic regression analyses were performed. A receiver operator characteristic (ROC) curve analysis was performed to find possible cutoff values dividing patients into high- and low-risk groups. Results. Seven of 80 (9%) patients had lung disease at baseline. Four of 80 (5%) had toxicity after chemotherapy and before the beginning of radiotherapy. These patients were excluded from further evaluation. At a median time of 10 months (range 9–18), 9/69 patients (13%) developed lung radiological changes on computed tomography (CT) after treatment. Four of nine patients were diagnosed RTOG grade ≥ 2. On multivariate analyses, left-lung V30 (p = 0.004, OR = 1.108 95% CI 1.033–1.189) and total-lung V30 (p = 0.009, OR = 1.146 95% CI 1.035–1.270) resulted to be predictors of lung CT changes with a cutoff value of 16% and 15%, respectively. When only symptomatic RILI was considered a left-lung V30 cutoff value of 32% was estimated. Conclusion. Bleomycin and RT may cause lung injury in a small, but significant fraction of HL patients. Left-lung V30 predicts the risk of developing asymptomatic or symptomatic RILI after sequential chemo-radiotherapy.

Guideline on the management of primary resistant and relapsed classical Hodgkin lymphoma

Summary of key recommendations ● Repeat biopsy is generally recommended in Hodgkinlymphoma (HL) patients thought to have relapsed, andshould be considered in those who have residual fluoro-deoxyglucose (FDG)-avid lesions post-therapy (1C).● Positron-emission tomography/computerized tomogra-phy (PET-CT) is the preferred restaging modality aftersalvage therapy (1B).● The aim of salvage treatment should be to achieve anFDG-PET-negative remission (1B).● The choice of a first-line salvage regimen in patients eli-gible for autologous stem cell transplantation (ASCT)should be based on patient factors and familiarity ofthe treatment centre with the regimen (2C).● Regimens containing stem cell toxic agents (such as car-mustine and melphalan) should be avoided if possibleuntil stem cells have been successfully collected andcryopreserved if ASCT is planned (1B).● There is currently no evidence to support intensivesequential induction/consolidation strategies prior toASCT (1B).● Consider switching to an alternative non-cross-resistantsalvage regimen if there are residual FDG-avid lesionsafter first line salvage treatment and the intent is toproceed to ASCT (2B).● In patients not eligible for ASCT, combined modalitytherapy should be considered especially in early stagerelapse and in patients who have not received priorradiotherapy or who have relapsed outside of the initialradiotherapy field (2B).● In patients unlikely to tolerate the toxicities associatedwith more intensive regimens, palliation with either a sin-gle agent or with a multi-agent oral regimen with or with-out intravenous vinblastine should be considered (2C).● Early consideration of involvement of palliative care ser-vices is recommended, particularly in those not eligiblefor high dose therapy (1C).● ASCT is the standard treatment for patients withrelapsed disease who achieve an adequate response tosalvage therapy (1A).● ASCT is also the standard treatment for patients withprimary resistant disease who achieve an adequateresponse to salvage therapy (1B).● ASCT is not recommended in those failing to achievean adequate response (1B).Guideline

Doses to Carotid Arteries After Modern Radiation Therapy for Hodgkin Lymphoma: Is Stroke Still a Late Effect of Treatment?

Hodgkin lymphoma (HL) survivors are at an increased risk of stroke because of carotid artery irradiation. However, for early-stage HL involved node radiation therapy (INRT) reduces the volume of normal tissue exposed to high doses. Here, we evaluate 3-dimensional conformal radiation therapy (3D-CRT), volumetric-modulated arc therapy (VMAT), and proton therapy (PT) delivered as INRT along with the extensive mantle field (MF) by comparing doses to the carotid arteries and corresponding risk estimates. We included a cohort of 46 supradiaphragmatic stage I-II classical HL patients. All patients were initially treated with chemotherapy and INRT delivered as 3D-CRT (30 Gy). For each patient, we simulated MF (36 Gy) and INRT plans using VMAT and PT (30 Gy). Linear dose-response curves for the 20-, 25-, and 30-year risk of stroke were derived from published HL data. Risks of stroke with each technique were calculated for all patients. Statistical analyses were performed with repeated measures analysis of variance. The mean doses to the right and left common carotid artery were significantly lower with modern treatment compared with MF, with substantial patient variability. The estimated excess risk of stroke after 20, 25, and 30 years was 0.6%, 0.86%, and 1.3% for 3D-CRT; 0.67%, 0.96%, and 1.47% for VMAT; 0.61%, 0.96%, and 1.33% for PT; and 1.3%, 1.72%, and 2.61% for MF. INRT reduces the dose delivered to the carotid arteries and corresponding estimated risk of stroke for HL survivors. Even for the subset of patients with lymphoma close to the carotid arteries, the estimated risk is low.

Prognostic value of RS COX-2 and radiotherapy in Hodgkin lymphoma

Prognostic value of RS COX-2 and radiotherapy in Hodgkin lymphoma

SU-E-T-285: Use of Computational Human Phantoms Combined with a Treatment Planning System to Study the Sensitivity of Reconstructed Normal Tissue Dose to Patient Size and Assumptions On Second Tumor Location

Purpose: Epidemiologic studies of second cancer risk from radiotherapy require reconstruction of normal tissue doses for patients treated years ago and often rely on a single estimate, usually a mean tissue dose or less frequently, a point-dose at the site of second cancer development. However, uncertainties of dose estimates due to assumptions made in dose reconstruction, e.g., body size and location of the tumor, are rarely quantified. To assess the uncertainty of the estimated incidental breast dose from radiotherapy for Hodgkin Lymphoma, we investigated the sensitivity of the point-dose to dosimetric assumptions using computational human phantoms of different body sizes imported into a commercial treatment planning system (TPS). Methods: We converted three adult female hybrid phantoms representing the 20th, 50th, and 80th weight percentiles to DICOM images that we imported to a TPS featuring a three-dimensional convolution/superposition algorithm. We simulated opposite mantle fields with 6 MV photons and typical lung blocks (transmission, 5%) to deliver 40 Gy at the phantom mid-plane. We located a point in the left breast 1.7 cm below the surface and in-field to reconstruct point-dose for each phantom. We retrieved the lateral dose profile starting at the point and crossing the block boundary. Results: Point-doses were 43, 44, and 46 Gy for the three phantoms with 20th, 50th, and 80th weight percentiles, respectively. To deliver 40 Gy at mid-plane of the phantoms, a greater number of monitor units were required for thicker phantoms, resulting in a greater shallow dose. The lateral dose profile showed that the point-dose estimate can vary by a factor of 10 depending on whether the point is under the block or not. Conclusion: Our new dose reconstruction strategy, combining computational human phantoms and a TPS, enabled us to examine the sensitivity of point-dose estimate to patient size and assumed second tumor location.

Tumor mutation status of Hodgkin lymphoma survivors with secondary lung adenocarcinoma.

9600 Background: In a multi-institutional, retrospective study of 1976 patients treated for Hodgkin's lymphoma (HL) from 1969-2007, 55 patients developed second primary lung cancers a median of 19.5 years after treatment. Of these 55 cases, 32 were identified as lung adenocarcinoma (ACA). The development of targeted therapies in recent years has made the detection of specific genomic alterations important for disease prognosis and treatment in lung ACA. The prevalence of certain genomic alterations (EGFR, ALK, and KRAS) is highly correlated with smoking history. We hypothesize that the prevalence of genomic alterations also may differ in patients with a significant exposure to radiation. Methods: This observational retrospective case series includes 6 patients treated with mediastinal radiation for HL who subsequently developed lung ACA. All patients were treated at Ohio State University Wexner Medical Center. Patients were identified by searching billing diagnosis codes in the electronic medical record and by query of the physicians in the department of thoracic oncology at our institution. IRB approval was obtained. Results: The average age at diagnosis of HL was 25 years (range 18-46) and the average age at diagnosis of lung cancer was 58 (range 52-73). All patients were treated with radiation therapy; two patients were treated additionally with chemotherapy. None of the patients received HDT-ASCT. The average time from diagnosis of HL to diagnosis of lung cancer was 33 years. Of our six cases, 2 were positive for EGFR mutations and the other four were triple negative (-EGFR, -ALK, -KRAS). Three were never smokers, one had a 1.5 pack year history, and two had 10 pack year histories. Lung cancer stages at diagnosis were 1B (n=2), 2B (n=1), 3A (n=2), 4 (n=1). Conclusions: To our knowledge, this is the first report of mutational status of second primary lung ACA following radiation therapy for Hodgkin disease. Although the number of patients is small, the higher prevalence of the EGFR mutation in this sample suggests that ACA related to radiation therapy may have a similar mutational profile to that of never smokers. Further investigation is needed to define the disease characteristics of lung ACA in HL survivors.

Breast cancer risk following Hodgkin lymphoma radiotherapy in relation to menstrual and reproductive factors.

Background:Women treated with supradiaphragmatic radiotherapy (sRT) for Hodgkin lymphoma (HL) at young ages have a substantially increased breast cancer risk. Little is known about how menarcheal and reproductive factors modify this risk.Methods:We examined the effects of menarcheal age, pregnancy, and menopausal age on breast cancer risk following sRT in case–control data from questionnaires completed by 2497 women from a cohort of 5002 treated with sRT for HL at ages <36 during 1956–2003.Results:Two-hundred and sixty women had been diagnosed with breast cancer. Breast cancer risk was significantly increased in patients treated within 6 months of menarche (odds ratio (OR) 5.52, 95% confidence interval (CI) (1.97–15.46)), and increased significantly with proximity of sRT to menarche (Ptrend<0.001). It was greatest when sRT was close to a late menarche, but based on small numbers and needing reexamination elsewhere. Risk was not significantly affected by full-term pregnancies before or after treatment. Risk was significantly reduced by early menopause (OR 0.55, 95% CI (0.35–0.85)), and increased with number of premenopausal years after treatment (Ptrend=0.003).Conclusion:In summary, this paper shows for the first time that sRT close to menarche substantially increases breast cancer risk. Careful consideration should be given to follow-up of these women, and to measures that might reduce their future breast cancer risk.