Clinical Target Volume Expansion Research Articles

Use of Cystourethroscopy to Define the Gross Tumour Volume in Radiation Treatment Planning for Canine Genitourinary Carcinomas.

Radiotherapy (RT) is increasingly utilised for definitive-intent treatment of canine genitourinary carcinomas (CGUC). At our institution, the standard approach is to irradiate tomographically abnormal tissues gross tumour volume (GTV) plus a clinical target volume (CTV) expansion of 2 cm. Cystourethroscopy is often incorporated into the treatment planning workflow, though an optimal approach has yet to be defined. This observational study evaluated cystourethroscopy as a tool for identifying gross lesions that can be targeted with RT. We hypothesised that in most cases, addition of cystourethroscopy would result in a larger GTV than would be drawn with computed tomography (CT) alone. Medical records from 54 dogs diagnosed with CGUC between 2013 and 2023 were reviewed; each had been evaluated before RT using CT and cystourethroscopy. The GTV was initially defined as the tomographically evident disease on a post-contrast sagittal plane CT scan, and then lesions visualised with cystourethroscopy (suspected or confirmed to be tumour) were added. Beyond what was visible on CT, cystourethroscopy extended the GTV by a median of 6.5 cm distally into the urethra (range: 1.5-31.8 cm) and therefore resulted in GTV enlargement in 26 of 54 (48%) cases. Addition of our standard 2 cm CTV expansion to a CT-defined GTV (without use of data from cystourethroscopy) would have underestimated the extent of grossly abnormal tissue in 35% (19/54) of cases. These results suggest that incorporating cystourethroscopy into treatment planning workflows may improve local tumour control by reducing the risk of a geographic miss.

The influence of anisotropy on the clinical target volume of brain tumor patients

Objective. Current radiotherapy guidelines for glioma target volume definition recommend a uniform margin expansion from the gross tumor volume (GTV) to the clinical target volume (CTV), assuming uniform infiltration in the invaded brain tissue. However, glioma cells migrate preferentially along white matter tracts, suggesting that white matter directionality should be considered in an anisotropic CTV expansion. We investigate two models of anisotropic CTV expansion and evaluate their clinical feasibility. Approach. To incorporate white matter directionality into the CTV, a diffusion tensor imaging (DTI) atlas is used. The DTI atlas consists of water diffusion tensors that are first spatially transformed into local tumor resistance tensors, also known as metric tensors, and secondly fed to a CTV expansion algorithm to generate anisotropic CTVs. Two models of spatial transformation are considered in the first step. The first model assumes that tumor cells experience reduced resistance parallel to the white matter fibers. The second model assumes that the anisotropy of tumor cell resistance is proportional to the anisotropy observed in DTI, with an ‘anisotropy weighting parameter’ controlling the proportionality. The models are evaluated in a cohort of ten brain tumor patients. Main results. To evaluate the sensitivity of the model, a library of model-generated CTVs was computed by varying the resistance and anisotropy parameters. Our results indicate that the resistance coefficient had the most significant effect on the global shape of the CTV expansion by redistributing the target volume from potentially less involved gray matter to white matter tissue. In addition, the anisotropy weighting parameter proved useful in locally increasing CTV expansion in regions characterized by strong tissue directionality, such as near the corpus callosum. Significance. By incorporating anisotropy into the CTV expansion, this study is a step toward an interactive CTV definition that can assist physicians in incorporating neuroanatomy into a clinically optimized CTV.

Proton LET Optimization Via Iterative Convex Relaxation Method

If not optimized, the LET distribution can greatly impact normal tissue toxicity near tumor targets, because the LET often peaks at the distal edge of Bragg peak. LET optimization can account for biological effectiveness of protons during treatment planning, for minimizing biological proton dose and hot spots to normal tissues. However, the LET optimization is nonlinear and nonconvex to solve, which poses a great challenge in optimization. This work will develop an effective LET optimization method via iterative convex relaxation (ICR). In contrast to the generic nonlinear optimization method, such as Quasi-Newton (QN) method, that does not account for specific characteristics of LET optimization, ICR is tailored to LET modeling and optimization in order to effectively and efficiently solve the LET problem. Specifically, nonlinear dose-averaged LET term is iteratively linearized and becomes convex during ICR, while nonconvex dose-volume constraint and minimum-monitor-unit constraint are also handled by ICR, so that the solution for LET optimization is obtained by solving a sequence of convex and linearized convex subproblems. Since the high LET mostly occurs near the target, a 1cm normal-tissue expansion of clinical target volume (CTV) (excluding CTV), i.e., CTV1cm, is defined to as an auxiliary structure during treatment planning, where LET is minimized. ICR was validated in comparison with QN for abdomen, lung, and head-and-neck (HN) cases. ICR was effective for LET optimization, as ICR substantially reduced the LET and biological dose in CTV1cm the ring, with preserved dose conformality to CTV. Compared to QN, ICR had smaller LET, physical and biological dose in CTV1cm, and higher conformity index values; ICR was also computationally more efficient, which was about 3 times faster than QN. A lung case is presented in the table, where the quantities from top to bottom are computational time T (unit: second); total objective F, dose objective Fd and LET objective FL (unit: 10-3); conformity index for physical dose CId and biological dose CIb; mean LET L (unit: keV/μm), mean physical dose d and mean biological dose b (in ratio to prescription dose) for CTV1cm; mean LET L (unit: keV/μm), mean physical dose d and mean biological dose b (in ratio to prescription dose; unit: 10-1) for the heart. A LET-specific optimization method based on ICR has been developed for solving proton LET optimization, which has been shown to be more computationally efficient than generic nonlinear optimizer via QN, with better plan quality in terms of LET, biological and physical dose conformality.

Evaluating the geometric and dosimetric impact of applying anisotropic CTV to PTV margins in image-guided post-prostatectomy radiation therapy.

Guidelines for clinical target volume (CTV) to planning target volume (PTV) margins in post-prostatectomy radiation therapy (PPRT) are varied and often not clearly defined. Assessment of appropriateness of margins is commonly measured on prevalence of geographic miss. Cone-beam CT (CBCT) images (n = 92) for 10 PPRT patients were incorporated to provide on-treatment information on the appropriateness of six different CTV expansion margins in terms of geographic miss and change in dose-volume statistics for CTV, rectum and bladder. Uniform margins included 10 mm, 5 mm, 10 mm + 5 mm posteriorly and 5 mm + 3 mm posteriorly. In addition, two anisotropic margins were evaluated by separating the superior and inferior portions of the CTV before expansion. Treatment plans were created for each PTV retrospectively. The frequency of geographic miss was the smallest for the large uniform expansions but resulted in the highest organ-at-risk (OAR) doses. Geographic miss in the smaller uniform and anisotropic PTVs was more prevalent but commonly to a small volume < 1% of CTV. When averaged over all CBCT fractions, V95% dose for all CTV margins remained > 99%. The anisotropic expansions generated smaller irradiated target volumes and consequently saw up to 7.3% reduction in bladder dose when compared with similar uniform expansion margins. Supplementing the incidence of geographic miss with dosimetric information on target coverage and OAR doses provides more informed assessment of the appropriateness of different CTV expansion margins. Our study extends the evaluation of anisotropic margins for PPRT.

Gross tumor volume margin and local control in p16-positive oropharynx cancer patients treated with intensity modulated proton therapy.

To determine if the extent of high-dose gross tumor volume (GTV) to clinical target volume (CTV) expansion is associated with local control in patients with p16-positive oropharynx cancer (p16+ OPC) treated with definitive intensity modulated proton therapy (IMPT). We performed a retrospective analysis of patients with p16+ OPC treated with IMPT at a single institution between 2016 and 2021. Patients with a pre-treatment PET-CT and restaging PET-CT within 4months following completion of IMPT were analyzed. Sixty patients were included for analysis with a median follow-up of 17 months. The median GTV to CTV expansion was 5 mm (IQR: 2 mm). Thirty-three percent of patients (20 of 60) did not have a GTV to CTV expansion. There was one local failure within the expansion group (3%). Excellent local control was achieved using IMPT for p16+ OPC independent of GTV expansion. IMPT with minimal target expansions represent a potential harm-minimization technique for p16-positive oropharynx cancer.

An iterative convex relaxation method for proton LET optimization

Objective: A constant relative biological effectiveness of 1.1 in current clinical practice of proton radiotherapy (RT) is a crude approximation and may severely underestimate the biological dose from proton RT to normal tissues, especially near the treatment target at the end of Bragg peaks that exhibits high linear energy transfer (LET). LET optimization can account for biological effectiveness of protons during treatment planning, for minimizing biological proton dose and hot spots to normal tissues. However, the LET optimization is usually nonlinear and nonconvex to solve, for which this work will develop an effective optimization method based on iterative convex relaxation (ICR). Approach: In contrast to the generic nonlinear optimization method, such as Quasi-Newton (QN) method, that does not account for specific characteristics of LET optimization, ICR is tailored to LET modeling and optimization in order to effectively and efficiently solve the LET problem. Specifically, nonlinear dose-averaged LET term is iteratively linearized and becomes convex during ICR, while nonconvex dose-volume constraint and minimum-monitor-unit constraint are also handled by ICR, so that the solution for LET optimization is obtained by solving a sequence of convex and linearized convex subproblems. Since the high LET mostly occurs near the target, a 1 cm normal-tissue expansion of clinical target volume (CTV) (excluding CTV), i.e. CTV1cm, is defined to as an auxiliary structure during treatment planning, where LET is minimized. Main results: ICR was validated in comparison with QN for abdomen, lung, and head-and-neck cases. ICR was effective for LET optimization, as ICR substantially reduced the LET and biological dose in CTV1cm the ring, with preserved dose conformality to CTV. Compared to QN, ICR had smaller LET, physical and biological dose in CTV1cm, and higher conformity index values; ICR was also computationally more efficient, which was about 3 times faster than QN. Significance: A LET-specific optimization method based on ICR has been developed for solving proton LET optimization, which has been shown to be more computationally efficient than generic nonlinear optimizer via QN, with better plan quality in terms of LET, biological and physical dose conformality.

Five Fraction External Beam Partial Breast Irradiation: A User's Guide.

Mature follow up from multiple randomized trials have demonstrated the safety and efficacy of external beam partial breast irradiation (PBI) for appropriately selected patients with early stage breast cancer. Despite this evidence, external beam PBI remains underutilized. In this user guide we outline patient selection, workflow, and address possible challenges to aid in implementation of evidence-based external beam PBI. Review of the current guidelines for PBI suitability, surgical considerations, treatment technique, simulation, contouring, and treatment planning, citing the latest published literature to support PBI utilization. Prospective data supports the use of 30 Gy in 5 fractions delivered with intensity modulated radiation therapy on a daily or every other day basis for a significant proportion of early stage breast cancer patients. The surgical cavity must be clearly visualized on treatment planning scan, recommend 3-5 weeks post-operatively, and the recommended clinical target volume expansion on the surgical cavity is 0.5-1.0 cm. A planning target volume expansion, based on motion management and image guidance, of 0.5-1.0 cm should be used. Organ at risk dose constraints of heart V3Gy ≤10% and contralateral breast Dmax ≤1 Gy are often achievable. Five fraction external beam PBI is a highly effective treatment with very limited toxicity for patients with early stage breast cancer following breast conserving surgery. Commonly utilized intensity modulated treatment planning techniques with plan delivery on standard linear accelerators results significant normal tissue sparing and makes implementation feasible at most radiation oncology centers.

Recommendations of the clinical target volume for the para-aortic region based on the patterns of lymph node metastasis in patients with biliary tract cancer.

Even though the clinical target volume (CTV) in biliary tract cancer (BTC) patients has been proposed by several previous studies, the para aortic CTV for BTC is still not well-defined. The objective of this study was to determine the precise delineation of the para aortic CTV for BTC according to the distribution pattern and failure pattern of lymph nodes. Computed tomography (CT)-, magnetic resonance imaging (MRI)- or positron emission tomography-computed tomography (PET-CT)-generated images of patients with BTC from 2015 to 2020 were analyzed retrospectively. The distribution patterns of lymph nodes in different regions were summarized. The diagnosed para aortic lymph nodes (PALNs) were manually mapped to standard axial CT images. The asymmetric CTV expansions from the para aortic were defined according to the distance from the volumetric centre of lymph node to the most proximal border of aorta. A total of 251 positive lymph nodes were found in the study cohort (n = 61 patients, 92 PALN). All PALNs were projected onto axial CT image of the standard patient. PALNs were concentrated in the 16a2 and 16b1 regions, and the involvement rates were 17% and 13% respectively. Therefore, the upper boundary of 16a2 and the lower boundary of 16b1 were defined as the cranial and caudal border of para aortic CTV, respectively. For the study cohort, the mean distance from the volume center of all lymph nodes in 16a2 and 16b1 to the proximal border of the aorta was 9 mm (range 4-24) in the front, 7 mm (range 3-14) on the left, and 12 mm (range 5-29) on the right. For the validation cohort (n=19 patients, 56 PALN), the mean distance from the center of the lymph node to the border of the aorta were both 10 mm on the left (range 5-20) and right (range 6-23). The mean distance in front of the aorta was 9 mm (range 5-23). Finally, a CTV expansion from the aorta of 18 mm in the front, 12 mm on the left, and 24 mm on the right resulted in 96% (73/76) coverage of PALNs in the study cohort. At the time of the validation, the described CTV could include 96% (47/49) of recurrent PALNs in the validation cohort. The involvement rates of PALNs in 16a2 and 16b1 were the highest. Based on the distribution of PALNs, a new para-aortic CTV was defined to construct a more accurate target volume for adjuvant radiotherapy in BTC.

Evaluation of the ITV-margin and variables affecting bladder and mesorectal deformation during long course neoadjuvant radiotherapy for rectal cancer.

Internal target volume (ITV) margins were estimated by evaluating the movement of mesorectum and bladder during neoadjuvant long-course radiation therapy (RT) for rectal cancer. In this prospective study, 23 patients with rectal cancer had planning CT (pCT) and weekly cone beam CT (CBCT) in supine position during preoperative long-course RT. Mesorectal wall motion was analyzed based on the coordinates of the most anterior, posterior, left and right points on the pCT and CBCT. Overlap volume (OV) between the pCT bladder and CBCT mesorectum was generated. Variables that might affect relative bladder volume (ratio of CBCT to pCT bladder volumes), anterior mesorectal wall position, and OV were studied. ITV margins were also calculated. In females, smaller OV and less movement of the upper anterior mesorectal wall were identified, suggesting smaller ITV margins might be required compared to males. The relative bladder volume did not change significantly over time and was correlated with OV: the larger the relative bladder volume, the less the OV. ITV margin of 0.8 to 1.1 cm in right-left direction is satisfactory. Posteriorly, only 8 to 9 mm margin is required for upper and mid rectal regions but double of this is required for inferior third. Anteriorly, 1.3 cm margin is adequate for lower and mid rectal regions and 2.4 cm is required superiorly. An anisotropic ITV expansion of clinical target volume (CTV) for rectal cancer radiotherapy contouring provides a robust method to encompass the deformation of bladder and mesorectum. The ITV margin should take into account sex and distance from the anal verge.

MRI-Guided Accelerated Partial Breast Irradiation: Treatment Outcomes and Patient Reported Cosmesis

<h3>Purpose/Objective(s)</h3> Accelerated Partial Breast Irradiation (APBI) is a valid treatment option for women with early-stage breast cancer (BC) who meet the "suitable" criteria per ASTRO APBI guidelines. Magnetic Resonance Imaging guided APBI (MRgAPBI) results in less set up uncertainty and possibly tighter planning target volume (PTV) margins. This study aims to report MRgAPBI treatment outcomes and patient reported cosmesis. <h3>Materials/Methods</h3> This IRB approved retrospective study included early-stage BC patients who underwent lumpectomy with or without sentinel lymph node biopsy and were treated consecutively at our institution with MRgAPBI between 2018 and 2020, with a minimum follow up of 6 months. Charts were reviewed for patient and tumor characteristics, APBI induced adverse events, and treatment outcomes. Patients reported their breast appearance as "Poor, Fair, Good, or Excellent", two weeks after APBI completion and at their last follow up. <h3>Results</h3> The study included 19 eligible patients. Mean patients age was 72 years old (range 51 – 89), 68% had invasive ductal carcinoma (IDC), and 32% had ductal carcinoma in-situ. Mean tumor size was 9 mm (range 4-16 mm), 53%, 37%, and 10% had grade 1, 2, and 3 disease respectively. All patients had ER / PR positive disease, all IDC patients had HER2 negative disease, and a median Ki67 of 5% (range 1 – 60%). In patients with IDC, 8%, 69%, and 23% had stage pT1a, pT1b, and pT1c respectively. All patients had lymph node negative disease. Mean closest surgical margin was 5.75 mm (range 3-11 mm). 32% of patients received 30 Gy in 5 once daily fractions of 6 Gy given every other day, and 68% received 38.5 Gy in twice daily fractions of 3.85 Gy. All patients' plans met the dose constraints including the ratio of volume receiving at least 95% of the prescription dose to the whole breast target volume (< 15%). Median on-table treatment time was 30 minutes (range 23-40 minutes). All patients had a 1 cm expansion from the lumpectomy cavity to clinical target volume (CTV). CTV expansion to PTV ranged from 0-3 mm. Acute treatment induced adverse events included grade 1 dermatitis (16%), grade 1 breast pain (11%), and grade 1 fatigue (11%). All acute adverse events were resolved within 3 months. No patients experienced late adverse events. At a median follow up of 18 months (range 6 – 24 months), no patient had local-regional recurrence or distant metastases. At 2 weeks post treatment, 6%, 65%, and 29% of women described their breast appearance as "Fair", "Good", and "Excellent" respectively. At their last follow up, 41%, and 59% of women described their breast appearance as "Good", and "Excellent" respectively. <h3>Conclusion</h3> MRgAPBI in our early single institution experience is an effective and well tolerated treatment modality for women with early-stage BC who meet "suitable" criteria per ASTRO APBI guidelines. All patients reported their cosmetic outcomes as good or excellent and none had local, regional or distant recurrence at a median follow up of 18 months. Longer follow up and larger cohorts are required.

Toward MR-integrated proton therapy: modeling the potential benefits for liver tumors

Magnetic resonance imaging (MRI)-integrated proton therapy (MRiPT) is envisioned to improve treatment quality for many cancer patients. However, given the availability of alternative image-guided strategies, its clinical need is yet to be justified. This study aims to compare the expected clinical outcomes of MRiPT with standard of practice cone-beam CT (CBCT)-guided PT, and other MR-guided methods, i.e. offline MR-guided PT and MR-linac, for treatment of liver tumors. Clinical outcomes were assessed by quantifying the dosimetric and biological impact of target margin reduction enabled by each image-guided approach. Planning target volume (PTV) margins were calculated using random and systematic setup, delineation and motion uncertainties, which were quantified by analyzing longitudinal MRI data for 10 patients with liver tumors. Proton treatment plans were created using appropriate PTV margins for each image-guided PT method. Photon plans with margins equivalent to MRiPT were generated to represent MR-linac. Normal tissue complication probabilities (NTCP) of the uninvolved liver were compared. We found that PTV margin can be reduced by 20% and 40% for offline MR-guided PT and MRiPT, respectively, compared with CBCT-guided PT. Furthermore, clinical target volume expansion could be largely alleviated when delineating on MRI rather than CT. Dosimetric implications included decreased equivalent mean dose of the uninvolved liver, i.e. up to 24.4 Gy and 27.3 Gy for offline MR-guided PT and MRiPT compared to CBCT-guided PT, respectively. Considering Child–Pugh score increase as endpoint, NTCP of the uninvolved liver was significantly decreased for MRiPT compared to CBCT-guided PT (up to 48.4%, p < 0.01), offline MR-guided PT (up to 12.9%, p < 0.01) and MR-linac (up to 30.8%, p < 0.05). Target underdose was possible in the absence of MRI-guidance (D90 reduction up to 4.2 Gy in 20% of cases). In conclusion, MRiPT has the potential to significantly reduce healthy liver toxicities in patients with liver tumors. It is superior to other image-guided techniques currently available.

Designing a New Planning Target Volume Based on Rotation in Patients With Oropharyngeal Cancer

Studies show that rotation is a significant source of target displacement. The standard isotropic expansion of Clinical Target Volume (CTV) to Planning Target Volume (PTV) neglects rotation. While imaging and 6D couch corrections perform a single shift through isocenter, they poorly track off-axis rotations through the spine or spine shifts that produce twists or arching. This study aims to determine dosimetric differences in head and neck patients when a standard expansion PTV is replaced by one that tracks the space occupied by target due to uncorrected rotational error. To perform off-axis rotation, a hypothetical point was placed in the center of the cervical spinal canal on Computed Tomography (CT) scan and the image was rotated around the longitudinal axis ±5°. Comparison plans were generated using a standard 3mm isotropic CTV expansion against the new PTV formed of the rotated CTV to evaluate mean dose reduction to superior Pharyngeal Constrictor Muscle (PCM). A published Normal Tissue Complication Model (NTCP) was used to predict dysphagia probability, based on the dose to superior PCM and supraglottis. The average percent change for PTV volume and overlap with superior, middle and inferior PCMs in a pool of 20 patients was -19%, -37%, -59% and -45.2%. The new rotational PTV causes more reduction in the superior PCM overlap in base of tongue lesions compared to tonsillar lesions (57.8% versus 25.8%, p = 0.01 as well as middle PCM overlap (73% versus 49%). The smallest isotropic expansion that covers the target when the spine rotates ±5° was 5 mm. 35% of patients required an expansion more than 3 mm to account for off-axis rotation. In 10 patients randomly selected for VMAT planning, the average change to the volume overlap of PTV70 with superior PCM using the standard and new PTV was 45% (8-100%), with an average mean dose reduction of 2.7 Gy. Based on the NTCP model, 50% of cases had a 30% or more probability of swallowing complications. Using the new technique, the NTCP decreased to less than 30% in 80% of these patients. Considering other Organs at Risk (OARs) constraints, there was not a difference between the new plan versus the standard plan. Designing a new PTV based on spinal rotation result in less volume overlap between PTV and PCM and can ultimately lead to less mean superior PCM dose and risk of dysphagia. A standard 3mm isotropic expansion is insufficient to cover the target volume due to spine rotation, and a 5mm margin is needed.

Is Clinical Target Volume Necessary? A Failure Pattern Analysis in Patients with Locally Advanced Non-Small Cell Lung Cancer Treated with Concurrent Chemoradiotherapy Using Intensity-Modulated Radiotherapy Technique

Background Our previous dosimetric study showed that for locally advanced non-small cell lung cancer (LA-NSCLC), radiotherapy with intensity-modulated radiotherapy (IMRT) technique could deliver sufficient dose coverage to subclinical regions and reduce the dose to normal tissues with the omission of clinical target volume (CTV). To further clinically validate this strategy, we conducted the current study to analyze the failure pattern for patients with LA-NSCLC treated with concurrent chemotherapy and CTV-omitted IMRT. We also investigated the effects of target volumes on lymphopenia during radiotherapy to further test the potential benefits of CTV omission in anti-tumor immunotherapy. Methods A total of 63 patients with LA-NSCLC treated with CTV-omitted IMRT with concurrent chemotherapy were enrolled in this study. Their planning target volume (PTV) (also PTV-g) was expanded directly from gross tumor volume (GTV). A virtual CTV was expanded from GTV, and the PTV generated from virtual CTV was named planning target volume with CTV expansion (PTV-c). Treatment failures were divided into local, regional, and distant failures, and local-regional recurrences were classified into inside PTV-g (IN-PTV-g), between PTV-g and PTV-c (PTV-g-c), and outside PTV-c (OUT-PTV-c). The relationship between lymphopenia during radiotherapy and the target volumes was also evaluated using Spearman's correlation analysis. Results Among the 60 patients with detailed follow-up data for recurrences, 46 (76.7%) experienced recurrences, with 18 (30.0%) being local recurrence, 5 (8.4%) being regional failure, and 33 (55.0%) being distant failure. For the 21 patients with local-regional recurrences, 16, 6, and 1 were IN-PTV-g, OUT-PTV-c, and PTV-g-c recurrences, respectively. Lymphopenia during radiotherapy was associated with both GTV and PTV, with larger volumes linked to severe lymphopenia. Conclusions CTV omission is feasible for LA-NSCLC treated with concurrent chemoradiotherapy and does not compromise failure inside the subclinical region. The radiation volumes were associated with lymphopenia during radiotherapy, with larger volumes related to severe lymphopenia. This finding supports the further exploration of CTV omission for immunotherapy.

Prophylactic Extended-Field Irradiation in Patients With Cervical Cancer: A Literature Review.

Currently, the standard radiation field for locally advanced cervical cancer patients without evidence of para-aortic lymph node (PALN) metastasis is the pelvis. Due to the low accuracy of imaging in the diagnosis of PALN metastasis and the high incidence of PALN failure after pelvic radiotherapy, prophylactic pelvic and para-aortic irradiation, also called extended-field irradiation (EFI), is performed for patients with cervical cancer. In the era of concurrent chemoradiotherapy, randomized controlled trials are limited, and whether patients with cervical cancer can benefit from prophylactic EFI is still controversial. With conformal or intensity-modulated radiation therapy, patients tolerate prophylactic EFI very well. The severe toxicities of prophylactic EFI are not significantly higher than those of pelvic radiotherapy. We recommend delivering prophylactic EFI to cervical cancer patients with common iliac lymph nodes metastasis. Clinical trials are needed to investigate whether patients with ≥3 positive pelvic lymph nodes and FIGO stage IIIB disease can benefit from prophylactic EFI. According to the distribution of PALNs, it is reasonable to use the renal vein as the upper border of the radiation therapy field for patients treated with prophylactic EFI. The clinical target volume expansion of the node from the vessel should be smaller in the right para-caval region than in the left lateral para-aortic region. The right para-caval region above L2 or L3 may be omitted from the PALN target volume to reduce the dose to the duodenum. More clinical trials on prophylactic EFI in cervical cancer are needed.

Is clinical target volume necessary?-a failure pattern analysis in patients with locally advanced non-small cell lung cancer treated with concurrent chemoradiotherapy using intensity-modulated radiotherapy technique.

BackgroundOur previous dosimetric study showed that for locally advanced non-small cell lung cancer (LA-NSCLC), radiotherapy with intensity-modulated radiotherapy (IMRT) technique could deliver sufficient dose coverage to subclinical regions and reduce the dose to normal tissues with the omission of clinical target volume (CTV). To further clinically validate this strategy, we conducted the current study to analyze the failure pattern for patients with LA-NSCLC treated with concurrent chemotherapy and CTV-omitted IMRT. We also investigated the effects of target volumes on lymphopenia during radiotherapy to further test the potential benefits of CTV omission in anti-tumor immunotherapy.MethodsA total of 63 patients with LA-NSCLC treated with CTV-omitted IMRT with concurrent chemotherapy were enrolled in this study. Their planning target volume (PTV) (also PTV-g) was expanded directly from gross tumor volume (GTV). A virtual CTV was expanded from GTV, and the PTV generated from virtual CTV was named planning target volume with CTV expansion (PTV-c). Treatment failures were divided into local, regional, and distant failures, and local–regional recurrences were classified into inside PTV-g (IN-PTV-g), between PTV-g and PTV-c (PTV-g-c), and outside PTV-c (OUT-PTV-c). The relationship between lymphopenia during radiotherapy and the target volumes was also evaluated using Spearman’s correlation analysis.ResultsAmong the 60 patients with detailed follow-up data for recurrences, 46 (76.7%) experienced recurrences, with 18 (30.0%) being local recurrence, 5 (8.4%) being regional failure, and 33 (55.0%) being distant failure. For the 21 patients with local–regional recurrences, 16, 6, and 1 were IN-PTV-g, OUT-PTV-c, and PTV-g-c recurrences, respectively. Lymphopenia during radiotherapy was associated with both GTV and PTV, with larger volumes linked to severe lymphopenia.ConclusionsCTV omission is feasible for LA-NSCLC treated with concurrent chemoradiotherapy and does not compromise failure inside the subclinical region. The radiation volumes were associated with lymphopenia during radiotherapy, with larger volumes related to severe lymphopenia. This finding supports the further exploration of CTV omission for immunotherapy.

Consensus on Contouring Primary Breast Tumors on MRI in the Setting of Neoadjuvant Partial Breast Irradiation in Trials

PurposeOur purpose was to present and evaluate expert consensus on contouring primary breast tumors on magnetic resonance imaging (MRI) in the setting of neoadjuvant partial breast irradiation in trials. Methods and MaterialsExpert consensus on contouring guidelines for target definition of primary breast tumors on contrast-enhanced MRI in trials was developed by an international team of experienced breast radiation oncologists and a dedicated breast radiologist during 3 meetings. At the first meeting, draft guidelines were developed through discussing and contouring 2 cases. At the second meeting 6 breast radiation oncologists delineated gross tumor volume (GTV) in 10 patients with early-stage breast cancer (cT1N0) according to draft guidelines. GTV was expanded isotropically (20 mm) to generate clinical target volume (CTV), excluding skin and chest wall. Delineations were reviewed for disagreement and guidelines were clarified accordingly. At the third meeting 5 radiation oncologists redelineated 6 cases using consensus-based guidelines. Interobserver variation of GTV and CTV was assessed using generalized conformity index (CI). CI was calculated as the sum of volumes each pair of observers agreed upon, divided by the sum of encompassing volumes for each pair of observers. ResultsFor the 2 delineation sessions combined, mean GTV ranged between 0.19 and 2.44 cm3, CI for GTV ranged between 0.28 and 0.77, and CI for CTV between 0.77 and 0.94. The largest interobserver variation in GTV delineations was observed in cases with extended tumor spiculae, blood vessels near or markers within the tumor, or with increased enhancement of glandular breast tissue. Consensus-based guidelines stated to delineate all visible tumors on contrast enhanced–MRI scan 1 to 2 minutes after contrast injection and if a marker was inserted in the tumor to include this. ConclusionsExpert-based consensus on contouring primary breast tumors on MRI in trials has been reached. This resulted in low interobserver variation for CTV in the context of a uniform 20 mm GTV to CTV expansion margin.

Abstract P4-12-21: Implementing a real-time magnetic resonance imaging guided accelerated partial breast irradiation program

Abstract Motivation: Clinical evidence has shown that accelerated partial breast irradiation (APBI) for early stage breast cancer patients result in local recurrence control rates and cosmetic outcomes comparable to whole breast irradiation. Approaches to APBI include brachytherapy, intraoperative radiation therapy and external beam radiation therapy (EBRT). EBRT is the least invasive approach, most widely available, and does not require additional training. For EBRT APBI, based on NSABP B39/RTOG 0413 protocol, the clinical target volume (CTV) is generated by applying a 1.5 cm margin to the lumpectomy bed and the planning target volume (PTV) is generated by applying an additional 1 cm margin from the CTV to account for set up uncertainties.Real-time magnetic resonance imaging guided radiation therapy (MRgRT) allow for reduced treatment margins by decreasing treatment setup uncertainties. In this work, we share our experience in implementing a MRI guided accelerated partial breast irradiation (MRgAPBI) program into a new clinic with a linear accelerator capable of real-time MRI imaging. Methods: We have surveyed institutions in which rely on MRI guidance for APBI treatments through a comprehensive literature review and onsite visits. These visits included our radiation therapists, physicists, and radiation oncologists. There are two main components in implementing a new radiotherapy program: 1) patient simulation and immobilization techniques, and 2) treatment planning and delivery techniques. These techniques were studied and modified for our clinical workflow. Results: Literature review revealed a single institution report addressing their MRgAPBI experience. For immobilization, we adopted two techniques observed during two site visits. However, these techniques were later modified to allow for patient customization. For small breasted patients, a foam tube placed along the sternum is used and for large breasted patients, we employed custom made acrylic brackets placed superior to the shoulders which are then built into the patient's immobilization cradle for individualized set up. For patient comfort, the contralateral arm is placed down along the patient’s side, whereas the ipsilateral arm is moved up away from the radiation field. This also allows for lateral clearance for beam selection. For treatment planning, consensus on optimal margin for expansion from the lumpectomy bed is of utmost importance. A single institution MRgAPBI report described a 1 cm expansion from the lumpectomy bed to PTV while NSABP B39 indicated a 2.5 cm expansion. This reduction in margin was justified by the utilization of real-time MRgRT. We have come to consensus to use a 1.5 cm expansion around the lumpectomy cavity, which accounts for the CTV expansion per NSABP B39 and to forgo the PTV expansion given the minimal setup uncertainty with online MRgRT. Our initial experience showed significant changes in the lumpectomy cavity shape and volume when the gap between patient simulation and the start of treatment exceeded a week. We have thus reduced the time between simulation and treatment to 1 week to address this issue. Conclusion: Implementing a new MRgAPBI program requires a comprehensive evaluation of available resources and published reports, as well as, team visits to expert MRgAPBI centers. Both immobilization techniques and lumpectomy margin expansions for treatment planning should be well thought of prior to starting a similar program. In our experience, time between simulation and treatment of 1 week showed minimal changes in the shape and size of the planning volume. Additional verification will need to be conducted within a prospective setting and larger cohort. In order to setup a successful program, teamwork is essential between all groups including radiation therapists, dosimetrists, physicists, and radiation oncologists. Citation Format: Eenas A. Omari, Jennifer Gambla, Hahn P. Mai, Muaiad Kittaneh, Tarita O. Thomas, Raymond B. Wynn, Anil Sethi, William Small Jr, Tamer Refaat. Implementing a real-time magnetic resonance imaging guided accelerated partial breast irradiation program [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P4-12-21.

Practice Patterns Among Radiation Oncologists Treating Pediatric Patients With Proton Craniospinal Irradiation

PurposeCraniospinal irradiation (CSI) is an important component of therapy for many pediatric central nervous system malignancies. Proton therapy is increasingly available and used for minimizing radiation exposure to normal tissues. The absence of an exit dose with proton therapy mandates decisions regarding coverage of the vertebral bodies (VB) in non–skeletally mature patients. Although the contents within the thecal sac represent the true clinical target volume (CTV), some physicians target the entire VB in growing children because of concerns over asymmetrical growth. This study aims to assess current practice patterns regarding VB coverage for pediatric patients undergoing CSI. Methods and MaterialsPediatric radiation oncologists were identified from the Particle Therapy Co-Operative Group pediatric subcommittee membership or affiliation with US proton centers. Potential participants were contacted by e-mail with a link to an institutional review board–approved, anonymized web-based survey distributed in June 2017 with follow-up in October 2017. The survey used skip logic and included up to 11 questions regarding practice patterns. ResultsThirty-three physicians responded to the survey (39%), 5 of which were excluded for lack of recent pediatric proton CSI experience. Of the 28 included responses, 23 physicians sometimes treat the entire VB and 5 physicians report always treating the entire VB. Most common responses regarding anterior CTV expansion for uncertainty were no expansion (n = 9) and 3 to 4 mm (n = 8). Most physicians modify the anterior CTV margin to protect normal structures, most commonly esophagus (n = 15), thyroid (n = 6), heart (n = 5), bowel (n = 4), and pharynx (n = 2). ConclusionsVertebral body coverage in proton CSI varies among radiation oncologists in respect to target delineation, CTV expansions, and modifications for organs at risk. These data suggest the radiation oncology community may benefit from a standardized approach to pediatric proton-based CSI.

Inter-observer variability in target delineation increases during adaptive treatment of head-and-neck and lung cancer

Introduction: Inter-observer variability (IOV) in target volume delineation is a well-documented source of geometric uncertainty in radiotherapy. Such variability has not yet been explored in the context of adaptive re-delineation based on imaging data acquired during treatment. We compared IOV in the pre- and mid-treatment setting using expert primary gross tumour volume (GTV) and clinical target volume (CTV) delineations in locoregionally advanced head-and-neck squamous cell carcinoma (HNSCC) and (non-)small cell lung cancer [(N)SCLC].Material and methods: Five and six observers participated in the HNSCC and (N)SCLC arm, respectively, and provided delineations for five cases each. Imaging data consisted of CT studies partly complemented by FDG-PET and was provided in two separate phases for pre- and mid-treatment. Global delineation compatibility was assessed with a volume overlap metric (the Generalised Conformity Index), while local extremes of IOV were identified through the standard deviation of surface distances from observer delineations to a median consensus delineation. Details of delineation procedures, in particular, GTV to CTV expansion and adaptation strategies, were collected through a questionnaire.Results: Volume overlap analysis revealed a worsening of IOV in all but one case per disease site, which failed to reach significance in this small sample (p-value range .063–.125). Changes in agreement were propagated from GTV to CTV delineations, but correlation could not be formally demonstrated. Surface distance based analysis identified longitudinal target extent as a pervasive source of disagreement for HNSCC. High variability in (N)SCLC was often associated with tumours abutting consolidated lung tissue or potentially invading the mediastinum. Adaptation practices were variable between observers with fewer than half stating that they consistently adapted pre-treatment delineations during treatment.Conclusion: IOV in target volume delineation increases during treatment, where a disparity in institutional adaptation practices adds to the conventional causes of IOV. Consensus guidelines are urgently needed.

High Local Control Rates of p16-Positive Squamous Cell Carcinomas of the Oropharynx Following Intensity Modulated Radiation Therapy Without a Clinical Target Volume Expansion

High Local Control Rates of p16-Positive Squamous Cell Carcinomas of the Oropharynx Following Intensity Modulated Radiation Therapy Without a Clinical Target Volume Expansion