Impact of mediastinal tumor burden and lymphatic spread in locally advanced non-small-cell lung cancer: A secondary analysis of the multicenter randomized PET-Plan trial.

PURPOSE: The aim of this secondary analysis of the prospective randomized phase 2 PET-Plan trial (ARO-2009-09; NCT00697333) was to evaluate the impact of mediastinal tumor burden and lymphatic spread in patients with locally advanced non-small-cell lung cancer (NSCLC). METHODS: All patients treated per protocol (n = 172) were included. Patients received isotoxically dose-escalated chemoradiotherapy up to a total dose of 60-74 Gy in 30-37 fractions, aiming as high as possible while adhering to normal tissue constraints. Radiation treatment (RT) planning was based on an 18F-FDG PET/CT targeting all lymph node (LN) stations containing CT positive LNs (i.e. short axis diameter > 10 mm), even if PET-negative (arm A) or targeting only LN stations containing PET-positive nodes (arm B). LN stations were classified into echelon 1 (ipsilateral hilum), 2 (ipsilateral station 4 and 7), and 3 (rest of the mediastinum, contralateral hilum). The endpoints were overall survival (OS), progression-free survival (PFS), and freedom from local progression (FFLP). RESULTS: The median follow-up time (95 % confidence interval [CI]) was 41.1 (33.8 - 50.4) months. Patients with a high absolute number of PET-positive LN stations had worse OS (hazard ratio [HR] = 1.09; 95 % CI 0.99 - 1.18; p = 0.05) and PFS (HR = 1.12; 95 % CI 1.04 - 1.20; p = 0.003), irrespective of treatment arm allocation. The prescribed RT dose to the LNs did not correlate with any of the endpoints when considering all patients. However, in patients in arm B (i.e., PET-based selective nodal irradiation), prescribed RT dose to each LN station correlated significantly with FFLP (HR=0.45; 95 % CI 0.24-0.85; p = 0.01). Furthermore, patients with involvement of echelon 3 LN stations had worse PFS (HR = 2.22; 95 % CI 1.16-4.28; p = 0.02), also irrespective of allocation. CONCLUSION: Mediastinal tumor burden and lymphatic involvement patterns influence outcome in patients treated with definitive chemoradiotherapy for locally advanced NSCLC. Higher dose to LNs did not improve OS, but did improve FFLP in patients treated with PET-based dose-escalated RT.

AB061. Oligodendroglioma in a 10-year-old girl with history of mediastinal mass and radiotherapy: a case report.

BACKGROUND: Oligodendroglioma is a part of diffusely infiltrating gliomas with poorly understood pathological aspect often manifesting histologic overlap among other intracranial tumors, though it only consisted 5% in total. Its occurrences among pediatric is a rare finding, constituted <1% of total brain tumors in the population, but with molecularly distinct properties to its adult version. Metachronous pediatric oligodendroglioma plus mediastinal mass is even more uncommon, as history of double primary tumor serves as a groundbreaking point in understanding individual pathology. This study reports a rare case of pediatric oligodendroglioma with history of mediastinal mass. CASE DESCRIPTION: This study reports a rare case of pediatric oligodendroglioma with history of mediastinal mass. A 10-year-old female presented to our emergency department with altered consciousness level in the past couple of weeks, and progressively worsening for 3 days. Moreover, she withstands a yearlong headache, plus continuously worsens weakness on the left side of the extremities for 6 months, right sided weakness of face and visual disturbances appeared at least 4 months prior presentation; no seizures were observed. History of pericardial effusion due to mediastinal mass was also recorded in 3 years before with history of pericardial tapping, with cytology showed malignant lesion; with history of 5 times radiotherapy cycle for treatment purpose, and patient discontinued therapy due to loss of follow up. Non-contrast head computed tomography (CT)-scan observed a mix-density lesion on the frontotemporoparietal region with calcification. On magnetic resonance imaging (MRI), mix-intensity lesion was found suggesting a glioma lesion. Patient underwent removal of tumor, with gross tumor removal was achieved. Histopathology result of oligodendroglioma was found. CONCLUSIONS: The management of pediatric oligodendroglioma in our case involves wide range of discipline to elaborate its interaction with prior metachronous mediastinal mass, and findings of double primary tumor should raise any suspicion for any tumor-related genetic mutations.

Radiation exposure of the glandular mammary tissue in women patients with mediastinal Hodgkin lymphoma treated with protons.

PURPOSE: Secondary breast cancer is a frequent late adverse event of mediastinal Hodgkin lymphoma radiotherapy. Secondary breast cancers overwhelmingly correspond to ductal carcinoma and develop from the glandular mammary tissue. In addition, during childhood, radiation overexposure of the glandular tissue may lead to a late breast hypotrophy at adult age. The aim of this study was to evaluate the radiation exposure to the glandular tissue in patients treated for mediastinal Hodgkin lymphoma with intensity-modulated proton therapy, in order to evaluate the potential dosimetric usefulness of its delineation for breast sparing. MATERIALS AND METHODS: Sixteen consecutive intermediate-risk mediastinal female patients with Hodgkin lymphoma treated with consolidation radiation with deep inspiration breath hold intensity-modulated proton therapy to the total dose of 30Gy were included. Breasts were delineated according to the European Society for Radiotherapy and Oncology guidelines for treatment optimization ("clinical organ at risk"). The glandular tissue ("glandular organ at risk") was retrospectively contoured on the initial simulation CT scans based on Hounsfield unit (HU) values, using a range between -80HU and 500HU. RESULTS: The mean and maximum doses delivered to the glandular organ at risk were significantly lower than the mean and maximum doses delivered to the clinical organ at risk, but were statistically correlated. Glandular organ at risk volumes were significantly smaller. CONCLUSION: Optimizing the treatment plans on the clinical breast contours will systematically lead to overestimation of the dose received to the glandular tissue and, consequently, to an indistinct and involuntary improved glandular tissue sparing. As such, our findings do not support the consideration of the glandular tissue as an additional organ at risk when planning intensity-modulated proton therapy for mediastinal Hodgkin lymphoma in female patients.

First Experience of Radionuclide Therapy With 177Lu-FAPI-2286 in a Patient With Metastatic Mediastinal Sarcoma.

ABSTRACT: Fibroblast activation protein (FAP) is a new promising molecular target for theragnostic approach. FAP inhibitors (FAPIs) labeled with 177Lu could be potentially a therapeutic radiopharmaceutical. Here, we presented the experience of 4 cycles of 177Lu-FAPI in a 67-year-old man with an unresectable mediastinal sarcoma.

Evidence for external beam radiotherapy in mediastinal Hodgkin and non-Hodgkin lymphoma - systematic review.

INTRODUCTION AND OBJECTIVE: Proton beam therapy (PBT) provides the opportunity for a more localized delivery of high energy protons and may reduce the damage to healthy tissues and vital organs. The aim of this review was to assess the effects of proton therapy for patients diagnosed with Hodgkin or non-Hodgkin lymphoma treated with mediastinal irradiation. REVIEW METHODS: A systematic search of EMBASE, MEDLINE via OVID and Cochrane Library was conducted in May 2022 according to PRISMA guidelines to identify relevant data on the efficacy and toxicity of proton beam therapy for patients diagnosed with Hodgkin or non-Hodgkin lymphoma. BRIEF DESCRIPTION OF THE STATE OF KNOWLEDGE: Of 566 screened abstracts (430 after de-duplication) 11 studies with a total of 529 patients were included. All studies were case series published between 2011-2021. Median range of follow-up time was 15-63.6 months. The overall survival (OS) for 2 years varied from 91% - 98% for 5 of the included studies. Three of the included studies had favourable outcomes with 2-year progression-free survival (PFS) ranging from 73% - 94%. Skin reaction, oesophagitis and fatigue were found to be the most common grade 1 and grade 2 toxicities. No acute or late grade 4 and higher toxicities/adverse events were observed. SUMMARY: There are data indicating that PBT may to be an effective treatment against mediastinal Hodgkin and non-Hodgkin lymphoma. Because all the studies were case series, the authors of this review have little confidence in the evidence. There remains a need for well-designed randomized controlled trials to inform about the optimal approach to proton irradiation in HL and NHL.

Pencil beam scanning proton therapy for mediastinal lymphomas in deep inspiration breath-hold: a retrospective assessment of plan robustness.

PURPOSE/BACKGROUND: The aim of this study was to evaluate pencil beam scanning (PBS) proton therapy (PT) in deep inspiration breath-hold (DIBH) for mediastinal lymphoma patients, by retrospectively evaluating plan robustness to the clinical target volume (CTV) and organs at risk (OARs) on repeated CT images acquired throughout treatment.  Methods: Sixteen mediastinal lymphoma patients treated with PBS-PT in DIBH were included. Treatment plans (TPs) were robustly optimized on the CTV (7 mm/4.5%). Repeated verification CTs (vCT) were acquired during the treatment course, resulting in 52 images for the entire patient cohort. The CTV and OARs were transferred from the planning CT to the vCTs with deformable image registration and the TPs were recalculated on the vCTs. Target coverage and OAR doses at the vCTs were compared to the nominal plan. Deviation in lung volume was also calculated. RESULTS: The TPs demonstrated high robust target coverage throughout treatment with D98%,CTV deviations within 2% for 14 patients and above the desired requirement of 95% for 49/52 vCTs. However, two patients did not achieve a robust dose to CTV due to poor DIBH reproducibility, with D98%,CTV at 78 and 93% respectively, and replanning was performed for one patient. Adequate OAR sparing was achieved for all patients. Total lung volume variation was below 10% for 39/52 vCTs. CONCLUSION: PBS PT in DIBH is generally a robust technique for treatment of mediastinal lymphomas. However, closely monitoring the DIBH-reproducibility during treatment is important to avoid underdosing CTV and achieve sufficient dose-sparing of the OARs.

Evaluation of a New Method for CyberKnife Treatment for Central Lung and Mediastinal Tumors by Tracheobronchial Tracking.

BACKGROUND: CyberKnife treatment for central lung tumors and mediastinal tumors can be difficult to perform with marker less. PURPOSE: We aimed to evaluate a novel tracheobronchial-based method (ie, tracheobronchial tracking) for the purpose of minimally invasive CyberKnife treatment for central lung and mediastinal tumors. METHODS: Five verification plans were created using an in-house phantom. Each plan included five irradiation sessions. The reference plan irradiated and tracked the simulated tumor (using the target tracking volume, TTV). Trachea plans tracked the simulated tracheo-bronchus and irradiated the simulated tumor and included two types of subplans: correlated plans in which the displacement of the simulated tracheobronchial and the simulated tumor were correlated, and non-correlated plans in which these factors were not correlated. Moreover, 15 mm and 25 mm TTVs were evaluated for each plan. The sin waveform and the patient's respiratory waveform were prepared as the respiratory model. Evaluations were performed by calculating the dose difference between the radiophotoluminescent glass dosimeter (RPLD)-generated mean dose values (generated by the treatment planning system, TPS) and the actual absorbed RPLD dose. Statistical analyses were performed to evaluate findings for each plan. Correlation and prediction errors were calculated for each axis of each plan using log files to evaluate tracking accuracy. RESULTS: Dose differences were statistically significant only in comparisons with the non-correlated plan. When evaluated using the sin waveform, the mean values for correlation and prediction errors in each axis and for all plans were less than 0.6 mm and 0.1 mm, respectively. In the same manner, they were less than 1.1 mm and 0.2 mm when evaluated using the patient's respiratory waveform. CONCLUSION: Our newly-developed tracheobronchial tracking method would be useful in facilitating minimally invasive CyberKnife treatment in certain cases of central lung and mediastinal tumors.

Voluntary deep inspiration breath-hold with volumetric modulated arc therapy in pediatric patients with mediastinal Hodgkin lymphoma.

Background: Deep inspiration breath-hold (DIBH) has been established to decrease normal tissue radiation dose in breast cancer. Methods: Forty-nine patients had two CT scans during DIBH or free breathing. Chest-wall position, setup verification and breath-hold monitoring were performed. Cone-beam CT and a surface image system were used for verification. Results: A total of 1617 breath-holds were analyzed in 401 fractions. The mean time bit was 6.01 min. The mean breaths-holds per fraction was 4.96. The median for intra-breath hold variability was 3 mm. No patient stopped treatment for intolerance. Clinical target volume margins were calculated as 0.36, 0.36 and 0.32 for the three translational positions. The mean saved volume was 26.3%. Conclusion: Voluntary DIBH is feasible, tolerable and easy to apply for children with Hodgkin lymphoma involving the mediastinum.

Deep inspiration breath-hold (DIBH) is a radiotherapy maneuver to decrease the exposure of normal tissues during the radiation of the target organ. It was developed for the treatment of breast cancer, both intact breast and chest wall, after mastectomy. For mediastinal Hodgkin lymphoma, especially in children and adolescents, DIBH will benefit in decreasing the radiation dose to the lungs and heart in this category of patients who still have normal growing tissues. We treated 49 pediatric and adolescent patients with DIBH and precise radiotherapy (volumetric modulated arc therapy) to augment the benefit of lowering the dose to normal tissues. All patients were trained and coached to breath-hold for more than 20 s. No patient stopped treatment due to poor tolerance or discomfort. Only one breath-hold was required for CT simulation in all populations (100%). The mean number of breath-holds per treatment fraction was 5.1 ± 1.8. The mean treatment time was 6 ± 1.8 min. DIBH is feasible, tolerable and easy to apply for children and adolescents with Hodgkin lymphoma involving the mediastinum. A considerable dose volume could be saved, hence decreasing the rate of side effects.

Radiotherapy for mediastinal lymphoma in breath hold using surface monitoring and nasal high flow oxygen: Clinical experiences and breath hold stability.

PURPOSE: In this study we describe the clinical introduction and evaluation of radiotherapy in mediastinal lymphoma in breath hold using surface monitoring combined with nasal high flow therapy (NHFT) to prolong breath hold duration. MATERIALS AND METHODS: 11 Patients with mediastinal lymphoma were evaluated. 6 Patients received NHFT, 5 patients were treated in breath hold without NHFT. Breath hold stability as measured by a surface scanning system was evaluated, as well as internal movement based on cone beam computed tomography (CBCT) before and after treatment. Based on internal movement, margins were determined. In a parallel planning study we compared free breathing plans with breath hold plans using the determined margins. RESULTS: Average inter breath hold stability was 0.6 mm for NHFT treatments, and 0.5 mm for non-NHFT treatments (p > 0.1). Intra breath hold stability was 0.8 vs. 0.6 mm (p > 0.1) on average. Using NHFT, average breath hold duration increased from 34 s to 60 s (p < 0.01). Residual CTV motion derived from CBCTs before and after each fraction was 2.0 mm for NHFT vs 2.2 mm for non-NHFT (p > 0.1). Combined with inter-fraction motion, a uniform mediastinal margin of 5 mm appears to be sufficient. In breath hold, mean lung dose is reduced by 2.6 Gy (p < 0.001), while mean heart dose is reduced by 2.0 Gy (p < 0.001). CONCLUSION: Treatment of mediastinal lymphoma in breath hold is feasible and safe. The addition of NHFT approximately increases breath hold durations with a factor two while stability is maintained. By reducing breathing motion, margins can be decreased to 5 mm. A considerable dose reduction in heart, lungs, esophagus, and breasts can be achieved with this method.

Predicted cardiac and second cancer risks for patients undergoing VMAT for mediastinal Hodgkin lymphoma.

BACKGROUND AND PURPOSE: To predict treatment-related cardiovascular disease (CVD) and second cancer 30-year absolute mortality risks (AMR30) 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 AMR30 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 AMR30 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 AMR30 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.

Systematic review for deep inspiration breath hold in proton therapy for mediastinal lymphoma: A PTCOG Lymphoma Subcommittee report and recommendations.

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.

Cardiotoxicity model-based patient selection for Hodgkin lymphoma proton therapy.

INTRODUCTION: Hodgkin lymphoma (HL) is a highly curable hematological malignancy. Consolidation radiation therapy techniques have made significant progresses to improve organ-at-risk sparing in order to reduce late radiation-induced toxicity. Recent technical breakthroughs notably include intensity modulated proton therapy (IMPT), which has demonstrated a major dosimetric benefit at the cardiac level for mediastinal HL patients. However, its implementation in clinical practice is still challenging, notably due to the limited access to proton therapy facilities. In this context, the purpose of this study was to estimate the benefit of IMPT for HL proton therapy for diverse cardiac adverse events and to propose a general frame for mediastinal HL patient selection strategy for IMPT based on cardiotoxicity reduction, patient clinical factors, and IMPT treatment availability. MATERIAL AND METHODS: This retrospective dosimetric study included 30 mediastinal HL patients treated with VMAT. IMPT plans were generated on the initial simulation scans. Dose to the heart, to the left ventricle and to the valves were retrieved to calculate the relative risk (RR) of ischemic heart disease (IHD), congestive heart failure (CHF) and valvular disease (VD). Composite relative risk reduction (cRRR) of late cardiotoxicity, between VMAT and IMPT, were calculated as the weighted mean of relative risk reduction for IHD, CHF and VD, calculated across a wide range of cardiovascular risk factor combinations. The proportion of mediastinal HL patients who could benefit from IMPT was estimated in European countries, based on the country population and on the number of active gantries, to propose country-specific cRRR thresholds for patient selection. RESULTS: Compared with VMAT, IMPT significantly reduced average mean doses to the heart (2.36 Gy vs 0.99 Gy, p < 0.01), to the left ventricle (0.67 Gy vs 0.03, p < 0.01) and to the valves (1.29 Gy vs. 0.06, p < 0.01). For a HL patient without cardiovascular risk factor other than anthracycline-based chemotherapy, the relative risks of late cardiovascular complications were significantly lower after IMPT compared with VMAT for ischemic heart disease (1.07 vs 1.17, p < 0.01), for congestive heart failure (2.84 vs. 3.00, p < 0.01), and for valvular disease (1.01 vs. 1.06, p < 0.01). The median cRRR of cardiovascular adverse events with IMPT was 4.8%, ranging between 0.1% and 30.5%, depending on the extent of radiation fields and on the considered cardiovascular risk factors. The estimated proportion of HL patients currently treatable with IMPT in European countries with proton therapy facilities ranged between 8.0% and 100% depending on the country, corresponding to cRRR thresholds ranging from 24.0% to 0.0%. CONCLUSION: While a statistically significant clinical benefit is theoretically expected for ischemic heart disease, cardiac heart failure and valvular disease for mediastinal HL patients with IMPT, the overall cardiotoxicity risk reduction is notable only for a minority of patients. In the context of limited IMPT availability, this study proposed a general model-based selection approach for mediastinal HL patient based on calculated cardiotoxicity reduction, taking into consideration patient clinical characteristics and IMPT facility availability.

Dramatic response to local radiotherapy in a refractory metastatic mediastinal yolk sac tumor patient harboring a germline BRCA2 frameshift mutation: a case report.

Mediastinal yolk sac tumors (YSTs) are highly aggressive germ cell tumors with an extremely poor prognosis. Radiotherapy plays an important role in the treatment of mediastinal YSTs. To maximize benefit from radiotherapy in patients with mediastinal YSTs, exploring functionally relevant biomarkers is essential. Previous studies have demonstrated that mutations in DNA-damage repair (DDR) genes, including BRCA1/2, potentially enhance sensitivity to radiotherapy in solid tumors. However, DDR-gene mutations, as possible predictive biomarkers for radiotherapy in primary mediastinal YSTs, have not yet been reported. Herein, we report a 29-year-old male patient with a refractory metastatic primary YST involving a germline frameshift mutation in the BRCA2 gene (NM_000059.3: exon11: c.4563_4564delAT: L1522fs). During treatment alternation, the patient was found to respond poorly to chemotherapy with or without an immune checkpoint inhibitor but well to radiotherapy. Finally, the patient achieved approximately 17 months of overall survival. To the best of our knowledge, this case report is the first to describe a remarkable response to local radiotherapy in a patient with a refractory metastatic mediastinal YST involving a DDR-gene mutation (germline BRCA2 frameshift variation). This case report provides insightful clues for precision radiotherapy in clinical practice.

Consolidative active scanning proton therapy for mediastinal lymphoma: selection criteria, treatment implementation and clinical feasibility.

AIMS: Proton therapy (PT) represents an advanced form of radiotherapy with unique physical properties which could be of great advantage in reducing long-term radiation morbidity for cancer survivors. Here, we aim to describe the whole process leading to the clinical implementation of consolidative active scanning proton therapy treatment (PT) for mediastinal lymphoma. METHODS: The process included administrative, technical and clinical issues. Authorization of PT is required in all cases as mediastinal lymphoma is currently not on the list of diseases reimbursable by the Italian National Health Service. Technically, active scanning PT treatment for mediastinal lymphoma is complex, due to the interaction between actively scanned protons and the usually irregular and large volumes to be irradiated, the nearby healthy tissues and the target motion caused by breathing. A road map to implement the technical procedures was prepared. The clinical selection of patients was of utmost importance and took into account both patient and tumor characteristics. RESULTS: The first mediastinal lymphoma was treated at our PT center in 2018, four years after the start of the clinical activities. The treatment technique implementation included mechanical deep inspiration breath-hold simulation computed tomography (CT), clinical target volume (CTV)-based multifield optimization planning and plan robustness analysis. The ultimate authorization rate was 93%. In 4 cases a proton-photon plan comparison was required. Between May 2018 and February, 2021, 14 patients were treated with consolidative PT. The main clinical reasons for choosing PT over photons was a bulky disease in 8 patients (57%), patient's age in 11 patients (78%) and the proximity of the lymphoma to cardiac structures in 10 patients (71%). With a median follow-up of 15 months (range, 1-33 months) all patients but one (out-of-field relapse) are without evidence of disease, all are alive and no late toxicities were observed during the follow-up period. CONCLUSIONS: The clinical implementation of consolidative active scanning PT for mediastinal lymphoma required specific technical procedures and a prolonged experience with PT treatments. An accurate selection of patients for which PT could be of advantage in comparison with photons is mandatory.

Technical challenges in the treatment of mediastinal lymphomas by proton pencil beam scanning and deep inspiration breath-hold.

PURPOSE: To comprehensively describe the treatment of mediastinal lymphoma by pencil beam scanning (PBS) proton therapy. METHODS: Fourteen patients underwent PBS proton treatment in a supine position in deep inspiration breath-hold (DIBH). Three DIBH computed tomography (CT) scans were acquired for each patient to delineate the Internal Target Volume (ITV). Intensity-modulated proton therapy (IMPT) was planned by min-max robust optimization on the ITV, with a 6 mm setup and 3.5% range uncertainties. Robustness analysis was performed and dose coverage was visually inspected on the corresponding voxel-wise minimum map. Layer repainting was set equal to 5 to compensate for cardiac motion. Intra-fraction reproducibility during treatment was assessed by repeated daily DIBH X-ray imaging. Finally, an additional CT was acquired at half treatment to estimate the impact of inter-fraction dosimetric reproducibility. RESULTS: IMPT guaranteed robust mediastinal target coverage and organs-at-risk sparing. However, visual voxel-wise robustness evaluation showed that in five patients a second optimization with focused objectives in the cost-function was necessary to achieve a robust coverage of the target regions at the interface between lungs and soft tissue. In six patients, repainting was not used due to excessive treatment time length and poor patient compliance. Intra-fraction average reproducibility was within 1 mm/1degree. On repeated CT scans, inter-fraction setup errors and/or anatomical changes showed minimal dosimetric differences in CTV coverage. CONCLUSION: IMPT in DIBH is effective and reproducible to treat mediastinal lymphomas. Caution is recommended to guarantee robust dose delivery to high-risk regions at the interface between lungs and soft tissue.