Results Of Radiotherapy Research Articles

The value of subcutaneous xenografts for individualised radiotherapy in HNSCC: Robust gene signature correlates with radiotherapy outcome in patients and xenografts

PurposeTo assess the robustness of prognostic biomarkers and molecular tumour subtypes developed for patients with head and neck squamous cell carcinoma (HNSCC) on cell-line derived HNSCC xenograft models, and to develop a novel biomarker signature by combining xenograft and patient datasets. Materials and methodsMice bearing xenografts (n = 59) of ten HNSCC cell lines and a retrospective, multicentre patient cohort (n = 242) of the German Cancer Consortium-Radiation Oncology Group (DKTK-ROG) were included. All patients received postoperative radiochemotherapy (PORT-C). Gene expression analysis was conducted using GeneChip Human Transcriptome Arrays. Xenografts were stratified based on their molecular subtypes and previously established gene classifiers. The dose to control 50 % of tumours (TCD50) was compared between these groups. Using differential gene expression analyses combining xenograft and patient data, a gene signature was developed to define risk groups for the primary endpoint loco-regional control (LRC). ResultsTumours of mesenchymal subtype were characterized by a higher TCD50 (xenografts, p < 0.001) and lower LRC (patients, p < 0.001) compared to the other subtypes. Similar to previously published patient data, hypoxia- and radioresistance-related gene signatures were associated with high TCD50 values. A 2-gene signature (FN1, SERPINE1) was developed that was prognostic for TCD50 (xenografts, p < 0.001) and for patient outcome in independent validation (LRC: p = 0.007). ConclusionGenetic prognosticators of outcome for patients after PORT-C and subcutaneous xenografts after primary clinically relevant irradiation show similarity. The identified robust 2-gene signature may help to guide patient stratification, after prospective validation. Thus, xenografts remain a valuable resource for translational research towards the development of individualized radiotherapy.

Clinical outcomes of stereotactic body radiation therapy for malignant pleural mesothelioma

BackgroundThe objective of this study is to determine the outcomes and toxicities of patients with malignant pleural mesothelioma (MPM) treated with stereotactic body radiotherapy (SBRT). Materials and methodsData were extracted from an institutional tumor registry for patients diagnosed with mesothelioma and treated with SBRT. Kaplan-Meier and Cox regression analyses were employed to determine local control (LC) and overall survival (OS). ResultsForty-four patients with 59 total treated tumors from December 2006 to April 2022 were identified. Fifty-one (86.4 %) cases had oligoprogressive disease (five sites or less). The median prescription dose delivered was 3000 cGy in 5 fractions (range: 2700–6000 cGy in 3–8 fractions). Fifty-one (86.4 %) tumors were in the pleura, 4 (6.8 %) spine, 2 (3.4 %) bone, 1 (1.7 %) brain, and 1 (1.7 %) pancreas.The median follow-up from SBRT completion for those alive at last follow-up was 28 months (range: 14–52 months). The most common toxicities were fatigue (50.8 %), nausea (22.0 %), pain flare (15.3 %), esophagitis (6.8 %), dermatitis (6.8 %), and pneumonitis (5.1 %). There were no grade ≥ 3 acute or late toxicities. There were 2 (3.4 %) local failures, one of the pleura and another of the spine. One-year LC was 92.9 % (95 % CI: 74.6–98.2 %) for all lesions and 96.3 % (95 % CI: 76.5–99.5 %) for pleural tumors. One-year LC was 90.9 % (95 % CI: 68.1–97.6 %) for epithelioid tumors and 92.1 % (95 % CI: 72.1–98.0 %) for oligoprogressive tumors. One-year OS from time of SBRT completion was 36.4 % (95 % CI: 22.6–50.3 %). On multivariable analysis, KPS was the lone significant predictor for OS (p = 0.029). ConclusionsOur single-institutional experience on patients with MPM suggests that SBRT is safe with a low toxicity profile and potentially achieve good local control.

Advanced hepatocellular carcinoma with major portal vein invasion: Therapeutic outcomes of hepatic arterial infusion chemotherapy vs concurrent radiotherapy.

Hepatocellular carcinoma (HCC) with major portal vein invasion (MPVI) presents very poor outcomes. Hepatic artery infusion chemotherapy (HAIC) and radiation therapy (RT) have both been found to be effective for advanced HCC. In this retrospective study, we compared the therapeutic outcomes of our "new" HAIC regimen with and without concurrent RT, before and after propensity score matching (PSM) in treating HCC patients with MPVI. One hundred forty patients with MPVI received HAIC alone and 35 patients underwent concurrent HAIC and RT during a 16-year period. The left subclavian artery was adopted as the entry site for a temporary catheter placement for a 5-day chemoinfusion. The Modified Response Evaluation Criteria in Solid Tumors (mRECIST) was adopted to assess the objective response rate (ORR). The Kaplan-Meier curve was used to calculate progression-free survival (PFS) and overall survival (OS) between the two groups. Univariate and multivariate analyses by Cox regression model were used to assess hazard ratios. Of the 140 patients with Child-Pugh A liver function, the median OS was 17.0 months. In the initial cohort, higher ORR and PFS were found in the concurrent RT group than in the HAIC alone group (80% vs 66.4% and 9 vs 8 months, respectively) but shorter OS (10.5 vs 14.5 months, p = 0.039) was observed. After PSM, the OS was 10 and 15 months ( p = 0.012), respectively. Multivariable Cox regression analysis revealed that the significant factors for adjusting hazard ratios for OS were Child-Pugh classification, alpha fetal protein (AFP) level, and hepatic vein invasion. HAIC is an effective treatment for advanced HCC patients with MPVI. Concurrent HAIC and full-dose RT were associated with worse clinical outcomes.

The impact of surgical-oncologic textbook outcome in patients with stage I to III pancreatic ductal adenocarcinoma: A cross-validation study of two national registries

BackgroundUsing national registries, we aimed to evaluate oncologic textbook outcomes in pancreatic ductal adenocarcinoma patients. MethodsPatients with stage I to III pancreatic ductal adenocarcinoma and surgical resection from 2010 to 2020 in the US and Germany were identified using the National Cancer Database and National Cancer Registries data. The surgical-oncologic textbook outcome was defined as complete oncologic resection with no residual tumor and ≥12 harvested lymph nodes. The composite endpoint was defined as surgical-oncologic textbook outcome and receipt of perioperative systemic and/or radiation therapy. ResultsIn total, 33,498 patients from the National Cancer Database and 14,589 patients from the National Cancer Registries were included. In the National Cancer Database, 28,931 (86%) patients had complete oncologic resection with no residual tumor, and 11,595 (79%) in the National Cancer Registries. 8,723 (26%) patients in the National Cancer Database and 556 (4%) in the National Cancer Registries had <12 lymph nodes harvested. The National Cancer Database shows 26,135 (78%) underwent perioperative therapy and 8,333 (57%) in the National Cancer Registries.Surgical-oncologic textbook outcome was achieved in 21,198 (63%) patients in the National Cancer Database and in 11,234 (77%) patients from the National Cancer Registries. 16,967 (50%) patients in the National Cancer Database and 7,878 (54%) patients in the National Cancer Registries had composite textbook outcome.Median overall survival in patients with composite textbook outcomes was 32 months in the National Cancer Database and 27 months in the National Cancer Registries (P < .001). In contrast, those with non-textbook outcomes had a median overall survival of 23 months in the National Cancer Database and 20 months in the National Cancer Registries (P < .001). ConclusionSurgical-oncologic textbook outcomes were achieved in > 50% of stage I to III pancreatic ductal adenocarcinoma for both the National Cancer Database and the National Cancer Registries. Failure to achieve textbook outcomes was associated with impaired survival across both registries.

Molecular subtypes of breast cancer predicting clinical benefits of radiotherapy after breast-conserving surgery: a propensity-score-matched cohort study

BackgroundBased on the molecular expression of cancer cells, molecular subtypes of breast cancer have been applied to classify patients for predicting clinical outcomes and prognosis. However, further evidence is needed regarding the influence of molecular subtypes on the efficacy of radiotherapy (RT) after breast-conserving surgery (BCS), particularly in a population-based context. Hence, the present study employed a propensity-score-matched cohort design to investigate the potential role of molecular subtypes in stratifying patient outcomes for post-BCS RT and to identify the specific clinical benefits that may emerge.MethodsFrom 2006 to 2019, the present study included 59,502 breast cancer patients who underwent BCS from the Taiwan National Health Insurance Research Database. Propensity scores were utilized to match confounding variables between patients with and without RT within each subtype of breast cancer, namely luminal A, luminal B/HER2-negative, luminal B/HER2-positive, basal-like, and HER2-enriched ones. Several clinical outcomes were assessed, in terms of local recurrence (LR), regional recurrence (RR), distant metastasis (DM), disease-free survival (DFS), and overall survival (OS).ResultsAfter post-BCS RT, patients with luminal A and luminal B/HER2-positive breast cancers exhibited a decrease in LR (adjusted hazard ratio [aHR] = 0.18, p < 0.0001; and, 0.24, p = 0.0049, respectively). Furthermore, reduced RR and improved DFS were observed in patients with luminal A (aHR = 0.15, p = 0.0004; and 0.29, p < 0.0001), luminal B/HER2-negative (aHR = 0.06, p = 0.0093; and, 0.46, p = 0.028), and luminal B/HER2-positive (aHR = 0.14, p = 0.01; and, 0.38, p < 0.0001) breast cancers. Notably, OS benefits were found in patients with luminal A (aHR = 0.62, p = 0.002), luminal B/HER2-negative (aHR = 0.30, p < 0.0001), basal-like (aHR = 0.40, p < 0.0001), and HER2-enriched (aHR = 0.50, p = 0.03), but not luminal B/HER2-positive diseases. Remarkably, when considering DM, luminal A patients who received RT demonstrated a lower cumulative incidence of DM than those without RT (p = 0.02).ConclusionIn patients with luminal A breast cancer who undergo BCS, RT could decrease the likelihood of tumor metastasis. After RT, the tumor’s hormone receptor status may predict tumor control regarding LR, RR, and DFS. Besides, the HER2 status of luminal breast cancer patients may serve as an additional predictor of OS after post-BCS RT. However, further prospective studies are required to validate these findings.

Treatment outcomes of radiotherapy with concurrent weekly cisplatin in older patients with locally advanced head and neck squamous cell carcinoma

BackgroundTri-weekly cisplatin and radiotherapy (CDDP + RT) is a standard of care for locally advanced head and neck squamous cell carcinoma (LA-HNSCC) but is sometimes challenging to complete in older patients. Weekly CDDP + RT has shown mild toxicity compared to tri-weekly CDDP + RT for LA-HNSCC and is a promising option for older adults. We aimed to report the treatment outcomes and prognostic factors in patients with LA-HNSCC treated with weekly CDDP + RT.MethodsWe analyzed patients aged ≥ 70 years who started weekly CDDP + RT for LA-HNSCC between July 2006 and October 2022. LA-HNSCC includes cancer in the oropharynx, hypopharynx, or larynx with a clinical stage of 3 or 4 without distant metastases based on the Union for International Cancer Control staging system 8th edition. The radiation dose of 70 Gy was delivered in 35 fractions by 3-dimensional conformal radiotherapy, intensity-modulated radiotherapy, or proton beam therapy. The primary endpoint was the 3-year overall survival (OS), and the secondary endpoints were the 3-year progression-free survival (PFS) and 3-year cause-specific survival (CSS). The Kaplan–Meier method was used to calculate survival rates, and the log-rank test was used to evaluate statistical significance. A Cox proportional hazards model was used for the multivariate analysis of prognostic factors.ResultsThe median age of the 49 patients was 72 (range: 70–78) years. The median CDDP dose was 200 (40–280) mg/ m2, and 47 patients completed scheduled radiotherapy. Forty-eight patients (98.0%) had a performance status of ≥ 1 at the initial visit. The 3-year OS, PFS, and CSS were 80.9% (95% confidence interval [CI]: 64.8–90.7), 58.9% (95%CI: 42.7–73.3), and 85.0% (95%CI: 68.7–93.4), respectively. In the multivariate analysis, the cumulative CDDP dose (< 200 or ≥ 200 mg/m2) was a significant factor for OS (hazard ratio: 0.29 [95% CI 0.08–0.97], p = 0.044). There was one case of early mortality. Grade 3 or higher late adverse events were observed in four patients (8.2%).ConclusionsWeekly CDDP + RT in older patients led to good survival outcomes with an acceptable rate of adverse events. CDDP should be administered at a dose of at least 200 mg/m2 in older patients.Trial registration Retrospectively registered

Treatment Outcome of Response-Based Radiation Therapy in Children and Adolescents With Central Nervous System Nongerminomatous Germ Cell Tumors: Results of a Prospective Study

The optimal dose and range of radiation therapy for central nervous system nongerminomatous germ cell tumors (NGGCTs) have not been uniformly established. Therefore, this study aimed to investigate the effect of individualized radiation therapy, based on the response to induction chemotherapy combined with surgery, on the prognosis of patients with NGGCTs. Based on the imaging examination and tumor markers after induction chemotherapy and pathologic results of second-look surgery, patients with NGGCT received different radiation therapy strategies, including 30.6 Gy whole ventricular irradiation+tumor-bed boost to 54 Gy, 30.6 Gy craniospinal irradiation+tumor-bed boost to 54 Gy, 36 Gy craniospinal irradiation+tumor-bed boost to 54 Gy, and 36 Gy craniospinal irradiation+54 Gy tumor-bed boost with 45 Gy to metastatic spinal lesions. A total of 51 patients were enrolled between January 2015 and March 2021, with a median age of 10.3 years. The 3-year event-free survival and overall survival (OS) of the entire cohort were 70.2% ± 6.9% and 77.5% ± 6.0%, respectively. The 3-year OS of patients achieving partial response after induction chemotherapy was higher than that of patients with stable disease (P=.03) or progressive disease (P=.002). The 3-year event-free survival and OS of the 18 patients receiving 30.6 Gy whole ventricular irradiation and 54 Gy tumor-bed boost were 88.9% ± 7.4% and 94.4% ± 5.4%, respectively. The results suggest that an individualized radiation therapy strategy based on response to induction chemotherapy and surgery is a feasible and promising means of achieving reduction in dose and extent of radiation in patients while still providing good response.

Outcomes of stereotactic ablative radiotherapy for the treatment of stage I and II non-small-cell lung cancer: an eight-year retrospective single-institution experience

Outcomes of stereotactic ablative radiotherapy for the treatment of stage I and II non-small-cell lung cancer: an eight-year retrospective single-institution experience

Trends in whole-brain radiotherapy and survival outcomes in the era of molecular testing in lung cancer

Trends in whole-brain radiotherapy and survival outcomes in the era of molecular testing in lung cancer

Abstract A160: The FGFR axis is a potential radiosensitization target

Abstract Background: Establishing methods that sensitize cancers to photons is important for improving the treatment outcome of radiotherapy. Although sequencing has been widely used to identify druggable mutations in various cancers, this strategy have not been used extensively to identify new targets for radiotherapy sensitization. Thus, we performed clinical sequencing of radiotherapy-treated patient samples and investigated whether inhibition of the identified candidate targets resulted in radiosensitization in vitro and in vivo. Material and Methods: Ninety-eight patients with newly diagnosed and pathologically confirmed cervical cancer who had been treated with definitive radiotherapy were analyzed. DNA was extracted from formalin fixed and paraffin embedded pre-treatment tumor biopsy specimens. The exons of 409 cancer-related genes were sequenced using a next generation sequencer. Identified mutations were analyzed for correlations with clinical outcome. The radiosensitization induced by inhibition of the candidate target was investigated in in vitro clonogenic assays and nude mouse xenograft models using radioresistant cancer cell lines and small molecule inhibitors. The in vitro sensitizer enhancement ratio (SER) was calculated as the ratio of radiation dose required to reduce clonogenic cell survival by 50% without drug to that with drug. Results: Recurrent mutations were identified in PIK3CA (35.7%), ARID1A (25.5%), NOTCH1 (19.4%), FGFR3 (16.3%), FBXW7 (19.4%), TP53 (13.3%), EP300 (12.2%), and FGFR4 (10.2%). The prevalence of mutations in FGFR family genes combined (24.5%) was almost as high as that for well-studied PIK3CA and ARID1A. Fifty-five percent (21/38) of the identified FGFR mutations were located in the tyrosine kinase domain. Five-year progression-free survival (PFS) rates for FGFR mutation-positive patients (n = 24) were significantly worse than those for FGFR mutation-negative patients (n = 74) (43.9% vs. 68.5%). Multivariate analysis identified FGFR mutations as significant predictors of worse 5 year PFS, independent of clinicopathological variables. To investigate whether the FGFR axis can be targeted by drugs to increase radiosensitization, the radiosensitizing effect of a human-administrable selective pan-FGFR inhibitor LY2874455 was investigated. LY2874455 (at 100 nM) showed a potent in vitro radiosensitizing effect (SER: 1.62, 1.53, and 1.31 for A549, H1299, and H1703 cells, respectively). In A549 xenograft models, the combination of X-rays (10 Gy on day 1) and LY2874455 (3 mg/kg body weight, once daily, on Day 1–7) led to significantly greater suppression of tumor growth than either treatment with X-rays or LY2874455 alone, with no evidence of toxicities. LY2874455 treatment inhibited ERK signaling, the main target of the FGFR axis, both in vitro and in vivo. Conclusion: These data indicate that targeting the FGFR axis with LY2874455 could potentially be used to sensitize cancers to radiotherapy, which warrants clinical validation. Citation Format: Takahiro Oike, Eisuke Horigome, Akiko Adachi, Narisa Dewi Maulany Darwis, Atsushi Shibata, Tatsuya Ohno. The FGFR axis is a potential radiosensitization target [abstract]. In: Proceedings of the AACR-NCI-EORTC Virtual International Conference on Molecular Targets and Cancer Therapeutics; 2023 Oct 11-15; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2023;22(12 Suppl):Abstract nr A160.

Portal-hypertension features are associated with ascites occurrence and survival in patients with hepatocellular carcinoma treated by external radiotherapy.

We studied the impact of Portal hypertension (PHT) on ascites occurrence and on radiotherapy outcome in cirrhotic patients with hepatocellular carcinoma (HCC). All cirrhotic patients that received radiotherapy for HCC between 2012 and 2022 were included. Portal hypertension-Score was built using univariate analysis with the presence of esophageal varices (EV), platelet count, history of acute variceal bleeding (AVB) and spleen size. Time-to-events data were estimated using Kaplan-Meier method with log-rank and Cox-models. 60 patients were included (female 27%, age 67 years-old, Child-Pugh A 82%, alcoholic/non-alcoholic steatohepatitis/hepatitis C virus 55/40/32%). 38% and 15% presented history of ascites and AVB respectively, 25% had large EV, 53.5% presented PHT score ≥ 5. 92% were BCLC-0/A, median tumor size was 30mm. At 6months, ascites incidence was 19% and precluded access to further HCC treatment for all patients with HCC recurrence. All PHT parameters included in the score and PHT score ≥ 5 (hazard ratio (HR)=14.07, p=0.01) were associated with ascites occurrence. Transplantation free survival and recurrence free survival at 1year were 56% and 47% respectively. Albi grade 3 (HR=3.01; p=0.04) was independently associated with Transplantation free survival. Radiotherapy should be cautiously performed in patients with PHT score ≥ 5 because of ascites occurrence risk precluding access to further HCC treatments.

Efficient Radial-Shell Model for 3D Tumor Spheroid Dynamics with Radiotherapy

Understanding the complex dynamics of tumor growth to develop more efficient therapeutic strategies is one of the most challenging problems in biomedicine. Three-dimensional (3D) tumor spheroids, reflecting avascular microregions within a tumor, are an advanced in vitro model system to assess the curative effect of combinatorial radio(chemo)therapy. Tumor spheroids exhibit particular crucial pathophysiological characteristics such as a radial oxygen gradient that critically affect the sensitivity of the malignant cell population to treatment. However, spheroid experiments remain laborious, and determining long-term radio(chemo)therapy outcomes is challenging. Mathematical models of spheroid dynamics have the potential to enhance the informative value of experimental data, and can support study design; however, they typically face one of two limitations: while non-spatial models are computationally cheap, they lack the spatial resolution to predict oxygen-dependent radioresponse, whereas models that describe spatial cell dynamics are computationally expensive and often heavily parameterized, impeding the required calibration to experimental data. Here, we present an effectively one-dimensional mathematical model based on the cell dynamics within and across radial spheres which fully incorporates the 3D dynamics of tumor spheroids by exploiting their approximate rotational symmetry. We demonstrate that this radial-shell (RS) model reproduces experimental spheroid growth curves of several cell lines with and without radiotherapy, showing equal or better performance than published models such as 3D agent-based models. Notably, the RS model is sufficiently efficient to enable multi-parametric optimization within previously reported and/or physiologically reasonable ranges based on experimental data. Analysis of the model reveals that the characteristic change of dynamics observed in experiments at small spheroid volume originates from the spatial scale of cell interactions. Based on the calibrated parameters, we predict the spheroid volumes at which this behavior should be observable. Finally, we demonstrate how the generic parameterization of the model allows direct parameter transfer to 3D agent-based models.

Common Variants in Osteopontin and CD44 Genes as Predictors of Treatment Outcome in Radiotherapy and Chemoradiotherapy for Non-Small Cell Lung Cancer.

Osteopontin (OPN)-CD44 signaling plays an important role in promoting tumor progression and metastasis. In cancer, OPN and CD44 overexpression is a marker of aggressive disease and poor prognosis, and correlates with therapy resistance. In this study, we aimed to evaluate the association of single nucleotide polymorphisms (SNPs) in the OPN and CD44 genes with clinical outcomes in 307 non-small cell lung cancer (NSCLC) patients treated with radiotherapy or chemoradiotherapy. The potential impact of the variants on plasma OPN levels was also investigated. Multivariate analysis showed that OPN rs11730582 CC carriers had a significantly increased risk of death (p = 0.029), while the CD44 rs187116 A allele correlated with a reduced risk of locoregional recurrence (p = 0.016) in the curative treatment subset. The rs11730582/rs187116 combination was associated with an elevated risk of metastasis in these patients (p = 0.016). Furthermore, the OPN rs1126772 G variant alone (p = 0.018) and in combination with rs11730582 CC (p = 7 × 10-5) was associated with poor overall survival (OS) in the squamous cell carcinoma subgroup. The rs11730582 CC, rs187116 GG, and rs1126772 G, as well as their respective combinations, were independent risk factors for unfavorable treatment outcomes. The impact of rs11730582-rs1126772 haplotypes on OS was also observed. These data suggest that OPN and CD44 germline variants may predict treatment effects in NSCLC.

Prognostic value of hypoxia-responsive gene expression profile in patients diagnosed with head and neck squamous cell carcinoma

Head and neck squamous cell carcinoma (HNSCC) is a disease associated with a severe mortality and high risk of distant metastasis and local recurrence. Currently, surgery and radiotherapy are the main treatment modes, however, therapeutic efficacy of radiotherapy is linked to tumor resistance. Hypoxia has been shown to affect outcome of radiotherapy in HNSCC patients. The aim of this study was to verify the expression of the previously identified hypoxia-responsive genes (CA9, CASP14, LOX, GLUT3, SERPINE1, AREG, EREG, CCNB1 and KIF14) in HNSCC patient material as well as assess their prognostic potential. Tumor biopsies obtained before start of radiotherapy from 32 HNSCC patients classified as responders or non-responders were investigated in this study. The mRNA expression was quantified using RT-qPCR. The mRNA expression of CA9, SERPINE1 and KIF14 was significantly higher in the analyzed patient material compared with the non-cancerous oral tissue. Moreover, the KIF14 mRNA expression was significantly higher in the responder group compared to non-responders. Further studies demonstrated that knockdown of KIF14 reverses its radiosensitizing capability. Additionally, low expression of KIF14 mRNA correlated with significantly shorter OS (overall survival). In conclusion, our results suggest that KIF14 might be a useful prognostic and predictive marker in HNSCC.

Dosimetric comparison of stereotactic MR-guided radiation therapy (SMART) and HDR brachytherapy boost in cervical cancer

The standard of care in locally advanced cervical cancer (LACC) is concomitant chemoradiotherapy followed by high-dose-rate brachytherapy (HDR-BT). Although previous studies compared HDR-BT with stereotactic body radiotherapy (SBRT), there is scarce data regarding the dosimetric outcomes of stereotactic MR-guided adaptive radiation therapy (SMART) boost in lieu of HDR-BT. In this single-institutional in-silico comparative study, LACC patients who were definitively treated with external beam radiotherapy followed by HDR-BT were selected. Target volumes and organs at risk (OARs) were delineated in MRI and HDR-planning CT. An HDR-BT and a SMART boost plan were generated with a prescribed dose of 28 Gy in four fractions for all patients. The HDR-BT and SMART boost plans were compared in regard to target coverage as well OARs doses. Mean EQD2 D90 to HR-CTV and IR-CTV for HDR-BT plans were 89.7 and 70.5 Gy, respectively. For SMART, the mean EQD2 D90 to HR-PTV, HR-CTV, and IR-CTV were 82.9, 95.4, and 70.2 Gy, respectively. The mean D2cc EQD2 of bladder, rectum, and sigmoid colon for HDR-BT plans were 86.4, 70.7, and 65.7 Gy, respectively. The mean D2cc EQD2 of bladder, rectum, and sigmoid colon for SMART plans were 81.4, 70.8, and 73.6 Gy, respectively. All dose constraints in terms of target coverage and OARs constraints were met for both HDR-BT and SMART plans. This dosimetric study demonstrates that SMART can be applied in cases where HDR-BT is not available or ineligible with acceptable target coverage and OAR sparing. However, prospective clinical studies are needed to validate these results.

Real-World Utilization of Radiation Therapy in Multiple Myeloma: An Analysis of the Connect MM Registry

Radiation therapy (RT) is an important treatment modality for patients with multiple myeloma (MM). Although patients are living longer with MM, they are more likely to have comorbidities related to treatment, such as bone pain; however, RT can provide symptom relief. To date, the characterization of patients who have received RT in the real-world setting has been limited. The Connect® MM Registry is a large, US multicenter, prospective observational cohort study of adult patients with newly diagnosed MM from mostly community sites. RT utilization and outcomes were analyzed quarterly throughout treatment. Factors associated with RT use were identified via multivariable analysis. A total of 3011 patients were enrolled in the Connect MM Registry with 903 patients (30%) having received RT at any time. There was a significant difference (P < .05) in overall RT use among patients with an Eastern Cooperative Oncology Group performance status of 0 to 1 versus ≥2, International Staging System disease stage I/II versus III, a history of plasmacytoma or a novel agent in their first regimen, and any number of bone lesions or severe osteoporosis/fracture. RT use was associated with having bone lesions or severe osteoporosis (vs not having bone lesions). Additionally, RT use was associated with ethnicity (Hispanic vs not) and Connect MM Registry cohort (cohort 1 [enrolled 2009-2011] vs 2 [enrolled 2012-2016]). In the 6 months before death, increased RT use was associated with increasing number of treatment lines (P < .0001) and high- versus standard-risk disease (per International Myeloma Working Group criteria; P = .0028). Real-world results from the Connect MM Registry show RT is frequently used and is associated with clinical factors, including performance status and disease stage. Earlier in MM diagnosis, RT may be used as an adjunct to palliate symptoms or delay systemic therapy. Toward the end of life, RT is more frequently used for palliation when treatment options are often limited.

Jorge clinical study: 10-year outcomes of risk-adapted radiotherapy defined by multiparametric MRI for prostate cancer.

To analyze the 10-year biochemical relapse-free survival (BRFS), locoregional relapse-free survival (LRFS), metastasis-free survival (MFS), and overall survival (OS) in patients diagnosed with localized prostate adenocarcinoma treated with radiotherapy (RT) ± androgen deprivation therapy (ADT), according to the risk groups based on multiparametric magnetic resonance imaging (mpMRI) instead of digital rectal exam (DRE). We retrospectively evaluated 140 consecutive patients diagnosed with localized prostate adenocarcinoma, stratified into different risk groups-low (LR), intermediate (IR), and high (HR) by mpMRI results. After a median follow-up of 104months, in LR group (n = 15), 10-year BRFS was 86.7%, 10-year LRFS was 86.7%, 10-year MFS was 93.3%, and 10-year OS was 100%. In IR group (n = 80), 10-year BRFS was 80.5%, 10-year LRFS was 86.1%, 10-year MFS was 92.6%, and 10-year OS was 76%. In HR group (n = 45), 10-year BRFS was 72.8%, 10-year LRFS was 78.7%, 10-year MFS was 82.1%, and 10-year OS was 77% (2 deaths from prostate cancer). According to mpMRI results, 36 (25.7%) patients change the risk group and 125 (89.28%) patients change the TNM stage. There was a trend for higher metastatic relapse in patients who switched from IR to HR (due to mpMRI) versus the patients who remained in the IR (20%, vs. 1.81% p = 0.059). Multivariate analysis showed that locoregional relapse was strongly associated with distant relapse (OR = 9.28; 95%CI: 2.60-33.31). There were no cases of acute grade 3 toxicity. Late grade 3 genitourinary, gastrointestinal, and sexual toxicity were 2.8%, 0.7%, and 1.2%, respectively. This is the first study with a 10-year median follow-up of patients diagnosed with localized prostate cancer treated with radiotherapy according to the risk groups established by mpMRI. Our findings show that mpMRI is a key tool to diagnose and establish risk groups in these patients, to optimize their treatment.

Five-year outcomes in carbon-ion radiotherapy for postoperative pelvic recurrence of rectal cancer: A prospective clinical trial (GUNMA 0801)

IntroductionCarbon-ion radiotherapy (C-ion RT) is associated with favorable clinical outcomes for the pelvic recurrence of rectal cancer. However, few long-term follow-up studies after C-ion RT have been conducted. Hence, we performed an updated analysis of a prospective clinical trial of C-ion RT for the postoperative pelvic recurrence of rectal cancer. Materials and methodsThe study included 28 patients. Inclusion criteria were patients with confirmed pelvic recurrence of rectal cancer without distant metastasis; those who underwent curative resection of their primary disease and regional lymph nodes without gross or microscopic residual disease; and those who had radiographically measurable tumors. The total dose of C-ion RT for all the patients was 73.6 Gy (relative biological effectiveness) administered in 16 fractions. ResultsThe median follow-up duration in all patients and those who survived were 51.2 and 69.2 months, respectively. The follow-up rate at the time of analysis was 96.4%. The 5-year overall survival and local control rates were 50% and 83%, respectively. Four patients had local recurrence, and 17 died of rectal cancer. Regarding late toxicities, two patients developed grade 3 pelvic infection, and nine developed grade 2 peripheral neuropathy. ConclusionOur updated analysis of a prospective clinical trial of C-ion RT for postoperative pelvic recurrence of rectal cancer confirmed its long-term efficacy and safety. These results suggest that C-ion RT may be a safe and effective treatment option for the postoperative pelvic recurrence of rectal cancer.

Daily fraction dose-adjusted radiotherapy policy to avoid prolonging the overall treatment time for early glottic squamous cell carcinoma: a single-institutional retrospective study.

The objective of this study was to determine the outcomes of radical radiotherapy for early glottic squamous cell carcinoma (EGSCC) with the policy of increasing the fraction size during radiotherapy when the overall treatment time (OTT) was expected to be prolonged. Patients diagnosed with clinical T1-2N0M0 EGSCC, who were treated with radical radiotherapy between 2008 and 2019 at Hokkaido University Hospital, were included. Patients received 66Gy in 33 fractions for T1 disease and 70Gy in 35 fractions for T2 disease as our standard regimen (usual group [UG]). If the OTT was expected to extend for >1 week, the dose fraction size was increased from 2.0to 2.5Gy from the beginning or during radiotherapy (adjusted group [AG]). At this time, we performed a statistical analysis between UG and AG. In total, 116 patients were identified, and the treatment schedules of 29 patients were adjusted. The median follow-up was 60.9months. In the T1 group, the cumulative 5-year local failure rate was 12.0% in the AG and 15.4% in the UG, and in the T2 group, the rate was 40.7% in the AG and 25.3% in the UG. There were no significant differences between the AG and UG. Similarly, no significant differences were observed for overall survival and progression-free survival rates. Our single-institutional retrospective analysis of EGSCC patients suggested that a method of adjusting the radiotherapy schedule to increase fraction size from the beginning or during the course may be effective in maintaining treatment outcomes.

Accelerated three-dimensional conformal radiotherapy for early-stage glottic cancer in reducing dose to the internal carotid artery and pharyngeal constrictor muscles.

We evaluated clinical and dosimetric outcomes of radiotherapy using two anterior oblique portals (AOP), to reduce the dose to the bilateral internal carotid arteries (CAs) and pharyngeal constrictor muscle (PCM) during early-stage glottic cancer (ESGC) treatment. We identified patients with ESGC who underwent definitive radiotherapy between June 2014 and May 2020. Among the 66 patients, 32 (48%) underwent radiotherapy using AOP, and the remaining underwent typical radiotherapy using parallel opposed lateral portals (POLP). The median follow-up duration was 53 months. No significant differences were observed in the 5-year local failure (0%/9.4%), progression-free survival (90.6%/90.8%), and overall survival (90.6%/91.0%) rates between the two groups. The grade ≥2 acute mucositis incidence rate was significantly lower in the AOP group (44%/85%). Radiotherapy using AOP maintained an adequate dose coverage to the target while markedly reducing the CAs and PCM doses. Radiotherapy with AOP resulted in favorable clinical and dosimetric outcomes.