Magnetic resonance imaging-guided high-dose planned adaptive intensity-modulated radiation therapy for locally advanced cervical cancer

Curative Radiation Therapy for Locally Advanced Cervical Cancer: Brachytherapy Is NOT Optional

Magnetic Resonance–Guided Radiation Therapy to Boost Cervical Cancer When Brachytherapy Is Not Available: A Case Report

Comparison of Intensity Modulated Radiation Therapy, Adaptive Radiation Therapy, Proton Radiation Therapy, and Adaptive Proton Radiation Therapy for Small Cell Lung Cancer

Patients with nasopharyngeal carcinoma undergoing intensity-modulated radiation therapy may experience significant anatomic changes throughout the entire treatment course, and adaptive radiation therapy may be necessary to maintain optimal dose delivered both to the targets and to the critical structures. The timing of adaptive radiation therapy, however, is largely unknown. This study was to evaluate the dosimetric benefits of a 3-phase adaptive radiation therapy technique for nasopharyngeal carcinoma. Twenty patients with nasopharyngeal carcinoma treated with intensity-modulated radiation therapy were recruited prospectively. After fractions 5 and 15, each patient had repeat computed tomography scans, and adaptive replans with recontouring the targets and organs at risk on the new computed tomography images were generated and used for subsequent treatment (replan 1 and replan 2). Two hybrid intensity-modulated radiation therapy plans (plan 1 and plan 2) were generated by superimposing the initial plan (plan 0) to each repeated new computed tomography image, reflecting the actual dose delivered to the targets and organs at risk if no changes were made to the original plan. Dosimetric comparisons were made between the adaptive replans (adaptive radiation therapy plans: plan 0 + replan 1 + replan 2) and their corresponding nonadaptive radiation therapy plans (plan 0 + plan 1 + plan 2). Comparing with the nonadaptive radiation therapy plans, the adaptive radiation therapy plans resulted in a significant improvement in conformity index for planning target volumes for primary disease, involved lymph node, high-risk clinical target volume, and low-risk clinical target volume (PTVnx, PTVnd, PTV1, and PTV2, respectively). Median V95 for PTVnx; D95, D99, V100, V95, and V93 for PTVnd; D99 and V100 for PTV1; and D95, D99, V100, V95, and V93 for PTV2 were increased significantly. There were significant dose–volume reductions, including maximum doses to the brainstem and temporal lobes, mean doses to the glottis, V50 for the supraglottis, Dmean and V30 for the left parotid, median dose to the right optic nerve, and V55 for the skin. The 3-phase adaptive intensity-modulated radiation therapy for patients with nasopharyngeal carcinoma results in improvements in target coverage and conformity index and decreased doses to some organs at risk.

A phase II study of adaptive two-step intensity-modulated radiotherapy (IMRT) with chemotherapy for nasopharyngeal cancer (NPC) (JCOG1015) was conducted to evaluate the efficacy and safety. Patients aged 20-75years with stages II-IVB NPC were enrolled. As adaptive two-step IMRT, computed tomography planning was performed twice before IMRT for the initial plan of 46Gy/23 fractions and during treatment for the boost plan of 24Gy/12 fractions with a total dose of 70Gy. Chemotherapy (cisplatin 80mg/m2/3-weeks × 3 courses) was administered concurrently with IMRT, followed by adjuvant chemotherapy (cisplatin at 70mg/m2 with 5-FU 700 at mg/m2 for 5days/4weeks × 3 courses). Between 2011 and 2014, 75 patients were enrolled from 12 institutions. The 3-year overall survival (OS) for the 75 patients was 88%, and the upper and lower limits of the 95% CI of 78%-94% were higher than the expected 3-year OS of 75% for the target population adjusted by the actual proportion of stage II:III:IV = 21%:44%:35%. The 3-year progression-free survival (PFS) and loco-regional PFS were 71% [59-80%] and 77% [66-85%], respectively. Although no grade 4-5 late toxicities were observed, 15 patients (20%) developed grade 3 late toxicities. Grade 2 xerostomia was noted in 26%, 12%, and 9% at 1, 2, and 3years after starting IMRT, respectively. Adaptive two-step IMRT for NPC demonstrated an excellent 3-year OS with acceptable toxicities. This method may be one treatment option for locally advanced NPC.

Introduction: The prognosis of recurrent pancreatic cancer is poor even after curative resection. There have been no reports of MRI-guided radiation therapy for locally recurrent pancreatic cancer after curative resection and chemotherapy. Case Presentation: A 66-year-old man with pancreatic cancer was referred to our institution for local recurrence after failure of surgical resection and second-line chemotherapy. He did not want to undergo further chemotherapy, so high-dose MRI-guided adaptive radiation therapy was performed in daily doses of 2.5 Gy to a total dose of 70 Gy over a period of 5.5 weeks. Three months after radiation therapy, the recurrent tumors disappeared and his CA19-9 level was within normal range without chemotherapy. There were no adverse events during treatment and three months of follow-up. Conclusions: High-dose MRI-guided adaptive radiation therapy may be safe and useful for locally recurrent pancreatic cancer.

The purpose of this study is to evaluate the dosimetric gain of the adaptive radiotherapy (ART) over conventional intensity modulated radiation therapy (IMRT) by using as the deformable image registration technique for dose mapping and summation to assess the dosimetric difference on target and organs at risk (OARs) dose. We retrospectively collected planning CT images and fractional CT images from nine lung cancer patients who were treated with adaptive IMRT. During fractional treatments, new tumor and organ contours are generated using the deformable image registration and a new IMRT plan is generated for the follow up treatments for each patient. The resulting deformation moving vector fields are also used to map and accumulate dose from the first 20 fractions to the sequential 10 fractions for final total dose calculation. The organs at risk (OARs) and the tumor of dosimetric parameters are compared between the ART and conventional IMRT plan. The evaluation results showed that when using the ART technique, the mean GTV volume is reduced by 53.2%, the mean tumor dose is increased by 0.41Gy, the mean lung V20 and V30 are decreased by 2.17% and 3.32%, the mean heart V30 and V40 are decreased by 1.14% and 2.98%, respectively, and the maximum dose of spinal cord is decreased by 1.21Gy when compared with the conventional IMRT. This work demonstrated the feasibility of ART to achieve better target coverage and OARs sparing over the conventional IMRT, and it will potentially reduce the radiation side effect and increase the local control rate.

The purpose of this study was to investigate the feasibility and effectiveness of high-dose planned adaptive intensity-modulated radiation therapy (IMRT) with helical tomotherapy (HT) for cutaneous angiosarcoma (cAS) of the scalp. This retrospective cross-sectional included atotal of 12consecutive patients with cAS of the scalp who underwent high-dose planned adaptive IMRT with HT. Prescribed doses were 72.5-74 Gy in 35-37 fractions for the gross tumor volume plus a1-2 mm margin (PTV1), 58-60 Gy in 29-30 fractions for the clinical target volume plus a2-3 mm margin (PTV2), and 46 Gy in 23fractions for the clinical target volume plus a5-15 mm margin (PTV3) over periods of 7.5, 6and 4.5weeks, respectively. The estimated 1‑year and 2‑year overall survival rate were 65.6% and 27.3%, respectively, and the local progression-free survival at 2years was 74.1%. All local recurrences were either in or marginal to the PTV2 or PTV3. No local recurrence was observed in the PTV1. All patients tolerated the treatment without grade3 or higher adverse events during the radiotherapy period. No late adverse events were observed during the follow-up period. Planned adaptive high-dose IMRT with HT has the potential to improve local control rate without increasing adverse events.

MRI in Radiation Oncology After the COVID-19 Pandemic

Limited data have been published regarding the effect of adaptive radiotherapy (ART) on clinical outcome in patients with nasopharyngeal carcinoma (NPC). We compared the long-term outcomes in patients with locally advanced NPC treated by adaptive intensity-modulated radiotherapy (IMRT) replanning versus IMRT. 200 NPC patients with stage T3/T4 were included between October 2004 and November 2010. Patients in both treatment groups were matched using propensity score matching method at the ratio of 1:1. Clinical outcomes were analyzed with Kaplan-Meier method, log-rank test and Cox regression. After matching, 132 patients (66 patients in each group) were included for analysis. The median follow-up for the IMRT replanning group was 70months, while the IMRT group was 69months. The 5-year local-regional recurrence-free survival (LRFS) rate was higher in IMRT replanning group (96.7 vs. 88.1%, P=0.022). No significant differences in distant metastasis-free survival (DMFS), progression-free survival (PFS) and overall survival (OS) were observed between the two groups. 21.2% patients in IMRT replanning group and 28.8% patients in IMRT group had distant metastasis. In multivariable analysis, IMRT replanning was identified as an independent prognostic factor for LRFS (hazard ratio 0.229; 95% CI 0.062-0.854; P=0.028), but not for DMFS, PFS and OS. IMRT replanning provides an improved LRFS for stage T3/T4 NPC patients compared with IMRT. Distant metastasis remains the main pattern of treatment failure. No significant advantage was observed in DMFS, PFS and OS when adaptive replanning was used.

Despite technological advances in radiation therapy (RT) and cancer treatment, patients still experience adverse effects. Proton therapy (PT) has emerged as a valuable RT modality that can improve treatment outcomes. Normal tissue injury is an important determinant of the outcome; therefore, for this review, we analyzed 2 databases: (1) clinical trials registered with ClinicalTrials.gov and (2) the literature on PT in PubMed, which shows a steady increase in the number of publications. Most studies in PT registered with ClinicalTrials.gov with results available are nonrandomized early phase studies with a relatively small number of patients enrolled. From the larger database of nonrandomized trials, we listed adverse events in specific organs/sites among patients with cancer who are treated with photons and protons to identify critical issues. The present data demonstrate dosimetric advantages of PT with favorable toxicity profiles and form the basis for comparative randomized prospective trials. A comparative analysis of 3 recently completed randomized trials for normal tissue toxicities suggests that for early stage non-small cell lung cancer, no meaningful comparison could be made between stereotactic body RT and stereotactic body PT due to low accrual (NCT01511081). In addition, for locally advanced non-small cell lung cancer, a comparison of intensity modulated RTwith passive scattering PT (now largely replaced by spot-scanned intensity modulated PT), PT did not provide any benefit in normal tissue toxicity or locoregional failure over photon therapy. Finally, for locally advanced esophageal cancer, proton beam therapy provided a lower total toxicity burden but did not improve progression-free survival and quality of life (NCT01512589). The purpose of this review is to inform the limitations of current trials looking at protons and photons, considering that advances in technology, physics, and biology are a continuum, and to advocate for future trials geared toward accurate precision RT that need to be viewed as an iterative process in a defined path toward delivering optimal radiation treatment. A foundational understanding of the radiobiologic differences between protons and photons in tumor and normal tissue responses is fundamental to, and necessary for, determining the suitability of a given type of biologically optimized RT to a patient or cohort.

2182: Chemoradiotherapy Using Intensity-Modulated Radiation Therapy (IMRT) for Locally Advanced Cervical Esophageal Cancer

MTE06.01 Radiotherapy Techniques in Lung Cancer

Adaptive radiotherapy (ART) provides greater benefits than intensity-modulated radiotherapy (IMRT) regarding dosimetric outcomes in patients with cervical cancer. To investigate the clinical benefits of ART, we have collected data from 115 cervical cancer patients who underwent radical radiotherapy at our institution. Fifty-nine patients received a single course of IMRT. Fifty-six patients underwent offline ART, defined as the reduction of the gross tumor volume (GTV) by at least 30% after 30 Gy of radiotherapy, followed by a modified treatment plan for the second-stage. After treatment, 53 patients of ART group achieved a partial response (PR) or completement response (CR), resulting in an objective response rate (ORR) of 94.6% for the ART group, compared to 93.2% for the IMRT group. Patients in both groups exhibited no significant differences in acute toxicities. However, the incidence of chronic constipation was significantly higher in the IMRT group compared to the ART group (p = 0.021). With a median follow-up time of 27 months, the ART group experienced a higher mortality (10/56) than the IMRT group (6/59). However, the difference between the two groups was not statistically significant. In summary, ART may be advantageous in reducing the incidence of chronic constipation among patients with locally advanced cervical cancer, and both clinical prognosis and near-term survival are satisfactory.

Development and implementation of chronological and anti-chronological adaptive dose accumulation strategies in adaptive intensity-modulated radiation therapy (IMRT) for head-and-neck cancer. An algorithm based on Newton iterations was implemented to efficiently compute inverse deformation fields (DFs). Four verification steps were performed to ensure a valid dose propagation: intra-cell folding detection finds zero or negative Jacobian determinants in the input DF; inter-cell folding detection is implemented on the resolution of the output DF; a region growing algorithm detects undefined values in the output DF; DF domains can be composed and displayed on the CT data. In 2011, one patient with nonmetastatic head and neck cancer selected from a three phase adaptive DPBN study was used to illustrate the algorithms implemented for adaptive chronological and anti-chronological dose accumulation. The patient received three 18F-FDG-PET/CTs prior to each treatment phase and one CT after finalizing treatment. Contour propagation and DF generation between two consecutive CTs was performed in Atlas-based autosegmentation (ABAS). Deformable image registration based dose accumulations were performed on CT1 and CT4. Dose propagation was done using combinations of DFs or their inversions. We have implemented a chronological and anti-chronological dose accumulation algorithm based on DF inversion. Algorithms were designed and implemented to detect cell folding.