Late Radiation Toxicity Research Articles

Genetic markers of late radiation toxicity in the era of image-guided radiotherapy: lower toxicity rates reduce the predictive value of γ-H2AX foci decay ratio in patients undergoing pelvic radiotherapy

BackgroundA predictive assay for late radiation toxicity would allow more personalized treatment planning, reducing the burden of toxicity for the more sensitive minority, and improving the therapeutic index for the majority. In a previous study in prostate cancer patients, the γ-H2AX foci decay ratio (γ-FDR) was the strongest predictor of late radiation toxicity. The current study aimed to validate this finding in a more varied group of patients with pelvic cancer. Additionally, the potential correlation between the γ-FDR and patient-reported outcomes was investigated.MethodsProstate and gynecological cancer patients with ≥ 24 months of follow-up were included in the current analysis. Toxicity was evaluated by physician (CTCAE version 4) and patient (EORTC questionnaires). γ-FDRs were determined in ex vivo irradiated lymphocytes. Correlation between γ-FDR and toxicity was assessed using both linear and logistic regression analyses. The highest toxicity grade recorded during follow-up was used. The association between global quality of life and γ-FDR was tested by comparing the change in quality of life over time in patients with γ-FDR < or ≥ 3.41, a previously established threshold.ResultsEighty-eight patients were included. Physician-assessed and patient-reported cumulative grade ≥ 2 toxicity was 25% and 29%, respectively; which is much lower than in the previous cohort (i.e., 51% CTCAE grade ≥ 2). Patients with toxicity exhibited less favorable dose-volume parameters. In men, these parameters showed significant improvement compared to the previous cohort. The proportion of patients with a low γ-FDR increased with severity of toxicity, but this trend was not statistically significant. In addition, a γ-FDR < 3.41 was not correlated with the development of moderate to severe toxicity. Post-treatment decline in global quality of life was minimal, and similar for patients with γ-FDR < or ≥ 3.41.ConclusionsIn the present study, the γ-H2AX foci decay ratio could not be validated as a predictor of late radiation toxicity in patients with pelvic cancer. Improved radiotherapy techniques with smaller irradiated bladder and bowel volumes have probably resulted in less toxicities. Future studies on genetic markers of toxicity should be powered on these lower incidences. We further recommend taking persistency, next to severity, into consideration.

Single pre-operative radiation therapy (SPORT-CK) trial for low-risk breast cancer: Early results of a phase 2 study

Background and purposePreoperative partial breast irradiation (PBI) is a novel technique that can be used in patients with early-stage breast cancer with the goal of limiting the irradiated breast volume, toxicity and number of fractions. The aim of this trial is to assess the toxicity, surgical, oncologic and cosmetic outcomes of preoperative PBI. Materials and MethodsIn this single-arm phase II trial, we enrolled women ≥ 60 years, with unifocal low-risk breast invasive ductal carcinoma (cT1N0, grade 1–2, ER+, Her2-). Patients were treated with a single fraction of 20 Gy of preoperative PBI using volumetric modulated arc therapy (VMAT). Patients then underwent breast-conserving surgery (BCS) +/- sentinel lymph node biopsy within 72 h of radiation. Primary outcomes were rate of surgical complications and early toxicity. Secondary outcomes were cosmesis at 12 months, chronic toxicity and ipsilateral breast tumor recurrence. ResultsTwenty-five patients were recruited with a median age of 67 years, and a median follow-up of 60 months. Sentinel biopsy was positive in 1 out of 24 patients (4 %). Two patients received adjuvant RT for close margins or positive lymph nodes. Within the first 90 days, none of the patients had surgical complications; almost all had grade 0 to 1 acute and late RTOG skin toxicity. The cosmetic outcome was rated between good and excellent in all cases by physicians and patients, except for one patient who self-rated her cosmesis as fair as of the third year. There were no recurrences. ConclusionPreoperative single-fraction PBI is a safe and feasible treatment for elderly patients with low-risk early-stage breast cancer, with no surgical complications, very low rates of acute and late radiation toxicity, and excellent cosmetic outcomes. Randomized controlled trials are needed to compare preoperative to adjuvant PBI in this patient population.

The Clinical Course of the Late Toxicity of Definitive Radiotherapy in Cervical Cancer.

Background and Objectives: This study aimed to investigate the clinical course and characteristics of late toxicity over time following the completion of definitive radiotherapy (RT) in patients with cervical cancer. Materials and Methods: We retrospectively reviewed the medical records of 60 patients with cervical cancer who underwent pelvic external beam radiotherapy followed by intracavitary brachytherapy. Late toxicity was assessed for the lower gastrointestinal (GI) tract and bladder organ at 6, 12, 24, 36, and >36 months post-RT. We examined the onset and prevalence of late toxicity at each time point. Clinical remission and interventions for managing late toxicity were also investigated. Results: The peak onset of lower GI toxicity occurred 12 months after RT completion, with a median symptom duration of 9.9 months (range, 0.1-26.3 months), and exhibited its highest prevalence rate of 15.5% at 24 months post-RT. Most GI toxicities developed and resolved within three years post-RT, with a prevalence rate of 8.1% at three years, followed by a decreasing trend. Bladder toxicity first peaked at 24 months post-RT and continued to occur beyond 36 months, showing the re-increasing pattern in the prevalence rate after 36 months (23.5%). In terms of clinical remission, 66.7% of lower GI toxicities (12 of 18 patients) and 60% of bladder toxicities (9 of 15 patients) achieved complete remission by the last follow-up date. Conclusions: Late toxicities of the GI and bladder following definitive RT in cervical cancer are partially reversible and exhibit distinct patterns of onset and prevalence over time. A systematic follow-up strategy should be established for the early detection and timely intervention of late toxicity by understanding these clinical courses.

Clinical Outcome Comparison between CT-Guided Versus all MRI-Guided Scenarios in Brachytherapy for Cervical Cancer: A Single-Institute Experience

ObjectivesImage-guided adaptive brachytherapy (IGABT) is the standard of care for patients with cervical cancer. The objective of this study was to compare the treatment outcomes and adverse effects of computed tomography (CT)-guided and magnetic resonance imaging (MRI)-guided scenarios. Materials and MethodsData of patients with cervical cancer treated using external beam radiotherapy followed by IGABT from 2012 to 2016 were retrospectively reviewed. CT-guided IGABT was compared with the three modes of MRI-guided IGABT: pre-brachytherapy (MRI Pre-BT) without applicator insertion for fusion, planning MRI with applicator in-place in at least 1 fraction (MRI ≥1Fx), and MRI in every fraction (MRI EveryFx). Patient characteristics, oncologic outcomes, and late radiation toxicity were analyzed using descriptive, survival, and correlation statistics. ResultsOverall, 354 patients were evaluated with a median follow-up of 60 months. The 5-year overall survival (OS) rates were 61.5%, 65.2%, 54.4%, and 63.7% with CT-guided, MRI PreBT, MRI ≥1Fx, and MRI EveryFx IGABT, respectively with no significant differences (p = 0.522). The 5-year local control (LC) rates were 92.1%, 87.8%, 80.7%, and 76.5% (p = 0.133), respectively, with a significant difference observed between the CT-guided and MRI ≥1Fx (p = 0.018). The grade 3–4 late gastrointestinal toxicity rates were 6% in the CT-guided, MRI ≥1Fx, and MRI EveryFx, and 8% in MRI PreBT. The grade 3–4 late genitourinary toxicity rates were 4% in the CT-guided, 2% in MRI PreBT, 1% in MRI ≥1Fx, and none in MRI EveryFx. No significant differences were observed in the oncologic and toxicity outcomes among MRI PreBT, MRI ≥1Fx, and MRI EveryFx. ConclusionsCT-guided IGABT yielded an acceptable 5-year OS, LC, and toxicity profile compared with all MRI scenarios and is a potentially feasible option in resource-limited settings.

Research Trends and Evolution in Radiogenomics (2005-2023): Bibliometric Analysis.

Radiogenomics is an emerging technology that integrates genomics and medical image-based radiomics, which is considered a promising approach toward achieving precision medicine. The aim of this study was to quantitatively analyze the research status, dynamic trends, and evolutionary trajectory in the radiogenomics field using bibliometric methods. The relevant literature published up to 2023 was retrieved from the Web of Science Core Collection. Excel was used to analyze the annual publication trend. VOSviewer was used for constructing the keywords co-occurrence network and the collaboration networks among countries and institutions. CiteSpace was used for citation keywords burst analysis and visualizing the references timeline. A total of 3237 papers were included and exported in plain-text format. The annual number of publications showed an increasing annual trend. China and the United States have published the most papers in this field, with the highest number of citations in the United States and the highest average number per item in the Netherlands. Keywords burst analysis revealed that several keywords, including "big data," "magnetic resonance spectroscopy," "renal cell carcinoma," "stage," and "temozolomide," experienced a citation burst in recent years. The timeline views demonstrated that the references can be categorized into 8 clusters: lower-grade glioma, lung cancer histology, lung adenocarcinoma, breast cancer, radiation-induced lung injury, epidermal growth factor receptor mutation, late radiotherapy toxicity, and artificial intelligence. The field of radiogenomics is attracting increasing attention from researchers worldwide, with the United States and the Netherlands being the most influential countries. Exploration of artificial intelligence methods based on big data to predict the response of tumors to various treatment methods represents a hot spot research topic in this field at present.

The spectrum of late radiation sequelae in head and neck cancer

ABSTRACT Introduction: Concurrent Chemoradiation is the standard of care in the treatment of unresectable locally advanced head and neck cancer. Some of the acute side effects seen after or alongside the head and neck radiotherapy include dermatitis, mucositis, xerostomia, dysphagia and swallowing dysfunction. Evolving data demonstrate that acute toxicities may persist long-term and develop into late effects. In addition, late effects may manifest months or years after completion of therapy, persisting for years or even lifelong, far longer than previously believed. When severe, late effects may profoundly affect function and quality of life. The present study was conducted to analyze the spectrum of late radiation toxicities in head and neck cancer patients treated with radical external beam radiation therapy and to determine its prevalence and severity. Materials and Methods: This prospective observational study was conducted in the Department of Radiotherapy, Christian Medical College and Hospital, Ludhiana. In all patients with a histopathological diagnosis of head and neck carcinoma who have received radical radiation therapy alone or definitive chemoradiation as part of cancer-directed therapy. Results: Salivary gland toxicity was the most common toxicity encountered in head and neck cancer survivors resulting in dysphagia followed by dental caries, subcutaneous late effects and dysphagia. As expected, the spectrum of side effects correlated with the primary site, stage of disease and ECOG performance status. Conclusion: Technological advancement in radiation planning and equipment has resulted in a reduction in the most feared side effects of radiation which has led to improvement in the quality of life of the survivors. As no technology can entirely protect normal tissues from irradiation, utmost care should be taken to minimize the radiation dose received by normal tissues by following preventive and supportive measures.

A single-center experience of the upright proton therapy for skull-base chordomas and chondrosarcomas: Updated results

AimTo access efficacy and safety of the upright proton therapy for the skull-base chordomas and chondrosarcomas. Materials and methodsThe study encompasses single-center experience of proton therapy in chordomas (CA) and chondrosarcomas (CSA) of skull-base localization. We evaluate overall survival, local control and toxicity. Tumor response was assessed in accordance with RANO criteria. Treatment-related toxicity was evaluated with the help of CTCAE v 5.0 scale. ResultsProton therapy in the upright position was utilized for 51pts (patients) with CA-CSA (40 pts with chordoma and 11pts with chondrosarcoma) at the A. Tsyb Medical Radiological Research Center in 2016–2023. Median tumor volume constituted 30 cm3 (IQR (interquartile range) 15–41 cm3). Median total dose was 70 GyRBE. Median number of fractions was 35. Overall survival (OS) at 1-, 2- and 3-year rates reached 98.0 %, 88.6 % and 82.7 %, respectively. Median follow-up time was 36 months. The 1-, 2- and 3-year local control (LC) rates constituted, respectively, 98 %, 78.6 % and 66.3 %. Prior surgery showed statistically significant association with better prognosis (p = 0.023). Brainstem-to-tumor dose coverage compromise became the major pattern of LC failure (p = 0.03). The late radiation toxicity reactions included temporal lobe necrosis grade 2 in 2 pts, xerostomia grade 1 in 1pt, radiation cataract grade 2 in 1pt and persistent headache grade 2 in 4 pts. Severe late toxicity reactions were observed in 2 cases (4 %): 1 myelitis grade 3 and brainstem damage grade 5 in 1pt. ConclusionLocal control was achieved in the majority of patients receiving the scanning-beam upright proton therapy for skull-base CA-CSA. The LC rates after a surgery-radiotherapy combination treatment were higher compared with irradiation alone. Pattern of failure is mostly brainstem-tumor dose compromise. The high OS and LC rates were accompanied by low toxicity incidence. Even in complex case of the skull base CA-CSA upright proton therapy shows promising clinical outcomes.

Influence of intensity-modulated radiation therapy on long-term survival and late injury in patients with nasopharyngeal carcinoma after induction chemotherapy.

e24048 Background: To retrospectively analyze the effect of nasopharyngeal primary tumor (GTVnx) target delineation after induction chemotherapy on the long-term survival and late injury of patients after intensity-modulated radiotherapy, so as to provide a reference for the optimal treatment of nasopharyngeal carcinoma. Methods: Retrospective analysis was performed on 52 patients with nasopharyngeal carcinoma who underwent target delineation and radiotherapy after induction chemotherapy in our department from December 2011 to October 2013. All patients underwent long-term survival follow-up and analysis of late injury. The survival rate was calculated by Kaplan-Meier method and log-rank test, Univariate prognostic analysis was performed. Cox model was used to conduct multivariate prognostic analysis. The late radiation toxicity was Evaluation by RTOG/EORTC. Results: From December 2011 to October 2013,52 patients were enrolled in the study group. The follow-up period was up to December 2020. Among them, 23 patients died and the mortality rate was 44.23%, the recurrence rate was 0.38%. Serious adverse reactions occurred in 7 cases (13.2%). The 1,3,5,8 year survival rates were as follows: OS was 94.2%, 82.7%, 65.4%, 49.6%, LRFS was 96.2%, 82.7%, 63.5%, 46.2%, the survival rates of DMFS were 94.2%, 78.8%, 59.6% and 44.2%. Conclusions: The 5 and 8-years OS, LRFS and DMFS of NPC after induction chemotherapy patients treated with IMRT was relatively high, Distant metastasis was the main cause of treatment failure, The main late injuries include grade Ⅰ / Ⅱ hearing impairment, dysphagia dental, caries, xerostomia, the grade Ⅲ and Ⅳ late radiation injury was lower.

Results of Definitive (Chemo)radiotherapy Using Computed Tomography-based Brachytherapy for Cervical Cancer.

Concurrent cisplatin-based chemoradiotherapy (CCRT) is the standard treatment for locally advanced cervical cancer. Especially, CCRT with magnetic resonance imaging (MRI) or computed tomography-based image-guided brachytherapy (CT-based 3D-IGBT) for cervical cancer has resulted in good LC rates. However, progression-free survival (PFS) and overall survival (OS) rates for locally advanced cervical cancer are still low and could be improved. The aim of the study was to evaluate treatment efficacy and late toxicity of external beam radiotherapy (EBRT) and CT-based IGBT with or without concurrent chemotherapy in patients with squamous cell carcinoma of the uterine cervix and investigate patterns of failure. We retrospectively analyzed clinical data of cervical squamous cell carcinoma patients treated with definitive radiotherapy with or without concurrent chemotherapy at Saitama Medical University International Medical Center. Local control (LC), PFS, patterns of failure, and late toxicity were the evaluated outcomes. Overall, 290 patients were enrolled in the study. Median follow-up was 51.5 months. During follow-up, 74 patients developed recurrence: 10 patients with intra-pelvic failure only, 45 with extra-pelvic failure only, and 19 with both. The 3-year LC was 100% for T1b-T2a, 96.8% for T2b, 89.5% for T3b, and 88.5% for T4 disease. The 3-year PFS was 100% for stage IB-IIA, 89.0% for stage IIB, 70.7% for stage IIIB, 72.6% for stage IIIC1r, and 40.1% for stage IVA. The incidence of grade 3-4 gastrointestinal and genitourinary toxicities was 3.0% and 1.7%, respectively. Combination of EBRT and CT-based IGBT with or without concurrent chemotherapy produced favorable LC with acceptable rates of late toxicities. However, extra-pelvic failures frequently occurred and PFS was less satisfactory in patients with stage III-IVA disease, which indicated the need for additional treatment in these patients.

Hyperbaric Oxygen Therapy for Management of Late Radiation Toxicity—A Honey of a Trial?

Hyperbaric Oxygen Therapy for Management of Late Radiation Toxicity—A Honey of a Trial?

The AsiDNA™ decoy mimicking DSBs protects the normal tissue from radiation toxicity through a DNA-PK/p53/p21-dependent G1/S arrest.

AsiDNA™, a cholesterol-coupled oligonucleotide mimicking double-stranded DNA breaks, was developed to sensitize tumour cells to radio- and chemotherapy. This drug acts as a decoy hijacking the DNA damage response. Previous studies have demonstrated that standalone AsiDNA™ administration is well tolerated with no additional adverse effects when combined with chemo- and/or radiotherapy. The lack of normal tissue complication encouraged further examination into the role of AsiDNA™ in normal cells. This research demonstrates the radioprotective properties of AsiDNA™. In vitro, AsiDNA™ induces a DNA-PK/p53/p21-dependent G1/S arrest in normal epithelial cells and fibroblasts that is absent in p53 deficient and proficient tumour cells. This cell cycle arrest improved survival after irradiation only in p53 proficient normal cells. Combined administration of AsiDNA™ with conventional radiotherapy in mouse models of late and early radiation toxicity resulted in decreased onset of lung fibrosis and increased intestinal crypt survival. Similar results were observed following FLASH radiotherapy in standalone or combined with AsiDNA™. Mechanisms comparable to those identified in vitro were detected both in vivo, in the intestine and ex vivo, in precision cut lung slices. Collectively, the results suggest that AsiDNA™ can partially protect healthy tissues from radiation toxicity by triggering a G1/S arrest in normal cells.

Examining patient-reported late toxicity and its association with quality of life and unmet need for symptom management among nasopharyngeal cancer survivors: a cross-sectional survey.

Alongside the improved survival of nasopharyngeal cancer (NPC), late radiation toxicities are alarmingly hampering survivors' quality of life. A patient-reported symptom burden survey is lacking to address the unmet need for symptom management among local NPC survivors. A single-center cross-sectional survey was conducted on 211 NPC survivors who had completed radiation therapy for three to 120 months. We employed the Chinese version M. D. Anderson Symptom Inventory - Head & Neck Module (MDASI-HN-C), Functional Assessment of Cancer Therapy - Head & Neck (FACT-HN-C), and a question extracted from the Cancer Survivors' Unmet Needs Measure (CaSUN). Two hundred valid responses were collected. Participants suffered from at least four moderate to severe symptoms (mean = 4.84, SD = 4.99). The top five severe symptoms were dry mouth, mucus problems, difficulty swallowing or chewing, teeth or gum problems, and memory problems. MDASI-HN-C subscales were negatively correlated with the physical, emotional, functional, and HN-specific domains of the FACT-HN-C. The unmet need for symptom management was positively associated with symptom burden, either general symptoms (Adjusted odds ratio [ORadj] = 1.566, 95% CI = 1.282 - 1.914, p < 0.001) or top-5 symptoms (ORadj = 1.379, 95% CI = 1.185 - 1.604, p < 0.001), while negatively associated with post-RT time (ORadj = 0.981, 95% CI [0.972, 0.991], p < 0.001). Virtually all NPC survivors suffer from late toxicities, which interplay with survivors' perceptions intricately to affect their unmet needs for symptom management. Personalized supportive care strategies with regular assessments and stratifications are warranted.

Mogućnosti radioterapije u lečenju pedijatrijskog Hočkinovog limfoma

Pediatric Hodgkin lymphoma is a malignant, lymphoproliferative disease of children and adolescents. Radiotherapy is an important form of treatment. The possibility of late toxicity of radiotherapy is a limiting factor in the application of radiotherapy as a treatment modality in pediatric patients. The technological progress of radiotherapy and the introduction of advanced radiotherapy techniques and proton therapy have improved the precision of radiotherapy and reduced the risk of long-term consequences. These technologies enabled targeted treatment, significantly reducing the exposure of healthy tissues and organs to radiation. All existing treatment recommendations and conducted cooperative studies have shown that radiation therapy is effective in the treatment of pediatric Hodgkin lymphoma, especially when combined with chemotherapy. On the other hand, there is the possibility of late toxicity to organs in growth and development, as well as the possibility of occurrence of secondary malignancies, which must be carefully considered when deciding on the implementation of radiotherapy. Radiation therapy represents an important therapeutic approach in the combined treatment of pediatric Hodgkin lymphoma. The combined therapeutic approach has improved treatment results, and advanced radiotherapy techniques will reduce the risk of side effects. Indications for the use of radiotherapy should be carefully evaluated in the treatment of pediatric patients with Hodgkin lymphoma.

Proton Radiation Therapy for Stage IIA/IIB Testicular Seminoma.

Testicular seminoma affects young men and is associated with very favorable prognosis. The evolution in treatment paradigm has focused on minimizing acute and especially late toxicities. Following orchiectomy, while surveillance is favored in Stage I patients, radiotherapy (RT) is a standard treatment option for de novo or relapsed stage IIA or select non-bulky stage IIB disease. Despite low doses, standard RT fields to paraaortic and pelvic lymphatics using x-rays exposes a large volume of uninvolved normal tissue/viscera to excess dose. This young patient population is especially vulnerable to risks of late RT toxicities including secondary malignancy. Proton beam therapy (PBT) has dosimetric advantage over x-ray-based RT due to lack of exit dose, and comparative dosimetric/modeling studies show significant sparing of uninvolved abdominal/pelvic organs. However, there is scant reported clinical data at this time for PBT. We review our early institutional outcomes with PBT for testicular seminoma. Single institution retrospective review from a tertiary care center of patients treated with PBT from 2013-2022 for testicular seminoma. Recurrence free (RFS) and overall survival (OS) were calculated from the completion of PBT. Toxicities were graded (Gr) using CTCAE v5.0. Four patients underwent PBT, median age 39 (range 36-47). All were Stage I at diagnosis (pT1b n = 3; pT2 n = 1) and were treated for recurrent stage II disease (IIA n = 3; IIB n = 1) at a median of 34 months from orchiectomy (range 3 - 74 months). Nodal extent included 2 with multiple paraaortic nodes, 1 with solitary paraaortic node and 1 with solitary pelvic node. PBT was delivered with pencil-beam scanning, treating paraaortic + ipsilateral pelvic fields (20 Gy in 10 fractions), then sequential boost to involved nodes (10 -16 Gy in 5-8 fractions). Typically, PA or posterior oblique fields were used to minimize dose to out-of-field abdominal/pelvic viscera. Treatment was well tolerated with minimal acute toxicities: fatigue Gr 1 (n = 3), nausea Gr 1 (n = 3). No Gr 2 or higher acute toxicities or significant late toxicities were observed. At median follow up of 30 months (range 3 - 54), no recurrences were observed, and RFS and OS were 100%. Two patients are without evidence of disease > 4 years post-treatment. In this case series, PBT for retroperitoneal and pelvic metastases in Stage IIA/IIB testicular seminoma was associated with oncologic efficacy with minimal toxicity. PBT reduces unnecessary dose to abdominal/pelvic organs compared to x-ray techniques, which is advantageous in young patients who have anticipated long-term survival. This is one of the few series reporting clinical outcomes of PBT in the management of seminoma. Randomized comparisons with x-ray approaches are impractical given the relatively low volume of patients receiving RT in modern seminoma management, so it is essential to report and track longitudinal outcomes across institutions to validate this approach.

Radiotherapy vs. Cystectomy for Treatment of Muscle Invasive Bladder Cancer in Very Elderly Patients

Radical cystectomy (RC) has long remained the principal treatment of muscle invasive bladder cancer (MIBC). It is, however, associated with significant morbidity, long recovery, and reported worse overall and cancer specific survival, particularly for the very elderly (age > = 80). Bladder preservation with transurethral resection of bladder tumor (TURBT) followed by radiotherapy (RT) +/- concurrent chemotherapy (ChT) is regarded as a curative-intent alternative to RC in well-selected patients. The optimal treatment strategy remains unclear in very elderly patients. We hypothesize that outcomes following RT vs RC are clinically equivalent for treatment of MIBC in very elderly patients. Patients > = 80 years old with T2-T4 N0-N1 bladder cancer treated definitively with RT versus RC were included. Exclusion criteria included history of pelvic RT, prior cystectomy, or palliative treatment intent. Clinicopathologic and treatment-related details, as well as clinical outcomes and toxicities were retrospectively abstracted. Kaplan-Meier analyses were performed. At a median follow-up of 17 months (range 0.25-190), 47 patients received RT vs 83 patients who underwent RC with median age of 86 years (80-97) vs 83 years (range 80-91) (p<0.01), respectively. Median Charlson Comorbidity Index was similar between groups (p = 0.35) with median 7 for both cohorts, predicting 0% estimated 10y survival. Most patients had cT2 tumors (91% vs 99%, p = 0.06), cN0 nodal status (96% vs 100%, p = 0.06), and urothelial carcinoma histology (79% vs 90%, p = 0.22). Most RT patients received concurrent ChT (90%) and a minority of RC patients received neoadjuvant ChT (16%). 70% of RT pts had complete TURBTs prior to RT. Common RT regimens were 50-55 Gy in 20-25 fractions or 60-64.8 Gy in 30-36 fractions, using IMRT (89%) or 3D conformal (11%) technique. Overall survival for RT vs RC at 1- and 2- years was 79% vs 85% and 57% and 69%, respectively (p = 0.20). Locoregional control at 1- and 2-years was 73% vs 70% and 63% vs 66% (p = 0.59), respectively. Progression free survival at 1- and 2-years was 69% vs 66% and 52% vs 54% (p = 0.75), respectively. No RT patients went on to receive salvage cystectomy. Treatment complications are listed in Table 1; the Clavien Dindo classification system was used to describe acute surgical complications of RC and the Common Terminology Criteria for Adverse Events (CTCAE) Dictionary v5.0 was used for acute and late toxicity of RT. In the very elderly, RT (with or without concurrent ChT) offers survival and locoregional control rates comparable to RC, with a favorable side effect profile. RT should be offered for definitive management of non-metastatic MIBC as an alternative to RC in selected, well- informed, and compliant very elderly patients.

Locally advanced cervical cancer: how the improvement in techniques in external beam radiotherapy and brachytherapy impacts on survival outcomes and long-term toxicities.

Platinum-based chemoradiotherapy and brachytherapy are the standard treatment for locally advanced cervical cancer. Reported long-term outcomes for treated with both IMRT and 3D-Image-guided-adaptive brachytherapy are lacking. This retrospective study included 165 patients with FIGO Stage IB-IVB cervical cancer, treated with chemoradiotherapy in combination with brachytherapy. External beam radiotherapy was delivered as IMRT/VMAT/TOMO helical or 3DCRT. The intracavitary brachytherapy treatment (ICBT) was performed using two different planning system (with or without optimization). Among the patient subgroups, comprising those who received IMRT/VMAT/Tomo helical and 3DCRT, as well as those who underwent ICBT planning optimization and those who did not, homogeneity was observed in terms of age, performance status, T stage, N status, TNM stage, and histology. With a median follow-up time of 60.5months, the 5-year overall survival (OS) in the 3DCRT and IMRT groups was 74.9% and 92.8%, respectively (p = 0.033). The 5-year OS in the ICBT planning optimization group was 93.7%, compared to 75% in the non-optimization group (p = 0.014). Regarding late radiation toxicities, patients in the IMRT group had a lower incidence of chronic rectal toxicity compared to those in the 3DCRT group (6.5% vs. 34.1%, p = 0.001). The group with ICBT planning optimization had a lower incidence of late urinary toxicities (10.4%) compared to the non-optimized ICBT planning group (18.2%, p = 0.012). Similarly, the ICBT planning optimization group had a lower incidence of late rectal toxicity (6.5% with 80% grade 1 and 20% grade 2) compared to the non-optimized ICBT planning group (34.1%, p = 0.001). In this series, the group of patients receiving optimized ICBT had an advantage in terms of OS and CSS suggesting that the use of new Treatment Planning Systems associated with 3D imaging, improves the long-term survival. Additionally, a significant reduction in late rectal and urinary toxicity has been observed.

Efficacy of scalp-sparing volumetric-modulated arc therapy approach in reducing scalp radiation dose for patients with glioblastoma: a cross-sectional study.

Radiation is integral to the treatment of glioblastoma (GBM). However, radiation-induced scalp toxicity can negatively impact patients' quality of life. Volumetric modulated arc therapy (VMAT) optimizes the dose to organs at risk (OARs). We hypothesize that a scalp-sparing VMAT (SSV) approach can significantly reduce undesirable doses to the scalp without compromising the target dose. This is a retrospective cross-sectional study of GBM patients who originally received radiation with non-SSV. We contoured the scalp as a 5 mm rind-like structure beneath the skin above the level of the foramen magnum. We replanned our patients using SSV techniques. We compared dosimetric data for the scalp, planning target volume (PTV), and select critical normal structures between non-SSV and SSV plans. Nineteen patients with newly diagnosed GBMs were included in our study. All patients received 60 Gy in 30 fractions. 9 patients received it in a single course. The rest received 46 Gy in 23 fractions to an initial volume followed by 14 Gy in 7 fractions to a cone-down volume (split course). New VMAT plans were generated after adding the scalp as an OAR. The median scalp volume was 416 cm3 (363-468 cm3). The median reductions in scalp Dmin, Dmax, and Dmean were 43.5% (-100% to 0%), 2.8% (+13.4% to -24.9%), and 15.7% (+2.1% to -39.9%) respectively. Median reductions in scalp D20cc and D30 cc were 19.5% (-2.7% to -54.5%), and 19.0% (-5.3% to -39.5%) respectively. The median volumes of the scalp receiving 30 Gy, 40 Gy, and 50 Gy were reduced by 42.3% (-70.6% to -12.5%), 72% (-100% to -2.3%), and 92.4% (-100% to +5.4%) respectively. There were no significant differences in the doses delivered to the PTV, brainstem, optic nerves, and optic chiasm between SSV and non-SSV plans. SSV can significantly reduce scalp radiation dose without compromising target coverage or critical normal structure doses. This may translate into reduced acute and late radiation toxicity to the scalp. A prospective trial evaluating the clinical benefits of SSV is ongoing (NCT03251027).

Safety and efficacy of stereotactic body radiotherapy (SBRT) to oligoresidual sites combine with osimertinib in stage IV EGFR mutant NSCLC patients: A prospective pilot study.

e21069 Background: Presently osimertinib is used as first-line therapy in stage IV EGFR mutation NSCLC patients. Unfortunately, acquired resistance gradually develops, resulting in disease progression in most patients after 1 to 2 years. A retrospective study demonstrates that similar to the first- and second-generation EGFR-TKIs, half of the patients experienced failure within the residual disease. Consolidative local therapy had been evaluated as a promising strategy to improve PFS and delayed the appearance of new metastatic lesions in the pre-osimertinib era. It is intriguing to hypothesize that new distant metastases may arise from drug-resistant tumor cells at the residual tumor lesions. Therefore, compared to the salvage SBRT, preemptive consolidative SBRT to all oligo-residual tumor sites could potentially prevent recurrence and improve survival. Of note, this proposal is challenging because both EGFR-TKI and thoracic radiation have a detrimental effect on pulmonary interstitial tissue. Two retrospective studies had reported severe pneumonitis with radiotherapy plus osimertinib. Therefore, the potential toxicity profile needs to evaluate prospectively. Therefore, we performed this preliminary trial (ChiCTR2100053807) to evaluate the safety of consolidation SBRT at maximal osimertinib response. Methods: Patients were enrolled if residual metastasis was limited to five sites. Consolidative SBRT was initiated to all residual sites with different doses (30–50Gy) and fractions (3-10) when maximal tumor shrinkage was achieved with osimertinib. The primary endpoint was an adverse reaction defined by the Common Terminology Criteria for Adverse Events, version 4.0. Results: 5 consecutive patients were enrolled between December 2021 and December 2022. 80% of their residual disease was located in the lungs and lymph nodes, which constituted targets for thoracic SBRT. The median time to maximal response was 3 months (range, 2-6). The median follow-up time from consolidative SBRT was 6 months（range,6-12）. The most common grade 1-2 adverse events included leukopenia (60%, n = 3), anorexia (40%, n = 2), lymphopenia (40%, n = 2), paronychia (40%, n = 2), rash (40%, n = 2), which were thought to be likely related to osimertinib. One patient suffered from grade 1 pulmonary fibrosis at 16 months after SBRT. There was no Grade 3/4 acute and late radiation toxicity. So far, no disease progression occur with a median follow-up time of 18 months（range, 13-19）. Conclusions: This pilot studydemonstrated concurrent treatment with osimertinib and SBRT for the oligo-residue disease at TKI maximum response was well tolerated. Future prospective, randomized studies are desirable to confirm these preliminary findings. Clinical trial information: ChiCTR2100053807 .

Early findings from the GARUDA trial: The impact of a genetic signature of late radiation toxicity on prostate cancer treatment decision making.

5089 Background: GARUDA (Germline DNA-Based Radiosensitivity Biomarker Influence on Toxicity Following Prostate Radiotherapy) was a single center phase II prospective study evaluating the impact of sharing results from a germline genetic signature (PROSTOX) characterizing patients as having a low or high risk of developing late &gt; 2 genitourinary (GU) toxicity from stereotactic body radiation therapy (SBRT) on decision making and toxicity. The goal of this early analysis was first to see if this information changed treatment choice, and second to see if patients categorized as genetically “low-risk” would have less late GU toxicity than those categorized as genetically “high-risk.” Methods: PROSTOX is a test of germline mutations run in the MiraDx CLIA-certified laboratory. Results were reported to the ordering physician and their patient for joint decision-making before proceeding with treatment selection. To be enrolled on the study patients could choose SBRT or moderately hypofractionated radiation therapy (MHFRT) for treatment of their prostate cancer. 279 men were screened for the GARUDA study between November 2020 and May of 2022. 71 withdrew for a variety of reasons, primarily choosing another location for treatment or form of treatment. 208 patients remained on the protocol and are included in this exploratory analysis. Statistical comparisons of stratified proportions are based on Gaussian approximations to Binomial probabilities. Results: The average age for the cohort was 72.12 with the majority being non-Hispanic and Caucasian. Overall, 85.15% (177) of patients were classified as low-risk and 14.9% of patients (31) were classified as high-risk for late grade &gt; 2 GU toxicity by PROSTOX. There was not a significant difference in predicted toxicity risk by age (72.45 vs 70.2), ethnicity or race. Regarding treatment choice based on toxicity score, in patients determined to be low-risk, 1.2% chose MHFRT, and 98.8% chose MRI- or CT-guided SBRT. In patients who were classified as high-risk, 44.8% chose MHFRT, and 55.2% chose MRI- or CT-guided SBRT. The difference in treatment choice was significant (p &lt; 0.001). In an early analysis of physician scored late &gt; 2 GU toxicity in patients with &gt; 18 months of follow-up (n = 57), 8.8% of patients had toxicity - 4.8% of those predicted to be low-risk, and 27.3% of those predicted to be high-risk (p = 0.015). Conclusions: In this exploratory analysis, predicting toxicity risk with PROSTOX significantly impacted patient and physician radiation treatment choice in localized prostate cancer. Early results also suggest that these changed treatment decisions lowered overall toxicity, which remained significantly different between patients classified as low-risk and high-risk. Analysis is ongoing to include patient reported outcomes and toxicity rates depending on treatment choice for those identified as high-risk. Clinical trial information: NCT04624256 .

Anti-PD-1 immunotherapy with dose-adjusted ultra-hypofractionated re-irradiation in patients with locoregionally recurrent head and neck cancer

IntroductionPatients with recurrent inoperable squamous-cell head-neck cancer (HNSCC) after chemo-radiotherapy have an ominous prognosis. Re-irradiation can be applied with some efficacy and high toxicity rates. Anti-PD-1 immunotherapy is effective in 25% of patients. Immunogenic death produced by large radiotherapy (RT) fractions may enhance immune response.Materials and methodsWe evaluated the efficacy and tolerance of ultra-hypofractionated immuno-radiotherapy (uhypo-IRT) in 17 patients with recurrent HNSCC and 1 with melanoma. Four of HNSCC patients also had oligometastatic disease. Using a dose/time/toxicity-based algorithm, 7, 7 and 4 patients received 1, 2 and 3 fractions of 8 Gy to the tumor, respectively. Nivolumab anti-PD-1 immunotherapy was administered concurrently with RT and continued for 24 cycles, or until disease progression or manifestation of immune-related adverse events (irAEs).ResultsEarly and late RT toxicities were minimal. Three patients developed irAEs (16%). After the 12th cycle, 7/17 (41.2%) and 5/17 (29.4%) patients with HNSCC showed complete (CR) and partial response (PR), respectively. CR was also achieved in the melanoma patient. The objective response rates in HNSCC patients were 57%, 86% and 66%, after 1, 2 and 3 fractions, respectively (overall response rate 70.6%). Most responders experienced an increase in peripheral lymphocyte counts. The median time to progression was 10 months. The 3-year projected locoregional progression-free survival was 35%, while the 3-year disease-specific overall survival was 50%.ConclusionsAnti-PD1 uhypo-IRT is safe and effective in patients with recurrent HNSCC. The high objective response rates and the long survival without evidence of disease support further trials on uhypo-IRT.