Radiotherapy For Hodgkin Lymphoma Research Articles

Future perspectives of radiation therapy for Hodgkin Lymphoma: Risk-adapted, response-adapted, and safer than before.

Classical Hodgkin lymphoma is a lymphoproliferative disease with a good prognosis mainly seen in young people. Nevertheless secondary malignancy, cardiac disease and infertility may affect the long survivors with significant impact on quality of life, morbidity and overall survival. In the last decades several treatment strategies were evaluated to reduce the toxicity of first line treatment such as avoiding radiotherapy or its reduction in terms of dosage and extension. Many trials including interim Positron Emission Tomography evaluation fail to compare efficacy between combined modality treatment versus chemotherapy alone in particular in early stage disease. In this review we analyze which subset of patients could take advantage from proton therapy in terms of toxicity and cost effectiveness.

Estimation of Mediastinal Toxicities after Radiotherapy for Hodgkin Lymphoma-A Normal Tissue Complication Analysis of the HD16/17 Trial by the German Hodgkin Study Group.

Hodgkin lymphoma is a hematologic malignancy with excellent outcomes even in advanced stages. Consequently, the importance of treatment-associated toxicity increases. However, the exact estimation of individualized rates is difficult due to different disease extents, treatment strategies and techniques. The following analysis aims at a pre-treatment estimation of relevant mediastinal toxicities. Normal tissue complication probability calculations were used to evaluate the toxicity rates for the heart, lungs and female breast of patients undergoing radiotherapy for early-stage Hodgkin lymphoma. Overall, 45 Patients of the HD16 and HD17 trials by the German Hodgkin study group were included and risks were calculated using the Lyman-Kutcher-Burman model. The median values for pericarditis, pneumonitis and fibrosis of the left or right breast were 0.0%, 0.0%, 0.7% and 0.6% in the HD16 cohort, and 0.0%, 0.1%, 1.1% and 1.0% in the HD17 cohort, respectively. Correspondingly, none of the included patients displayed any of the evaluated toxicities during clinical follow-up. The use of higher doses (30 Gy) in the HD17 cohort led to an increase in toxicity compared to the HD16 cohort (20 Gy). No significant influence of the planning target volume size or the radiation technique could be found in this study. Both the clinically observed and calculated toxicity rates corroborate the overall low-risk profile of radiotherapy for Hodgkin lymphoma. Further treatment individualization will be attempted in the future.

Quality Analysis of Radiation Therapy for Hodgkin Lymphoma in the HD 16/17 Trials: A Final Report By the Reference Radiation Oncology Panel of the German Hodgkin Study Group

The HD 16 and 17 trials by the German Hodgkin Study Group (GHSG) have evaluated the use of consolidative radiotherapy (RT) in early-favorable and -unfavorable stage Hodgkin lymphoma (HL), respectively (1, 2). Quality of RT planning and execution is pivotal for treatment outcome in HL with protocol violations jeopardizing prognosis (3). Consequently, the present work aims at a decisive analysis of quality and dosimetry in the modern era. Random samples of 100 involved-field RT (IFRT) plans in HD16 and 176 plans in HD17 (134 involved-node RT (INRT) and 42 IFRT) were selected for analysis. Evaluation was performed systematically by the reference radiation oncology panel using pre-chemotherapy imaging, recommendation by the reference radiation oncology and RT planning imaging and graded as "correct", "minor" or "major deviation", respectively. RT doses to the target volume and organs at risks (OAR) were analyzed using dose-volume histograms. Median RT doses were 20 Gy (19.8 Gy-21.6 Gy) in HD16 and 30 Gy in HD17 (IFRT: 18-30.6 Gy, INRT: 14 Gy-40 Gy). Overall, 84.0%, 69.0%, and 76.1% of RT series in HD16, the IFRT-group of HD17 and the INRT-group of HD17, respectively, were planned correctly. The main reason for major deviation was an insufficient coverage of an involved region (11 %-14.3 %). There was no significant difference in quality between IFRT and INRT in HD17 (p = 0.418 for any deviations; p = 0.466 for major deviations). In comparison to previous GHSG studies in the respective stages, a significant increase in correct RT-series (p<0.001) and decrease in major deviations (p<0.001) occurred. However, doses to OAR varied individually with median values of 4.3 Gy (0.2 Gy-9.2 Gy), 4.7 Gy (0.2 Gy-15.2 Gy) and 3.8 Gy (0.0 Gy-16.0 Gy) for mean doses to the right lung, left lung and heart in HD16, respectively. Correspondingly, values were 9.8 Gy (0.3 Gy-20.0 Gy), 10.5 Gy (0.2 Gy-26.5 Gy) and 13.1 Gy (0.5 Gy-30.4 Gy) for mean doses to the right lung, left lung and heart in HD17, respectively. The size of the planning target volume decreased significantly with INRT compared to IFRT (median values: 1163.1 ml vs. 1464.3 ml; p = 0.043). However, only some OAR-parameters (V25 of the right and left lung, respectively, thyroid and spinal cord) showed significant differences between INRT and IFRT in HD17. The use of intensity-modulated techniques in HD 17 resulted in an increase in V5 and V10 of the lungs with a concomitant decrease in V20-V30. Quality of RT in the planning and treatment of HL has improved significantly with the latest GHSG study generation. Future analyses will focus on a further individualization of treatment fields.

Forty Years After Mediastinal Radiotherapy for Hodgkin Lymphoma: How Late is Late Cardiotoxicity?

Forty Years After Mediastinal Radiotherapy for Hodgkin Lymphoma: How Late is Late Cardiotoxicity?

Relapse patterns in early-PET negative, limited-stage Hodgkin lymphoma (HL) after ABVD with or without radiotherapy-a joint analysis of EORTC/LYSA/FIL H10 and NCRI RAPID trials.

In the H10 and RAPID randomised trials, chemotherapy+radiotherapy (combined modalities treatment, CMT) was compared with chemotherapy (C) in limited-stage Hodgkin lymphoma (HL), with negative early positron emission tomography (ePETneg). We analysed patterns of relapses in the H10 trial, validated findings in the RAPID trial and performed a combined analysis stratified by trial. The impact of radiotherapy (RT) on risk of relapse was studied using adjusted Cox models, with time-varying effects. In H10, 1,059 ePETneg patients were included (465 European Organisation for Research and Treatment of Cancer (EORTC) favourable [F], 594 unfavourable [U]). Among the F patients, 2/227 (1%) relapsed after CMT, 30/238 (13%) after C: of these relapses, 21/30 (70%) occurred in less than 2 years and 25/30 (83%) affected originally involved areas. Among the U group, 16/292 (5%) relapsed after CMT: 8/16 (50%) in less than 2 years, 11/16 (69%) in originally involved areas. After C 30/302 (10%) relapsed: 27/30 (90%) in less than 2 years, and 26/30 (87%) in originally involved areas. Similar results were observed in 419 ePETneg RAPID patients (241 F, 128 U, 50 unclassified): among F patients, 6/118 (5%) relapsed after CMT; 13/123 (11%) after C: 11/13 (85%) in less than 2 years and 11/13 (85%) affecting originally involved areas. In U patients, 3/65 (5%) relapsed after CMT and 5/63 (8%) after C. In both trials, omitting RT in ePETneg HL resulted in more early relapses, mainly affecting originally involved areas. RT significantly reduced risk of early relapses in the combined stratified analysis.

Eosinophilic, polymorphic and pruritic eruption following radiotherapy for Hodgkin lymphoma

Eosinophilic, polymorphic and pruritic eruption following radiotherapy for Hodgkin lymphoma

Breast cancer and cardiovascular outcomes after breast cancer in survivors of Hodgkin lymphoma.

Hodgkin lymphoma (HL) survivors treated with chest radiotherapy have an increased risk of breast cancer (BC). Prior HL treatment and associated cardiovascular disease (CVD) risk may limit BC treatment options. It is unknown how treatment adaptations affect BC and CVD outcomes. The authors compared 195 BC patients treated with chest/axillary radiotherapy for HL (BC-HL) with 5988 age- and calendar year-matched patients with first primary BC (BC-1). Analyses included cumulative incidence functions and Cox regression models, accounting for tumor characteristics and BC treatment. Compared to BC-1 patients, BC-HL patients received anthracycline-containing chemotherapy (23.7% vs. 43.8%, p < .001) and breast-conserving surgery followed by radiotherapy (7.1% vs. 57.7%, p < .001) less often. BC treatment considerations were reported for 71% of BC-HL patients. BC-HL patients had a significantly higher risk of 15-year overall mortality than BC-1 patients (61% vs. 23%). Furthermore, risks of BC-specific mortality and nonfatal BC events were significantly increased among BC-HL patients, also when accounting for tumor and treatment characteristics (2.2- to 4.5-fold). BC-HL patients with a screen-detected BC had a significantly reduced (61%) BC-specific mortality. One-third of BC-HL patients had CVD at BC-diagnosis, compared to <0.1% of BC-1 patients. Fifteen-year CVD-specific mortality and CVD incidence were significantly higher in BC-HL patients than in BC-1 patients (15.2% vs. 0.4% and 40.4% vs. 6.8%, respectively), which was due to HL treatment rather than BC treatment. BC-HL patients experience a higher burden of CVD and worse BC outcomes than BC-1 patients. Clinicians should be aware of increased CVD risk when selecting BC treatment for HL survivors. Patients with breast cancer after Hodgkin lymphoma (BC-HL) may have limited options for BC treatment, due to earlier HL treatment and an associated increased risk of cardiovascular disease (CVD). BC treatment considerations were reported for 71% of BC-HL patients. We examined whether BC-HL patients have a higher risk of CVD or BC events (recurrences/metastases) compared to patients with breast cancer that had no earlier tumors (BC-1). We observed a higher burden of CVD and worse BC outcomes in HL patients compared to BC-1 patients. Clinicians should be aware of increased CVD risk when selecting BC treatment for HL survivors.

T022: Sharing decisions regarding radiotherapy for Hodgkin lymphoma: a qualitative study of the experiences of patients and clinicians in the UK

Figure 1: The radiotherapy decision-making process in current clinical practice, as described by patients and clinicians Background: Radiotherapy (RT) increases the chance of cure of Hodgkin lymphoma (HL) [1] but also has risks, including cardiac disease and second cancers [2]. Whilst guidelines broadly indicate which patients may benefit from RT, there are individual factors that can substantially affect the balance of benefit and risk. Little is known about how these factors are incorporated into decision-making, or patients’ preferences for involvement in decisions. This study aimed to explore the RT decision-making process, and better understand how patients’ preferences are taken into account. Methods: We conducted semi-structured interviews with 15 people treated for HL, and 12 clinicians who specialised in the treatment of HL. We used maximal variation sampling, and Braun and Clarke’s thematic analysis. The study was co-designed with four people previously treated for HL and approved by the North of Scotland Ethics Committee. Results: The decision about RT was commonly made by clinicians and presented to patients as a conclusion. Although patients acknowledged they could disagree with the clinicians’ recommendation, they often perceived themselves to be in a life-threatening situation with no real choice about treatment. Patients were highly engaged and keen to receive information, but the majority felt too overwhelmed by the complexity of their illness to participate in RT decisions. Patients and clinicians agreed that the ultimate responsibility for RT decisions lay with healthcare professionals, and that it was too challenging to lay the burden of this decision solely on the person with HL. Clinicians considered individual patient factors when recommending RT, and recognised the importance of ensuring that decisions were in line with a person’s values and preferences (Figure 1). Both patients and clinicians felt shared decision-making was hampered by the lack of easily accessible information predicting the risks of RT for an individual. Conclusion: Decisions about RT lay mostly with clinicians, but individual patient circumstances were considered. The availability of data to understand the risks of RT for an individual would enhance the decision-making process. Literature 1. Shaikh et al. Consolidation radiotherapy following positron emission tomography complete response in early-stage Hodgkin lymphoma: a meta-analysis. Leuk Lymphoma 2020;0:1 2. Gustavsson et al. A systematic overview of radiation therapy effects in Hodgkin’s lymphoma. Acta Oncol 2003;42:589

Spontaneous pregnancy after unprotected pelvic radiotherapy for hodgkin lymphoma: A case report

Spontaneous pregnancy after unprotected pelvic radiotherapy for hodgkin lymphoma: A case report

Molecular characterization of gastric adenocarcinoma diagnosed in patients previously treated for Hodgkin lymphoma or testicular cancer.

IntroductionThe risk of developing gastric cancer is increased in patients treated with radiotherapy for Hodgkin lymphoma (HL) or testicular cancer (TC). This study aims to assess if gastric adenocarcinoma after treatment for HL/TC (t-GC) is molecularly different from gastric adenocarcinoma in the general population.MethodsPatients were diagnosed with t-GC ≥5 years after treatment for HL/TC. Four molecular subtypes were identified using immunohistochemical and molecular analyses: Epstein-Barr virus (EBV), mismatch repair (MMR) deficiency or microsatellite instability (MSI), aberrant p53 staining as surrogate for chromosomal instability (sCIN), and a surrogate for genomic stability (sGS) without these aberrations. Results were compared with gastric cancer in the general population (p-GC) described in literature.ResultsMolecular subtyping of 90 t-GCs resulted in 3% EBV, 8% MSI, 36% sCIN and 53% sGS. 3/6 of MSI t-GCs had MLH1 promoter methylation and 2/6 were explained by double somatic mutations in MMR genes. T-GCs were more frequently sGS than p-GCs (53% vs. 38%, p = 0.04). T-GC was more frequently sGS in HL/TC patients diagnosed before 1990, than after 1990 (63% vs. 38%, p = 0.03). T-GCs located in the antrum, an area that receives high irradiation doses, were more frequently sGS (61% vs. 28% in p-GCs, p = 0.02).ConclusionOur results demonstrate that t-GCs are more frequently of the sGS subtype than p-GCs. An association of t-GC of the sGS subtype with prior anticancer treatment is suggested by the high frequency in HL/TC patients who were treated before 1990, a time period in which HL/TC treatments were more extensive.

Diaphragmatic weakness related to radiotherapy: 2 cases and a review

Post-radiation diaphragmatic weakness have rarely been described. We report two cases of post-radiation diaphragmatic weakness from our center, and review the other published cases, computing clinical, electromyography and magnetic resonance imaging data. Including our two cases, seven cases of post-radiation diaphragmatic weakness have been described. Most occurred after mantle-field radiotherapy for Hodgkin lymphoma (5/7), often in associations with chemotherapy (4/7). Other radiations-induced complications were found (5/7) such as brachial plexopathy, cardiac involvement or hypothyroidy. When studied, phrenic nerve conduction studies revealed different profiles, from clearly abnormal responses to limit amplitudes. Imaging can be a useful diagnostic tool, displaying abnormalities with sharp limits matching the radiation field. Data is limited about long-term evolution. Presentation of post-radiation diaphragmatic weakness seems relatively homogeneous. We propose a diagnosis work-up for post-radiation diaphragmatic weakness, to exclude potentially treatable differential diagnoses.

Surgical Management and Contralateral Breast Cancer Risk in Women with History of Radiation Therapy for Hodgkin Lymphoma: Results from a Population-Based Cohort.

Women with history of chest irradiation for Hodgkin lymphoma are at increased risk of developing bilateral breast cancer, although contralateral breast cancer risk estimates in this population remain undefined. We queried the SEER database for women treated with radiation therapy for Hodgkin lymphoma prior to age 30 years and were diagnosed with a subsequent breast cancer between 1990-2016. Trends in surgical management and the 5- and 10-year cumulative incidence of contralateral breast cancer were evaluated. The cohort included 295 women with a median age of 22 years (range 8-30 years) at Hodgkin lymphoma diagnosis, and 42 years (range 22-65 years) at breast cancer diagnosis. Overall, 263 (89.2%) presented with unilateral breast cancer, while 32 (10.8%) presented with synchronous bilateral breast cancer. Breast-conserving surgery was performed in 17.3% of patients, while mastectomy was performed in 82.7%. In 263 patients presenting with unilateral breast cancer, 50 (19.0%) underwent breast-conserving surgery and 213 (81.0%) underwent mastectomy. Subgroup analysis of mastectomy patients demonstrated a 40.5% bilateral mastectomy rate. The 5-year incidence of contralateral breast cancer in women who underwent unilateral surgery was 9.4% [95% confidence interval (CI), 5.6-15.4%], increasing to 20.2% (95% CI, 13.7-29.2%) at 10-year and 29.9% (95% CI, 20.8-41.9%) at 15-year follow-up. Women with a history of prior chest radiation for Hodgkin lymphoma with a diagnosis of breast cancer have a 10-year contralateral breast cancer risk of 20%. These findings support consideration of contralateral prophylactic mastectomy during surgical decision-making for management of this high-risk patient population.

Rolle der Radiotherapie beim Hodgkin-Lymphom

BackgroundThe role of radiotherapy (RT) in the treatment of Hodgkin lymphoma (HL) has changed considerably over time. Nevertheless, it remains an integral part of combined-modality therapy; however, the increasing use of immunotherapeutics means that the role of RT will be re-evaluated. This article provides an up-to-date review of RT in HL covering indications, target volume concepts, side effects, and a look to the future.Materials and methodsA review of RT in HL was performed using a literature search and current guidelines.ResultsAccording to current studies, modern RT in HL continues to be the standard of care in the early stages with 20 Gy involved site RT (IS-RT). In the intermediate stages, based on the HD17 study, positron emission tomography (PET)-guided 30 Gy IS-RT has become the standard of care, so that all PET-negative patients are no longer irradiated after chemotherapy. In advanced stages, local RT continues to be given in patients with positive PET after chemotherapy with 30 Gy. In addition, new target volume concepts, such as IS-RT, have led to a further reduction in RT fields, aiming for a reduction in late side effects and secondary malignancies. Looking ahead, the emergence of checkpoint immunotherapy has significantly changed the treatment of HL. The role and benefits of RT must now be explored in this environment as well, and initial results appear promising.ConclusionAlthough the role of RT in the treatment of HL has changed significantly over the decades, it appears that it will also remain an important part of combined-modality therapy for HL in the future.

Abstract PD7-07: Surgical management and contralateral breast cancer risk in women with a history of radiation therapy for Hodgkin lymphoma: Results from a population-based cohort

Abstract Background: Women with a history of chest radiation for Hodgkin lymphoma are at an increased risk of developing breast cancer. Although mastectomy has historically been recommended for surgical treatment of breast cancers in women with prior radiation exposure, surgical management trends and contralateral breast cancer risk in this population remain undefined. Methods: We performed a population-based retrospective study using the Surveillance, Epidemiology, and End Results (SEER) database from 1990-2016. Our cohort included women who received radiation for Hodgkin lymphoma prior to 30 years old and were diagnosed with a subsequent breast cancer. We evaluated trends in local therapy including rates of breast conserving surgery (BCS) and mastectomy. In those undergoing unilateral surgery, the Kaplan-Meier method was used to estimate the 5- and 10-year cumulative incidence of contralateral breast cancer. Results: Our final cohort included 295 women with a median age of 22 years (range, 8-30 years) at Hodgkin lymphoma diagnosis, and 42 years (range, 22-65 years) at breast cancer diagnosis. Of these patients, 263 (89.2%) presented with unilateral breast cancer, while 32 (10.8%) presented with synchronous bilateral breast cancer. Overall, BCS was performed in 17.3% of patients and mastectomy was performed in 82.7%. In the 263 patients presenting with unilateral breast cancer, 50 (19.0%) underwent BCS and 213 (81.0%) underwent mastectomy. Subgroup analysis of mastectomy patients with surgical laterality information available demonstrated a 40.5% bilateral mastectomy rate. In the entire cohort, the 5-year incidence of contralateral breast cancer in women who underwent unilateral surgery was 9.4% (95% CI, 5.6-15.4), increasing to 20.2% (95% CI, 13.7-29.2) at 10-years of follow up. Hormone receptor status of the index breast cancer was not associated with significant differences in the incidence of contralateral breast cancer (p=0.13). Conclusions: Women with a history of prior chest radiation for Hodgkin Lymphoma with a diagnosis with breast cancer have a 10-year contralateral breast cancer risk of 20%. These findings support consideration of contralateral prophylactic mastectomy during surgical decision-making in this high-risk patient population. Citation Format: Elisheva R Eisenberg, Anna Weiss, Ipshita Prakash, Sonia Skamene, Mark Basik, Jean Francois Boileau, Lissa Ajjamada, Michael Pollak, Stephanie M Wong. Surgical management and contralateral breast cancer risk in women with a history of radiation therapy for Hodgkin lymphoma: Results from a population-based cohort [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr PD7-07.

Clinicopathologic features of breast cancers diagnosed in women treated with prior radiation therapy for Hodgkin lymphoma: Results from a population-based cohort.

Childhood and young adult survivors of Hodgkin lymphoma (HL) are at elevated risk of developing breast cancer, yet little data exist on the tumor characteristics that develop in this high-risk patient population. The National Cancer Institute's Surveillance, Epidemiology, and End Results database was used to identify breast cancers diagnosed between 1990 and 2016 in women who had received prior radiation therapy for HL at age 30years or younger. Clinicopathologic features of subsequent breast cancers (breast cancer after radiation therapy for HL [BC-HL]) were examined and compared with breast cancers diagnosed in women who had no prior malignancy (breast cancer with no prior malignancy [BC-NPM]). In total, 321 breast cancers were identified in 257 women who had a history of radiation therapy for HL. The median age at HL diagnosis was 22years (interquartile range, 18-26years), and nearly all patients in the BC-HL group (97.9%) were diagnosed ≥8years after radiation therapy. Overall, 56 patients in the BC-HL group (21.8%) developed bilateral breast cancer. Compared with women who had BC-NPM, those who had BC-HL were younger (43 vs 60years; P<.001) and were less likely to present with ductal carcinoma in situ (8.4% vs 14.9%; P=.001). On multivariable analysis that included adjustment for age, invasive BC-HL was associated with smaller (≤2cm) tumor size (odds ratio, 1.64; 95% CI, 1.25-2.15) and upper outer quadrant tumors (odds ratio, 1.37; 95% CI, 1.04-1.81) compared with BC-NPM. In a subset analysis of 102 women who had HER2/neu status available, the distribution of biologic subtype was not significantly different between BC-HL and BC-NPM (P=.16). Breast cancers in women who previously received radiation therapy for HL are characterized by earlier onset disease, although most remain estrogen receptor-positive and have early stage disease at presentation. Women who have had radiation therapy for Hodgkin lymphoma at a young age are at increased risk of developing early onset breast cancer; however, most of these breast cancers are sensitive to hormones (estrogen receptor-positive) and are diagnosed at early stages. Because these breast tumors are estrogen receptor-positive, medications that prevent breast cancer by blocking the effect of or lowering hormone levels (also termed endocrine prevention) may be useful in this group of high-risk women.

416 A very severe aortic stenosis secondary to radiation therapy for Hodgkin lymphoma: a case report

Abstract Aims Hodgkin lymphoma is a highly curable disease, with survival rates around 85% at 5 years, thanks to its treatment, mainly based on radiation therapy alone or in association with chemotherapy. However, radiation therapy carries the risk of long-term complications, mainly represented by secondary malignancies or cardiovascular diseases. Indeed, patients treated with radiation remain at increased risk of coronary artery disease, congestive heart failure, valve disease, pericardial disease and sudden death. In particular, radiation-induced valve disease has been reported in approximately 10% of treated patients, with the most common being aortic or mitral regurgitation, followed by aortic stenosis. We describe the case of a very severe aortic valve stenosis developed 35 years after radiotherapy for Hodgkin Lymphoma. Methods A 60-years-old woman with history of Hodgkin Lymphoma treated with radiotherapy 35 years ago, no cardiovascular risk factors, complained progressive fatigue and worsening dyspnoea. She was referred to our centre from a spoke centre for congestive heart failure caused by aortic stenosis. At her arrival, we performed a transthoracic echocardiography finding a very-severe aortic stenosis (mean gradient 97 mmHg, AVA 0.3 cm2), a moderate functional mitral regurgitation and an important hypertrophy suspected of infiltrative pattern. No coronary artery disease was found at coronary angiography. Furthermore, she underwent a cardiac magnetic resonance showing a moderate left ventricular dilatation and hypertrophy with areas of non-ischaemic late gadolinium enhancement, significant for myocardial fibrosis with no specific pattern of infiltration. She was treated with surgical aortic valve replacement with biological prosthesis (Inspiris Resilia 21) with good results at the discharge echocardiography. Discussion Cardiovascular toxicity is nowadays the most common non-malignancy cause of death in radio-treated cancer survivors. At the level of the valvular apparatus, radiation damage is expressed with fibrosis of the myocardium and of the valvular endothelium, leading to thickening and calcification especially of the left-sided valves. Radio-treated patients have a 50% cumulative incidence of cardiovascular diseases at 40 years after treatment, and a clinically-relevant valve disease is found in approximately 6% of radio-treated patients at 20 years. Conclusions Thus, an early identification of the disease in a subclinical state is crucial. Nevertheless, there is still no consensus on the timing and the modality of cardiovascular screening after radiation therapy. Moreover, an elevated cardiovascular risk profile was found to be directly related to cardiotoxicity; this underlines the importance of identification and aggressive treatment of cardiovascular risk factors. Radiation dose reduction and the use of shields may further reduce the incidence of late cardiovascular complications in these patients.

Breast Dose in Young Women Treated for Hodgkin Lymphoma Between 2007 and 2018: A Single Institutional Study

<h3>Purpose/Objective(s)</h3> Women receiving supradiaphragmatic radiotherapy (RT) for Hodgkin Lymphoma (HL) aged ≤ 36y have a greater risk of breast cancer (BC) than the general population. Although RT fields have reduced in recent years, breast tissue (BT) is unavoidably irradiated in many women. Despite the long-term risk, dose to BT is not routinely nor consistently reported: published studies report inconsistent breast dose metrics, or only point dose to the site of a subsequent BC. We hypothesize breast dose from HL RT has decreased since the implementation of CT based RT, due to an increased awareness of BC risk. This study also aims to assess the correlations between dose metrics of suspected importance to RT induced BC. <h3>Materials/Methods</h3> All female patients with available RT plans aged ≤ 36y treated with supradiaphragmatic RT from 2007 to 2018 were included. Patients received 3D conformal RT to 30-36 Gy (8/68 received 20 Gy). BT was retrospectively contoured. Dose metrics V4 Gy (volume receiving ≥4 Gy) and V30 Gy (in % and cm³) and mean breast dose (MBD, Gy) were extracted for both breasts to consider total BT at risk. Correlations between dose metrics, and with the target volume (CTV, cm³), were assessed using Pearson's correlation coefficient. Time trends were investigated using chi-square analysis of linear fit. <h3>Results</h3> 68 patients were available for analysis. 1 patient was excluded from % volume and MBD analysis due to truncated BT. MBD was strongly positively correlated with V4 Gy_% (r > 0.9) and moderately positively correlated with V4 Gy_cm³ (r = 0.8), V30 Gy_% (r = 0.5) and V30 Gy_cm³ (r = 0.5). Results suggest no decrease over time for V4 Gy_cm³ or V30 Gy_cm³ (linear regression coefficients of 12 and 0.4; both χ² > 1000). For the 63 patients with CTV available, weak positive linear correlation was seen between CTV and V4 Gy_cm³ (r = 0.2), MBD (r = 0.4), and V30 Gy_cm³ (r = 0.4). Large variations in breast dose were seen between patients (see table). <h3>Conclusion</h3> This is believed to be the first systematic retrospective evaluation of individual breast dose in modern HL RT. Despite increased awareness, our data gives no evidence of reduction in breast dose over time. The large variation in breast dose suggests individualized risk assessment and follow up strategies are needed. This data supports the importance of developing optimized screening strategies through initiatives such as the Breast screening After Radiotherapy Dataset (BARD). Our analysis suggests V4 Gy, V30 Gy and MBD cannot be considered independent. Until there is more evidence of the dose level associated with BC risk, it is recommended that all three are reported with V4 Gy and V30 Gy expressed in cm³ to consider total breast tissue at risk.

Breast Hypoplasia and Decreased Lactation From Radiation Therapy in Survivors of Pediatric Malignancy: A PENTEC Comprehensive Review

Breast hypoplasia and impaired lactation are poorly studied sequelae of chest radiation therapy (RT) in children. The Pediatric Normal Tissue Effects in the Clinic female breast task force aimed to quantitate the radiation dose-volume effects on these endpoints. A literature search was conducted of peer-reviewed manuscripts evaluating breast hypoplasia and lactation after chest RT in children, yielding 789 abstracts. Only 2 studies on children irradiated at <4 years of age for angioma of the breast provided dosimetric data correlated with breast hypoplasia. For patients who received brachytherapy, the dose was converted to external beam RT in equivalent 2 Gy fractions (DEBRT), although the limitations of this type of mathematical conversion need to be recognized. We calculated relative risks (RR) and 95% confidence intervals (95% CIs) based on these data. Only 1 study was relevant to the lactation endpoint, in which patients were given RT for Hodgkin lymphoma at age 14 to 40 years. The 3 studies involved 206 patients in total. In patients <4 years old at the time of RT, the prevalence of patient-perceived breast hypoplasia was 38% (RR 2.5; 95% CI, 1.3-4.6) after DEBRT of <0.34 Gy, 61% (RR 4.0; 95% CI, 2.1-7.4) after DEBRT 0.34-0.97 Gy, and 97% (RR 6.3; 95% CI, 3.6-10.8) after DEBRT ≥0.97 Gy to the breast anlage. A simple linear regression model (r=0.72; P < .001) showed that the treated breast was smaller than the untreated breast by 13% at DEBRT=0.5 Gy, 20% at DEBRT=1 Gy, 32% at DEBRT=2 Gy, 51% at DEBRT=4 Gy, 66% at DEBRT=6 Gy, 79% at DEBRT=8 Gy, and 90% at DEBRT=10 Gy. The risk of unsuccessful breastfeeding was 39% after a median mediastinal dose of 41 Gy, compared with 21% in a sibling control group (P=.04). RT dose of ≥42 Gy was not associated with less breastfeeding success compared with <42 Gy, and data on lower doses were unavailable. Based on extremely limited data, young adults exposed to thoracic RT as children seem to be at significant risk of breast hypoplasia and impaired lactation. Doses as low as 0.3 Gy to immature breasts can cause breast hypoplasia. Additional studies are needed to quantify dose and technique effects with modern RT indications. Prospective collection of clinical outcomes and dosimetric factors would enhance our understanding of RT-induced breast hypoplasia and impaired lactation.

Combined skin-sparing mastectomy and immediate implant-based breast reconstruction: Outcome following mantle field irradiation versus outcome following whole-breast irradiation

Mastectomy may be needed in the context of previous radiotherapy in cases of breast carcinoma following mantle field radiotherapy for Hodgkin lymphoma or in cases of local relapse or second primary tumours after breast conserving therapy including whole-breast irradiation (BCT). The outcome of combined skin-sparing mastectomy and immediate implant-based breast reconstruction (SSM-IIBR) has been reported to be unfavourable in these cases. To compare the outcome of SSM-IIBR after mantle field radiotherapy to that after BCT and to compare both to the outcome observed in non-irradiated breasts. The prevalences of short-term events, device loss, long-term corrections and secondary reconstructions, and reversion to autologous tissue techniques of 42 SSM-IIBRs performed after mantle field irradiation were compared to those of 47 salvage SSM-IIBRs following BCT. Both outcomes were compared to the outcome in the contralateral, non-irradiated breast of the subgroup of 23 women in the BCT group. The groups were comparable in terms of patient- and procedure-related risk factors, except for time lapse after previous therapy, intraoperative device weight, and the fraction of immediate use of a definitive implant. The outcome of SSM-IIBR after mantle field irradiation significantly differs favourably from that after BCT. It matches the outcome observed in non-irradiated breasts. Skin-sparing mastectomy combined with immediate implant-based breast reconstruction is a fully justifiable option for women who previously underwent mantle field irradiation for Hodgkin lymphoma. We feel that the unfavourable outcome observed in women who previously underwent BCT necessitates an alternative reconstructive modality.

Current Situation of Proton Therapy for Hodgkin Lymphoma: From Expectations to Evidence.

Simple SummaryHodgkin lymphoma (HL) is a highly curable disease; in this context, the limitation of late adverse events is of prime importance for the patient. Proton therapy for mediastinal HL irradiation theoretically limits secondary cancer excess risk and should reduce late toxicities compared with classical radiation therapy techniques. However, due to the limited clinical experience, strong evidence is still lacking to support proton therapy in HL management despite excellent tolerance. In addition, randomized controlled trials are probably unrealistic in this context. National and international registries may be useful to strengthen support for HL proton therapy.Consolidative radiation therapy (RT) is of prime importance for early-stage Hodgkin lymphoma (HL) management since it significantly increases progression-free survival (PFS). Nevertheless, first-generation techniques, relying on large irradiation fields, delivered significant radiation doses to critical organs-at-risk (OARs, such as the heart, to the lung or the breasts) when treating mediastinal HL; consequently, secondary cancers, and cardiac and lung toxicity were substantially increased. Fortunately, HL RT has drastically evolved and, nowadays, state-of-the-art RT techniques efficiently spare critical organs-at-risks without altering local control or overall survival. Recently, proton therapy has been evaluated for mediastinal HL treatment, due to its possibility to significantly reduce integral dose to OARs, which is expected to limit second neoplasm risk and reduce late toxicity. Nevertheless, clinical experience for this recent technique is still limited worldwide. Based on current literature, this critical review aims to examine the current practice of proton therapy for mediastinal HL irradiation.