Mantle Field Research Articles

Second cancer risk 40 years after cure for Hodgkin lymphoma.

8039 Background: During the last decades Hodgkin Lymphoma (HL) treatment changed towards less toxic chemotherapy schemes and smaller radiation fields. The impact of these changes on second cancer (SC) risk is still unknown. Methods: We calculated standardized incidence ratios (SIR), comparing SC risk after HL treatment with expected risk, based on cancer incidence in the general population, and compared SC risk between treatment modalities, accounting for competing events, in a large Dutch cohort comprising 3,390 5-years HL survivors, aged 15-51 years at HL treatment and diagnosed between 1965-2000. Results: The median follow-up was 18.2 years; 23% of the patients was followed ≥25 years. During follow-up 734 SCs and 92 third cancers (TC) occurred. The SIR for any SC was 4.5 (95% confidence interval (95%CI) 4.1-4.9). SC risk was still elevated after 35 years of follow-up (SIR 3.9; 95%CI 2.5-5.8) and cumulative incidence (CI) reached 47.1% (95%CI 43.6-50.5) at 40 years follow-up. For TCs the SIR was 5.5 (95%CI 4.4-6.9); the 20-year CI was 22.3% (95%CI 17.8-27.2). Risks of NHL and leukemia strongly decreased in more recent treatment periods (P-trend <0.001). The CI of solid tumors (ST) between 5-19 years after HL treatment did not differ for patients treated between 1965-1979, 1980-1989 or 1990-2000 (P=0.21; 19-year CI 9.1%, 11.6% and 11.4%, respectively). Radiotherapy (RT) above the diaphragm increased risk of STs above the diaphragm (hazard ratio (HR) 2.4, P<0.001), while subdiaphragmatic RT was associated with a 1.7-fold increased HR of a subdiaphragmatic ST (P=0.001). An incomplete mantle field was associated with significantly lower breast cancer (BC) risk (hazard ratio (HR) 0.4, 95%CI 0.2-0.8). A cumulative procarbazine dose >4.2 g/m2 yielded a 1.3-fold increased HR (95%CI 1.0-1.7) for non-breast STs and a 2-fold (95%CI 1.2-3.1) increased HR for gastrointestinal STs, but was associated with a strongly decreased BC risk (HR 0.3, 95%CI 0.2-0.6). Conclusions: SC risk after HL has decreased with treatment changes over the last decades, due to strongly decreasing risk of leukemia and NHL. Smaller radiation fields and procarbazine doses >4.2 g/m2 are associated with lower breast cancer risk, while high procarbazine doses increase risk of gastrointestinal STs.

Traitement conservateur dans la prise en charge locorégionale du cancer du sein après lymphome de Hodgkin

PurposeTo report characteristics and outcome of breast cancer after irradiation for Hodgkin lymphoma with special focus on breast conservation surgery. Patients and methodsMedical records of 72 women who developed either ductal carcinoma in situ or stage I–III invasive carcinoma of the breast after Hodgkin lymphoma between 1978 and 2009 were retrospectively reviewed. ResultsMedian age at Hodgkin lymphoma diagnosis was 23 years old. Median total dose received by the mediastinum was 40Gy, mostly by a mantle field technique. Breast cancer occurred after a median time interval of 21 years. Ductal invasive carcinoma and ductal carcinoma in situ represented respectively 71% and 19% of the cases. Locoregional treatment for breast cancer consisted of mastectomy with or without radiotherapy in 39 patients and of lumpectomy with or without adjuvant radiotherapy in 32 patients. The isocentric lateral decubitus radiation technique was used in 17 patients after breast conserving surgery (57%). With a median follow-up of 7 years, 5-year overall survival rate and locoregional control rate were respectively 74.5% and 82% for invasive carcinoma and 100% and 92% for in situ carcinoma. Thirteen patients died of progressive breast cancer and contralateral breast cancer was diagnosed in ten patients (14%). ConclusionsBreast conserving treatment can be an option for breast cancers that occur after Hodgkin lymphoma despite prior thoracic irradiation. It should consist of lumpectomy and adjuvant breast radiotherapy with use of adequate techniques, such as the lateral decubitus isocentric position.

Cancer du sein après maladie de Hodgkin

Secondary breast cancer represents 6 to 9% of secondary neoplasia after treatments for Hodgkin Disease (HD). Mostly, they appear 10 years after the end of treatments for HD. The most important risk factors are mantle field irradiation and the young age. The means of screening and treatments are still in discussion. We report a case of bilateral intraductal and invasive carcinoma that occurred 16 years after treatments for HD, developing its particularities in diagnosis and treatment, particularly place of conservative treatments and sentinel lymph node biopsy.

Continuous Decline in Second Malignancy Occurrence in Patients with Hodgkin Lymphoma; Analysis of 1670 Patients Over the Past 5 Decades

Abstract▪2694▪This icon denotes a clinically relevant abstract INTRODUCTION:The treatment of Hodgkin's lymphoma has radically changed over time. The current treatment can achieve a high cure rate with less long-term side effects. We undertook this retrospective study from a single institution to determine how the rate of second malignancy (SM) has changed with the change in therapy and over the past five decades. METHODS:1670 patients diagnosed with Hodgkin's lymphoma between 1956 and 2009, were the subjects of this study. Characteristics examined included: age, gender, stage, B symptoms, bulk of the disease, type of chemotherapy, radiation (dose and field), type of radiation, relapse occurrence, treatment for relapse, type and date of occurrence of SM, status at last follow up.We looked at the relation between patient's characteristics, type of treatment, and time frame in which the treatment was delivered and the risk of developing SM.Pearson’s χ2 was used to analyze the difference in characteristics. Hazard ratios were calculated using logistic regression analysis for potential risk factors. Multivariate analysis was performed to determine the unique contribution of all significant variables in univariate analysis. RESULTS:Second malignancy was significantly associated with time frame at diagnosis, type of chemotherapy delivered, radiation type, dose, and field used.Out of 1670 patients 225 developed SM, 157 solid and 68 hematologic. Compared to patients treated after 1995, patients treated before 1985 had a statistically significant higher risk of developing SM (HR=6.2); same for those treated between 1985 and 1995 (HR=3.9), P< 0.0001. Patients who received MOPP therapy had a statistically higher risk of SM (HR=4.6) compared to patients treated with ABVD chemotherapy. Use of Cobalt radiation had a HR= 2.3 for developing SM (P<0.0001) compared to the use of linear accelerator. Radiation dose of > 36 Gy (HR=1.5; p=NS) the use of mantle field radiation in females (HR=2.9; p=0.004), and the use of subtotal nodal radiation (HR=1.9;p=0.03) were associated with a higher risk. Patients who developed cardiac disease had also a higher risk for SM (HR=3.2;p<0.0001).Risk for death was statistically associated with male gender (HR =0.7 for female; P<0.0001), Age > 60 (HR=8.8; P<0.0001), stage (HR advanced =3.5; P<0.0001), B symptoms (HR=1.5; p=0.001), use of Cobalt (HR=4.3; p<0.0001), subtotal nodal radiation (HR=3.9; P<0.0001) with females having a higher risk for death compared to males (HR= 8 for females versus 2.6 for males), MOPP chemotherapy (HR=3.9;p<0.0001), relapse (HR=7.0; p<0.0001), and occurrence of second malignancy (HR=3.9 for hematological, and 2.4 for solid; P<0.0001 for both). The risk of death decreased significantly comparing patients treated before 1970 (used as a reference) to those treated between 1971–1985, 1986–1995, and 1996–2009 with a HR of 0.6, 0.1, and 0.1 respectively (p< 0.0001). Multivariate analysis showed that the two most important predictors for occurrence of SM are the time frame at diagnosis and relapse (HR 4.2; P=0.0008 and 4.5; p<00001,respectively). CONCLUSION:Our data suggest that the improvement in HL cure rate using less toxic frontline regimens, and the use of modern radiation therapy techniques of smaller fields is associated with a continuous decrease in the rate of SM Disclosures:No relevant conflicts of interest to declare.

Comparison of Cardiac Doses after Involved Node Radiotherapy and Mantle Field Treatment for Hodgkin Lymphoma

Comparison of Cardiac Doses after Involved Node Radiotherapy and Mantle Field Treatment for Hodgkin Lymphoma

Rheology and metallogeny of the Maya-Selemdzha plume

Plumes (mantle jets) and associated hot mantle fields are widespread in tectonic shells of the Earth [4–6, 10, 14], eastern Asia and the adjacent marginal seas included [7, 9, 13]. In most cases, only lithospheric and, less commonly, asthenospheric parts of plumes (plume heads), which are characterized by peculiar geophysical features such as anomalous heat flow, lower velocities of seismic waves, and low electric resistivity in the lower crust, subcrustal and asthenospheric layers of the upper mantle, or uplifting or diffusion of the base of the crust and lithosphere [4, 7, 13, 14], are accessible for geological, geophysical, and geochemi� cal observations. Inasmuch as initiation and evolution of plumes are closely connected with collision and subduction of the lithospheric plates [9, 10], mantle convection [5, 6], and superposed rifting [4, 6, 9, 13, 14], diagnostics, spatial parametrization, and metallo� genic analysis of the concealed (frequently disturbed

Dose-response relationship for breast cancer induction at radiotherapy dose

PurposeCancer induction after radiation therapy is known as a severe side effect. It is therefore of interest to predict the probability of second cancer appearance for the patient to be treated including breast cancer.Materials and methodsIn this work a dose-response relationship for breast cancer is derived based on(i) the analysis of breast cancer induction after Hodgkin's disease,(ii) a cancer risk model developed for high doses including fractionation based on the linear quadratic model, and(iii) the reconstruction of treatment plans for Hodgkin's patients treated with radiotherapy,(iv) the breast cancer induction of the A-bomb survivor data.ResultsThe fitted model parameters for an α/β = 3 Gy were α = 0.067Gy-1 and R = 0.62. The risk for breast cancer is according to this model for small doses consistent with the finding of the A-bomb survivors, has a maximum at doses of around 20 Gy and drops off only slightly at larger doses. The predicted EAR for breast cancer after radiotherapy of Hodgkin's disease is 11.7/10000PY which can be compared to the findings of several epidemiological studies where EAR for breast cancer varies between 10.5 and 29.4/10000PY. The model was used to predict the impact of the reduction of radiation volume on breast cancer risk. It was estimated that mantle field irradiation is associated with a 3.2-fold increased risk compared with mediastinal irradiation alone, which is in agreement with a published value of 2.7. It was also shown that the modelled age dependency of breast cancer risk is in satisfying agreement with published data.ConclusionsThe dose-response relationship obtained in this report can be used for the prediction of radiation induced secondary breast cancer of radiotherapy patients.

Low incidence of long-term respiratory impairment in Hodgkin lymphoma survivors

Introduction of new chemotherapy regimens over the last decade resulted in 90% survival in patients with Hodgkin lymphoma (HL), which enhances significance of abrogating chemotherapy-related long-term toxicities in young subjects. The present trial evaluated incidence of long-term respiratory complications associated with adriamycin, bleomycin, vinblastine, and dacarbazine (ABVD) or bleomycin sulfate, etoposide phosphate, doxorubicin hydrochloride (Adriamycin), cyclophosphamide, vincristine sulfate (Oncovin), procarbazine hydrochloride, and prednisone (BEACOPP). Sixty-seven HL patients, 21 treated with ABVD and 46 with BEACOPP, underwent prospective respiratory evaluation. Median follow-up from chemotherapy completion to respiratory assessment was 61months. Abnormal lung function tests (LFT) were found in nine patients (13.6%)-three with functional dyspnea and six asymptomatic-with reduced DLCO (≤70%), VC, and TLC. Previous history of bleomycin pulmonary toxicity was found to be the only statistically significant factor for chronic respiratory impairment (75% vs. 10%, p = 0.007, relative risk (RR) = 28; 95% CI, 2.5-313). However, abnormal LFT tended to occur more frequently in patients receiving mantle field irradiation (18% vs. 9%, RR = 2.2), those who experienced respiratory infection (25% vs. 13%, RR = 2.25), and patients treated with ABVD compared to BEACOPP (19% vs. 11%, RR = 1.9). Long-term respiratory impairment in HL survivors is unusual and rarely results in functional discomfort. BEACOPP is "respiratory safe," being associated with a nonsignificant risk for long-term respiratory dysfunction.

Progressive Muscle Atrophy and Weakness After Treatment by Mantle Field Radiotherapy in Hodgkin Lymphoma Survivors

To describe the damage to the muscles and propose a pathophysiologic mechanism for muscle atrophy and weakness after mantle field radiotherapy in Hodgkin lymphoma (HL) survivors. We examined 12 patients treated by mantle field radiotherapy between 1969 and 1998. Besides evaluation of their symptoms, the following tests were performed: dynamometry; ultrasound of the sternocleidomastoid, biceps, and antebrachial flexor muscles; and needle electromyography of the neck, deltoid, and ultrasonographically affected arm muscles. Ten patients (83%) experienced neck complaints, mostly pain and muscle weakness. On clinical examination, neck flexors were more often affected than neck extensors. On ultrasound, the sternocleidomastoid was severely atrophic in 8 patients, but abnormal echo intensity was seen in only 3 patients. Electromyography of the neck muscles showed mostly myogenic changes, whereas the deltoid, biceps, and antebrachial flexor muscles seemed to have mostly neurogenic damage. Many patients previously treated by mantle field radiotherapy develop severe atrophy and weakness of the neck muscles. Neck muscles within the radiation field show mostly myogenic damage, and muscles outside the mantle field show mostly neurogenic damage. The discrepancy between echo intensity and atrophy suggests that muscle damage is most likely caused by an extrinsic factor such as progressive microvascular fibrosis. This is also presumed to cause damage to nerves within the radiated field, resulting in neurogenic damage of the deltoid and arm muscles.

Radiotherapy for supradiaphragmatic Hodgkin’s disease: Determination of the proper fetal shielding conditions using Monte Carlo methodology

This study aimed to estimate fetal dose from mantle field irradiation with 6 MV photons and to determine the proper fetal shielding conditions. The Monte Carlo N-particle code and mathematical phantoms representing pregnancy at the first, second and third trimesters of gestation were used to calculate fetal dose with or without the presence of a 5-cm-thick lead shield of dimensions 35 × 35 cm 2. Fetal exposure was calculated for lead thicknesses of 2, 3, 4, 6, 7 and 8 cm. The dependence of fetal dose upon the distance separating the shield from the beam edge and phantom’s abdomen was investigated. Dose measurements were performed on a physical phantom using thermoluminescent dosimetry. The radiation dose to an unshielded and shielded fetus was 0.578–0.861% and 0.180–0.641% of the prescribed tumor dose, respectively, depending upon the gestational age. The lead thickness increase from 2 to 5 cm led to a fetal dose reduction up to 23.4%. The use of 5- to 8-cm-thick lead resulted in dose values differing less than 4.5%. The shift of the lead from the closer to the more distant position relative to the field edge increased fetal dose up to 42.5%. The respective increase by changing the distance from the phantom’s abdomen was 21.9%. The difference between dose calculations and measurements at specific points was 8.3 ± 3.9%. The presented data may be used for fetal dose assessment with different shielding settings before treatment and, then, for the design and construction of the appropriate shielding device.

Outcomes of Nodular Lymphocyte Predominant Hodgkin's Lymphoma (NLPHL) Patients Treated with R-CHOP.

AbstractAbstract 2812 Introduction:Nodular lymphocyte predominant Hodgkin's lymphoma (NLPHL) constitutes 5% of Hodgkin's lymphoma (HL) diagnoses. Recently gene expression profiling has shown significant overlap between NLPHL, T-cell-rich B cell lymphoma (TCRBCL), and classical HL (Brune, V et al, J Exp Med, 2008). NLPHL patients also have an approximate 7% risk of transformation at 10 years to diffuse large B-cell lymphoma (DLBCL) and TCRBCL (Al-Mansour, M et al, JCO, 2010). Data from multiple groups (Nogova, L et al, Ann Onc, 2005, Chen, RC et al, JCO, 2010, Wirth, A et al, Cancer, 2005) support extended progression-free survivals (PFS) for stage IA/IIA patients treated with radiation alone. While chemotherapy is generally recommended for patients with stage IB/IIB or III/IV disease, there is lack of guidelines on whether classical HL-directed regimens, such as ABVD (doxorubicin, bleomycin, vinblastine, dacarbazine), or B-cell lymphoma-directed regimens, such as R-CHOP (rituximab, cychlophosphamide, doxorubicin, vincristine, prednisone) should be used. Given the similarities between NLPHL and indolent CD20+ B-cell non-Hodgkin's lymphoma (NHL), our group started using the R-CHOP regimen for patients with NLPHL requiring systemic therapy. In order to examine the potential efficacy of this approach, we conducted a retrospective analysis of treatment outcomes in patients who received R-CHOP versus other regimens treated at UT MDACC from 1995 to 2010. Results:83 patients were referred. 6 patients were found to have NLPHL with transformation to DLBCL or TCRBCL. 3 had alternative diagnoses. 11 lacked full immunophenotyping to confirm diagnosis. 63 patients had confirmed diagnoses of NLPHL (39 stage I/II and 24 stage III/IV). 52 NLPHL patients were evaluable (10 did not complete full treatment planning or were lost to follow-up and 1 is currently completing therapy). 7 patients had extranodal disease (thyroid, breast, lung, liver, bone marrow/cortex) and 8 had spleen involvement. Overall their median age at diagnosis was 40, male:female ratio was 2.5, and median follow-up is 46 months (range 8–149 months). 6 patients had relapse of NLPHL, 2 patients had transformation at a median of 39 months (1 to DLBCL, 1 to TCRBCL), 4 patients died (1 from acute myelogenous leukemia with deletion 7, 1 from DLBCL, 2 from unrelated causes while in remission), and 2 patients underwent autologous stem cell transplant (1 for relapsed NLPHL in 3rd complete remission and 1 for transformation to TCRBCL). Therapies for stage I/II NLPHL included: surgical excision alone (2 patients with stage IA disease declined radiation treatment), subtotal nodal irradiation (STNI), mantle field radiation, involved field radiation (IFRT), rituximab (R) alone and plus IFRT, ABVD plus STNI, R-ABVD, COPP (cyclophosphamide, vincristine, procarbazine, prednisone) plus IFRT, and R-CHOP alone and plus IFRT. Therapies for stage III/IV included: mantle field radiation (1 patient who declined chemotherapy), NOVP (mitoxantrone, vincristine, vinblastine, prednisone) plus mantle field radiation, ABVD, R-ABVD, R-CHOP alone and plus IFRT. A total of 15 patients received R-CHOP alone (4 stage I/II, 11 stage III/IV) and 5 patients received R-CHOP plus IFRT (4 stage I/II, 1 stage III/IV). Response to R-CHOP as assessed by CT scan criteria was 100% overall response rate (ORR) with 90% complete remissions (CR). No R-CHOP patients have had relapses or transformation with a median follow-up of 42 months (range 8–111 months). One patient treated with R-CHOP died of unrelated causes while in remission. However, with other therapies 19% have relapsed after median remissions of 38 months (range 4 to 72 months). R-CHOP when compared to other treatments has a trend towards improved PFS (Figures 1, 2, and 3). Survival rates for NLPHL patients at 5 years with 95% confidence intervals are: R-CHOP: PFS 0.95 (0.86, 1), OS (overall survival) 0.95 (0.86, 1) and other therapies: PFS 0.71 (0.55, 0.92), OS 0.91 (0.8, 1). [Display omitted] [Display omitted] [Display omitted] Conclusions:Our data demonstrates that RCHOP is an effective regimen for the treatment of patients with NLPHL. A prospective evaluation of R-CHOP as a front-line treatment of NLPHL is under consideration. Disclosures:Fanale:Seattle Genetics: Research Funding; Novartis: Honoraria, Research Funding; Millenium: Research Funding; Genentech: Research Funding. Off Label Use: Given the CD20 positivity of nodular lymphocyte predominant Hodgkin lymphoma (NLPHL) rituximab has been evaluated previously for relapsed NLPHL and was shown to be efficacious. Rituximab however is not FDA approved for NLPHL. This is a retrospective study that evaluates the use of R-CHOP and other therapies for NLPHL. Current NCCN guidelines support consideration of R-CHOP for NLPHL treatment, and given the rarity of the disease there is no one defined preferred chemotherapy regimen. This information will be disclosed to the audience. Fayad:Genentech: Research Funding. Rodriguez:Genentech: Research Funding. Shah:Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Millenium: Research Funding; Novartis: Research Funding. Younes:Genentech: Honoraria, Research Funding; SBIO: Honoraria, Research Funding; Novartis: Honoraria, Research Funding; Seattle Genetics: Honoraria, Research Funding.

Effect of organ size and position on out-of-field dose distributions during radiation therapy

Mantle field irradiation has historically been the standard radiation treatment for Hodgkin lymphoma. It involves treating large regions of the chest and neck with high doses of radiation (up to 30 Gy). Previous epidemiological studies on the incidence of second malignancies following radiation therapy for Hodgkin lymphoma have revealed an increased incidence of second tumors in various organs, including lung, breast, thyroid and digestive tract. Multiple other studies, including the Surveillance, Epidemiology and End Results, indicated an increased incidence in digestive tract including stomach cancers following mantle field radiotherapy. Assessment of stomach dose is challenging because the stomach is outside the treatment field but very near the treatment border where there are steep dose gradients. In addition, the stomach can vary greatly in size and position. We sought to evaluate the dosimetric impact of the size and variable position of the stomach relative to the field border for a typical Hodgkin lymphoma mantle field irradiation. The mean stomach dose was measured using thermoluminescent dosimetry for nine variations in stomach size and position. The mean doses to the nine stomach variations ranged from 0.43 to 0.83 Gy when 30 Gy was delivered to the treatment isocenter. Statistical analyses indicated that there were no significant differences in the mean stomach dose when the stomach was symmetrically expanded up to 3 cm or shifted laterally (medial, anterior or posterior shifts) by up to 3 cm. There was, however, a significant (P > 0.01) difference in the mean dose when the stomach was shifted superiorly or inferiorly by ⩾2.5 cm.

Locoregional Treatment for Breast Carcinoma after Hodgkin's Lymphoma: The Breast Conservation Option

Locoregional Treatment for Breast Carcinoma after Hodgkin's Lymphoma: The Breast Conservation Option

An integrated gravity model for Europe's crust and upper mantle

We present an integrated gravity model of the European lithosphere based on an analysis of a number of new data-sets, leading to a much higher resolution than provided by previous models. First of all, a recent crustal model (EuCRUST-07) is used to quantify the crustal contribution to the observed gravity field and to identify the effect of mantle heterogeneity. The new gravity field model is based on a combination of satellite (CHAMP and GRACE) and terrestrial data. We also use these data-sets to estimate residual mantle gravity anomalies and residual topography, reflecting the effect of mantle density variations induced by temperature and compositional heterogeneity. The separation of these effects is vital for a proper assessment of mantle structure and evolution. In addition, we utilize a new tomographic model for P- and S-velocity anomalies beneath Europe, which is a-priori corrected for crustal structure using EuCRUST-07. The seismic velocity anomalies were subsequently converted into temperature anomalies using a mineral physics approach. We estimate the effect of temperature variations on the gravity field and subtract it from the total mantle field. The residual fields point to an important role of compositional density anomalies in the upper mantle. A number of key features of the compositional density distribution, so far invisible in seismic tomography data, are detected for the first time.

SU‐DD‐A2‐01: Mechanistic Model of Radiation Induced Cancer after Fractionated Radiotherapy: Fit to Breast Cancer Risk after Radiation Therapy for Hodgkin's Disease

Purpose: The strongly elevated risk of breast cancer after radiotherapy for Hodgkin's lymphoma has become a major concern for female survivors of this disease. The risk of breast cancer after Hodgkin's lymphoma has been mainly attributed to supradiaphragmatic radiotherapy. Women treated with mantle field radiation experience up to 30‐fold increased risks for breast cancer compared with their peers in the general population. As a consequence radiation volumes and dose prescription for the treatment of Hodgkin's lymphoma have been reduced. The aim of this study is to develop a dose‐response model for breast cancer using risk data from epidemiological studies Hodgkin's disease patients treated with radiation therapy. Materials and Methods: The linear‐quadratic model of cell kill is applied to normal tissues which are unintentionally irradiated during a cancer treatment with radiotherapy. Tumor induction is modeled such that each transformation process results in a tumor cell. The microscopic transformation parameter was chosen such that in the limit of low dose and acute exposure the parameters of the linear‐no‐threshold model for tumor induction were approached. Results: The differential equations describing carcinoma and sarcoma induction were solved analytically. Cancer induction in this model is a function of treatment dose, the cell kill parameters (a, b), the tumor induction variable (μ) and the repopulation parameter (R). The dose‐response relationship for breast cancer was derived based on (i) the cancer risk model described above, (i) the analysis of breast cancer induction after Hodgkin's disease, and (iii) the reconstruction of mantle field treatment plans for Hodgkin's patients treated with radiotherapy. The fitted model parameters for an a/b=3 Gy were a=0.067Gy‐1 and R=0.62. Conclusions: The developed model can be used to further optimize involved field radiotherapy for Hodgkin's lymphoma with regard to second cancer induction.

The late effects of mantle field radiotherapy: The information and support needs of women survivors of Hodgkin's disease

Purpose To improve understanding of the information and support needs of women at risk from breast cancer after earlier treatment with mantle field radio therapy for Hodgkin's disease. Method A multiple case study approach presenting the detailed accounts of three participants has been used to represent the issues raised by a wider sub-set of 15 Hodgkin's disease survivors. These women were participants in a larger qualitative study of 50 long term survivors of adolescent cancer. They were interviewed in depth either face to face or via the telephone. Data were analysed using methods of data reduction, display and conclusion drawing, three case studies were then purposively selected to illustrate key themes in the wider data set. Key Results Discovering the risk of late effect breast cancer, particularly via the media, caused shock. Reliable information was difficult to locate and the support needs of the women were not met by medical services. The impact of the new risk was exacerbated by the earlier cancer experience. Conclusion Information on the risk of late effects to cancer survivors regarded as trustworthy is not easy to access. When the risk of a treatment related malignancy is identified there must be a reliable way of informing both those at risk and primary health care physicians who then need to take into account the cancer history of the patient and its ongoing effect on their emotional vulnerability.

Radiotherapy in Early-Stage Favourable Hodgkin`s Lymphom: Experiences of the German Hodgkin Study Group

Since its beginning, more than 15.000 patients with Hodgkin's lymphoma (HL) have been enrolled into the multicentre randomized trials of the German Hodgkin Study Group (GHSG). Within 4 study generations the treatment of HL has been developed stepwise by using the results of the completed protocols. According to radiotherapy, the study group successfully evaluated different dose-effect relationships and could also prove the efficacy of involved field radiotherapy in early stages in combination with effective chemotherapy. According to the recent final analysis of the HD10 trial for patients with early-favourable HL, a radiation dose of 20 Gy to the involved lymph node areas preceded by short-term chemotherapy (ABVD x 2) is the standard for these patients. An extensive radiotherapy quality assurance program, performed by the GHSG radiotherapy reference centre in Cologne, has proven to be successful and necessary to ensure that with reduced radiation doses and volumes a precise treatment, as defined by the protocol, can be performed by the participating radiotherapy departments. In the early years, radiotherapy was the only curative treatment for this systemic disease, but the reports of Kaplan and Rosenberg (2) and Peters (3) in the fifties and seventies showed that irradiation of involved lymph node regions only resulted in high local and distant recurrences. The introduction of linear accelerator based high dose extended field (EF)-radiotherapy by Kaplan in Stanford was a milestone in the evolution of definitive curative radiotherapy strategies. The application of the mantle field for supradiaphragmatic and the inverted Y (with or without including the spleen or splenic pedicle) for infradiaphra- gmatic disease resulted in a dramatic improvement of survival rates in the early stages I and II (Ann Arbor) from 25 - 30 % in the sixties to 65 - 80 % in the eighties (4). Kaplan reported about a close relationship between radiation dose and cure rates in the case of definitive radiotherapy. A dose of at least 40 Gy resulted in local recurrences below 5% and is today the standard dose for radiotherapy only outside protocols. Despite complete remission rates after radiotherapy of 90 - 100%, the overall recurrence rate (including in-field, marginal and distant relapses) was between 20 and 30%. Analysis of the relapses revealed some stage migrating risk factors: large mediastinal mass, extra nodal involvement, number of involved lymph node areas (> 3) and high ESR.

Breast Cancer in Patients with Hodgkin's Lymphoma Predominantly Treated with Anthracycline – Based Chemotherapy with or without Radiotherapy: A Preliminary Analysis.

Abstract BACKGROUND: Hodgkin's lymphoma (HL) is a highly curable neoplasm with &amp;gt;70-80% of the patients becoming long-term survivors. The success of treatment however, is associated with long term complications, namely breast cancer, especially if treated with extended-field radiotherapy (RT) at a curative dose as monotherapy. The oncogenic effect of limited field and relatively low-dose RT combined with anthracycline-based chemotherapy (CT) – the current standard of treatment for early stage disease - is not well investigated. The aim of the study is to describe the incidence of breast cancer in a series of patients treated predominantly with anthracycline-based CT with or without RT of limited field and dose.PATIENTS AND METHODS: Among 1125 patients in our database, 479 were females and were evaluated for the occurrence of breast cancer. Important baseline features were: Median age 28 years (14-81); clinical stage I, II, III, IV 17%, 55%, 15%, 13%; B-symptoms 37%; Nodular sclerosis 77%, mixed cellularity 15%, lymphocyte predominance 6%; Anthracycline based CT 86%, MOPP-based CT 12%, RT only without CT 2%; Radiotherapy 74%, mostly to the involved field, usually 2800-3000 cGy. The cumulative incidence of breast cancer was estimated by the Kaplan-Meier method.RESULTS: The median follow-up of the 479 female patients was 88 months: 36% were followed-up for &amp;gt;10 years. At the time of the analysis 6 cases of breast cancer were recorded for a 5-, 10- and 20-year cumulative incidence of 0.5%, 1.7% and 4.4%. The median age of the 6 patients was 43 years (26-54) at diagnosis of HL and 46.5 years (33-63) at breast cancer diagnosis. Clinical stages were I (n=1), II (n=3), III (n=1) and IV (n=1) and 4/6 patients had B-symptoms at diagnosis. All patients were in their 1st complete remission when breast cancer was diagnosed at a median time of 67 months from HL diagnosis (8-198). All 6 patients had received anthracycline-based CT and had been irradiated at a median dose of 2870 cGy, but the mediastinum or the axillae were included in the RT field only in 3/6 patients. Among 646 male patients, a single case of breast cancer was recorded in a 49 year old patient, 265 months after high-dose (4300 cGy) mantle field RT followed by MOPP/ABVDx6.DISCUSSION: In a series of female patients with HL, a median age of 28 years at diagnosis and a median follow-up of ∼7.5 years (&amp;gt;10 years in 36% of them), who were predominantly treated with modern CT with or without limited field and dose RT, the 10- and 20-year incidence of breast cancer was 1.7% and 4.4%, with 6 cases recorded. Three of the cases developed clearly outside the irradiation field. We also recorded a single case of male breast cancer, which was very likely treatment related. Whether these cases are in excess of those expected for the population studied, as well as the features and outcome of breast cancer in HL survivors are currently being investigated. Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 6069.

Dropped-head Syndrome Due to High-dose Irradiation: Figure 1.

Dropped-head syndrome is a rare disorder characterized by weakness of neck extensor muscles causing an inability to extend the neck and resulting in a chin-on-chest deformity1. We observed 2 such cases. Patient 1, a 55-year-old woman, had a history of Hodgkin’s lymphoma and high-dose mantle field irradiation 24 years prior to …

Breast Cancer Risk in Female Survivors of Hodgkin's Lymphoma: Lower Risk After Smaller Radiation Volumes

We assessed the long-term risk of breast cancer (BC) after treatment for Hodgkin's lymphoma (HL). We focused on the volume of breast tissue exposed to radiation and the influence of gonadotoxic chemotherapy (CT). We performed a cohort study among 1,122 female 5-year survivors treated for HL before the age of 51 years between 1965 and 1995. We compared the incidence of BC with that in the general population. To assess the risk according to radiation volume and hormone factors, we performed multivariate Cox regression analyses. After a median follow-up of 17.8 years, 120 women developed BC (standardized incidence ratio [SIR], 5.6; 95% CI, 4.6 to 6.8), absolute excess risk 57 per 10,000 patients per year. The overall cumulative incidence 30 years after treatment was 19% (95% CI, 16% to 23%); for those treated before age 21 years, it was 26% (95% CI, 19% to 33%). The relative risk remained high after prolonged follow-up (> 30 years after treatment: SIR, 9.5; 95% CI, 4.9 to 16.6). Mantle field irradiation (involving the axillary, mediastinal, and neck nodes) was associated with a 2.7-fold increased risk (95% CI, 1.1 to 6.9) compared with similarly dosed (36 to 44 Gy) mediastinal irradiation alone. Women with >or= 20 years of intact ovarian function after radiotherapy at young ages (< 31 years) experienced significantly higher risks for BC than those with fewer than 10 years of intact ovarian function. Reduction of radiation volume appears to decrease the risk for BC after HL. In addition, shorter duration of intact ovarian function after irradiation is associated with a significant reduction of the risk for BC.