Does the protocol-required uniform margin around the CTV adequately account for setup inaccuracies in whole breast irradiation?

PURPOSE: To use cone-beam computed tomography (CBCT) imaging to determine the impacts of patient characteristics on the magnitude of geometric setup errors and obtain patient-specific planning target volume (PTV) margins from the correlated patient characteristics in whole breast irradiation (WBI). METHODS: Between January 2019 and December 2019, a total of 97 patients who underwent breast-conserving surgery, followed by intensity-modulated radiation therapy in WBI, were scanned with pre-treatment CBCT for the first three treatment fractions and weekly for the subsequent fractions. Setup errors in the left-right (LR), superior-inferior (SI) and anterior-posterior (AP) directions were recorded and analyzed with patient characteristics-including age, tumor location, body mass index (BMI), chest circumference (CC) and breast volume (BV)-to examine the predictors for setup errors and obtain specific PTV margins. RESULTS: A total of 679 CBCT images from 97 patients were acquired for analysis. The mean setup errors for the whole group were 2.32 ± 1.21 mm, 3.71 ± 2.21 mm and 2.75 ± 1.56 mm in the LR, SI and AP directions, respectively. Patients' BMI, CC and BV were moderately associated with setup errors, especially in the SI directions (R = 0.40, 0.43 and 0.22, respectively). Setup errors in the SI directions for patients with BMI > 23.8 kg/m2, CC > 89 cm and BV > 657 cm3 were 4.56 ± 2.59 mm, 4.77 ± 2.42 mm and 4.30 ± 2.43 mm, respectively, which were significantly greater than those of patients with BMI ≤ 23.8 kg/m2, CC ≤ 89 cm and BV ≤ 657 cm3 (P < 0.05). Correspondingly, the calculated PTV margins in patients with BMI > 23.8 kg/m2, CC > 89 cm and BV > 657 cm3 were 4.25/7.95/4.93 mm, 4.37/7.66/5.24 mm and 4.22/7.54/5.29 mm in the LR/SI/AP directions, respectively, compared with 3.64/4.64/5.09 mm, 3.31/4.50/4.82 mm and 3.29/5.74/4.73 mm for BMI ≤ 23.8 kg/m2, CC ≤ 89 cm and BV ≤ 657 cm3, respectively. CONCLUSIONS: The magnitude of geometric setup errors was moderately correlated with BMI, CC and BV. It was recommended to set patient-specific PTV margins according to patient characteristics in the absence of daily image-guided treatment setup.

The Prognosis and Feasibility of Extensive Clinical Target Volume in Postoperative Radiotherapy for Esophageal Squamous Cell Carcinoma: A Phase II Clinical Trial.

BACKGROUND: This trial aims to explore the feasibility and safety of postoperative radiotherapy covering all regional lymph node areas for locally advanced thoracic esophageal squamous cell carcinoma patients treated with intensity-modulated radiation therapy (IMRT). METHODS: This was a single-center single-arm, phase II clinical trial initiated in 2014. Patients who were treated with radical transthoracic resection and had negative margins within 3 months and histologically confirmed esophageal squamous cell carcinoma (pT3-4 or N+, M0 determined by the 7th edition of the AJCC guidelines) were recruited in this trial. Postoperative radiotherapy was performed with a total dose of 40 Gy in 20 fractions using IMRT. Clinical target volumes (CTVs) included the tumor bed, anastomosis, bilateral supraclavicular region, mediastinal lymph nodes, left gastric lymph nodes and celiac trunk lymph nodes. The primary endpoint was the 2-year local control rate, and the secondary endpoints were overall survival (OS) and adverse events (AEs). RESULTS: A total of 70 eligible patients were recruited from 2014 to 2016. The 2-year local control rate, as the primary endpoint, was 67.3%. In addition, the median OS was 57.0 months, with 1-year and 3-year OS rates of 92.8% and 60.9%, respectively. Among the patients, 28/40 (40%) developed locoregional recurrence, with 25.7% involving hematogenous recurrences. All reported AEs occurred during the course of IMRT or within 6 months thereafter. None of them suffered grade 4 hematological or nonhematological AEs. Nearly all patients completed the entire course of postoperative radiotherapy, with a completion rate of 97.1%. CONCLUSION: For an extensive target volume, 40 Gy is feasible and shows acceptable toxicity in patients with locally advanced thoracic esophageal squamous cell carcinoma, although the local recurrence rate is relatively high. Our findings provide a basis for further exploration of high-dose radiation with extensive CTV combined with chemotherapy. CLINICAL TRIAL REGISTRATION: [http://www.clinicaltrials.gov/ct2/results?cond=&term=NCT02384811&cntry=&state=&city=&dist=], identifier [NCT02384811].

Involved-Field Irradiation in Definitive Chemoradiotherapy for Locoregional Esophageal Squamous Cell Carcinoma: Results From the ESO-Shanghai 1 Trial.

PURPOSE: To evaluate the feasibility and efficacy of involved-field irradiation in definitive chemoradiation therapy for locoregional esophageal squamous cell carcinoma. METHODS AND MATERIALS: Patterns in recurrence and elective nodal failure were analyzed in patients from the previously published ESO-Shanghai 1 trial, who received definitive chemoradiation therapy with involved-field irradiation to 61.2 Gy in 34 fractions using intensity modulated radiation therapy planning. Nodal regions were delineated using the lymph node map from the sixth edition of the American Joint Committee on Cancer staging system. Elective nodal failure was defined as recurrence in the regional nodal area outside the planning target volume. Extensive elective nodal failure, defined as an extensive nodal area regardless of tumor location, was calculated for additional analysis. The incidental (ie, mean) irradiation dose of each node and each region was evaluated. RESULTS: With a median follow-up of 48.7 months among survivors, the 3-year actuarial rate for overall survival was 53.6%, and the median overall survival was 44.8 months (95% confidence interval, 34.6-55.0). Of the 436 patients included in this study, 258 patients (59.2%) experienced treatment failure. Elective nodal failure was experienced by 37 patients (8.5%), 7 (1.6%) of whom encountered nodal-only failure. The 3-year actuarial rates of elective nodal control and elective nodal-only control were 89.7% and 97.9%, respectively. The median incidental dose of these nodes was 33.2 Gy (interquartile range [IQR], 1.3-50.7 Gy). The median distance of each node to the planning target volume was 1.4 cm (IQR, 0.6-4.9 cm). Extensive elective nodal failure was experienced by 51 patients (11.6%), and 20 (4.6%) patients had nodal-only failure. The 3-year extensive elective nodal control and extensive elective nodal control-only rates were 86.0% and 94.3%, respectively. The median incidental dose of these nodes was 23.2 Gy (IQR, 1.1-53.5 Gy). The median distance of each node to the planning target volume was 2.0 cm (IQR, 0.6-5.5 cm). CONCLUSION: Involved-field irradiation can achieve a low rate of isolated nodal failure and a satisfactory survival outcome. The use of elective nodal irradiation may be unnecessary in definitive chemoradiation therapy for the treatment of locoregional esophageal squamous cell carcinoma.

Simultaneously avoiding the hippocampus and hypothalamic-pituitary axis during whole brain radiotherapy: A planning study.

Whole brain radiotherapy (WBRT) is the preferred treatment for multiple brain metastases, and patients with limited-stage small cell lung cancer undergo prophylactic cranial irradiation after complete remission. However, neurotoxicity remains a complication. In addition to protecting the hippocampus from irradiation to preserve cognitive function, it is also critical to avoid irradiating the hypothalamic-pituitary axis to preserve endocrine and immune function. This study aimed to evaluate the feasibility of delivering WBRT while protecting the hippocampus and hypothalamic-pituitary axis. Thirteen patients with limited-stage small cell lung cancer were enrolled in this study. The hippocampus, hypothalamus, and pituitary gland were contoured based on T1-weighted magnetic resonance imaging. The prescribed dose to the whole brain planning target volume was 25 Gy in 10 fractions. Two treatment plans using equispaced coplanar intensity-modulated radiotherapy (IMRT) were generated: WBRT with hippocampus avoidance (H-A) and WBRT with hippocampus, hypothalamus, and pituitary gland avoidance (H-HP-A). Both "H-A" and "H-HP-A" plans successfully protected the hippocampus, which received mean doses of 9.1 and 9.6 Gy, respectively (p = 0.0002), whereas the "H-HP-A" plan decreased the doses to both the hypothalamus (mean dose 11.06 Gy) and the pituitary gland (mean dose 10.66 Gy). Both "H-A" and "H-HP-A" plans showed similar target coverage of 95.1%. The homogeneity index of the "H-A" plan was slightly better than that of the "H-HP-A" plan (0.20 vs 0.23, p= 0.0012). In conclusion, the use of equispaced coplanar IMRT was found to simultaneously protect the hippocampus and hypothalamic-pituitary axis while delivering WBRT with acceptable target coverage and homogeneity.

A new strategy for volumetric-modulated arc therapy planning using AutoPlanning based multicriteria optimization for nasopharyngeal carcinoma.

BACKGROUND: A new strategy for making the appropriate choice of the representative optimization parameters in planning processes and accurate selection criteria during Pareto surface navigation for general multicriteria optimization (MCO) was recommended in the study. The purpose was to combine both benefits of AutoPlanning optimization and MCO (APMCO) for achieving an individual volumetric-modulated arc therapy (VMAT) plan according to the clinically achieved patient-specific tradeoff among conflicting priorities. The preclinical investigation of this optimization approach for nasopharyngeal carcinoma (NPC) radiotherapy was performed and compared to general MCO VMAT. METHODS: A total of 60 NPC patients with various stages were enrolled in this study. General MCO and APMCO plans were generated for each patient on the treatment planning system. The differences between two planning schemes were evaluated and compared. RESULTS: All plans were capable of achieving the prescription requirement. The planning target volume coverage and conformation number were remarkably similar between general MCO and APMCO plans. There were no significant differences in most of organs at risk (OARs) sparing. However, in APMCO plans, relatively remarkable decreases were observed in the mean dose (Dmean) to the glottic larynx and pharyngeal constrictor muscles. The reductions of average Dmean to the two OARs were 10.5% (p < 0.0001) and 8.4% (p < 0.0001), respectively. APMCO technique was found to increase the planning time for an average of approximately 5 h and did not lead to a significant increase of monitor units compared to general MCO. CONCLUSIONS: The potential of the APMCO strategy is best realized with a clinical implementation that exploits individual generation of Pareto surface representations without manual interaction. It also assists physicians to ensure navigation in a more efficient and straightforward manner.

Is it possible for knowledge-based planning to improve intensity modulated radiation therapy plan quality for planners with different planning experiences in left-sided breast cancer patients?

BACKGROUND: Knowledge-based planning (KBP) is a promising technique that can improve plan quality and increase planning efficiency. However, no attempts have been made to extend the domain of KBP for planners with different planning experiences so far. The purpose of this study was to quantify the potential gains for planners with different planning experiences after implementing KBP in intensity modulated radiation therapy (IMRT) plans for left-sided breast cancer patients. METHODS: The model libraries were populated with 80 expert clinical plans from treated patients who previously received left-sided breast-conserving surgery and IMRT with simultaneously integrated boost. The libraries were created on the RapidPlanTM. 6 planners with different planning experiences (2 beginner planners, 2 junior planners and 2 senior planners) generated manual and KBP optimized plans for additional 10 patients, similar to those included in the model libraries. The plan qualities were compared between manual and KBP plans. RESULTS: All plans were capable of achieving the prescription requirement. There were almost no statistically significant differences in terms of the planning target volume (PTV) coverage and dose conformality. It was demonstrated that the doses for most of organs-at-risk (OARs) were on average lower or equal in KBP plans compared to manual plans except for the senior planners, where the very small differences were not statistically significant. KBP data showed a systematic trend to have superior dose sparing at most parameters for the heart and ipsilateral lung. The observed decrease in the doses to these OARs could be achieved, particularly for the beginner and junior planners. Many differences were statistically significant. CONCLUSIONS: It is feasible to generate acceptable IMRT plans after implementing KBP for left-sided breast cancer. KBP helps to effectively improve the quality of IMRT plans against the benchmark of manual plans for less experienced planners without any manual intervention. KBP showed promise for homogenizing the plan quality by transferring planning expertise from more experienced to less experienced planners.

Intensity modulated radiotherapy with fixed collimator jaws for locoregional left-sided breast cancer irradiation.

The purpose of this study is to evaluate the intensity modulated radiotherapy (IMRT) with the fixed collimator jaws technique (FJT) for the left breast and regional lymph node. The targeted breast tissue and the lymph nodes, and the normal tissues were contoured for 16 left-sided breast cancer patients previously treated with radiotherapy after lumpectomy. For each patient, treatment plans using different planning techniques, i.e., volumetric modulated arc therapy (VMAT), tangential IMRT (tangential-IMRT), and IMRT with FJT (FJT-IMRT) were developed for dosimetric comparisons. A dose of 50Gy was prescribed to the planning target volume. The dose-volume histograms were generated, and the paired t-test was used to analyze the dose differences. FJT-IMRT had similar mean heart volume receiving 30Gy (V30 Gy) with tangential-IMRT (1.5% and 1.6%, p = 0.41), but inferior to the VMAT (0.8%, p < 0.001). In the average heart mean dose comparison, FJT-IMRT had the lowest value, and it was 0.6Gy lower than that for the VMAT plans (p < 0.01). A significant dose increase in the contralateral breast and lung was observed in VMAT plans. Compared with tangential-IMRT and VMAT plans, FJT-IMRT reduced the mean dose of thyroid, humeral head and cervical esophageal by 47.6% (p < 0.01) and 45.7% (p < 0.01), 74.3% (p =< 0.01) and 73% (p =< 0.01), and 26.7% (p =< 0.01) and 29.2% (p =< 0.01). In conclusion, compared with tangential-IMRT and VMAT, FJT-IMRT plan has the lowest thyroid, humeral head and cervical esophageal mean dose and it can be a reasonable treatment option for a certain subgroup of patients, such as young left-breast cancer patients and/or patients with previous thyroid disease.