Photon-based Radiotherapy Research Articles

Treatment of loco-regional recurrence of nasopharyngeal carcinoma in a non-endemic area: oncologic outcomes, morbidity, and proposal of a prognostic nomogram.

The study assessed outcomes and toxicities of different treatment modalities for local and/or regional recurrent nasopharyngeal carcinoma (NPC) in a non-endemic area. Patients treated with curative intent for recurrent NPC with salvage surgery, photon-based radiotherapy, proton therapy (PT), with or without chemotherapy, at different Italian referral centers between 1998 and 2020 were included. Adverse events and complications were classified according to the Common Terminology Criteria for Adverse Events. Characteristics of the patients, tumors, treatments, and complications are presented along with uni- and multivariate analysis of prognostic factors. A survival predictive nomogram is also provided. A total of 140 patients treated from 1998 to 2020 were retrospectively assessed. Cases with lower age, comorbidity rate, stage, and shorter disease-free interval (DFI) preferentially underwent endoscopic surgery. More advanced cases underwent re-irradiation, fairly distributed between photon-based radiotherapy and PT. Age and DFI were independent factors influencing overall survival. No independent prognostic effect of treatment modality was observed. No significant difference in the morbidity profile of treatments was observed, with 40% of patients experiencing at least one adverse event classified as G3 or higher. Recurrent NPC in a non-endemic area has dissimilar aspects compared to its endemic counterpart, suggesting the need for further studies that can guide the choice of the best treatment modality.

Treatment of childhood-onset craniopharyngioma patients using proton beam therapy vs photon-based radiation therapy in the prospective Kraniopharyngeom 2007 trial

Searchable abstracts of presentations at key conferences in endocrinology ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

Cancer Control, Toxicity, and Secondary Malignancy Risks of Proton Radiation Therapy for Stage I-IIB Testicular Seminoma

This study's objective was to report cancer control and toxicity outcomes after proton radiation therapy (RT) in testicular seminoma and to compare secondary malignancy (SMN) risks with photon-based treatment alternatives. Consecutive patients with stage I-IIB testicular seminoma treated with proton RT at a single institution were retrospectively analyzed. Kaplan-Meier estimates for disease-free and overall survival were computed. Toxicities were scored using Common Terminology Criteria for Adverse Events version 5.0. Photon comparison plans, including 3-dimensional conformal RT (3D-CRT) and intensity modulated RT (IMRT)/volumetric arc therapy (VMAT), were created for each patient. Dosimetric parameters and SMN risk predictions for different in-field organs-at-risk were compared between the techniques. Excess absolute SMN risks were estimated with organ equivalent dose modeling. Twenty-four patients were included (median age, 38.5 years). The majority of patients had stage II disease (IIA, 12 [50.0%]; IIB, 11 [45.8%]; IA, 1 [4.2%]). Seven (29.2%) and 17 (70.8%) patients had de novo and recurrent disease, respectively (de novo/recurrent: IA, 1/0; IIA, 4/8; IIB, 2/9). Most acute toxicities were mild (grade 1 [G1], 79.2%; G2, 12.5%) with G1 nausea being most common (70.8%). No serious events (G3-5) occurred. With a median follow-up time of 3 years (interquartile range, 2.1-3.6 years), 3-year disease-free and overall survival rates were 90.9% (95% confidence interval,68.1%-97.6%) and 100% (95% confidence interval, 100%-100%), respectively. There were no documented late toxicities in the follow-up period, including worsening serial creatinine levels suggestive of early nephrotoxicity. Proton RT had significant reductions in mean organ-at-risk doses to the kidneys, stomach, colon, liver, bladder, and body compared with both 3D-CRT and IMRT/VMAT. Proton RT had significantly lower SMN risk predictions compared with 3D-CRT and IMRT/VMAT. Cancer control and toxicity outcomes using proton RT in stage I-IIB testicular seminoma are consistent with existing photon-based RT literature. However, proton RT may be associated with significantly lower SMN risks.

Proton Therapy for Unresectable and Medically Inoperable Locally Advanced Pancreatic Cancer: Results From a Multi-Institutional Prospective Registry

Compared with photon-based techniques, proton beam radiation therapy (PBT) may improve the therapeutic ratio of radiation therapy (RT) for locally advanced pancreatic cancer (LAPC), but available data have been limited to single-institutional experiences. This study examined the toxicity, survival, and disease control rates among patients enrolled in a multi-institutional prospective registry study and treated with PBT for LAPC. Between March 2013 and November 2019, 19 patients with inoperable disease across 7 institutions underwent PBT with definitive intent for LAPC. Patients received a median radiation dose/fractionation of 54 Gy/30 fractions (range, 50.4-60.0 Gy/19-33 fractions). Most received prior (68.4%) or concurrent (78.9%) chemotherapy. Patients were assessed prospectively for toxicities using National Cancer Institute Common Terminology Criteria for Adverse Events, version 4.0. Kaplan-Meier analysis was used to analyze overall survival, locoregional recurrence-free survival, time to locoregional recurrence, distant metastasis-free survival, and time to new progression or metastasis for the adenocarcinoma cohort (17 patients). No patients experienced grade ≥3 acute or chronic treatment-related adverse events. Grade 1 and 2 adverse events occurred in 78.7% and 21.3% of patients, respectively. Median overall survival, locoregional recurrence-free survival, distant metastasis-free survival, and time to new progression or metastasis were 14.6, 11.0, 11.0, and 13.9 months, respectively. Freedom from locoregional recurrence at 2 years was 81.7%. All patients completed treatment with one requiring a RT break for stent placement. Proton beam RT for LAPC offered excellent tolerability while still maintaining disease control and survival rates comparable with dose-escalated photon-based RT. These findings are consistent with the known physical and dosimetric advantages offered by proton therapy, but the conclusions are limited owing to the patient sample size. Further clinical studies incorporating dose-escalated PBT are warranted to evaluate whether these dosimetric advantages translate into clinically meaningful benefits.

Cardiovascular Substructure Dose and Cardiac Events following Proton- and Photon-Based Chemoradiotherapy for Non-Small Cell Lung Cancer

Radiation therapy (RT) plays a critical role in treating locally advanced non-small cell lung cancer but has been associated with deleterious cardiac effects. We hypothesized that RT dose to certain cardiovascular substructures may be higher among those who experience post-chemoradiation (CRT) cardiac events, and that dose to specific substructures-the great vessels, atria, ventricles, and left anterior descending coronary artery-may be lower with proton- versus photon-based RT. In this retrospective review, we selected 26 patients who experienced cardiac events after CRT for locally advanced non-small cell lung cancer and matched them to 26 patients who did not experience cardiac events after CRT. Matching was done based on RT technique (protons vs photons), age, sex, and cardiovascular comorbidity. For each patient, the whole heart and 10 cardiovascular substructures on the RT planning computerized tomography scan were manually contoured. Dosimetric comparisons were made between those who did and did not experience cardiac events and between the proton and photon groups. There was no significant difference in heart or any cardiovascular substructure dose between those patients who experienced post-treatment cardiac events and those who did not (P > .05 for all). The mean heart dose in the patients receiving proton therapy was significantly lower than the mean heart dose in the patients receiving photon therapy (P=.032). The left ventricle, right ventricle, and the left anterior descending artery also had significantly lower doses (by multiple measures) when treated with protons (P=.0004, P < .0001, and P=.0002, respectively). Proton therapy may have a significant effect on decreasing dose to individual cardiovascular substructures compared with photon therapy. There was no significant difference in heart dose or dose to any cardiovascular substructure between patients who did and did not experience post-treatment cardiac events. Further research should be done to assess the association between cardiovascular substructure dose and post-treatment cardiac events.

Clinical Impact of Proton Beam Therapy for Postoperative Lymph Node Oligorecurrence of Esophageal Cancer.

Radiotherapy is a salvage therapy type for postoperative recurrence of esophageal cancer. Compared to conventional photon-based radiotherapy, proton beam therapy can reduce the irradiated dose to the surrounding organs, facilitating the management of patients who are unfit for radiotherapy. In this study, the outcomes and toxicity of proton beam therapy for postoperative lymph node oligorecurrence of esophageal cancer were investigated. We retrospectively evaluated the clinical outcomes and toxicity of 13 sites in 11 patients treated with proton beam therapy for postoperative lymph node oligorecurrence of esophageal cancer. In total, eight men and three women with a median age of 68 years (range=46-83 years) were included. The median follow-up period was 20.2 months. During the follow-up period, four patients died of esophageal cancer. Eight of the 11 patients developed recurrence; of these, seven patients had recurrence outside the irradiated field, and one had recurrence inside and outside the irradiated field. The 2-year overall survival, progression-free survival, and local control rates were 48.0%, 27.3%, and 84.6%, respectively. The median survival time was 22.4 months. There were no severe acute or late adverse events. Proton beam therapy could be a safe and effective treatment method for postoperative lymph node oligorecurrence of esophageal cancer. It may be beneficial even in cases where conventional photon-based radiotherapy is difficult to administer in combination with increased doses or with chemotherapy.

Toxicity Profile of Intensity Modulated Radiotherapy Vs. 3D-Conformal Radiotherapy in Head and neck cancer: A Retrospective study

Background: Most head and neck patients have historically been treated with photon-based radiation techniques such as intensity modulated radiation therapy (IMRT), there is a growing awareness of the potential clinical benefits of proton therapy over IMRT in the definitive, postoperative and reirradiation settings given the unique physical properties of protons. Aim of the work: to assess toxicity profile of IMRT in comparison to 3D conformal radiotherapy (3DCRT) and to assess predictors for progression free survival and overall survival rates. Patients and Methods: This retrospective cohort study included 131 head and neck cancer patients who were recruited from El Hussein University Hospital over 10 years then they were divided into 2 groups according to the type of radiotherapy. Results: Both groups were comparable regarding age, sex and associated medical disorders except for ischemic heart disease and smoking. Sites of primary tumors were comparable except tongue and nasopharynx. Most of 3DCRT group received TPF as induction chemotherapy and most of IMRT group received concurrent chemotherapy. Dose of irradiation was higher significantly among IMRT group. Grades of early and late toxicity were higher among 3DCRT group. There was no statistically significant difference between both groups regarding response to treatment. Mortality cases were higher significantly among 3DCRT group. Cox regression analysis was performed to assess predictors for progression free survival and overall survival in each group. Conclusion: IMRT provide good choice as radiotherapy technique for head and neck cancers with adequate efficacy similar to other techniques and better toxicity profile.

Preoperative short-course radiation therapy with PROtons compared to photons in high-risk RECTal cancer (PRORECT): Initial dosimetric experience

Background and purposeNeoadjuvant short-course radiotherapy(SCRT) followed by full-dose systemic chemotherapy is an established treatment modality in locally advanced rectal cancer (LARC). Until recently, SCRT has been exclusively delivered with photons. Proton beam therapy (PBT) may minimize acute toxicity, which in turn likely impacts favorably on the tolerability to subsequent chemotherapy. The aim of this study is a dosimetric comparison between SCRT with photons and protons in the randomized phase II trial PRORECT (NCT04525989). Materials and methodsFrom June 2021 to June 2022, twenty consecutive patients with LARC have been treated according to study protocol. For each patient, both a VMAT and a PBT treatment plans have been generated and compared pairwise. ResultsDose-volume histogram (DVH) analysis revealed that SCRT with protons significantly reduced radiation dose to pelvic organs at risk including bladder, bones, and bowel in comparison to SCRT with photons. Photon and proton treatment plans had equivalent conformity and homogeneity indexes. ConclusionPreoperative SCRT with protons offers a significant reduction of radiation dose to normal tissues compared with current photon-based radiotherapy technique. Demonstrated dosimetric advantages may translate into measurable clinical benefits in patients with LARC. Clinical implications of the dosimetric superiority of SCRT with protons will be presented in the coming reports from the PRORECT trial.

Late Toxicity of Moderately Hypofractionated Intensity-Modulated Proton Therapy Treating the Prostate and Pelvic Lymph Nodes for High-Risk Prostate Cancer

To evaluate late gastrointestinal (GI) and genitourinary (GU) toxicity of moderately hypofractionated intensity modulated proton therapy (IMPT) targeting the prostate and pelvic lymph nodes. A target accrual of 56 patients with high-risk or unfavorable intermediate risk prostate cancer were enrolled into a prospective study (ClinicalTrials.gov: NCT02874014)of moderately hypofractionated IMPT. IMPT with pencil beam scanning was used to deliver 6750 and 4500 cGy relative biological effectiveness in 25 dailyfractions simultaneously to the prostate and pelvic lymph nodes, respectively. All received androgen deprivation therapy. Late GI and GU toxicity was prospectively assessed using Common Terminology Criteria for Adverse Events version 4.0, at baseline, weekly during radiation therapy, 3-month postradiation therapy, and then every 6 months. Actuarial rates of late GI and GU toxicity were estimated using Kaplan-Meier method. Median age was 75.5 years. Fifty-four patientswere available for late toxicity evaluation. Median follow-up was 43.9 months (range, 16-66). The actuarial rate of late grade ≥2 GI toxicity at both 2 and 3 years was 7.4% (95% confidence interval [CI], 0.2%-14.2%). The actuarial rate of late grade 3 GI toxicity at both 2 and 3 years was 1.9% (95% CI, 0%-5.4%). One patient experienced grade 3 GI toxicity with proctitis. The actuarial rate of late grade ≥2 GU toxicity was 20.5% (95% CI, 8.9%-30.6%) at 2 years, and 29.2 % (95% CI, 15.5%-40.7%) at 3 years. None had grade 3 GU toxicity. The presence of baseline GU symptoms was associated with a higher likelihood of experiencing late grade 2 GU toxicity. A moderately hypofractionated IMPT targeting the prostate and regional pelvic lymph nodes was generally well tolerated. Patients with pre-existing GU symptoms had a higher rate of late grade 2 GU toxicity. A phase 3 study is needed to assess any therapeutic gain of IMPT, in comparison with photon-based radiation therapy.

Intensity-modulated proton and carbon-ion radiation therapy in the management of major salivary gland carcinomas

Primary major salivary gland carcinomas (SGCs) present with diverse histological types that are known to be largely radioresistant with a high tendency to develop distant metastasis (DM). Photon-based radiotherapy (RT) is limited in terms of its therapeutic effect and toxicities. In view of the physical and biological advantages of intensity-modulated proton and/or carbon-ion radiation therapy, we aimed to evaluate the short-term therapeutic effect and toxicities in patients with major SGCs treated with this form of radiation therapy. Between August 2015 and November 2019, a total of 55 consecutive and non-selected major SGC patients who received particle RT at the Shanghai Proton and Heavy Ion Center (SPHIC) were retrospectively analyzed. The 2-year overall survival (OS), progression-free survival (PFS), local-regional recurrence-free survival (LRRFS), and distant metastasis-free survival (DMFS) rates, as well as prognostic factors were analyzed. Additionally, acute and late toxicities were also analyzed. With a median follow-up time of 24 (range, 6-57) months, the 2-year OS, PFS, LRRFS, and DMFS rates were 91.6%, 78.6%, 94.2%, and 83.9%, respectively. At the time of this analysis, four patients had developed local or regional recurrence, and seven additional patients had developed DM. Three patients had died due to disease progression, and another patient with recurrence experienced a late Grade 5 event (hemorrhage) at 9 months after re-irradiation with carbon ion and subsequently died. Otherwise, none of the patients had grade 3 or higher treatment-induced acute or late adverse effects except one who developed grade 3 acute mucositis. Overall, intensity-modulated proton and/or carbon-ion radiation therapy provided satisfactory therapeutic effectiveness in our major SGCs patients with a low incidence of acute and late toxicities.

The role of carbon-ion radiotherapy in the treatment of adenoid cystic carcinoma of the nasopharynx

Nasopharyngeal adenoid cystic carcinoma (NACC) is a distinct subgroup of adenoid cystic carcinoma (ACC) with limited surgical access but predilection of regional and distant metastasis. Although radiotherapy is an integral treatment for patients with NACC, photon-based radiotherapy yielded suboptimal local control. Because of its advantages in biology and physics properties, carbon-ion radiotherapy (CIRT) was attempted for the treatment of head and neck ACC; however, the use of CIRT specifically for NACC has not been investigated. Patients with NACC that received CIRT alone or a combination of CIRT and proton beam therapy (PBT) at the Shanghai Proton and Heavy Ion Center (SPHIC) between July 2016 and March 2019 were included in the analysis. Patients with newly diagnosed NACC received combined therapy of CIRT (as boost) and PBT, and those with recurrent disease received CIRT alone. Overall survival (OS), local progression-free survival (LPFS), regional progression-free survival (RPFS), and distant metastasis-free survival (DMFS) were calculated by Kaplan-Meier method. A total of 22 patients were included in this analysis. Among those, 18 patients had newly diagnosed NACC (17 with locally advanced disease), and 4 had recurrent NACC including 2 failed previous irradiation. After a median follow-up of 30.9 months, the 2-year OS rate, PFS rate, LPFS rate, RPFS rate and DMFS rate were 100%, 84.8%, 94.4%, 100%, and 84.8%, respectively. Three patients experienced grade 3 mucositis or xerostomia. No late toxicity of grade ≥3 was observed. CIRT alone or in combination with PBT appeared to be a promising modality for the treatment of NACC and produced satisfactory local disease control and toxicity profile. Distant metastasis remained to be a substantial mode for treatment failure. Further follow-up is necessary to evaluate long-term survivals and late toxicity profile.

Carbon Ion Irradiation Downregulates Notch Signaling in Glioma Cell Lines, Impacting Cell Migration and Spheroid Formation.

Photon-based radiotherapy upregulates Notch signaling in cancer, leading to the acquisition of the stem cell phenotype and induction of invasion/migration, which contributes to the development of resistance to therapy. However, the effect of carbon ion radiotherapy (CIRT) on Notch signaling in glioma and its impact on stemness and migration is not explored yet. Human glioma cell lines (LN229 and U251), stable Notch1 intracellular domain (N1ICD) overexpressing phenotype of LN229 cells, and Notch inhibitor resistant LN229 cells (LN229R) were irradiated with either photon (X-rays) or (carbon ion irradiation) CII, and expressions of Notch signaling components were accessed by RT-PCR, Western blotting, and enzymatic assays and flow cytometry. Spheroid forming ability, cell migration, and clonogenic assay were used to evaluate the effect of modulated Notch signaling by irradiation. Our results show that X-ray irradiation induced the expression of Notch signaling components such as Notch receptors, target genes, and ADAM17 activity, while CII reduced it in glioma cell lines. The differential modulation of ADAM17 activity by CII and X-rays affected the cell surface levels of NOTCH1 and NOTCH2 receptors, as they were reduced by X-ray irradiation but increased in response to CII. Functionally, CII reduced the spheroid formation and migration of glioma cells, possibly by downregulating the N1ICD, as stable overexpression of N1ICD rescued these inhibitory effects of CII. Moreover, LN229R that are less reliant on Notch signaling for their survival showed less response to CII. Therefore, downregulation of Notch signaling resulting in the suppression of stemness and impaired cell migration by CII seen here may reduce tumor regrowth and disease dissemination, in addition to the well-established cytotoxic effects.

Risk of Secondary Malignant Neoplasms in Children Following Proton Therapy vs. Photon Therapy for Primary CNS Tumors

<h3>Purpose/Objective(s)</h3> Central nervous system tumors are the second most common primary neoplasms seen in children and radiation therapy is a key component in management of most of these tumors. Secondary malignant neoplasms (SMNs) are rare but dreaded complications, particularly in the pediatric population. Proton beam therapy (PBT) can potentially minimize the risk of SMNs compared to conventional photon radiation therapy (RT). Multiple recent studies with mature data have reported the risk of SMNs after PBT. We performed this systematic review and meta-analysis to characterize and compare the incidence of SMNs after proton and photon-based radiation for pediatric CNS tumors. <h3>Materials/Methods</h3> A systematic search of literature on electronic (PubMed, Cochrane Central, and Embase) databases was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) method. We included studies reporting incidence and nature of SMNs in pediatric patients with primary CNS tumors. The crude incidence of SMNs and all secondary neoplasms were separately extracted, the random-effects model was used for pooled analysis and subgroup comparison was performed between studies using photons vs protons. <h3>Results</h3> Twenty-four studies (21 with conventional RT and 4 with PBT) were included for meta-analysis after performing the systematic review. A total of 418 SMNs and 645 any secondary neoplasms were seen in 38163 patients overall. The most common secondary neoplasms seen were gliomas (40.6%) followed by meningiomas (38.7%), sarcomas (4.8%), thyroid cancers (4.2%), and basal cell carcinomas (1.3%). The overall median follow-up was 8.8 years (range: 3.3 to 23.2 years), while the median latency to a secondary cancer was 9.8 years (range: 5 to 23 years). The median latency to a secondary cancer for photons and protons was 11.9 years (range: 5 to 23 years) and 5.9 years (range: 5 to 6.7 years), respectively. The pooled incidence of SMNs was 1.8% (95% CI: 1.1% – 2.6%, I²=94%) with photons and 1.5% (95% CI: 0 - 4.5%, I²=81%) with protons. There was no significant difference among the two subgroups (p = 0.91). Similarly, the pooled incidence of all secondary neoplasms was not different among the two subgroups [photons: 3.6% (95% CI: 2.5% – 4.8%, I²=96%) vs protons: 1.5% (95% CI: 0 – 4.5%, I²=80%); p = 0.21]. <h3>Conclusion</h3> We observed a slightly lower rate of SMN with PBT at 1.5% compared to 1.8% with photon-based RT for pediatric CNS tumors, although the difference was not statistically significant. We observed a shorter latency to secondary cancers with proton therapy compared to photon-based radiation, which may be related to secondary neutron exposure. With increasing use of techniques that decrease the irradiated tissue volume outside the clinical target volume, like pencil beam scanning proton therapy and VMAT, further studies with longer follow-up are warranted to evaluate the risk of secondary cancers in patients treated with these newer modalities.

Cardiac Substructure Dose and Cardiac Events Following Proton- vs. Photon-Based Chemoradiotherapy for Non-Small Cell Lung Cancer

<h3>Purpose/Objective(s)</h3> Radiotherapy plays a critical role in treating locally advanced non-small cell lung cancer (LA-NSCLC) but is known to have deleterious effects on the heart. We hypothesized that dose to specific cardiovascular substructures – the great vessels, atria, ventricles, and left anterior descending coronary artery - may be lower with proton- versus photon-based radiotherapy, and that dose to certain substructures may be higher among those who experience post-chemoradiation (CRT) cardiac events. <h3>Materials/Methods</h3> In this single institution retrospective review, we created two cohorts from a larger number of patients treated with definitive CRT for LA-NSCLC. We matched 26 patients who experienced cardiac events after CRT to 26 patients who did not experience cardiac events after CRT, based on age, sex, cardiovascular comorbidity, and radiation modality (proton vs photon). In each group, half the patients were treated with proton therapy, and the other half with photon therapy. The cardiac events included acute coronary syndrome (ACS), coronary artery disease (CAD), myocardial infarction (MI), heart failure, and atrial fibrillation/flutter. For each patient, the whole heart and ten cardiac substructures on the radiation therapy planning computerized tomography (CT) scan were contoured. Dosimetric comparisons were made between the proton and photon cohorts, and between those who experienced cardiac events and those who did not. <h3>Results</h3> The mean whole heart dose in the patients receiving proton therapy was significantly lower than the mean heart dose in the patients receiving photon therapy (median 7.36 Gy vs 13.75 Gy, p=0.032). Other structures that had significantly lower mean dose when treated with protons were the left ventricle (median 0.364 Gy vs 4.68 Gy, p=0.0004), right ventricle (median 0.433 Gy vs 10.56 Gy, p<0.0001), and the LAD (median 1.19 Gy vs 12.27 Gy p=0.0002). There was no significant difference in whole heart dose or any cardiac substructure dose between those patients who experienced post-treatment cardiac events and those who did not (p>0.05 for all). Mean whole heart dose correlated with mean dose to each substructure except the aortic arch and the superior vena cava. Amongst all the associations, the strongest correlation was seen between the left ventricle and the left anterior descending artery (Spearman rho = .908). <h3>Conclusion</h3> Proton therapy may have a significant effect on sparing individual cardiac substructures from excess radiation dose when compared to photon therapy. In our analysis, there was no significant difference in heart dose or dose to any cardiac substructure between patients who experienced post-treatment cardiac events. Further research needs to be done to understand clinical significance of the association between cardiac substructure dose and post-treatment cardiac events.

Para-Aortic Radiation Therapy for Oligorecurrent Prostate Cancer

<h3>Purpose/Objective(s)</h3> Patients with oligorecurrent prostate cancer (PCa) limited to the pelvic lymph nodes (LNs) are often treated with whole pelvis radiotherapy (RT) with excellent clinical outcomes, as demonstrated in a phase 2 clinical trial. For oligorecurrent PCa in the para-aortic (PA) LNs, although the standard of care is systemic therapy only, RT may also be beneficial. The purpose of this study is to retrospectively assess the safety and efficacy of RT to the PA LNs (PA-RT) in this population. <h3>Materials/Methods</h3> We identified a sequential cohort of patients with oligorecurrent PCa to the PA LNs (≤5) after pelvic RT at our institution from 2015 to 2021. Eligible patients had oligorecurrent PCa to the PA LNs treated with elective, conventionally fractionated PA-RT plus simultaneous integrated boost (SIB) to LN+ disease. The primary endpoint was defined as progression-free survival (PFS) at 2 years using Kaplan-Meier estimation. PFS was defined as the time from PA-RT to the first event: biochemical failure (PSA 50% above post-treatment nadir and at least 4 ng/mL), escalation of therapy, clinical progression, or death. Secondary endpoints included 2-year biochemical failure-free survival (BFFS), 2-year overall survival (OS) and treatment-related toxicity. <h3>Results</h3> In total, 34 patients were included (median age 66 years), and 82.4% were status post-prostatectomy. The median time from diagnosis to PA-RT was 5.7 years. The median PSA at PA-RT was 3.15 ng/mL (IQR 1.30-5.90), and 23.5% had castration-resistant PCa (CRPC). All patients were treated to the PA region with 50 Gy (88.2%) or 45 Gy (11.8%) in 25 daily fractions. LN+ disease received a SIB to a median dose of 62.5 Gy (range 60-65 Gy). Most received photon-based RT, while 21.1% were treated with proton therapy. Nearly all (97.1%) patients had androgen deprivation therapy (ADT) monotherapy (median duration 20 months), and 52.9% had ADT plus abiraterone. The median follow-up time from PA-RT was 21.5 months. The primary endpoint, PFS at 2-years, was 83.4% (95% CI: 68.6-100%). 2-year BFFS was 90.4% and OS 100%. 8 patients had castration resistant PCa with trend to worse PFS (p=0.14). There were no grade 3 or higher acute toxicities. There were 10 (29.4%) grade 2 acute toxicities, 8 were gastrointestinal. There were 2 (5.9%) grade 3 chronic toxicities (small bowel obstruction and hematuria requiring intervention). There were 4 (11.8%) chronic grade 2 toxicities. <h3>Conclusion</h3> PA-RT for oligorecurrent PCa has low toxicity with encouraging early disease control. These preliminary results show similar outcomes to RT for oligorecurrent PCa limited to the pelvis; however, these results require validation in prospective studies.

Multi-Institutional Investigation of Dose-Escalated Photon Radiotherapy for Intracranial Ependymoma

<h3>Purpose/Objective(s)</h3> Adjuvant radiotherapy (RT) is an important modality of treatment for intracranial ependymoma. The most recently published Children's Oncology Group (COG) Study ACNS0121 recommended 54 Gy after gross total resection (GTR) for patients (pts) <18 months of age and 59.4 Gy for all other pts; however, the optimal RT dose remains unclear. Thus, we sought to characterize outcomes after dose-escalated photon radiotherapy (≥59.4 Gy) for intracranial ependymoma. <h3>Materials/Methods</h3> We conducted an Institutional Review Board-approved multi-institutional retrospective cohort analysis of pts who received surgery and radiation for grade II and III intracranial ependymoma between 1997-2021 before the age of 30 years. We recorded clinical and treatment characteristics, and outcomes. Progression-free survival (PFS) and overall survival (OS) were analyzed by Kaplan-Meier method and Tarone-Ware test. <h3>Results</h3> We identified 53 pts who were diagnosed at median age of 6.2 years (range: 0.9-29.9) and of which 20 (37.7%) were female. 20 (37.7%), 41 (77.4%), and 3 (5.7%) pts had anaplastic histology, infratentorial tumors, and metastatic disease at diagnosis, respectively. 15 (28.3%) pts received pre-RT chemotherapy and 10 pts (18.9%) had disease progression before RT. After median of 1 surgery (range: 1-5), 41 (77.4%) pts had a GTR before RT. 32 (60.4%) pts received ≥59.4 Gy. Median age at diagnosis was significantly lower for patients in the <59.4 Gy group compared to ≥59.4 Gy (3.9 vs. 8.7 years, p=0.01). Other factors were not significantly different between the two groups; however, fewer patients had anaplastic histology in the <59.4 Gy group compared to ≥59.4 Gy (23.8% vs. 46.9%, p=0.15). Median follow-up was 20.1 (range: 0.1-21.9) and 8.4 (range: 0.9-16.6) years for the <59.4 Gy and ≥59.4 Gy groups, respectively. PFS (8-year rates of 31.6% vs. 49.7%, p=0.24) and OS (8-year rates of 46.3% vs. 66.3%, p=0.19) were not significantly different between the <59.4 Gy and ≥59.4 Gy groups. Given anaplastic histology portends poor outcome, we examined outcomes for pts with grade 2 ependymoma, and found no significant difference in PFS (8-year rates of 40.0% vs. 61.5%, p=0.11) and OS (8-year rates of 46.7% vs. 64.8%, p=0.13) between the <59.4 Gy and ≥59.4 Gy groups. Median time to recurrence was 1.3 years (range: 0.3-14.7). Of the 29 recurrences in cohort, 7 (24.1%) occurred 5 years after RT. <h3>Conclusion</h3> In a modest sample size of pts undergoing photon-based RT for intracranial ependymoma, we found that there was a non-significant trend to PFS and OS being longer in pts receiving ≥59.4 Gy. Interestingly, 24.1% of recurrences in our cohort occurred 5 years or longer after RT, indicating that intracranial ependymoma can have a long disease course and long follow-up is important when studying outcomes. Future studies with larger cohorts and prospective design are still needed.

Proton Beam Therapy for Esophageal Cancer.

Simple SummaryEarly-stage esophageal cancer is managed surgically, with the addition of radiotherapy for locally advanced disease. Current photon-based radiotherapy results in a high treatment-related complications, due to proximal organ involvement. The anatomic location of the esophagus raises challenges due to the anatomical changes associated with diaphragmatic motion, weight loss, tumor changes, and set-up variability. These propelled the interest in proton beam therapy (PBT), which theoretically offers a reduction in the radiation exposure to healthy neighboring tissues with improvements in the therapeutic ratio. In this review, we present the role of PBT for esophageal cancer, including treatment planning, early clinical comparisons with photon-based techniques, ongoing trials, current challenges, toxicities, and issues of equity and health services.Early-stage esophageal cancer is often primarily managed surgically, with the addition of radiotherapy for locally advanced disease. However, current photon-based radiotherapy regimens and surgery results in a high incidence of treatment-related cardiac and pulmonary complications due to the involvement of proximal organs at risk. In addition, the anatomic location of the esophagus raises challenges for radiotherapy due to the anatomical changes associated with diaphragmatic motion, weight loss, tumor changes, and set-up variability. These challenges propelled the interest in proton beam therapy (PBT), which theoretically offers a reduction in the radiation exposure to healthy neighboring tissues with improvements in the therapeutic ratio. Several dosimetric studies support the potential advantages of PBT for esophageal cancer treatment however, translation of these results to improved clinical outcomes remains unclear with limited clinical data, especially in large populations. Studies on the effect on quality of life are likewise lacking. Here, we review the existing and emerging role of PBT for esophageal cancer, including treatment planning, early clinical comparisons of PBT with photon-based techniques, recently concluded and ongoing clinical trials, challenges and toxicities, effects on quality of life, and global inequities in the treatment of esophageal cancer.

JS5-1 Particle therapy: past, present, and future

Charged particles such as protons and carbon-ions are known to have physical advantages in radiotherapy for deep-seated tumors because of their desirable dose distributions for the target volume with fewer portals compared with photons, and they can therefore reduce radiation-induced morbidities by reducing irradiated volumes and doses at the surrounding normal tissues, theoretically, but it had been argued that particle therapy was truly effective and more feasible than photon-based radiotherapy.

Proton Therapy in the Management of Pancreatic Cancer.

Simple SummaryRadiation treatment plays a pivotal a role in the management of pancreatic cancer, mainly in the neoadjuvant setting for borderline resectable tumors and in the definitive setting for unresectable localized disease. Most of the studies on pancreatic cancer use photon-based radiation therapy modalities. However, there is a growing interest in the application of protons therapy for gastrointestinal cancers. This review summarizes the literature on the use of proton therapy in the management of pancreatic cancer. Radiation therapy plays a central role in the treatment of pancreatic cancer. While generally shown to be feasible, proton irradiation, particularly when an ablative dose is planned, remains a challenge, especially due to tumor motion and the proximity to organs at risk, like the stomach, duodenum, and bowel. Clinically, standard doses of proton radiation treatment have not been shown to be statistically different from photon radiation treatment in terms of oncologic outcomes and toxicity rates as per non-randomized comparative studies. Fractionation schedules and concurrent chemotherapy combinations are yet to be optimized for proton therapy and are the subject of ongoing trials.

RARE-09. Treatment of childhood-onset craniopharyngioma patients using proton beam therapy versus photon-based radiation therapy in the prospective KRANIOPHARYNGEOM 2007 trial

BACKGROUND: Proton beam therapy (PBT) compared to photon-based radiotherapy (XRT) offers the benefit to administer lower radiation doses to critical organs thereby possibly minimizing the risk of sequelae in patients with residual craniopharyngiomas (CP) after hypothalamus-sparing surgery. The validation in large CP patient cohorts is still pending. PATIENTS AND METHODS: Of 290 childhood-onset CP patients included 2007-2019 in the prospective multicenter trial KRANIOPHARYNGEOM 2007, 99 (34%) received external RT (65% PBT, 35% XRT). Outcome was compared between the different groups in terms of overall (OS) and event-free survival (EFS), quality of life (QoL using PEDQOL), functional capacity (FMH), and auxological data (BMI and height SDS) one, three and five years after irradiation/CP diagnosis. RESULTS: PBT became the predominant irradiation technique during the study period (used in 23% and 77% of all irradiated patients registered within the first and second half of the enrollment period, respectively). PBT as well as XRT were associated with high (p<0.001) EFS (PBT: 0.917 ± 0.040; XRT: 0.940 ± 0.041) compared to non-RT (EFS: 0.669 ± 0.044). OS was similar in all groups. No differences between PBT, XRT and non-RT CP patients concerning functional capacity and anthropometric parameters (height SDS, BMI SDS) have been obtained. Only in the PEDQOL domain “physical function”, proxy-assessed QoL was lower one year after PBT when compared to XRT treated and non-irradiated CP patients. CONCLUSION: PBT is similar efficient in preventing relapses and recurrences in childhood-onset CP patients. During follow-up, no clinically relevant differences between PBT and XRT in terms of QoL, functional capacity and degree of obesity as a marker of hypothalamic syndrome were detectable. While PBT is increasingly applied, studies on larger CP cohorts with longer follow-up after RT are warranted to analyze, whether it can prevent sequelae such as hypothalamic syndrome and severe obesity compared to XRT.