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Anthracyclines (AC) or mediastinal radiotherapy (RT) are associated with cardiotoxicity. However, limited imaging studies examine early changes (<1yr) or their relative contribution to cardiotoxicity. We sought to address this by simultaneous cardiac 18F-FDG PET/MRI. In a prospective study, patients (pts) with mediastinal lymphoma had cardiac 18F-FDG PET/MRI at 4 timepoints: Baseline, 2 weeks post AC, 2 weeks post RT, 6 months (m) post RT. Esophageal & lung cancer pts had concurrent platinum-based chemoradiotherapy and had 3 scans: Baseline, post RT, 6m post RT. MRI assessed biventricular ejection fractions (EF%) and volumes (V), myocardial T1, T2 maps and late gadolinium enhancement (LGE). 18F-FDG PET was used to assess cardiac inflammation and to obtain segmental standardized mean and max uptake values (SUV) in the myocardium. Paired t-tests or Wilcoxon signed-rank were used to assess significance. Patient advocates contributed to the design and evaluation of the study. 24 pts were recruited between Nov 21 – Jun 23, (8 lymphoma, 11 esophageal, 5 lung) mean age 57y (23-80). The mean AC dose for lymphoma pts was 244 mg/m2 and mean heart dose (MHD) was 2.3 Gy, 15.3 Gy for esophageal and 11.0 Gy for lung. We observed significant reductions in both ventricular EF% and V in the post RT scans. On average the left ventricle (LV) recovered by 6m, however, the right ventricle (RV) EF% and stroke V remained reduced, Table 1. Notably, the RVEF% remained reduced by >10% for 8 pts, 6 of whom were esophageal with MHD >15 Gy, in these pts there was also abnormal focal 18F-FDG uptake in the basal myocardial segments in the 6m post RT scans which was not present on earlier scans. When analyzing only the lymphoma pts, all the above parameters decreased after AC but not after RT and all recovered by 6m apart from RVEF% which remained reduced (-6% ± 6 p=0.08). LGE, T1 and T2 did not change significantly from baseline. To our knowledge, this is the first study to report that RV myocardial function is significantly reduced following AC and RT, it persisted at 6m post RT and was >10% in 38% of pts. Most of these patients received MHD >15Gy and had abnormal myocardial 18F-FDG PET uptake in the basal region which received the highest RT doses suggesting an inflammatory component to the process of cardiotoxicity. A reduction in RVEF% and focal myocardial 18F-FDG PET uptake may be useful biomarkers of early cardiotoxicity and initiation of cardio-oncology follow up. [ABSTRACT FROM AUTHOR]

Radiotherapy (RT) is an effective treatment for residual lymphoma early after CD19 chimeric antigen receptor T cell therapy (CAR T). However, there are concerns regarding the effect of RT on CAR T. We investigated the effect of different RT planning techniques on the dose to circulating blood to develop CAR T sparing RT using a published computational framework to compute hematological doses (HEDOS) We analyzed 33 RT treatment plans for 11 lesions. Each lesion was planned with 3 RT techniques. Technique A: a conventional VMAT plan, B: a blood sparing technique with lower number of arcs and dose optimization for blood vessels (BV) and blood rich organs (BRO) and C: the same as B but delivered with Flattening Filter Free (FFF) beams to increase dose rate (DR) and reduce beam on time (BOT). Fractional blood doses were calculated using HEDOS, which simulates individual blood particles as they travel through the body, dictated by intra- and inter-organ blood flow. The % of blood volume that received 0, 0.05 and 0.5 Gy was estimated for each RT technique. Wilcoxon test was used to test for significance. BV dose was reduced by B & C, with wide variation between different cases. However, the differences between the mean BV dose of the whole group did not reach statistical significance. Techniques B & C reduced BOT, especially C due to its higher DR (1400 vs 600 MU/min). BOT reduction had the largest influence on the volume of irradiated blood and thus C significantly reduced the blood dose compared to A & B (Table 1). The % blood volume receiving 0 Gy was highest for C. C also reduced the blood volume that received > 0.05 Gy / fraction, a dose level that can induce cell death/inactivation due to the highly radiosensitive nature of lymphocytes. This is the first study to develop a blood sparing (and potentially CAR T sparing) RT by modifying treatment parameters to account for the circulating nature of the blood. Using a dynamic dose calculation method, BOT has a large effect compared to other modifications. Reducing BOT to < 60 seconds had the greatest blood dose-sparing effect. This blood sparing RT could have other potential applications such as reducing risk for lymphopenia after RT. [ABSTRACT FROM AUTHOR]

Radiotherapy is an accepted bridging prior to CD19 CAR T in large B cell lymphoma (LBCL) and is sometimes used post CAR T for residual disease. However, consolidation (cRT) is not well established and there is no agreed standard for patient selection, timing, doses or techniques. Concern also exists regarding effect on circulating CAR T in responding patients. We initiated a prospective protocol for the use of RT with CAR T to: (1) standardize the selection of patients, (2) promote the use of RT consolidation post CAR T according to pre defined criteria, and (3) optimize the use of CAR T sparing RT in the consolidation setting. The eligibility criteria included LBCL patients approved for CD19 CAR T and no contraindication for RT. Patients were selected for pathway A (Bridging RT alone) if most sites of disease can be covered with RT. Pathway B (bridging systemic therapy ± cRT) was selected for rapidly progressing disease, wide-spread extranodal disease (e.g. liver, lung, bone, peritoneum) or LDH >2xULN. Baseline PET CT was reviewed and sites at high risk for local recurrence (≥5cm or SUVmax ≥15) were recorded. cRT post CAR T was given to high-risk lesions which on D28 PET CT showed a Deauville score (DS) 3-4 or 5 (but partial response). RT was planned 6-8 weeks post CAR T, with CAR T sparing technique. 28 patients were entered between Nov 2021 – Oct 2023, 10 in pathway A & 18 in pathway B. Median age was 55 years. 51.7% had stage 4 (20% vs. 68.4% in A vs. B). 44.8% had bulky disease, 24.1% ≥2 extranodal sites, and 48.2% high LDH. 1 patient in pathway A did not receive CAR T due to PD. RT dose was 20-36Gy (10-12#) in pathway A, all delivered with VMAT and with no gaps. Pathway B doses were 25-37.5Gy / 5-15# (23/26 sites treated with VMAT) and with no gaps. Planning modifications for early cRT post CAR T included: (1) contouring and dose-optimisation of blood vessels (BV) and blood-rich OARs (BR-OAR) to reduce doses to blood, and (2) measures to reduce beam-on time to account for the circulating nature of blood; hypofractionation (2.5 – 5 Gy/#, median = 3), limited beam angles (e.g. partial single arcs) avoiding BV and BR-OAR, and flattening filter free (FFF) beams. Overall response rate at 1 month was 86.2% (41.4% DS 1-3) and 48.2% at 6 months. With a median follow-up of 180 days, 9 patients progressed (4 in pathway A and 5 in pathway B) and 5 died, all due to disease progression. Data on local disease control, progression-free and overall survival will be provided at the meeting. Significant toxicity included 2 G3 ICANS but no CRS G≥ 3. No G≥3 toxicity reported after cRT. Implementing a comprehensive protocol of RT bridging and post CAR T RT consolidation with selection of patients based on pre-defined criteria was feasible. All patients but one completed treatment according to protocol. The disease control outcomes and the toxicity are promising, particularly in the RT consolidation setting. [ABSTRACT FROM AUTHOR]

Purpose: Adjuvant proton beam therapy (PBT) is increasingly available to patients with breast cancer. It achieves better planned dose distributions than standard photon radiation therapy and therefore may reduce the risks. However, clinical evidence is lacking., Methods and Materials: A systematic review of clinical outcomes from studies of adjuvant PBT for early breast cancer published in 2000 to 2022 was undertaken. Early breast cancer was defined as when all detected invasive cancer cells are in the breast or nearby lymph nodes and can be removed surgically. Adverse outcomes were summarized quantitatively, and the prevalence of the most common ones were estimated using meta-analysis., Results: Thirty-two studies (1452 patients) reported clinical outcomes after adjuvant PBT for early breast cancer. Median follow-up ranged from 2 to 59 months. There were no published randomized trials comparing PBT with photon radiation therapy. Scattering PBT was delivered in 7 studies (258 patients) starting 2003 to 2015 and scanning PBT in 22 studies (1041 patients) starting 2000 to 2019. Two studies (123 patients) starting 2011 used both PBT types. For 1 study (30 patients), PBT type was unspecified. Adverse events were less severe after scanning than after scattering PBT. They also varied by clinical target. For partial breast PBT, 498 adverse events were reported (8 studies, 358 patients). None were categorized as severe after scanning PBT. For whole breast or chest wall ± regional lymph nodes PBT, 1344 adverse events were reported (19 studies, 933 patients). After scanning PBT, 4% (44/1026) of events were severe. The most prevalent severe outcome after scanning PBT was dermatitis, which occurred in 5.7% (95% confidence interval, 4.2-7.6) of patients. Other severe adverse outcomes included infection, pain, and pneumonitis (each ≤1%). Of the 141 reconstruction events reported (13 studies, 459 patients), the most prevalent after scanning PBT was prosthetic implant removal (34/181, 19%)., Conclusions: This is a quantitative summary of all published clinical outcomes after adjuvant PBT for early breast cancer. Ongoing randomized trials will provide information on its longer-term safety compared with standard photon radiation therapy., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Background and Purpose: To predict treatment-related cardiovascular disease (CVD) and second cancer 30-year absolute mortality risks (AMR 30 ) for patients with mediastinal Hodgkin lymphoma in a large multicentre radiation oncology network in Ireland., Material and Methods: This study includes consecutive patients treated for mediastinal lymphoma using chemotherapy and involved site radiotherapy (RT) 2016-2019. Radiation doses to heart, left ventricle, cardiac valves, lungs, oesophagus, carotid arteries and female breasts were calculated. Individual CVD and second cancer AMR 30 were predicted using Irish background population rates and dose-response relationships., Results: Forty-four patients with Hodgkin lymphoma were identified, 23 females, median age 28 years. Ninety-eight percent received anthracycline, 80% received 4-6 cycles ABVD. Volumetric modulated arc therapy (VMAT) ± deep inspiration breath hold (DIBH) was delivered, median total prescribed dose 30 Gy. Average mean heart dose 9.8 Gy (range 0.2-23.8 Gy). Excess treatment-related mean AMR 30 from CVD was 2.18% (0.79, 0.90, 0.01, 0.13 and 0.35% for coronary disease, heart failure, valvular disease, stroke and other cardiac diseases), 1.07% due to chemotherapy and a further 1.11% from RT. Excess mean AMR 30 for second cancers following RT were: lung cancer 2.20%, breast cancer in females 0.34%, and oesophageal cancer 0.28%., Conclusion: For patients with mediastinal lymphoma excess mortality risks from CVD and second cancers remain clinically significant despite contemporary chemotherapy and photon-RT. Efforts to reduce the toxicity of combined modality treatment, for example, using DIBH, reduced margins and advanced RT, e.g. proton beam therapy, should be continued to further reduce potentially fatal treatment effects., (© 2022. The Author(s).)

Importance: Hodgkin lymphoma (HL) survivors have higher rates of colorectal cancer, which may be associated with subdiaphragmatic radiation therapy and/or alkylating chemotherapy. Although radiation dose-response associations with breast, lung, stomach, pancreatic, and esophageal cancer after HL have been demonstrated, the association of radiation therapy with colorectal cancer remains unclear., Objective: To quantify the rate of colorectal cancer according to radiation dose to the large bowel and procarbazine dose among HL survivors., Design, Setting, and Participants: A nested case-control study examined 5-year HL survivors at 5 hospital centers in the Netherlands. Participants had been diagnosed with HL in 1964 to 2000, when they were 15 to 50 years of age, and were followed for a median of approximately 26 years. Survivors of HL who developed colorectal cancer and survivors who were selected as controls were individually matched on sex, age at HL diagnosis, and date of HL diagnosis. Data were analyzed from July 2021 to October 2022., Exposures: Mean radiation doses to the large bowel were estimated by reconstructing individual radiation therapy treatments on representative computed tomography data sets., Main Outcomes and Measures: Excess rate ratios (ERRs) were modeled to evaluate the excess risk associated with each 1-gray increase in radiation dose, and potential effect modification by procarbazine was explored., Results: The study population included 316 participants (mean [SD] age at HL diagnosis, 33.0 [9.8] years; 221 [69.9%] men), 78 of whom were HL survivors who developed colorectal cancer (cases) and 238 who did not (controls). The median (IQR) interval between HL and colorectal cancer was 25.7 (18.2-31.6) years. Increased colorectal cancer rates were seen for patients who received subdiaphragmatic radiation therapy (rate ratio [RR], 2.4; 95% CI, 1.4-4.1) and those who received more than 8.4 g/m2 procarbazine (RR, 2.5; 95% CI, 1.3-5.0). Overall, colorectal cancer rate increased linearly with mean radiation dose to the whole large bowel and dose to the affected bowel segment. The association between radiation dose and colorectal cancer rate became stronger with increasing procarbazine dose: the ERR per gray to the whole bowel was 3.5% (95% CI, 0.4%-12.6%) for patients who did not receive procarbazine, and increased 1.2-fold (95% CI, 1.1-1.3) for each 1-g/m2 increase in procarbazine dose., Conclusions and Relevance: This nested case-control study of 5-year HL survivors found a dose-response association between radiation therapy and colorectal cancer risk, and modification of this association by procarbazine. These findings may enable individualized colorectal cancer risk estimations, identification of high-risk survivors for subsequent screening, and optimization of treatment strategies.

Purpose: To systematically review all dosimetric studies investigating the impact of deep inspiration breath hold (DIBH) compared with free breathing (FB) in mediastinal lymphoma patients treated with proton therapy as compared to IMRT (intensity-modulated radiation therapy)-DIBH., Materials and Methods: We conducted a systematic review in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guideline using the PubMed database to identify studies of mediastinal lymphoma patients with dosimetric comparisons of proton-FB and/or proton-DIBH with IMRT-DIBH. Parameters included mean heart (MHD), lung (MLD), and breast (MBD) doses, among other parameters. Case reports were excluded. Absolute differences in mean doses > 1 Gy between comparators were considered to be clinically meaningful., Results: As of April 2021, eight studies fit these criteria (n = 8), with the following comparisons: proton-FB vs IMRT-DIBH (n = 5), proton-DIBH vs proton-FB (n = 5), and proton-DIBH vs IMRT-DIBH (n = 8). When comparing proton-FB with IMRT-DIBH in 5 studies, MHD was reduced with proton-FB in 2 studies, was similar (<1 Gy difference) in 2 studies, and increased in 1 study. On the other hand, MLD and MBD were reduced with proton-FB in 3 and 4 studies, respectively. When comparing proton-DIBH with proton-FB, MHD and MLD were reduced with proton DIBH in 4 and 3 studies, respectively, while MBD remained similar. Compared with IMRT-DIBH in 8 studies, proton-DIBH reduced the MHD in 7 studies and was similar in 1 study. Furthermore, MLD and MBD were reduced with proton-DIBH in 8 and 6 studies respectively. Integral dose was similar between proton-FB and proton-DIBH, and both were substantially lower than IMRT-DIBH., Conclusion: Accounting for heart, lung, breast, and integral dose, proton therapy (FB or DIBH) was superior to IMRT-DIBH. Proton-DIBH can lower dose to the lungs and heart even further compared with proton-FB, depending on disease location in the mediastinum, and organ-sparing and target coverage priorities., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Laila Konig reports personal fees from Accuray Inc. and Novocure GmbH outside the submitted work., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Objectives: Cone-beam computed tomography (CBCT) for radiotherapy treatment verification has increased in frequency; therefore, it is crucial to optimise image quality and radiation dose to patients. The aim of this study was to implement optimised CBCT protocols for the Varian TrueBeams for most tumour sites in adult patients., Methods: A combination of patient size-specific CBCT protocols from the literature and developed in-house was used. Scans taken before and after optimisation were compared by senior radiographers and physicists to evaluate how changes affected image quality and clinical usability for online image registration. The change in dose for each new CBCT protocol was compared to the Varian default. A clinical audit was performed following implementation to evaluate the changes in imaging dose for all patients receiving a CBCT during that period., Results: Ten CBCT protocols were introduced including head and neck and patient-size-specific thorax and pelvis/abdomen protocols. Scans from 102 patients with images before and after optimisation were assessed, none of the scans showed image quality changes compromising clinical usability and for some image quality was improved. Between November 2020 and June 2021, 1185 patients had CBCTs using the new protocols. The imaging dose was reduced for 52% of patients, remained the same for 37% and increased for 12%., Conclusions: This study showed that substantial dose reductions and image quality improvements can be achieved with simple changes in the default settings of the Varian TrueBeam CBCT without affecting the radiographers' confidence in online image registration., Advances in Knowledge: This study represents a comprehensive assessment and optimisation of CBCT protocols for most sites, validated on a large cohort of patients.

Deep inspiration breath-hold (DIBH) is an advanced radiotherapy technique that has been shown to have dosimetric benefits in the treatment of patients with mediastinal lymphoma. Whilst there is much published data on the use of DIBH in breast radiotherapy, reports on the use of the technique in mediastinal lymphoma patients remain limited. As the first NHS centre in the UK to implement DIBH in this pt group, we have evaluated our experience and success in using this technique over a 5 year period., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Crown Copyright © 2022 Published by Elsevier B.V. on behalf of European Society for Radiotherapy & Oncology.)

Deep inspiration breath-hold, butterfly volumetric modulated arc therapy and daily imaging techniques for mediastinal lymphoma patients have been introduced in a single department. Whilst introducing these techniques, there were many practical lessons to be learned across the patient pathway, from pre-treatment through to treatment delivery.Therapeutic radiographers were key members of the multi-disciplinary team implementing these techniques. This work reflects on the experience of introducing these advanced techniques for mediastinal lymphoma patients and the lessons learnt., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Crown Copyright © 2022 Published by Elsevier B.V. on behalf of European Society for Radiotherapy & Oncology.)

Purpose: In some patients with Hodgkin lymphoma (HL), proton beam therapy (PBT) may reduce the risk of radiation-related cardiovascular disease (CVD) and second cancers (SC) compared with photon radiation therapy (RT). Our aim was to identify patients who benefit the most from PBT in terms of predicted 30-year absolute mortality risks (AMR 30 ) from CVD and SC, taking into account individual background, chemotherapy, radiation, and smoking-related risks., Methods and Materials: Eighty patients with supradiaphragmatic HL treated with PBT between 2015 and 2019 were replanned using optimal photon RT. To identify patients predicted to derive the greatest benefit from PBT compared with photon RT, doses and AMR 30 from CVD and SC of the lung, breast, and esophagus were compared for all patients and across patient subgroups., Results: For patients with mediastinal disease below the origin of the left main coronary artery (n = 66; 82%), PBT reduced the mean dose to the heart, left ventricle, and heart valves by 1.0, 2.7, and 3.6 Gy, respectively. Based on U.S. mortality rates, PBT reduced CVD AMR 30 by 0.2%, from 5.9% to 5.7%. The benefit was larger if the mediastinal disease overlapped longitudinally with the heart by ≥40% (n = 23; 29%). PBT reduced the mean dose to the heart, left ventricle, and heart valves by 3.2, 5.6, and 5.1 Gy, respectively, and reduced CVD AMR 30 by 0.8%, from 7.0% to 6.2%. For patients with axillary disease (n = 25; 31%), PBT reduced the mean lung dose by 2.8 Gy and lung cancer AMR 30 by 0.6%, from 2.7% to 2.1%. Breast and esophageal doses were also lower with PBT, but the effects on AMR 30 were negligible. The effect of smoking on CVD and lung cancer AMR 30 was much larger than radiation and chemotherapy and the differences between radiation modalities., Conclusions: The predicted benefit of PBT is not universal and limited to certain categories of patients with lymphoma and lower mediastinal or axillary disease. Smoking cessation should be strongly encouraged in smokers who require thoracic RT., (Copyright © 2021 The Author(s). Published by Elsevier Inc. All rights reserved.)

Purpose: The contemporary management of early-stage Hodgkin lymphoma (ES-HL) involves balancing the risk of late adverse effects of radiotherapy against the increased risk of relapse if radiotherapy is omitted. This study provides information on the risk of radiation-related cardiovascular disease to help personalize the delivery of radiotherapy in ES-HL., Methods: We predicted 30-year absolute cardiovascular risk from chemotherapy and involved field radiotherapy in patients who were positron emission tomography (PET)-negative following three cycles of doxorubicin, bleomycin, vinblastine, and dacarbazine chemotherapy within a UK randomized trial of PET-directed therapy for ES-HL. Cardiac and carotid radiation doses and chemotherapy exposure were combined with established dose-response relationships and population-based mortality and incidence rates., Results: Average mean heart dose was 4.0 Gy (range 0.1-24.0 Gy) and average bilateral common carotid artery dose was 21.5 Gy (range 0.6-38.1 Gy), based on individualized cardiovascular dosimetry for 144 PET-negative patients receiving involved field radiotherapy. The average predicted 30-year radiation-related absolute excess overall cardiovascular mortality was 0.56% (range 0.01%-6.79%; < 0.5% in 67% of patients and > 1% in 15%), whereas average predicted 30-year excess incidence was 6.24% (range 0.31%-31.09%; < 5% in 58% of patients and > 10% in 24%). For cardiac disease, the average predicted 30-year radiation-related absolute excess mortality was 0.42% (0.79% with mediastinal involvement and 0.05% without) and for stroke, it was 0.14%., Conclusion: Predicted excess cardiovascular risk is small for most patients, so radiotherapy may provide net benefit. However, for a minority of patients receiving high doses of radiation to cardiovascular structures, it may be preferable to consider advanced radiotherapy techniques to reduce doses or to omit radiotherapy and accept the increased relapse risk. Individual assessment of cardiovascular and other risks before treatment would allow personalized decision making about radiotherapy in ES-HL., Competing Interests: Johanna RamrothEmployment: Gilead Sciences (I)Stock and Other Ownership Interests: Gilead Sciences Laura Clifton-HadleyResearch Funding: Various pharmaceutical companies Peter J. HoskinResearch Funding: Varian Medical Systems, Astellas Pharma, Bayer, Roche, Pfizer, Elekta John RadfordStock and Other Ownership Interests: AstraZeneca, ADC TherapeuticsHonoraria: Takeda, ADC TherapeuticsConsulting or Advisory Role: Takeda, Seattle Genetics, NovartisSpeakers' Bureau: Takeda, Seattle Genetics, NovartisResearch Funding: TakedaTravel, Accommodations, Expenses: Takeda, ADC Therapeutics Tim IllidgeConsulting or Advisory Role: Takeda, Nordic NanovectorSpeakers' Bureau: Takeda, Bristol Myers Squibb, RocheResearch Funding: AstraZeneca/MedImmune, MSD OncologyTravel, Accommodations, Expenses: RocheNo other potential conflicts of interest were reported.

Background and Purpose: Breast cancer radiotherapy can increase the risk of subsequent primary oesophageal cancer, with risk increasing according to oesophagus radiation dose. We describe oesophagus exposure from modern breast cancer regimens and discuss the risks of oesophageal cancer for women irradiated recently., Materials and Methods: A systematic review was undertaken of oesophagus doses from breast cancer radiotherapy regimens published during 2010-2020. Mean and maximum oesophagus doses were described for different target regions irradiated and different radiotherapy techniques., Results: In 112 published regimens from 18 countries, oesophagus doses varied with target region. For partial breast irradiation, average mean oesophagus dose was 0.2 Gy (range 0.1-0.4) in four regimens; maximum dose was not reported. For breast or chest wall radiotherapy, average oesophagus doses were mean 1.8 Gy (range 0.1-10.4) in 24 regimens and maximum 6.7 Gy (range 0.4-14.3) in seven regimens. For radiotherapy including a nodal region, average oesophagus doses were higher: mean 11.4 Gy (range <0.1-29.3) in 61 regimens and maximum 34.4 Gy (range 3.4-51.3) in 55 regimens. Average mean oesophagus doses were >10 Gy for intensity modulated nodal radiotherapy, but lower for other node techniques., Conclusions: Mean oesophagus doses from partial breast and breast/chest wall regimens were usually less than 2 Gy, hence radiation-risks will be very small. However, for radiotherapy including lymph nodes, average mean oesophagus dose of 11.4 Gy may nearly double oesophageal cancer risk. Consideration of oesophageal exposure during nodal radiotherapy planning may reduce the risks of radiation-related oesophageal cancer for women irradiated today., Competing Interests: Conflicts of interest None., (Copyright © 2021 The Authors. Published by Elsevier B.V. All rights reserved.)

In the last decades, the substantial technical progress in radiation oncology offered the opportunity for more accurate planning and delivery of treatment. At the same time, the evolution of systemic treatment and the advent of modern diagnostic tools allowed for more accurate staging and consequently a safe reduction of radiotherapy (RT) target volumes and RT doses in the treatment of lymphomas. As a result, incidental irradiation of organs at risk was reduced, with a consequent reduction of severe late toxicity in long-term lymphoma survivors. Nevertheless, these innovations warrant that professionals pay attention to concurrently ensure precise planning and dose delivery to the target volume and safe sparing of the organs at risk. In particular, target and organ motion should be carefully managed in order to prevent any compromise of treatment efficacy. Several aspects should be taken into account during the treatment pathway to minimise uncertainties and to apply a valuable motion management strategy, when needed. These include: reliable image registration between diagnostic and planning radiologic exams to facilitate the contouring process, image guidance to limit positioning uncertainties and to ensure the accuracy of dose delivery and management of lung motion through procedures of respiratory gating and breath control. In this review, we will cover the current clinical approaches to minimise these uncertainties in patients treated with modern RT techniques, with a particular focus on mediastinal lymphoma. In addition, since uncertainties have a different impact on the dose deposition of protons compared to conventional x-rays, the role of motion management and position verification in proton beam therapy (PBT) will be discussed in a separate section.

Background and Purpose: Radiation-related heart disease (RRHD) can occur many decades after thoracic radiotherapy for Hodgkin lymphoma (HL) or childhood cancer (CC). To quantify the likely risk of RRHD for patients treated today, dose-response relationships derived from patients treated in previous decades are used. Publications presenting these dose-response relationships usually include estimates of uncertainties in the risks but ignore the effect of uncertainties in the reconstructed cardiac doses., Materials/methods: We assessed the systematic and random uncertainties in the reconstructed doses for published dose-response relationships for RRHD risk in survivors of HL or CC. Using the same reconstruction methods as were used in the original publications, we reconstructed mean heart doses and, wherever possible, mean left-ventricular doses for an independent case-series of test patients. These patients had known, CT-based, cardiac doses which were compared with the reconstructed doses to estimate the magnitude of the uncertainties and their effect on the dose-response relationships., Results: For all five reconstruction methods the relationship between reconstructed and CT-based doses was linear. For all but the simplest reconstruction method, the dose uncertainties were moderate, the effect of the systematic uncertainty on the dose-response relationships was less than 10%, and the effects of random uncertainty were small except at the highest doses., Conclusions: These results increase confidence in the published dose-response relationships for the risk of RRHD in HL and CC survivors. This may encourage doctors to use these dose-response relationships when estimating individualised risks for patients-an important aspect of personalising radiotherapy treatments today., (Copyright © 2020 The Author(s). Published by Elsevier B.V. All rights reserved.)

Hodgkin lymphoma (HL) survivors treated with radiotherapy and/or chemotherapy are known to have increased risks of heart failure (HF), but a radiation dose-response relationship has not previously been derived. A case-control study, nested in a cohort of 2617 five-year survivors of HL diagnosed before age 51 years during 1965 to 1995, was conducted. Cases (n = 91) had moderate or severe HF as their first cardiovascular diagnosis. Controls (n = 278) were matched to cases on age, sex, and HL diagnosis date. Treatment and follow-up information were abstracted from medical records. Mean heart doses and mean left ventricular doses (MLVD) were estimated by reconstruction of individual treatments on representative computed tomography datasets. Average MLVD was 16.7 Gy for cases and 13.8 Gy for controls ( P difference = .003). HF rate increased with MLVD: relative to 0 Gy, HF rates following MVLD of 1-15, 16-20, 21-25, and ≥26 Gy were 1.27, 1.65, 3.84, and 4.39, respectively ( P trend < .001). Anthracycline-containing chemotherapy increased HF rate by a factor of 2.83 (95% CI: 1.43-5.59), and there was no significant interaction with MLVD ( P interaction = .09). Twenty-five-year cumulative risks of HF following MLVDs of 0-15 Gy, 16-20 Gy, and ≥21 Gy were 4.4%, 6.2%, and 13.3%, respectively, in patients treated without anthracycline-containing chemotherapy, and 11.2%, 15.9%, and 32.9%, respectively, in patients treated with anthracyclines. We have derived quantitative estimates of HF risk in patients treated for HL following radiotherapy with or without anthracycline-containing chemotherapy. Our results enable estimation of HF risk for patients before treatment, during radiotherapy planning, and during follow-up., (© 2017 by The American Society of Hematology.)