Hypofractionated Radiotherapy Group Research Articles

Choosing Wisely between Radiotherapy Dose-Fractionation Schedules: The Molecular Graded Prognostic Assessment (molGPA) for Elderly Glioblastoma (eGBM-molGPA)

This study aimed to develop a graded prognostic assessment (GPA) model integrating genomic characteristics in patients with elderly glioblastoma (eGBM), and compare the efficacy between conventionally fractionated radiotherapy (CFRT) vs. hypofractionated radiotherapy (HFRT) in each risk group. Patients aged ≥65 years who underwent surgical resection followed by radiotherapy (RT) with or without temozolomide (TMZ) for newly diagnosed IDH-wildtype eGBM between 2006 and 2021 were included in this multicenter cohort study. Patients who were planned for a ≥6-week or ≤4-week radiotherapy were regarded as being treated with CFRT or HFRT, respectively. Based on the prognostic factors significantly identified through multivariate analysis for overall survival (OS), we developed the molecular GPA for eGBM (eGBM-molGPA) and assigned 0.0, 0.5, and 1.0 points in proportion to the corresponding hazard ratio (HR) of each factor. Then, the survival outcomes by treatment groups were evaluated according to the eGBM-molGPA scores. A total of 334 and 239 patients who underwent CFRT and HFRT were included, respectively, and 86% of patients were treated with TMZ-based chemoradiation. With a median follow-up of 17.4 months for survivors, the median OS was 18.7 months for CFRT plus TMZ group, 15.1 months for HFRT plus TMZ group, and 10.4 months for RT alone group, respectively (all p<0.001). In the multivariate analysis, Karnofsky performance scale, surgical extent, TMZ, and the methylation status of the MGMT promoter were identified as strong prognostic factors for OS, with an estimated HR of greater than 1.5 (all p<0.001). Additionally, subventricular zone involvement, temporalis muscle thickness, RT regimen, and the mutation status of TERT promoter and TP53 gene were found to be significant prognostic factors for OS, with an estimated HR of less than 1.5. The eGBM-molGPA was established based on these prognostic factors (Table 1) and patients were allocated to three risk groups, which included high risk (total score of 3.0-4.5), intermediate risk (1.5-2.5), and low risk (0.0-1.0). Patients treated with CFRT plus TMZ had significantly improved OS compared to those treated with HFRT plus TMZ or RT alone in the low and intermediate risk groups (p<0.001). However, in the high-risk group, there was no significant difference in OS between treatment options (p = 0.770). CFRT plus TMZ can be a more effective strategy for selected eGBM patients compared to HFRT. For high-risk patients, a protracted treatment schedule might not be beneficial. The novel eGBM-molGPA can be used as a clinical tool for choosing wisely among treatment options. Further prospective studies are warranted to establish optimal RT guidelines for eGBM patients.

LMAP-04 CHOOSING WISELY BETWEEN RADIOTHERAPY DOSE-FRACTIONATION SCHEDULES: THE MOLECULAR GRADED PROGNOSTIC ASSESSMENT (MOLGPA) FOR ELDERLY GLIOBLASTOMA (EGBM-MOLGPA)

Abstract This study aimed develop a prognostic model integrating genomic characteristics in patients with elderly glioblastoma (eGBM), and compare the efficacy between conventionally fractionated radiotherapy (CFRT) vs. hypofractionated radiotherapy (HFRT). Patients aged ≥65 years who underwent radiotherapy for IDH-wildtype eGBM between 2006 and 2021 were included. Patients planned for a ≥6-week or ≤4-week radiotherapy were regarded as being treated with CFRT (334 patients; median, 60 Gy in 30 fractions) or HFRT (239 patients; median, 45 Gy in 15 fractions), respectively. We developed the molecular graded prognostic assessment score for eGBM (eGBM-molGPA) and assigned 0.0, 0.5, and 1.0 points in proportion to the corresponding hazard ratio (HR) of each prognostic factor for overall survival (OS). Temozolomide-based chemoradiation was applied for 86% of patients. With a median follow-up of 17.4 months, the median OS was 18.7 months for CFRT plus temozolomide group, 15.1 months for HFRT plus temozolomide group, and 10.4 months for RT alone group. The eGBM-molGPAwas established based on prognostic factors from multivariate analysis (performance, extent of resection, temozolomide, methylation of the MGMT promoter, subventricular zone involvement, temporalis muscle thickness, and the mutation status of TERT promoter and TP53 gene) and patients were allocated to three risk groups (high risk, total score 3.0–4.5; intermediate risk, 1.5–2.5; low risk, 0.0–1.0). Patients treated with CFRT plus temozolomide had significantly improved OS compared to those treated with HFRT plus temozolomide or radiotherapy alone in the low and intermediate risk groups (p&amp;lt;0.001). However, in the high-risk group, there was no significant difference in OS between treatment options. CFRT plus temozolomide can be a more effective strategy for selected eGBM patients compared to HFRT. For high-risk patients, a protracted treatment schedule might not be beneficial. The novel eGBM-molGPA can be used as a clinical tool for choosing wisely among radiotherapy options.

Analysis of risk factors of radiation-induced toxicity in limited-stage small cell lung cancer treated with hypofractionated intensity-modulated radiotherapy

Objective: To compare the incidence of radiation-related toxicities between conventional and hypofractionated intensity-modulated radiation therapy (IMRT) for limited-stage small cell lung cancer (SCLC), and to explore the risk factors of hypofractionated radiotherapy-induced toxicities. Methods: Data were retrospectively collected from consecutive limited-stage SCLC patients treated with definitive concurrent chemoradiotherapy in Cancer Hospital of Chinese Academy of Medical Sciences from March 2016 to April 2022. The enrolled patients were divided into two groups according to radiation fractionated regimens. Common Terminology Criteria for Adverse Events (CTCAE, version 5.0) was used to evaluate the grade of radiation esophagus injuries and lung injuries. Logistic regression analyses were used to identify factors associated with radiation-related toxicities in the hypofractionated radiotherapy group. Results: Among 211 enrolled patients, 108 cases underwent conventional IMRT and 103 patients received hypofractionated IMRT. The cumulative incidences of acute esophagitis grade ≥2 [38.9% (42/108) vs 35.0% (36/103), P=0.895] and grade ≥ 3 [1.9% (2/108) vs 5.8% (6/103), P=0.132] were similar between conventional and hypofractionated IMRT group. Late esophagus injuries grade ≥2 occurred in one patient in either group. No differences in the cumulative incidence of acute pneumonitis grade ≥2[12.0% (13/108) vs 5.8% (6/103), P=0.172] and late lung injuries grade ≥2[5.6% (6/108) vs 10.7% (11/103), P=0.277] were observed. There was no grade ≥3 lung injuries occurred in either group. Using multiple regression analysis, mean esophageal dose ≥13 Gy (OR=3.33, 95% CI: 1.23-9.01, P=0.018) and the overlapping volume between planning target volume (PTV) and esophageal ≥8 cm(3)(OR=3.99, 95% CI: 1.24-12.79, P=0.020) were identified as the independent risk factors associated with acute esophagitis grade ≥2 in the hypofractionated radiotherapy group. Acute pneumonitis grade ≥2 was correlated with presence of chronic obstructive pulmonary disease (COPD, P=0.025). Late lung injuries grade ≥2 was correlated with tumor location(P=0.036). Conclusions: Hypofractionated IMRT are tolerated with manageable toxicities for limited-stage SCLC patients treated with IMRT. Mean esophageal dose and the overlapping volume between PTV and esophageal are independently predictive factors of acute esophagitis grade ≥2, and COPD and tumor location are valuable factors of lung injuries for limited-stage SCLC patients receiving hyofractionated radiotherapy. Prospective studies are needed to confirm these results.

COMPARISON OF HYPOFRACTIONATED RADIOTHERAPY WITH CONVENTIONAL FRACTIONATED RADIOPTHERAPY IN POST MASTECTOMY BREAST CARCINOMA PATIENTS: TOXICITY, EFFICACY AND FEASIBILITY STUDY

Introduction :- Adjuvant radiotherapy plays crucial role in management of carcinoma breast patients. Altered fractionation schedules like hypofractionated radiotherapy (40 Gy/15 fractions/ 3 weeks) is time and resources saving as compared to conventional fractionation radiotherapy (50 Gy/ 25 fractions/ 5 weeks) which is time consuming. The aim of our study was to assess and compare toxicity, efcacy and feasibility of hypofractionated radiotherapy when compared with conventional fractionation radiotherapy in carcinoma breast patients. The data Materials and Methods:- of total 105 breast carcinoma patients was collected and evaluated in this retrospective study. This data includes sociodemographic features, tumor characteristics, treatment details and toxicity proles of patients. Acute and chronic radiation toxicities were assessed as per RTOG common toxicity criteria for adverse events. Efcacy and toxicity data was collected at the time of completion of radiotherapy and every follow up visit from our hospital records and this data was analyzed. In Results :- our study, age of patients ranges from 25-83 yrs, with median age of 49.5 yrs. 42 (40 %) patients were from postmenopausal group with Stage II as predominant stage with 47 (44.76 %) patients. 51 (48.57 %) patients received conventional fractionation radiotherapy (CRT) and 54 (51.42 %) patients received hypo fractionated radiotherapy (HRT). Acute Skin Toxicity was observed in 49/51 (96.07%) patients and 45/54 (83.33%) patients in CRT and HRT group respectively. Chronic skin toxicity was observed in 18/51 (35.29%) and 16/54 (29.62 %) patients in CRT and HRT group respectively. Locoregional failure was observed in 3/51(5.88 %) and 2/54 (3.70%) patients in CRT and HRT group respectively. Toxicity and efcacy comparison in CRT and HRT group patients was statistically non signicant (p &gt; 0.05) Hypofractionated radiotherapy in Conclusion:- adjuvant treatment of carcinoma breast patients is safe, effective, feasible, compliant and time saving treatment option when compared with conventional fractionated radiotherapy.

Combined Hypofractionated Radiotherapy and Chemotherapy Versus Hypofractionated Radiotherapy Alone for Cats with Localized Sinonasal Lymphoma.

Despite considering hypofractionated radiotherapy (HRT) a useful treatment option for feline localized sinonasal lymphoma (stage I), the benefits of additional chemotherapy remain controversial. This retrospective cohort study evaluated the efficacy of the early initiation of chemotherapy in combination with HRT (HRTC) to prolong the progression-free survival (PFS) and overall survival (OS) in cats with localized sinonasal lymphoma compared with HRT alone. While 24 eligible cats received HRT alone (HRT group), 18 received HRTC (HRTC group). The total median administered dose was 35 Gy, with one fraction per week, for a median of five fractions. In the HRTC group, the chemotherapy protocol was cyclophosphamide, doxorubicin, vincristine, and prednisolone (CHOP)-based and cyclophosphamide, vincristine, and prednisolone (COP)-based in 14 (78%) and 4 cats (22%), respectively. Cats in the HRTC group had significantly longer PFS (677 versus 104 days; P = .04) and OS (983 versus 263 days; P = .04) than those in the HRT group. Considering the poor outcome in the HRT group despite the cats having received rescue chemotherapy for progressive disease, the early initiation of additional chemotherapy along with HRT may be recommended for feline localized sinonasal lymphoma.

Real-World Practice of Hypofractionated Radiotherapy in Patients With Invasive Breast Cancer.

PurposeApplication of hypofractionated radiotherapy (HFRT) is growing in patients with breast cancer (BC). This study aimed to explore a real-world practice of HFRT in early and locally advanced BC.MethodsPatients with invasive BC between 2015 and 2019 were retrospectively reviewed. Radiotherapy (RT) was delivered by HFRT and conventionally fractionated radiotherapy (CFRT). Locoregional recurrence-free survival (LRRFS) and disease-free survival (DFS) were calculated by Kaplan–Meier curve and compared by Log-rank test. The effect of treatment modality on DFS was estimated by univariate and multivariable analyses.ResultsA total of 1,010 patients were included in this study, and 903 (89.4%) were treated with HFRT. At a median follow-up of 49.5 months, there was no significant difference in a 4-year cumulative incidence of LRRFS in HFRT group (1.5%) and in CFRT group (3.8%) (p = 0.23), neither in different nodal stages nor in N2–3 patients with different molecular subtypes. The 4-year DFS was 93.5% in HFRT group compared with 89.9% in CFRT group with no significant difference either (p = 0.17). Univariate and multivariable analyses also showed no significant difference in DFS between HFRT and CFRT group. However, DFS of HFRT group tended to be lower in N2–3 patients with triple negative BC compared with that of CFRT group (76.2% versus 100%).ConclusionHFRT can achieve similar cumulative incidence of LRRFS and DFS in patients with BC after lumpectomy or mastectomy, and also in different nodal stage, and in locally advanced stage with different molecular subtypes.

Moderately Hypofractionated Radiotherapy Without Chemotherapy in Elderly or Frail Patients With Head and Neck Cancer.

Comorbidity and frailty are relevant limitations of normofractionated combined radiochemotherapy for squamous cell head and neck cancer (HNSCC), especially in elderly patients. This retrospective study aimed to evaluate the efficacy and toxicity of moderately hypofractionated radiotherapy (HRT) without chemotherapy in patients ineligible for concurrent radiochemotherapy. Between 2011 and 2018, 51 elderly/frail patients with HNSCC were treated with either definitive (n=23) or adjuvant (n=28) moderate HRT. A dose of 45 Gy was given to the primary tumour region and cervical nodes with a sequential boost up to 50 in the adjuvant and 55 Gy in the definitive cure setting (2.5 Gy/fraction). Patient outcomes of locoregional control, overall survival, and acute and late toxicity were analysed. After a median follow-up of 6 months for the definitive HRT group and 28.5 months for the adjuvant HRT group, we found a median overall survival of 6 vs. 55 months (log-rank test: p<0.001) and a median locoregional control of 9 months vs. not reached (log-rank test: p=0.008), respectively. The 2-year rates of locoregional control were 28.5% for the definitive HRT group vs. 75.2% for the adjuvant HRT group. No acute or late grade 4-5 toxicity occurred; grade 3 toxicity was rarely documented. HRT in elderly/frail patients with HNSCC who are unfit for chemotherapy leads to acceptable local control with moderate toxicity in a short overall treatment time. Especially in the postoperative situation, HRT can be considered an appropriate alternative to normofractionated radio(chemo)therapy. Definitive HRT can be a treatment alternative, especially for multimorbid patients.

PO-1110 Local control in hypofractionated RT after breast-conservative surgery among young Egyptian patients

Purpose or Objective Since the beginning of coronavirus disease (COVID-19), there is a compelling reason for the use of hypofractionated radiotherapy (HFRT) schedules in cancer management to safeguard the patients and the treating physicians. However, conflicting data shows that young breast cancer (BC) patients have a higher locoregional relapse after breast-conservative surgery (BCS). Given this, we aim to compare the locoregional control between conventional radiotherapy (CRT) and HFRT after BCS in a cohort of young BC patients. Materials and Methods We retrospectively reviewed stage I-III BC patients in two centers diagnosed between 2008 and 2017 who underwent BCS and had follow-up data. Patients were categorized into two groups: CRT (50Gy in 25 fractions) vs. HFRT (40.5 - 42.5 Gy in 15-16 fractions). Boost was added to all patients. Results 247 patients were included in this analysis. Among them, 87 (35%) received CRT, while 160 (65%) were treated by HFRT. The clinicopathological characteristics of CRT vs. HFRT were as follows: The majority of the patients were T1 and T2, 92% in CRT vs. 94% in HFRT. N3 was rare in both groups, 8.3% vs. 5.1% in CRT vs. HFRT, respectively. The CRT had more stage 3 patients than HFRT, 35% vs. 23% respectively, but fewer stage 1 (18.1 vs. 23.5%, respectively). Estrogen/progesterone receptor (ER/PR) positive was 79.5% vs. 76.7%, HER2 enriched was 7% vs. 5%, while high Ki-67 was 56.3% vs. 71.4% in CRT vs. HFRT, respectively. Lymphovascular invasion was positive in 52.7% of CRT vs. 64.3% in HFRT, while the extracapsular extension was positive in 31% of CRT vs. 19.4% in HFRT. The distribution of tumor grades was similar across the groups. After a median follow up of 42 months (range: 5-135), 10% of the total 247 patients developed locoregional recurrences:13.8% (n=12) were in CRT group, whereas 8.1% (n=13) in HFRT, p = 0.158;the HFRT group had insignificant lower locoregional recurrences. In univariate and multivariate analysis, only very young age was an independent poor prognostic factor for locoregional failure. Conclusion We found no significant differences in locoregional control between CRT and the HFRT following BCS among young BC patients. In this COVID-19 pandemic, HFRT should also be considered in young BC patients to shorten the treatment time.

Comparison of hypofractionation and standard fractionation for post-prostatectomy salvage radiotherapy in patients with persistent PSA: single institution experience

BackgroundHypofractionated post-prostatectomy radiotherapy is emerging practice, however with no randomized evidence so far to support it’s use. Additionally, patients with persistent PSA after prostatectomy may have aggressive disease and respond less well on standard salvage treatment. Herein we report outcomes for conventionally fractionated (CFR) and hypofractionated radiotherapy (HFR) in patients with persistent postprostatectomy PSA who received salvage radiotherapy to prostate bed.MethodsSingle institution retrospective chart review was performed after Institutional Review Board approval. Between May 2012 and December 2016, 147 patients received salvage postprostatectomy radiotherapy. PSA failure-free and metastasis-free survival were calculated using Kaplan–Meier method. Cox regression analysis was performed to test association of fractionation regimen and other clinical factors with treatment outcomes. Early and late toxicity was assessed using Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0.ResultsSixty-nine patients who had persistent PSA (≥ 0.1 ng/mL) after prostatectomy were identified. Median follow-up was 67 months (95% CI 58–106 months, range, 8–106 months). Thirty-six patients (52.2%) received CFR, 66 Gy in 33 fractions, 2 Gy per fraction, and 33 patients (47.8%) received HFR, 52.5 Gy in 20 fractions, 2.63 Gy per fraction. Forty-seven (68%) patients received androgen deprivation therapy (ADT). 5-year PSA failure- and metastasis-free survival rate was 56.9% and 76.9%, respectively. Thirty patients (43%) experienced biochemical failure after salvage radiotherapy and 16 patients (23%) experienced metastatic relapse. Nine patients (13%) developed metastatic castration-resistant disease and died of advanced prostate cancer. Median PSA failure-free survival was 72 months (95% CI; 41–72 months), while median metastasis-free survival was not reached. Patients in HFR group were more likely to experience shorter PSA failure-free survival when compared to CFR group (HR 2.2; 95% CI 1.0–4.6, p = 0.04). On univariate analysis, factors significantly associated with PSA failure-free survival were radiotherapy schedule (CFR vs HFR, HR 2.2, 95% CI 1.0–4.6, p = 0.04), first postoperative PSA (HR 1.02, 95% CI 1.0–1.04, p = 0.03), and concomitant ADT (HR 3.3, 95% CI 1.2–8.6, p = 0.02). On multivariate analysis, factors significantly associated with PSA failure-free survival were radiotherapy schedule (HR 3.04, 95% CI 1.37–6.74, p = 0.006) and concomitant ADT (HR 4.41, 95% CI 1.6–12.12, p = 0.004). On univariate analysis, factors significantly associated with metastasis-free survival were the first postoperative PSA (HR 1.07, 95% CI 1.03–1.12, p = 0.002), seminal vesicle involvement (HR 3.48, 95% CI 1.26–9.6,p = 0.02), extracapsular extension (HR 7.02, 95% CI 1.96–25.07, p = 0.003), and surgical margin status (HR 2.86, 95% CI 1.03–7.97, p = 0.04). The first postoperative PSA (HR 1.04, 95% CI 1.00–1.08, p = 0.02) and extracapsular extension (HR 4.24, 95% CI 1.08–16.55, p = 0.04) remained significantly associated with metastasis-free survival on multivariate analysis.Three patients in CFR arm (8%) experienced late genitourinary grade 3 toxicity.ConclusionsIn our experience, commonly used hypofractionated radiotherapy regimen was associated with lower biochemical control compared to standard fractionation in patients with persistent PSA receiving salvage radiotherapy. Reason for this might be lower biological dose in HFR compared to CFR group. However, this observation is limited due to baseline imbalances in ADT use, ADT duration and Grade Group distribution between two radiotherapy cohorts. In patients with persistent PSA post-prostatectomy, the first postoperative PSA is an independent risk factor for treatment failure. Additional studies are needed to corroborate our observations.

Hypofractionated Radiotherapy Using Simultaneous Integrated Boost Technique with Concurrent and Adjuvant Temozolomide for Glioblastoma

Aim: This study was conducted to assess the safety and efficacy of postoperative hypofractionated radiotherapy (HRT) using simultaneous integrated boost (SIB) technique for glioblastoma (GBM) compared to conventional radiotherapy (CRT).&#x0D; Study Design: This was a prospective study with historical control arm.&#x0D; Place and Duration of the Study: Department of Clinical Oncology and Nuclear Medicine, Mansoura University Hospital, Mansoura, Egypt, between May 2017 and June 2019.&#x0D; Methods: The intervention (HRT) group included 30 patients who received 3D conformal HRT with SIB using field in field (FIF) technique to deliver a differential radiation dose to different targets. Planning target volume 60 (PTV60) includes the gross target volume (GTV) plus a 5-mm margin, and PTV45 includes the GTV plus a 15-mm margin. PTV60 will receive 60 Gy in 20 fractions, and PTV45 will receive 45 Gy in the same 20 fractions (one fraction daily and 5 days per week).The CRT group included 30 patients who received 3D conformal CRT with total dose 60 Gy in 2-Gy fractions delivered over 6 weeks. Both groups was planned to receive concurrent and adjuvant temozolamide.&#x0D; Results: The median PFS was 10 months in both groups. The median OS was 13 months in HRT group versus 12 months in CRT group which is statistically non significant. The toxicities were mild and acceptable. Performance status and adjuvant temozolamide were significant predictors that affect the overall survival.&#x0D; Conclusions: HRT with SIB using 3D conformal RTH with (FIF) technique in patients with GBM is a feasible and safe treatment and its results is comparable to the conventional radiotherapy.

Abstract 6509: Hypofractionated radiotherapy as a vaccine in combination with the TLR7/8 agonist resiquimod leads to significant abscopal tumor response and persistence antitumor immunity

Abstract High doses of ionizing radiation (IR) as delivered with hypofractionated radiotherapy (HFRT) can generate immunogenic cell death and elicit adaptive anti-tumor immunity through cross priming of tumor associated antigens. Resiquimod (R-848), a TLR7/8 agonist, generates a systemic antitumor immunity resulting in tumor regression and enhanced T-cell effector function in cutaneous T-cell lymphomas clinically. We hypothesized that combining HFRT with immunotherapy would boost the antitumorigenic effects of either monotherapies, and if so, could lead to a readily translated clinical modality. B16F10 (murine melanoma) and SCC7 (murine squamous cell carcinoma) cells were used as to grow flank subcutaneous syngeneic tumor models in C57BL/6J and C3H/HeJ mice respectively. Our studies indicate that intratumoral administration of resiquimod combined with HFRT to those tumors leads to a significantly stronger antitumor response than either single treatment in both tumor models. The combination therapy in the primary tumor led to complete tumor regression of the SCC7 tumors in 86% of the treated mice to just 14% rejection in the HFRT group alone. Tumor re-challenge of those mice led to tumor rejection in 83% in the combination group compared to 0% of the HFRT group indicating a potent systemic effect of the combined therapy. Furthermore, the combination therapy led to significant reduction of the index (treated) but moreover in the abscopal (untreated) tumors compared to either monotherapy confirming a systemic antitumor effect in this dual-tumor in vivo model. RT-qPCR analysis revealed an increase expression of Th-1 signature (IFNγ, IL-12, Prf1, GzmB) in both primary and abscopal tumors and flowcytometric analysis of the abscopal B16F10 tumors revealed an increase in CD8+ infiltration. A more thorough flowcytometric analysis following staining with the gp100 tetramer revealed an increased cross-priming against gp100 (PMEL) and enhanced gp100-specific T-cell infiltration within the tumor. Moreover, splenocytes that were re-stimulated in vitro with the gp100 peptide in an IFNγ ELISPOT assay, they increased in mice treated with the dual therapy. Finally, an in vitro study of B16F10 cells, which express TLR7/8 receptors, revealed a substantial increase in IFNβ and CCL5 expression with the dual treatment. Knocking down TLR7 and Tmem173 (STING) in those cells with siRNAs completely reversed the phenotypic IFN type I expression signature. In conclusion, the combination of HFRT with Resiquimod leads to very potent antitumor effects in both primary and abscopal melanoma and squamous cell carcinoma tumors driven by an enhanced systemic immunologic response. Our findings provide the rational for translating therapies combining radiotherapy and intratumoral resiquimod into early-phase clinical trials. Citation Format: Ilias V. Karagounis, Stefano Pierini, Noëlle François, Christoforos Thomas, Xiaowei Xu, Constantinos Koumenis, Andrea Facciabene, Amit Maity. Hypofractionated radiotherapy as a vaccine in combination with the TLR7/8 agonist resiquimod leads to significant abscopal tumor response and persistence antitumor immunity [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 6509.

Comparison of Treatment Outcome between Hypofractionated Radiotherapy and Conventional Radiotherapy in Postmastectomy Breast Cancer

Objective:The aim of this study was to compare Conventional fractionated radiotherapy (CFRT) and Hypofractionated radiotherapy (HFRT) in terms of treatment outcomes, such as in 5-year loco-regional recurrence free survival, disease free survival, overall survival, and distant metastatic free survival rates as well as toxicity. Materials and Methods:We retrospectively analyzed the data obtained from 462 breast cancer patients who received complete adjuvant radiotherapy treatment between January 2012 and December 2014. One hundred twenty eight patients received CFRT 2 Gy daily fractions at a total dose of 48-60 Gy (group 1), while 334 patients received HFRT 2.65-2.67 Gy daily for 15-19 fractions at a total dose of 39.7-47.8 Gy 9 (grup 2). Treatment outcome such as 5-year loco-regional recurrence free survival, disease free survival, overall survival, and distant metastatic free survival rates as well as toxicity were measured and compared between two groups. Results:Median follow-up was 65.7 months (ranging from 45.1 to 95.2 months). Five-year loco-regional recurrence free survival rate was 96.1% in both CFRT and HFRT groups (p=0.993). Five-year disease-free survival rate of CFRT group was higher (68.8%), but this difference was not significant (HFRT =63.5%) (p=0.396). These were complied with 5-year overall survival rate (71.9% and 64.7%, p=0.385). Five-year distant metastatic free survival rate was 85.9% in CFRT group and 79.6% in HFRT group (p=0.169). No difference was observed between two groups in terms of toxicities, including changes in chest wall appearance, skin fib rosis, brachial plexopathy, arm edema, pulmonary fibrosis, and cardiovascular events. Conclusion:The treatment outcomes of hypofractionated radiotherapy in the postmastectomy breast cancer patients is comparable to the outcomes of conventional treatment at the Chonburi Cancer Hospital as previously reported from other studies, and HFRT can be implemented in resource-limited settings.

Comparison of efficacy, safety, and costs between neoadjuvant hypofractionated radiotherapy and conventionally fractionated radiotherapy for esophageal carcinoma.

BackgroundWe compared the efficacy, safety, and costs of hypofractionated radiotherapy (HFRT) and conventional fractionated radiotherapy (CFRT) for the neoadjuvant treatment of esophageal cancer.Materials and MethodsOverall, 110 patients with esophageal cancer treated with neoadjuvant chemoradiotherapy from October 2002 to July 2017 were retrospectively included and divided into a HFRT group (42 patients received 30 Gray [Gy]/10 fractions for 2 weeks) and a CFRT group [68 patients received 40 Gy/20 fractions for 4 weeks]. Concurrent chemotherapy comprised cisplatin combined with either 5‐FU or taxane. Surgery was performed 3‐8 weeks after radiotherapy. We compared the outcomes, adverse events, and costs between the two groups.ResultsPathological downstaging was achieved in 78.6% of the HFRT group and 83.8% of the CFRT group (P = 0.612). Compared with the CFRT group, the HFRT group had similar pathological complete response (pCR) (33.3% vs 35.3%; P = 0.834), median overall survival (OS) (40.8 months vs 44.9 months; P = 0.772) and progression free survival (32.7 months vs 35.4 months; P = 0.785). The perioperative complication rates were also similar between the groups, but the treatment time and costs were significantly reduced in the HFRT group (P < 0.05). Finally, multivariate analysis identified cN0 stage, pathological downstaging and pCR as independent predictors of better OS.ConclusionPreoperative HFRT is effective and safe for esophageal cancer. Moreover, it is similar to CFRT in terms of overall survival and toxicity and is cost effective and less time consuming.

Hypofractionated versus conventional fractionated postmastectomy radiotherapy for patients with high-risk breast cancer: a randomised, non-inferiority, open-label, phase 3 trial

To our knowledge, no randomised study has compared postmastectomy hypofractionated radiotherapy with conventional fractionated radiotherapy in patients with breast cancer. This study aimed to determine whether a 3-week schedule of postmastectomy hypofractionated radiotherapy is as efficacious and safe as a 5-week schedule of conventional fractionated radiotherapy. This randomised, non-inferiority, open-label, phase 3 study was done in a single academic hospital in China. Patients aged 18-75 years who had undergone mastectomy and had at least four positive axillary lymph nodes or primary tumour stage T3-4 disease were eligible to participate. Patients were randomly assigned (1:1) according to a computer-generated central randomisation schedule, without stratification, to receive chest wall and nodal irradiation at a dose of 50 Gy in 25 fractions over 5 weeks (conventional fractionated radiotherapy) or 43·5 Gy in 15 fractions over 3 weeks (hypofractionated radiotherapy). The modified intention-to-treat population (including all eligible patients who underwent randomisation but excluding those who were considered ineligible or withdrew consent after randomisation) was used in primary and safety analyses. The primary endpoint was 5-year locoregional recurrence, and a 5% margin was used to establish non-inferiority (equivalent to a hazard ratio <1·883). This trial is registered at ClinicalTrials.gov, number NCT00793962. Between June 12, 2008, and June 16, 2016, 820 patients were enrolled and randomly assigned to the conventional fractionated radiotherapy group (n=414) or hypofractionated radiotherapy group (n=406). 409 participants in the conventional fractionated radiotherapy group and 401 participants in the hypofractionated radiotherapy group were included in the modified intention-to-treat analyses. At a median follow-up of 58·5 months (IQR 39·2-81·8), 60 (7%) patients had developed locoregional recurrence (31 patients in the hypofractionated radiotherapy group and 29 in the conventional fractionated radiotherapy group); the 5-year cumulative incidence of locoregional recurrence was 8·3% (90% CI 5·8-10·7) in the hypofractionated radiotherapy group and 8·1% (90% CI 5·4-10·6) in the conventional fractionated radiotherapy group (absolute difference 0·2%, 90% CI -3·0 to 2·6; hazard ratio 1·10, 90% CI 0·72 to 1·69; p<0·0001 for non-inferiority). There were no significant differences between the groups in acute and late toxicities, except that fewer patients in the hypofractionated radiotherapy group had grade 3 acute skin toxicity than in the conventional fractionated radiotherapy group (14 [3%] of 401 patients vs 32 [8%] of 409 patients; p<0·0001). Postmastectomy hypofractionated radiotherapy was non-inferior to and had similar toxicities to conventional fractionated radiotherapy in patients with high-risk breast cancer. Hypofractionated radiotherapy could provide more convenient treatment and allow providers to treat more patients. National Key Projects of Research and Development of China; the Chinese Academy of Medical Science Innovation Fund for Medical Sciences; and Beijing Marathon of Hope, Cancer Foundation of China.

Hypofractionated Radiotherapy for Anaplastic Thyroid Carcinoma: 15 Years of Experience in a Single Institution

Background: Anaplastic thyroid carcinoma (ATC) is a rare cancer and has a poor prognosis. Several radiation protocols have been reported, but the results were not satisfactory. Objective: The aim of this study was to determine the effect of hypofractionated radiotherapy. Methods: Thirty-three patients who received radiotherapy for ATC between January 2000 and December 2014 were retrospectively included. We defined hypofractionated radiotherapy as a single dose ≥5 Gy. Results: Nineteen patients were treated with hypofractionated radiotherapy. Twenty-eight patients died, and 27 of those patients died from ATC. Sixteen patients died from distant metastasis and 6 from local recurrence. In the hypofractionated radiotherapy group, local recurrence occurred in 5 patients and 1 of them died from active bleeding from a local tumor. There was local recurrence in 7 patients who received the other protocol, and 5 of them died from asphyxiation, active bleeding, or uncontrollable growth of a local tumor on the neck. The median overall survival (OS) was 5 months. In multivariate analysis, patients who received an equivalent dose in 2-Gy fractions (EQD₂) ≥50 Gy had significantly better OS (p = 0.016). In univariate analysis, patients who received hypofractionated radiotherapy did not have significantly better OS (p = 0.872) or local control (p = 0.090). The χ² test showed that significantly fewer patients died from local recurrence in the hypofractionated radiotherapy group (p = 0.025). Conclusions: Multivariate analysis showed that an EQD₂ ≥50 Gy resulted in better OS, and hypofractionated radiotherapy decreased the rate of mortality from local recurrence.

Hypofractionated Versus Conventional Fractionated Postmastectomy Radiotherapy for High-Risk Breast Cancer Patients: A Randomized, Phase III, Non-Inferiority, Open-Label Trial

Background: No randomized study has compared postmastectomy hypofractionated radiotherapy (HFRT) with conventional fractionated radiotherapy (CFRT) in breast cancer patients. This study aimed to determine whether a 3-week schedule of postmastectomy HFRT is as effective and safe as a 5-week schedule of CFRT. Methods: This randomized phase III non-inferiority open-label study was conducted in a single institution in China. We enrolled patients who had undergone mastectomy and had = 4 positive axillary lymph nodes or T3/4 disease. Patients were randomly assigned (1:1) using a random number generator to receive chest wall and nodal irradiation at a standard dose of 50 Gy in 25 fractions over 5 weeks (CFRT) or at a dose of 43.5 Gy in 15 fractions over 3 weeks (HFRT). The modified intention-to-treat population was used in primary and safety analyses. The primary endpoint was 5-year locoregional recurrence (LRR), and a 5% margin was used to establish non-inferiority. Findings: Between June 12, 2008 and June 16, 2016, 820 patients were recruited and randomly assigned to CFRT (n=411) or HFRT (n=409). Intention-to-treat analyses included 409 participants with CFRT and 401 with HFRT. At a median follow-up of 58.5 months (IQR 39.2-81.8), the 5-year cumulative incidence of LRR was 8.1% in the CFRT group and 8.3% in the HFRT group (absolute difference, 0.2%; 90% confidence interval [CI], -3.0-2.6; hazard ratio, 1.10; 90% CI, 0.72-1.69). The 5-year OS rate was 83.2% versus 85.6% (P=0.526). There were no significant differences in toxicities, except that the HFRT group had less acute skin toxicity than the CFRT group. Interpretation: Postmastectomy HFRT was non-inferior to and was as safe as CFRT in high-risk breast cancer patients. This option affords more convenient treatment and allows providers to treat more patients. Clinical Trial Number: The trial was registered at ClinicalTrials.gov, number NCT00793962. Funding Statement: This study was supported by the National Key Projects of Research and Development of China (2016YFC0904600); the Chinese Academy of Medical Science (CAMS) Innovation Fund for Medical Sciences (CIFMS, 2016-I2M-1-001); and Beijing Marathon of Hope, Cancer Foundation of China (LC2008A06). Declaration of Interests: The authors declare no competing interests. Ethics Approval Statement: This study is a randomized phase III non-inferiority, open-label trial, with patients recruited from a single academic hospital in China. The study protocol was approved by the local Ethics Committee.

Accelerated Hypofractionated Radiotherapy Versus Stereotactic Body Radiotherapy for the Treatment of Stage I Nonsmall Cell Lung Cancer-A Single Institution Experience With Long-Term Follow-Up.

Purpose:Although stereotactic body radiation therapy is one of the standard treatments for stage I nonsmall cell lung cancer, in the case of central tumors it carries the risk of severe adverse events for serial organs. Accelerated hypofractionated radiotherapy is considered a reasonable alternative to treat central tumors. We have been treating central tumors with accelerated hypofractionated radiotherapy using a 75 Gy/25 fr/5 weeks regimen, and we compared the results with those of stereotactic body radiation therapy using 48 Gy/4 fr/1 week.Methods:Patients with central tumors and/or unfit for 1-hour fixation were candidates for accelerated hypofractionated radiotherapy. Based on the proximity to the biologically effective dose at 10 Gy, above accelerated hypofractionated radiotherapy regimen was adopted.Results:From October 2003 to December 2010, 159 patients, who received either accelerated hypofractionated radiotherapy (103 cases) or stereotactic body radiation therapy (56 cases), were included in the analysis. In the accelerated hypofractionated radiotherapy group, 40 (39%) cases were central tumors, whereas all cases were peripheral tumors in the stereotactic body radiation therapy group. Overall 5-year local control and survival rates were 81.9% (95% confidence interval 73.6%-90.1%) and 46.5% (95% confidence interval 36.7%-56.2%), respectively for the accelerated hypofractionated radiotherapy group, and 75.4% (95% confidence interval 63.0%-87.8%) and 44.6% (95% confidence interval 31.6%-57.7%), respectively for the stereotactic body radiation therapy group (n.s.). Among central tumors, ultracentral tumors (21 cases) and the remaining central tumors (19 cases) were similar in both local control and survival. On multivariate analysis, hazard ratios for accelerated hypofractionated radiotherapy versus stereotactic body radiation therapy were <1 for both local control and survival. Pulmonary toxicity was similar in both groups. No serial organ toxicity was observed for central tumors.Conclusions:Accelerated hypofractionated radiotherapy with a 75 Gy/25 fr/5 weeks regimen is promising in that it can obtain similar local control and survival results to stereotactic body radiation therapy, and it can control both central and peripheral tumors without any serial organ toxicities. Based on these results, prospective multicenter trials are worth conducting, especially for ultracentral tumors.

Hypofractionated radiation therapy for breast cancer: long-term results in a series of 85 patients.

Whole-breast irradiation after conservative surgery is the standard treatment for early breast cancer. The purpose of this study is to report the late toxicity, cosmetic result, and disease control in a group of patients treated with hypofractionated radiotherapy (RT) comparing results with retrospective data of a control group who underwent conventional RT. From 2006 to 2008, 85 patients were treated with hypofractionated schedule to dose of 45 Gy, 2.25 Gy/fr, followed by a boost. We evaluated late toxicity, cosmetic result, and disease control. The data were compared to a control group of 70 patients who underwent conventional RT before 2006. At 8 years of follow-up, the cumulative incidence of late skin toxicity was 6.2 in the hypofractionated RT group and 7.5 in the standard RT group (p = 0.94). The cumulative incidence of late subcutaneous tissue toxicity was 11.6 in the hypofractionated RT group and 18.7 in the standard RT group (p = 0.23). Cosmetic outcome was rated as excellent or good in 84/85 patients of the hypofractionated RT group and in 68/70 patients of the conventional RT group (p = 0.7). No statistically significant differences were found in terms of local control (p = 0.05), disease-free survival (p = 0.06), or overall survival (p = 0.17) between the 2 groups. The present analysis, focused on long-term effects, disease control, and survival, confirms, in a daily practice setting, the low incidence of skin atrophy and fibrosis, the satisfactory cosmetic outcome, and the high grade of local and distant disease control with hypofractionated schedule.

TH‐AB‐304‐06: Investigation of Fractionation Issues in NTCP Modeling of Pneumonitis: An Analysis of Common NTCP Models for Hypo‐Fractionated and Standard‐Fractionated Data

Purpose:Previous studies showed that NTCP modeling of radiation pneumonitis for hypo‐fractionated radiotherapy (HFRT) has resulted in different model parameters, e.g. a much higher MLD5₀, than for standard‐fractionated RT (SFRT). This study investigates whether both fractionation schemes can be described by the same NTCP model.Methods:We retrospectively investigated lung DVHs of 487 patients. Of those, 377 were treated with HFRT (3–10 fractions, median Rx=54Gy) at 5 institutions, and 110 were treated with SFRT (23–47 fractions, median Rx=63Gy) at a single institution. NTD₂ was calculated using the LQ‐model and the low‐dose‐hyper‐radiosensitivity model (LDHRS). The latter could possibly explain the reduced toxicities observed in HFRT by assuming a threshold dose for induced repair. NTCP was modeled for all patients using the Lyman‐MLD and Lyman‐EUD model and compared with AICc. Goodness‐of‐fit was determined using Hosmer‐Lemeshow statistics.Results:Within the HFRT group and SFRT group, 7.4% and 10.6% of patients experienced pneumonitis grade&gt;=2 (CTCAE), respectively (median follow‐up=2.13 years). Optimal model parameters (Lyman‐MLD‐LQ: MLD5₀ (NTD)=38.3Gy, m=0.51, AICc=271.0; Lyman‐EUD‐LQ: EUD5₀ (NTD)=24.3Gy, m=0.55, a=0.6, AICc=271.3; Lyman‐MLD‐LDHRS: MLD 5₀(NTD)=42.5Gy, m=0.51, AICc=272.0) for all models yielded acceptable fits to the entire dataset and subgroups (pHL&gt;0.05). Differences in log‐likelihood and AICc values were not large enough to prefer one model over the other. The low volume‐effect parameter (a&lt;1) for the Lyman‐EUD‐LQ model suggests that lower doses‐per‐fraction (&lt;0.58Gy) may be an important factor determining NTCP. This is concurrent with the assumptions of the mechanistic LDHRS model.Conclusion:The results indicate that pneumonitis can, theoretically, be described by the same NTCP model for HFRT and SFRT using the investigated models. Furthermore, irradiation with low doses‐per‐fraction may play a role in causing toxicities. Prior findings of different NTCP model parameters for HFRT and SFRT may be due to extrapolation of the bias introduced by the individual datasets, such as differing volumes receiving low doses‐per‐fraction.This study was supported by the Elekta Collaborative Lung Research Group grant. Dr. Grills discloses stock ownership and is a member of the Greater Michigan Gamma Knife board of directors.

Post-mastectomy Hypofractionation Radiotherapy in Breast Cancer Patients

Background: Post-mastectomy radiotherapy reduces loco-regional recurrence in women with operable breast cancer and improves survival. Conventional fractionated radiotherapy has been limited by patient's compliance, travelling, unplanned interruption and others. Hypofractionated schedule would be more appealing and convenient. The present study was carried out to compare overall survival, disease free survival, loco regional control, and treatment toxicities, in patients treated with conventional fractionated radiotherapy and hypofractionated schedules. Methods: Forty-seven patients with breast cancer (stage T2-4, any N), underwent surgery and received adjuvant systemic treatment and radiotherapy. These patients randomly divided into two groups; conventional fractionated radiotherapy group (N: 22), and hypofractionated radiotherapy group (N: 25). Data of radiation toxicities, and disease relapse in both groups were compared using Chi-square test. Results: The median follow-up was 34 months (range: 13 – 53 months). Four-year overall survival rates were 100% for conventional radiotherapy group and 96% for hypofractionated radiotherapy group, with no significant difference (P value= 0.37). The 4 year disease free survival rate were 81% and 92% for conventional radiotherapy group and hypofractionation radiotherapy group, respectively (p-value= 0.47) and hazard ratio= 0.52 (0.09-2.13). Toxicities were comparable between the both groups. Conclusions: these data showed that hypofractionation 42 Gy radiotherapy in 16 fractions was safe and comparable to conventional fractionation in terms of overall survival, loco-regional tumor control and toxicities. These results need to be tested in large-scale multicenter randomized control trials.