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Primary adenoid cystic carcinoma of the trachea (ACC-T) is an extremely rare cancer of the central bronchial system. It is usually associated with an excellent prognosis. Surgery is the standard treatment for resectable tumors, while radiation therapy is used for unresectable tumors or medically inoperable patients. Radiation therapy can be delivered with photons, protons, or carbon ion therapy. In this report, we review a case of unresectable ACC-T in a middle-aged female patient who was treated with radiation therapy and review the potential benefits of the different types of radiation therapy.

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Purpose When treating esophageal cancer with radiation therapy, it is critical to limit the dose to surrounding structures, such as the lung and/or heart, as much as possible. Proton radiation therapy allows a reduced radiation dose to both the heart and lungs, potentially reducing the risk of cardiopulmonary toxicity. Here, we report disease control, survival, and toxicity outcomes among patients with esophageal cancer treated with proton radiation therapy and concurrent chemotherapy (chemoradiation therapy; CRT) with or without surgery. Materials and Methods We enrolled 17 patients with thoracic esophageal carcinoma on a prospective registry between 2010 and 2021. Patients received proton therapy to a median dose of 50.4-GyRBE (range, 50.4–64.8) in 1.8-Gy fractions.Acute and late toxicities were graded per the Common Terminology Criteria for Adverse Events, version 4.0 (US National Cancer Institute, Bethesda, Maryland). In addition, disease control, patterns of failure, and survival outcomes were collected. Results Nine patients received preoperative CRT, and 8 received definitive CRT. Overall, 88% of patients had adenocarcinoma, and 12% had squamous cell carcinoma. With a median follow-up of 2.1 years (range, 0.5–9.4), the 3-year local progression-free, disease-free, and overall survival rates were 85%, 66%, and 55%, respectively. Two patients (1 with adenocarcinoma and 1 with squamous cell carcinoma) recurred at the primary site after refusing surgery after a complete clinical response to CRT. The most common acute nonhematologic and hematologic toxicities, respectively, were grades 1 to 3 esophagitis and grades 1 to 4 leukopenia, both affecting 82% of patients. No acute cardiopulmonary toxicities were observed in the absence of surgical resection. Reagarding surgical complications, 3 postoperative cardiopulmonary complications occurred as follows: 1 grade 1 pleural effusion, 1 grade 3 pleural effusion, and 1 grade 2 anastomotic leak. Two severe late CRT toxicities occurred: 1 grade 5 tracheoesophageal fistula and 1 grade 3 esophageal stenosis requiring a feeding tube. Conclusion Proton radiation therapy is a safe, effective treatment for esophageal cancer with increasing evidence supporting its role in reducing cardiopulmonary toxicity.

Children’s Oncology Group (COG) trial AHOD0431 reduced systemic therapy and used response-adapted involved-field radiotherapy (IFRT) in early-stage pediatric classic Hodgkin lymphoma. We investigated the impact of positron emission tomographic response after 1 cycle (PET1) and on IFRT outcomes and pattern of relapse. Patients in AHOD0431 underwent PET1 response assessment after AVPC (doxorubicin, vincristine, prednisone, and cyclophosphamide). “Rapid early responders” (RERs) had a negative PET1 (PET1−); “slow early responders” (SERs) had a positive PET1 (PET1+). Patients with a partial response by computed tomographic and functional imaging after 3 chemotherapy cycles received 21-Gy IFRT, whereas complete responders had no IFRT. Progression-free survival (PFS) was evaluated for RERs and SERs treated with or without IFRT. Recurrence sites were initial, new, or both. Relapses involving initial sites were characterized as “within the PET1+ site” or “initially involved but outside the PET1+ site.” Median follow-up was 118 months. The 10-year PFS rate among RERs was 96.6% with IFRT and 84.1% without IFRT (P = .10), whereas SERs were 80.9% with IFRT and 64.0% without IFRT (P = .03). Among 90 RERs who did not receive IFRT, all 14 relapses included an initial site. Among 45 SERs receiving no IFRT, 14 of 16 relapses were in the initial site (9 PET1+ site only). Among 58 patients receiving IFRT, 5 of 10 relapses were in the PET1+ site. After 3 cycles of AVPC alone, RERs showed favorable results. Conversely, SERs had unfavorable outcomes with AVPC alone, although they improved with 21-Gy IFRT. RT remains an important component of treatment for SERs. This trial was registered at www.clinicaltrials.gov as #NCT00302003.

Yttrium-90 ibritumomab tiuxetan [(90)Y-IT] is a CD20-targeted radio-immuno conjugate. Clinical trials of (90)Y-IT as a first-line stand-alone treatment in follicular lymphoma (FL) and/or marginal zone lymphoma (MZL) showed high efficacy. However, long-term survival outcomes and toxicities are not well-defined.We report a retrospective single-institution, multi-center study of (90)Y-IT in previously untreated low grade (LG)-FL and MZL at Mayo Clinic Cancer Center between January 2000 and October 2019. We selected patients with LG-FL and MZL who received standard-dose (90)Y-IT as a single agent in the first line setting.The cohort (n = 51) consists of previously untreated LG-FL (n = 41) or MZL (n = 10). Median follow-up was 5.3 years (95% CI; 4.2, 6.2). Overall response rate (ORR) was 100% with complete response rate (CR) of 94%. Continuous CR was observed in 59% patients who had more than 2 years of follow-up. Long-term CR (7 years) was seen in 25% of patients. Median progression free survival (mPFS) for the whole cohort was not reached (NR) (95% CI; 4.9, NR). Bulky disease was associated with shorter median PFS of 3.5 years (CI 95%; 0.8, 4.9) compared to non-bulky disease NR (CI 95%; 5.8, NR), P = .02. The incidence of grade 3 or higher thrombocytopenia, neutropenia and anemia were 47%, 37%, and 4% respectively. No therapy-related myelodysplasia or acute myeloid leukemia were observed.Long real-life follow-up showed that single-agent (90)Y-IT is highly efficacious with durable long-term survival in previously untreated LG-FL and MZL without significant risk for secondary malignancies.

Analyze the pattern of disease failure after anti-CD19-directed chimeric antigen receptor T-cell therapy (CART) for non-Hodgkin lymphoma, assess the local control rate of bridging radiotherapy (bRT) and characterize in-field recurrences.We retrospectively reviewed 120 patients with NHL who received CART between 2018 and 2020. Baseline characteristics and treatment outcomes were compared between patients who received bRT and those who did not (noRT).Of the 118 patients included, 14 (12%) received bRT, while 104 (88%) did not. bRT group had more localized and extranodal disease. bRT was delivered with a median dose of 20 Gy (range: 15-36) in 5 fractions (range: 3-24). Pattern of failure analysis revealed that progression involving pre-existing sites was the predominant pattern of failure in both the bRT and noRT groups (86% and 88%, respectively). Median duration of response was 128 days (range: 25-547) for bRT group and 93 days (range: 22-965) for noRT group (p = 0.78). In the bRT group, only 2/15 sites irradiated had infield recurrence and where characterized by bulky disease, SUVMajority of progressions after CART infusion involve pre-existing sites. Bridging RT prior to CART provides excellent in-field local control and durable response. Patients with bulky disease, SUV

Children, adolescents, and young adults (CAYA) with relapsed/refractory classical Hodgkin lymphoma (cHL) without complete metabolic response (CMR) before autologous hematopoietic cell transplantation (auto-HCT) have poor survival outcomes. CheckMate 744, a phase 2 study for CAYA (aged 5-30 years) with relapsed/refractory cHL, evaluated a risk-stratified, response-adapted approach with nivolumab plus brentuximab vedotin (BV) followed by BV plus bendamustine for patients with suboptimal response. Risk stratification was primarily based on time to relapse, prior treatment, and presence of B symptoms. We present the primary analysis of the standard-risk cohort. Data from the low-risk cohort are reported separately. Patients received 4 induction cycles with nivolumab plus BV; those without CMR (Deauville score >3, Lugano 2014) received BV plus bendamustine intensification. Patients with CMR after induction or intensification proceeded to consolidation (high-dose chemotherapy/auto-HCT per protocol). Primary endpoint was CMR any time before consolidation. Forty-four patients were treated. Median age was 16 years. At a minimum follow-up of 15.6 months, 43 patients received 4 induction cycles (1 discontinued); 11 of whom received intensification, 32 proceeded to consolidation. CMR rate was 59% after induction with nivolumab plus BV, and 94% any time before consolidation (nivolumab plus BV ± BV plus bendamustine). One-year PFS rate was 91%. During induction, 18% of patients experienced grade 3/4 treatment-related adverse events. This risk-stratified, response-adapted salvage strategy had high CMR rates with limited toxicities in CAYA with relapsed/refractory cHL. Most patients did not require additional chemotherapy (bendamustine intensification). Additional follow-up is needed to confirm durability of disease control. ClinicalTrials.gov: NCT02927769.

The role of radiation therapy (RT) varies across hematologic malignancies (HM). Radiation oncology (RO) resident comfort with specific aspects of HM patient management is unknown. The International Lymphoma RO Group (ILROG) assessed resident HM training opportunities and interest in an HM away elective. RO residents (PGY2-5) in the Association of Residents in RO (ARRO) database (n = 572) were emailed an anonymous, web-based survey in January 2019 including binary, Likert-type scale (1 = not at all, 5 = extremely, reported as median [interquartile range]), and multiple-choice questions. Of 134 resident respondents (23%), 86 (64%) were PGY4/5 residents and 36 (27%) were in larger programs (≥ 13 residents). Residents reported having specialized HM faculty (112, 84%) and a dedicated HM rotation (95, 71%). Residents reported “moderate” preparedness to advocate for RT in multidisciplinary conferences (3 [2–3]); make HM-related clinical decisions (3 [2–4]); and critique treatment planning (3 [2–4]). They reported feeling “moderately” to “quite” prepared to contour HM cases (3.5 [3–4]) and “quite” prepared to utilize the PET-CT five-point scale (4 [3–5]). Overall, residents reported feeling “moderately” prepared to treat HM patients (3 [2–3]); 24 residents (23%) felt “quite” or “extremely” prepared. Sixty-six residents (49%) were potentially interested in an HM away elective, commonly to increase comfort with treating HM patients (65%). Therefore, HM training is an important component of RO residency, yet a minority of surveyed trainees felt quite or extremely well prepared to treat HM patients. Programs should explore alternative and additional educational opportunities to increase resident comfort with treating HM patients. Supplementary Information The online version contains supplementary material available at 10.1007/s13187-021-02098-9.

BACKGROUND AND PURPOSE We previously evaluated late cardiac disease in long-term survivors in the Childhood Cancer Survivor Study (CCSS) based on heart radiation therapy (RT) doses estimated from an age-scaled phantom with a simple atlas-based heart model (HAtlas). We enhanced our phantom with a high-resolution CT-based anatomically realistic and validated age-scalable cardiac model (HHybrid). We aimed to evaluate how this update would impact our prior estimates of RT-related late cardiac disease risk in the CCSS cohort. METHODS We evaluated 24,214 survivors from the CCSS diagnosed from 1970 to 1999. RT fields were reconstructed on an age-scaled phantom with HHybrid and mean heart dose (Dm), percent volume receiving ≥ 20 Gy (V20) and ≥ 5 Gy with V20 = 0 ( [Formula: see text] ) were calculated. We reevaluated cumulative incidences and adjusted relative rates of grade 3-5 Common Terminology Criteria for Adverse Events outcomes for any cardiac disease, coronary artery disease (CAD), and heart failure (HF) in association with Dm, V20, and [Formula: see text] (as categorical variables). Dose-response relationships were evaluated using piecewise-exponential models, adjusting for attained age, sex, cancer diagnosis age, race/ethnicity, time-dependent smoking history, diagnosis year, and chemotherapy exposure and doses. For relative rates, Dm was also considered as a continuous variable. RESULTS Consistent with previous findings with HAtlas, reevaluation using HHybrid dosimetry found that, Dm ≥ 10 Gy, V20 ≥ 0.1%, and [Formula: see text] ≥ 50% were all associated with increased cumulative incidences and relative rates for any cardiac disease, CAD, and HF. While updated risk estimates were consistent with previous estimates overall without statistically significant changes, there were some important and significant (P

Purpose Primary mediastinal B cell lymphoma (PMBCL) is a highly curable subtype of non-Hodgkin lymphoma that is diagnosed predominantly in adolescents and young adults. Consequently, long-term treatment-related morbidity is critical to consider when devising treatment strategies that include different chemoimmunotherapy strategies with or without radiation therapy. Furthermore, adaptive approaches using the end-of-chemotherapy (EOC) positron emission tomography (PET)/computed tomography (CT) scanning may help to determine which patients may benefit from additional therapies. We aimed to develop evidence-based guidelines for treating these patients. Methods and Materials We conducted a systematic review in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guideline using the PubMed database. The ARS expert committee, composed of radiation oncologists, hematologists, and pediatric oncologists, developed consensus guidelines using the modified Delphi framework. Results Nine studies met the full criteria for inclusion based on reporting outcomes on patients with primary mediastinal B cell lymphoma with EOC PET/CT response scored with the 5-point Deauville scale. These studies formed the evidence for these guidelines in managing patients with PMBCL according to the EOC PET response, including after a 5-point Deauville scale of 1 to 3, 4, or 5, and for patients with relapsed and refractory disease. The expert group also developed guidance on radiation simulation, treatment planning, and plan evaluation based on expert opinion. Conclusions Various treatment approaches exist in the management of PMBCL, including different chemoimmunotherapy regimens, the use of consolidative radiation therapy, and adaptive approaches based on EOC PET/CT response. These guidelines can be used by practitioners to provide appropriate treatment according to different disease scenarios.

The optimal approach to incorporate radiotherapy (RT) in conjunction with CAR T-cell Therapy (CART) for relapsed/refractory (r/r) B-cell non-Hodgkin lymphoma (bNHL) remains unclear. This study documents the RT local control rate among patients who received bridging radiotherapy (BRT) prior to CART and compares it to those who received salvage radiotherapy (SRT) post CART. It further reports on a promising way to utilize SRT for post CART disease, and identifies predictors for RT in-field recurrence.We retrospectively reviewed 83 patients with r/r bNHL who received CART and RT, either as BRT pre-CART infusion (n=35) or as SRT post-CART infusion (n=48), between 2018 and 2021. RT was defined as comprehensive (compRT) - treated all sites of active disease - or focal (focRT). Limited disease was defined as disease amenable to compRT, involving5 active disease sites.At time of RT, patients who received BRT prior to CART had bulkier disease sites (median diameter 8.7cm vs. 5.5cm; p=0.01) and were treated to significantly lower doses (median equivalent 2 Gy dose 23.3Gy vs. 34.5Gy, p=0.002), compared to SRT post CART. Among 124 total irradiated sites identified, 8/59 (13%) bridged-sites and 21/65 (32%) salvaged-sites experienced in-field recurrence translating to 1-year local control rate (LC) of 84% and 62%, respectively (p=0.009). Patients with limited post-CART disease (n=37) who received compSRT (n=26) had better overall survival (51% vs. 12%; p=0.028), freedom from subsequent progression (31% vs. 0%; p0.001) and freedom from subsequent event (19% vs. 0%; p=0.011) compared to patients with limited disease who received focSRT (n=11).BRT followed by CART appears to be associated with improved LC compared to SRT in r/r bNHL. Nonetheless, SRT offers a promising salvage intervention for limited (5 sites) relapsed post-CART disease if given comprehensively.

Data comparing outcomes in prostate cancer and factors affecting treatment choice are sparse. To inform the design of a comparative effectiveness clinical trial, we engaged patients in developing a 28‐question survey about decision making on treatment and research participation and dispersed it among men greater than or equal to 50 years of age. The 1046 respondents ranked long‐term clinical outcomes as most important in making treatment decisions, specific functional outcomes as slightly less important, and duration, location, and cost of treatment as least important. Treatment choice was strongly impacted by side effect profile. Responses to whether the subject would agree to participation in a randomized trial between two types of radiation with minimal differences in outcomes were “yes” in 15%, “no” in 39%, and “undecided” in 46%. Responses to whether the subject would agree to participation in a randomized trial between two treatment durations with similar outcomes were yes in 36%, no in 24%, and undecided in 40%. Findings suggest many potential patients have strong treatment preferences and are averse to randomization, particularly when outcomes of importance may be affected. Patient engagement in study design and novel nonrandomized trial designs may offer a path to increase clinical trial success.

Purpose Early stage (stages I-II) classical Hodgkin lymphoma (cHL) is a highly curable disease typically diagnosed in adolescents and young adults (AYAs). Proton therapy can also reduce the late toxicity burden in this population, but data on its comparative efficacy with photon radiotherapy in this population are sparse. We assessed outcomes in AYAs with cHL in a multi-institution retrospective review. Materials and Methods We identified 94 patients aged 15 to 40 years with stages I and II cHL treated with radiotherapy as part of their initial treatment between 2008 and 2017. We used Kaplan-Meier analyses and log-rank testing to evaluate survival differences between groups of patients. Results A total of 91 patients were included in the analysis. The 2-year progression-free survival (PFS) rate was 89%. Of the 12 patients who experienced progression after radiotherapy, 4 occurred out-of-field, 2 occurred in-field, and 6 experienced both in- and out-of-field progression. There was no significant difference in 2-year PFS among AYA patients by radiotherapy dose received (≥ 30 Gy, 91%; Conclusion Our cohort of AYA patients had comparable outcomes regardless of radiotherapy dose or modality used. For patients with significant risk of radiation-induced late effects, proton therapy is a reasonable treatment modality.

Proton therapy is a promising but controversial treatment in the management of prostate cancer. Despite its dosimetric advantages when compared with photon radiation therapy, its increased cost to patients and insurers has raised questions regarding its value. Multiple prospective and retrospective studies have been published documenting the efficacy and safety of proton therapy for patients with localized prostate cancer and for patients requiring adjuvant or salvage pelvic radiation after surgery. The Particle Therapy Co-Operative Group (PTCOG) Genitourinary Subcommittee intends to address current proton therapy indications, advantages, disadvantages, and cost effectiveness. We will also discuss the current landscape of clinical trials. This consensus report can be used to guide clinical practice and research directions.

Surgical treatment of pelvic sarcoma involving the bone is the standard of care but is associated with several sequelae and reduced functional quality of life (QOL). Treatment with photon and proton radiotherapy is associated with relapse. Carbon ion radiotherapy (CIRT) may reduce both relapse rates and treatment sequelae. The PROSPER study is a tricontinental, nonrandomized, prospective, three-arm, pragmatic trial evaluating treatments of pelvic sarcoma involving the bone. Patients aged at least 15 years are eligible for inclusion. Participants must have an Eastern Cooperative Oncology Group Performance Status score of two or less, newly diagnosed disease, and histopathologic confirmation of pelvic chordoma, chondrosarcoma, osteosarcoma, Ewing sarcoma with bone involvement, rhabdomyosarcoma (RMS) with bone involvement, or non-RMS soft tissue sarcoma with bone involvement. Treatment arms include (1) CIRT (n = 30) delivered in Europe and Asia, (2) surgical treatment with or without adjuvant radiotherapy (n = 30), and (3) proton therapy (n = 30). Arms two and three will be conducted at Mayo Clinic campuses in Arizona, Florida, and Minnesota. The primary end point is to compare the 1-year change in functional QOL between CIRT and surgical treatment. Additional comparisons among the three arms will be made between treatment sequelae, local control, and other QOL measures.

Purpose To compare the planning target volume (PTV) margins needed for prostate patients who have used hydrogel spacer or rectal balloon during proton treatments. Method Total of 190 prostate patients treated with proton therapy during 2017 were selected for this study. Of these patients, 96 had hydrogel spacer injection and 94 patients had only rectal balloons insertion. All patients had implanted gold markers inside the prostate for daily target alignment. Post-treatment radigraphs were obtained to evaluate prostate intrafraction motion. The systematic and random components of patient setup residual error and prostate intrafraction motion error were obtained. PTV margins were calculated using the van Herk formula for both patient groups. Results For setup residual error, the mean values in the superior-inferior (SI) direction and the variances in the left–right (LR) direction were statistically different between the two groups. For intrafraction motion, there were significant differences of the mean values in the SI direction and of the variances in both LR and anterior-posterior (AP) directions. The population PTV margins for hydrogel spacer group were 2.6 mm, 3.3 mm, and 1.6 mm in LR, SI, AP directions, respectively. For the rectal balloon group, the PTV margins were 2.1 mm, 3.1 mm, and 2.0 mm in LR, SI, AP directions, respectively. Conclusion Statistically significant differences were observed in the patient setup and prostate intrafraction motion errors of the two patient groups. However, under the current protocol of bladder preparation and daily marker-based x-ray image-guidance, population PTV margins were comparable between the two patient groups.

The incidence and predictors of pneumonitis for patients with unresectable, locally advanced non-small cell lung cancer (NSCLC) in the era of consolidation durvalumab have yet to be fully elucidated. In this large single institution analysis, we report the incidence of and factors associated with grade 2 + pneumonitis in NSCLC patients treated with the PACIFIC regimen.We identified all patients treated at our institution with definitive CRT followed by durvalumab from 2018 to 2021. Clinical documentation and imaging studies were reviewed to determine grade 2 + pneumonitis events, which required the following: 1) pulmonary symptoms warranting prolonged steroid taper, oxygen dependence, and/or hospital admission and 2) radiographic findings consistent with pneumonitis.One-hundred ninety patients were included. The majority received 60 Gray (Gy) in 30 fractions with concurrent carboplatin and paclitaxel. Median number of durvalumab cycles received was 12 (IQR: 4-22). At a median follow-up of 14.8 months, 50 (26.3%) patients experienced grade 2 + pneumonitis with a 1-year cumulative incidence of 27.8% (95% CI: 21.9-35.4). Seventeen (8.9%) patients experienced grade 3 + pneumonitis and 4 grade 5 (2.1%). Dosimetric predictors of pneumonitis included ipsilateral and total lung volume receiving 5 Gy or greater (V5Gy), V10Gy, V20Gy, V40Gy, and mean dose and contralateral V40Gy. Heart V5Gy, V10Gy, and mean dose were also significant variables. Overall survival estimates at 1 and 3 years were 87.4% (95% CI: 82.4-92.8) and 60.3% (95% CI: 47.9-74.4), respectively.We report a risk of pneumonitis higher than that seen on RTOG 0617 and comparable to the PACIFIC study. Multiple lung and heart dosimetric factors were predictive of pneumonitis.

Lymph node (LN) involvement is a poor prognostic factor for malignant pleural mesothelioma (MPM). However, to our knowledge, postresection outcomes of node-negative (cN0/pN0), occult pathologic nodal disease (cN0/pN+), and clinical node-positive disease (cN+) have not been compared to date.The National Cancer Data Base was queried for newly diagnosed, resected MPM with known clinical/pathologic LN information. Three cohorts were compared: cN0/pN0, cN+, and cN0/pN+. Multivariable logistic regression examined predictors of pathologic nodal upstaging. Kaplan-Meier analysis with propensity matching assessed overall survival (OS); multivariate Cox proportional hazards modeling examined predictors thereof.Of 1369 patients, 687 (50%) had cN0/pN0, 457 (33%) cN+, and 225 (16%) cN0/pN+ disease. Median follow-up was 29 months. In patients with cN0 disease, factors associated with pathologic nodal upstaging were younger age, greater number of examined LNs, and nonsarcomatoid histology (P .05 for all). Relative to pN0 cases, occult LN involvement (65% being pN2) was associated with 51% higher hazard of mortality on multivariate analysis (P = .005). Following propensity matching, the OS of cN0/pN+ was similar to cN+ cases (P = .281). On multivariate analysis, the number of involved LNs (continuous variable, P = .013), but not nodal tumor, node, metastasis (TNM) classification or LN ratio (P.05 for both), was associated with OS.Detecting occult nodal disease during resection for cN0 MPM is associated with poorer prognosis, with similar survival as cN+ cases, underscoring the importance of routine preoperative pathologic nodal assessment for potentially resectable MPM. The number of involved LNs (rather than current location-based classification) may provide more robust prognostic stratification for future TNM staging.

Pancreatic cancer is the fourth most common cause of cancer-related morality worldwide, and the prognosis remains poor despite aggressive therapy. Carbon ion radiotherapy has favorable radiobiological and physical characteristics in the treatment, including a higher linear energy transfer and higher relative biological effectiveness, which increase the cell kill while potentially reducing toxicities to nearby normal tissues. Although small, early clinical studies have shown promise in both the resectable and unresectable settings to improve local control and overall survival while minimizing toxicities. Currently, there are several trials, including 2 sponsored by institutions in the United States, investigating the role of carbon ion radiotherapy for the treatment of locally advanced pancreatic cancer.

Diffuse large B-cell lymphoma (DLBCL) is the most common type of non-Hodgkin lymphoma. Since the relapse rate of DLBCL to frontline chemoimmunotherapy and salvage autologous hematopoietic cell transplant is high, CD19-directed chimeric antigen receptor (CAR) T-cell therapy was adopted. Given the time interval needed for CAR T cells to be manufactured (3-5 weeks) and the aggressiveness of these relapsed/refractory lymphomas, some patients do not make it to the CAR T-cell infusion phase. This calls for a bridging therapy to control, debulk, and sensitize the disease during this period. Radiation therapy can serve this purpose and has shown promising results in some studies. Proton therapy, compared to standard radiation therapy, in some locations, can reduce the radiation dose to the organs at risk, which may lead to fewer side effects for patients with lymphomas. Thus, we hypothesize that proton therapy may serve as a promising bridging strategy to CAR T-cell therapy for some patients.

Purpose Mean heart dose (MHD) correlates with late cardiac toxicity among survivors of lymphoma receiving involved-field radiation therapy (IFRT). We investigated MHD and cardiac substructure dose across older and newer radiation fields and techniques to understand the value of evaluating MHD alone. Methods and Materials After institutional review board approval, we developed a database of dosimetry plans for 40 patients with mediastinal lymphoma, which included IFRT (anterior-posterior and posterior-anterior), involved-site radiation therapy (ISRT) + 3-dimensional conformal radiation therapy (3DCRT), ISRT + intensity modulated radiation therapy, and ISRT + proton therapy plans for each patient. Each plan was evaluated for dose to the heart and cardiac substructures, including the right and left ventricles (RV, LV) and atria (RA, LA); tricuspid, mitral (MV), and aortic valves; and left anterior descending coronary artery (LAD). Correlation between MHD and cardiac substructure dose was assessed with linear regression. A correlation was considered very strong, strong, moderate, or weak if the r was ≥0.8, 0.6-0.79, 0.4-0.59, or Results A very strong correlation was observed between MHD and the mean cardiac substructure dose for each plan as follows: IFRT—LV, RV, LA, MV and LAD; ISRT + 3DCRT—LV, RV, MV, TV, and LA; ISRT + intensity modulated radiation therapy—LV and RV; ISRT + proton therapy—none. The following strong correlations were observed: IFRT—RA; ISRT + 3DCRT—LAD, RA, AV; ISRT + IMRT—LA, RA, LAD, AV, TV, and MV; ISRT + proton therapy—LV only. Conclusions In the management of mediastinal lymphoma, more conformal treatment techniques can lead to more heterogeneous dose distributions across the heart, which translate into weaker relationships between mean heart dose and mean cardiac substructure doses. Consequently, models for assessing the risk of cardiac toxicity after radiation therapy that rely on MHD can be misleading when using modern treatment fields and techniques. Contouring the cardiac substructures and evaluating their dose is important when using contemporary RT.

Multiple clinical trials have assessed de-escalation strategies from combined modality therapy (CMT) to chemotherapy-alone for the treatment of early-stage classical Hodgkin lymphoma (cHL), confirming similar outcomes. The application of these data to the real-world is limited, however. We conducted a retrospective, multicenter cohort study comparing CMT vs chemotherapy-alone in patients with early-stage cHL (stage IA-IIB) treated between January 2010 and December 2020. Positron emission tomography (PET) scans after chemotherapy cycle 2 (PET2) were independently reviewed by a nuclear radiologist (Deauville score ≥4, positive; ≤3, negative). Patient outcomes were compared by using an intention-to-treat analysis. Among 125 patients (CMT, n = 63; chemotherapy-alone, n = 62) with a median follow-up of 59.8 months (95% CI, 48.6-71.0), no differences in overall survival were observed (5-year overall survival, CMT 98.0% vs chemotherapy-alone 95.1%; log-rank test, P = .38). However, there was reduced progression-free survival (PFS) with chemotherapy-alone among all patients (2-year PFS, CMT 95.1% vs chemotherapy-alone 75.3%; log-rank test, P = .005) and in those with bulky (n = 43; log-rank test, P < .001), unfavorable (n = 81; log-rank test, P = .002), or PET2-positive (n = 15; log-rank test, P = .02) disease. No significant differences in PFS were seen for patients with non-bulky (log-rank test, P = .35), favorable (log-rank test, P = .62), or PET2-negative (log-rank test, P = .19) disease. Based on our real-world experience, CMT seems beneficial for patients with early-stage cHL, especially those with PET2-positive and unfavorable disease. Chemotherapy-alone regimens can lead to comparable outcomes for patients with favorable, non-bulky, or PET2-negative disease. We conclude that although results seen in clinical trials are replicated in certain patient subgroups, other subgroups not fitting trial criteria do poorly when radiotherapy is excluded.

Combined modality therapy with multiagent chemotherapy and radiation therapy is a standard treatment option for aggressive mediastinal non-Hodgkin lymphomas (AMNHLs); however, concerns regarding acute and late radiation toxicities have fueled an effort to use systemic therapy alone. The use of proton therapy (PT) is a promising treatment option, but there are still limited data regarding clinical outcomes with this treatment modality. In this Particle Therapy Cooperative Group lymphoma subcommittee collaboration, we report outcomes of patients with AMNHL treated with pencil-beam scanning PT or double-scatter PT after chemotherapy.This was a multi-institutional retrospective observational cohort study of patients with AMNHL treated with PT following chemotherapy between 2011 and 2021. Progression-free survival (PFS), local recurrence-free survival (LRFS), and overall survival (OS) rates were estimated with the Kaplan-Meier method. PT toxicity was graded by the Common Terminology Criteria for Adverse Events version 5.0. A 2-tailed pairedTwenty-nine patients were identified. With a median follow-up time of 4.2 years (range, 0.2-8.9 years), the estimated 5-year PFS for all patients was 93%, 5-year LRFS was 96%, and estimated 5-year OS was 87%. Maximum acute grade 1 (G1) toxicities occurred in 18 patients, and 7 patients had maximum G2 toxicities. No G3+ radiation-related toxicities were observed. Average mean lung dose and lung V20 Gy were lower for patients treated with pencil-beam scanning PT compared with double-scatter PT (PT after chemotherapy for patients with AMNHL resulted in excellent outcomes with respect to 5-year PFS, LRFS, and OS without high-grade toxicities. Future work with larger sample sizes is warranted to further elucidate the role of PT in the treatment of AMNHL.

BACKGROUND Children with chest wall Ewing sarcoma with malignant pulmonary effusion or pleural stranding require hemithorax radiation, often with plans that exceed lung constraints. We investigated disease control and pneumonitis in children requiring hemithorax radiation. PROCEDURE Eleven children (median age 13 years) received hemithorax radiotherapy. Symptomatic radiation pneumonitis was considered National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) grade 1+ with respiratory symptoms. Mean lung dose (MLD), volume of lung exposed to a dose ≥5 Gy (V5), ≥20 Gy (V20), and ≥35 Gy (V35) were recorded. Adult and pediatric lung constraints were obtained from Quantitative Analysis of Normal Tissue Effects in the Clinic (QUANTEC) guidelines and Children's Oncology Group (COG) protocols, respectively. RESULTS Median hemithorax dose was 15 Gy (1.5 Gy/fraction). Median total dose was 51 Gy (1.8 Gy/fraction). Most plans delivered both protons and photons. The ipsilateral MLD, V5, and V20 were 27.2 Gy, 100%, and 48.3%; the bilateral MLD, V20, and V35 were 14.1 Gy, 22.8%, and 14.3%, respectively. One hundred percent, 36%, and 91% of treatments exceeded recommended adult ipsilateral lung constraints of V5

Radiation therapy (RT) is an integral component of potentially curative management of esophageal cancer (EC). However, RT can cause significant acute and late morbidity due to excess radiation exposure to nearby critical organs, especially the heart and lungs. Sparing these organs from both low and high radiation dose has been demonstrated to achieve clinically meaningful reductions in toxicity and may improve long-term survival. Accruing dosimetry and clinical evidence support the consideration of proton beam therapy (PBT) for the management of EC. There are critical treatment planning and delivery uncertainties that should be considered when treating EC with PBT, especially as there may be substantial motion-related interplay effects. The Particle Therapy Co-operative Group Thoracic and Gastrointestinal Subcommittees jointly developed guidelines regarding patient selection, treatment planning, clinical trials, and future directions of PBT for EC.

PURPOSE: The Children’s Oncology Group protocol AHOD0831, for pediatric patients with high-risk classical Hodgkin lymphoma (cHL), used response-adapted radiation fields, rather than larger involved-field radiation therapy (IFRT) that were historically used. This retrospective analysis of patterns of relapse among patients enrolled in the study was conducted to study the potential effect of a reduction in RT exposure. METHODS AND MATERIALS: From December 2009 to January 2012, 164 eligible patients under 22 years old with stage IIIB (43%) and stage IVB (57%) enrolled on AHOD0831. All patients received 4 cycles of doxorubicin, bleomycin, vincristine, etoposide, prednisone, and cyclophosphamide (ABVE-PC). Those patients with a slow early response (SER) after the first 2 ABVE-PC courses were nonrandomly assigned to 2 intensification cycles with ifosfamide/vinorelbine before the final 2 ABVE-PC cycles. Response-adapted RT (21 Gy) was prescribed to initial areas of bulky disease and SER sites. Rapid early response (RER) sites without bulk were not targeted. Imaging studies at the time of progression or relapse were reviewed centrally for this retrospective analysis. Relapses were characterized with respect to site (initial, new, or both; and initial bulk or initial nonbulk), initial chemotherapy response, and radiation field (in-field, out-of-field, or both). RESULTS: Of the entire cohort, 140 patients were evaluable for the patterns of failure analyses. To investigate the pattern of failure, this analysis focuses on 23 patients who followed protocol treatment and suffered relapses at a median 1.05 years with 7.97-year median follow-up time. These 23 patients (11 RER and 12 SER) experienced a relapse in 105 total sites (median, 4; range, 1–11). Of the 105 relapsed sites, 67 sites (64%) occurred within an initial site of involvement, with 12 of these 67 sites (18%) at an initial site of bulky disease and 63 of these 67 relapses (94%) occurring in sites that were not fluorodeoxyglucose (FDG)-avid after 2 cycles of ABVE-PC (PET2-negative). Of the 105 relapsed sites, 34 sites (32%) occurred in a new site of disease (that would not have been covered by RT); and, overall, only 4 of 140 patients (2.8%) (occurring in 3 RER and 1 SER) experienced isolated out-of-field relapses that would have been covered by historical IFRT. CONCLUSIONS: For a cohort of high-risk patients with cHL patients, most failures occurred in nonbulky, initially involved sites, largely due to response-based consolidation RT delivered to patients with bulky disease. In this analysis, we discovered low rates of failures outside of these modern risk-adapted radiation treatment volumes. Also, FDG uptake on PET2 did not identify most relapse sites.

BACKGROUND Positron emission tomography (PET)-based measures of baseline total-body tumor burden may improve risk stratification in intermediate-risk Hodgkin lymphoma (HL). MATERIALS AND METHODS Evaluable patients were identified from a cohort treated homogeneously with the same combined modality regimen on the Children's Oncology Group AHOD0031 study. Eligible patients had high-quality baseline PET scans. Metabolic tumor volume (MTV) and total lesion glycolysis (TLG) were each measured based on 15 thresholds for every patient. Univariate and multivariable Cox regression and Kaplan-Meier survival analyses assessed for an association of MTV and TLG with event-free survival (EFS). RESULTS From the AHOD0031 cohort (n = 1712), 86 patients were identified who (i) were treated with four cycles of doxorubicin, bleomycin, vincristine, etoposide, prednisone, cyclophosphamide (ABVE-PC) chemotherapy followed by involved field radiotherapy, and (ii) had a baseline PET scan that was amenable to quantitative analysis. Based on univariate Cox regression analysis, six PET-derived parameters were significantly associated with EFS. For each of these, Kaplan-Meier analyses and the log-rank test were used to compare patients with highest tumor burden (i.e., highest 15%) to the remainder of the cohort. EFS was significantly associated with all six PET parameters (all p

Hodgkin lymphoma (HL) is a highly curable form of cancer, and current treatment regimens are focused on improving treatment efficacy while decreasing the risk of late effects of treatment. The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for pediatric HL provide recommendations on the workup, diagnostic evaluation, and treatment of classic HL, including principles of pathology, imaging, staging, systemic therapy, and radiation therapy. This portion of the NCCN Guidelines focuses on the management of pediatric classic HL in the upfront and relapsed/refractory settings.

The purpose of this study was to examine factors associated with disparities in overall survival (OS) by race in pediatric Hodgkin Lymphoma (HL) patients. We evaluated clinical features and survival among patients ≤21 years of age diagnosed with stage I-IV HL from 2004 to 2015 from the National Cancer DataBase (NCDB) using a multivariable Cox proportional hazards model. Among 11,546 patients with pediatric HL, 9285 patients met eligibility criteria. Black patients experienced a 5-year OS of 91.5% vs 95.9% in White patients (

Purpose: Treatment success in lung cancer is no longer restricted to objective measures of disease-specific outcomes and overall survival alone but now incorporates treatment morbidity and subjective quality of life (QoL). This study reports how lung cancer patients, survivors, and caregivers define treatment success and prioritize treatment decisions. Materials and Methods: An online survey with both ranking and free-response questions was administered among lung cancer survivors and caregivers. Responses were used to evaluate treatment priorities, perceptions of treatment success based on Eastern Cooperative Oncology Group (ECOG) Performance Status, and troublesomeness of treatment-related toxicities. Results: Among 61 respondents (29 lung cancer survivors, 28 caregivers of survivors, and 4 who were both survivors and caregivers), cancer cure was the highest priority when making treatment decisions for 74.5% of respondents, with QoL during and after treatment ranking second and third. Seventy percent of respondents felt that treatment morbidity resulting in complete dependence on others and spending the entire day confined to bed or chair would represent unsuccessful treatment. Requiring oxygen use was ranked as a very or extremely troublesome treatment toxicity by 64%, followed by shortness of breath (62%), fatigue (49%), chronic cough (34%), and appetite loss (30%). Even with remission, a 3- to 7-day hospital admission for pneumonia during treatment was deemed an unsuccessful outcome by 30%. Conclusion: This study highlights the importance of physicians discussing in detail with their lung cancer patients their desires and goals. Accounting for factors like expected performance status following treatment, troublesomeness of treatment toxicities, and hospitalization rates may help guide treatment decisions.

Background Radiation-induced tumor immunity (RITI) influences primary tumor growth and development of metastases in preclinical cancer models with conventional radiotherapy. Antigen-specific immune responses have also been shown for prostate cancer treated with radiotherapy. We examined whether RITI can be induced in patients with non-small cell lung cancer (NSCLC) following proton radiotherapy. Methods Pre- and post-radiotherapy plasma samples from 26 patients with nonmetastatic NSCLC who received radiotherapy between 2010 and 2012 were evaluated by western blotting for IgG and IgM bands to assess RITI response to tumor antigens from lung cancer cell lines. Statistical analysis was used to evaluate any correlation among IgG or IgM and clinical outcomes. Results Twenty-one patients received proton therapy at 2 GyRBE/fraction (n = 17) or 6-12 Gy/fraction (n = 4); five received photon therapy at 2-2.5 GyRBE/fraction. Compared with the pretreatment baseline, new IgG or IgM binding was detected in 27% and 50% of patients, respectively. New IgG bands were detected in the 25-37 kD, 50-75 kD, and 75-100 kD ranges. New IgM bands were detected in the 20-25 kD, 25-37 kD, 37-50 kD, 50-75 kD, and 75-100 kD ranges. There was no difference in IgG and/or IgM RITI response in patients treated with photons versus protons, or in patients who received SBRT compared to standard fractionation (P > 0.05). There was no difference in overall survival, metastasis-free survival, or local control based on IgG and/or IgM RITI response (P > 0.05). Conclusion RITI can be induced in patients with NSCLC through upregulated IgG and/or IgM. RITI response was not associated with proton versus photon therapy or with clinical outcomes in this small cohort and should be examined in a larger cohort in future studies.

Objective: Thymic malignancies (TM) are rare tumors with long-term survivorship, causing concerns for radiotherapy-related late side effects. Proton therapy (PT) reduces the radiation dose to organ...

Studies demonstrate a decline of ∼10% in serum testosterone (ST) level after X-ray radiotherapy for prostate cancer. We evaluated changes in ST for patients with low- and intermediate-risk prostate cancer receiving 70-82Gy(RBE) using passive-scatter proton therapy (PT). ST was checked at baseline (n = 358) and at 60+ months after PT (n = 166). The median baseline ST was 363.3 ng/dl (range, 82.0-974.0). The median ST 5 years after PT was 391.5 ng/dl (range, 108.0-1061.0). The difference was not statistically significant (p = 0.9341). Passive-scatter PT was not associated with testosterone suppression at 5 years, suggesting that protons may cause less out-of-field scatter radiation than X-rays.

PURPOSE To investigate the impact of unfavorable risk factors among patients with locally advanced nonsmall cell lung cancer (LA-NSCLC) treated with proton therapy (PT). MATERIAL AND METHODS From May 2008 through July 2015, 90 consecutive patients with unresectable stage II-IV (oligometastatic) NSCLC were treated with PT. Unfavorable factors including age ≥80 years, stage IV, weight loss >10% in 3 months, performance status (PS) ≥2, FEV1

PURPOSE/OBJECTIVE(S) Prior estimates of radiation (RT)-associated cardiac disease risk in childhood cancer survivors are based on estimates of RT dose to the entire heart. We aimed to evaluate whether cardiac substructure RT dosimetry improves estimation of late cardiac disease risk. MATERIALS/METHODS We determined the cumulative incidence of CTCAE grade 3 - 5 cardiac disease (heart failure, coronary artery disease, valvular disease, arrhythmia, or pericardial disease) among 25,481 5-year survivors from CCSS diagnosed 1970 - 1999. Median age at diagnosis was 6.1 years (range 0 - 20) and at last follow-up was 29.8 years (5.6 - 65.9). We considered a single composite endpoint of any cardiac disease to best identify which substructures to prioritize for avoidance in RT planning to minimize the absolute risk of cardiac disease. We reconstructed RT fields for irradiated survivors (n = 12,228) on an age-scaled phantom and estimated mean RT dose to the heart, four chambers, four valves, and the left anterior descending (LAD), circumflex, main (LM), and right coronary arteries. Adjusted piecewise exponential models (including cumulative anthracycline dose) evaluated associations between mean RT dose to each structure and outcomes. Each substructure was individually added to a model with mean whole heart RT dose and the fit was assessed via the likelihood-ratio test to ascertain which substructures improved prediction of cardiac risk beyond whole heart dose. RESULTS At 35 years from diagnosis, the cumulative incidence of any cardiac disease was 7.0% (95% CI 6.5 - 7.6). When adding each substructure separately to a model with mean whole heart dose, the addition of mean LAD (χ2 = 29.1) or LM (χ2 = 34.6) RT dose significantly improved the risk estimation of any cardiac disease (P < 0.01). Among survivors with mean whole heart doses < 10 Gy, increasing mean LAD but not mean LM doses significantly increased risk of late cardiac disease. Even among those with a mean heart dose of < 5 Gy, mean LAD dose of ≥10 Gy was associated with a more than three-fold increased risk of cardiac disease (Table 1). CONCLUSION Even among survivors with low mean heart doses (< 5 Gy), mean LAD doses ≥10 Gy increased risk of cardiac disease. Thus, for pediatric RT planning we recommend limiting mean LAD dose to < 10 Gy, even when mean heart dose constraints can be achieved. Table 1. Relative rate of grade 3 - 5 cardiac disease in childhood cancer survivors by RT dose to the heart and LAD.

Purpose/Objective(s) COG AHOD0831 was a multi-center, prospective study that used a response-adapted approach for patients Materials/Methods Patients from AHOD0831 were identified who had baseline PET scans that were amenable to quantitative analyses. For each patient, metabolic tumor volume (MTV), total lesion glycolysis (TLG), maximum standardized uptake value (SUVmax), and peak SUV (SUVpeak) were obtained for mediastinal (m) and total body (t) disease. MTV was defined based on thresholds of SUV > 2.5 or > 40% SUVmax. TLG was defined as MTV * tumor SUVmean. EFS was assessed by Kaplan-Meier analyses. 2nd EFS was defined as the time to a second event, reflecting rates of successful salvage after a 1st relapse. Receiver operating characteristic analyses estimated the ability of PET parameters to predict EFS; optimized cutoff values were identified using a Youden index. Results Of 166 patients enrolled on AHOD0831, 94 (57%) had PET scans evaluable for quantitative analysis. For this subset: median age 15.5 years; 62% male; 67% white; 45% stage III, 55% stage IV; 86% bulk; 60% nodular sclerosis histology; 54% RER, 46% SER. These characteristics did not differ significantly from the complete AHOD0831 cohort. At a median follow-up of 49 months, 4-year EFS was 76% for the complete cohort (76% RERs, 75% SERs). Patients with high tMTVs and tTLGs, based on each threshold, were significantly more likely to be SERs (all P Conclusion RERs with a low baseline metabolic tumor burden experienced excellent EFS with less intensive therapy. Conversely, RERs with a high baseline tumor burden experienced poor EFS that was even worse than that of SERs. Thus, patients with a high metabolic tumor burden upfront may benefit from intensified therapy, even if they achieve a RER. PET-based measures of initial disease burden may contribute to risk-based treatment algorithms and improve outcomes in HL.

Purpose/Objective(s) Nonagenarians often present with advanced stage malignancies and complex prior treatment courses. Additionally, the fragility of this patient population can significantly limit surgical or systemic treatment options. Palliative radiotherapy is often offered in these challenging cases, however there is scarce data to help guide clinicians on which select patients may be most appropriate for radiotherapy versus other comfort care measures. Materials/Methods A retrospective analysis was performed evaluating all patients from September 2015 to December 2020 who underwent palliative radiotherapy and were ≥ 90 years old at the time of initial treatment. Data pertaining to patient demographics, radiation course details, and survival outcomes were compiled and analyzed using descriptive statistics. Results 35 patients were treated with palliative radiation therapy. Median age 92 (range 90-100). The median ECOG was 1 (range 0-4) and seven patients (20%) had an ECOG of 3-4. Only one patient (2.9%) had received radiotherapy prior to age 90 (8 Gy in 1 fraction). Median number of fractions for all courses was five fractions. Median follow up was 4.6 months. 17 patients (48.6%) presented with symptomatic distant metastases, including 16 for bone metastasis (94.1%) and one for painful right inguinal lymphadenopathy (37.5 Gy in 15 fractions). RT dose for osseous lesions included 6-8 Gy in 1 fraction (n = 10) and 20 Gy in 5 fractions (n = 6). The one month and three-month overall survival for distant palliation was 94.1% and 76.5%, respectively. Seven patients died, all due to their cancer. 18 patients (51.4%) underwent palliative radiotherapy for symptomatic local disease. Median RT dose was 30 Gy in 10 fractions (range, 8-45 Gy in 1-25 fractions). The most common primary anatomic site of progression was gastrointestinal (38.9%), including gastric (2), colorectal (4), and pancreatic (1) malignancies. 10 patients (55.5%) were Stage IV at presentation. Among the 8 patients with stage I-III cancer, four had irretractable gastrointestinal bleeding, three refused definitive treatment, and one presented with non-obstructive painful inoperable colon cancer. The one month and three-month overall survival was 72.2% and 61.1% for local palliation cohort. Six patients died of their cancer, while one patient died of cardiovascular comorbidities. Conclusion Nonagenarians tolerate palliative radiotherapy for distant metastases and locally progressive disease with over 70% of all patients surviving at least three months. Despite their age, radiotherapy should continue to be considered as palliative treatment for nonagenarians.

To report 5- and 7-year outcomes after image-guided moderately accelerated hypofractionated proton therapy (AHPT) for prostate cancer. We reviewed the first 582 prostate cancer patients enrolled on prospective outcomes tracking trial and treated with double-scattered moderately AHPT between 2008 and 2015. 269 patients had low-risk (LR) and 313 had intermediate-risk (IR) disease, including 149 with favorable intermediate-risk (FIR) and 164 with unfavorable intermediate-risk (UIR) disease. LR patients received a median 70.0GyRBE (2.5GyRBE/fraction) and IR patients received a median of 72.5 GyRBE. Seventeen patients (UIR, n = 12) received androgen deprivation therapy (ADT) for a median of 6 months. Toxicities were graded per the CTCAE, v4.0, and patient-reported quality-of-life data were reviewed. Median follow-up was 8.0 years (0.9���12.2). The 5- and 7-year rates of freedom from biochemical progression (FFBP) overall and in the LR and IR subsets, respectively, were 96.8/95.2%, 98.8/98.8%, and 95.0/91.9%. For the FIR and UIR subsets, they were 97.2/95.2% and 93.1/88.8%. Actuarial 5- and 7-year rates of late CTCAE, v4.0, grade 2 gastrointestinal (GI), grade 3 GI, and grade 3 genitourinary (GU) toxicities were 9.9%/11.2%, 1.4/1.4% and 1.3/2.1%, respectively. No grade ���4 GI or GU toxicities occurred. The mean (standard deviation, SD) IPSS and EPIC Composite bowel function and bother scores were 7 (SD = 5), 97 (SD = 7), and 94 (SD = 6), respectively at baseline, 7 (SD = 5), 92 (SD = 13), and 92 (SD = 9) at the 5-year follow-up, and 7 (SD = 5), 93 (SD = 12), and 92 (SD = 10) at the 7-year follow-up. Image-guided AHPT 5- and 7-year outcomes show high efficacy, minimal physician-assessed toxicity, and excellent patient-reported outcomes in this cohort.