Elective Clinical Target Volume Research Articles

Modelling the lymphatic metastatic progression pathways of OPSCC from multi-institutional datasets

The elective clinical target volume (CTV-N) in oropharyngeal squamous cell carcinoma (OPSCC) is currently based mostly on the prevalence of lymph node metastases in different lymph node levels (LNLs) for a given primary tumor location. We present a probabilistic model for ipsilateral lymphatic spread that can quantify the microscopic nodal involvement risk based on an individual patient’s T-category and clinical involvement of LNLs at diagnosis. We extend a previously published hidden Markov model (HMM), which models the LNLs (I, II, III, IV, V, and VII) as hidden binary random variables (RVs). Each represents a patient’s true state of lymphatic involvement. Clinical involvement at diagnosis represents the observed binary RVs linked to the true state via sensitivity and specificity. The primary tumor and the hidden RVs are connected in a graph. Each edge represents the conditional probability of metastatic spread per abstract time-step, given disease at the edge’s starting node. To learn these probabilities, we draw Markov chain Monte Carlo samples from the likelihood of a dataset (686 OPSCC patients) from three institutions. We compute the model evidence using thermodynamic integration for different graphs to determine which describes the data best.The graph maximizing the model evidence connects the tumor to each LNL and the LNLs I through V in order. It predicts the risk of occult disease in level IV is below 5% if level III is clinically negative, and that the risk of occult disease in level V is below 5% except for advanced T-category (T3 and T4) patients with clinical involvement of levels II, III, and IV. The provided statistical model of nodal involvement in OPSCC patients trained on multi-institutional data may guide the design of clinical trials on volume-deescalated treatment of OPSCC and contribute to more personal guidelines on elective nodal treatment.

Nordic anal cancer (NOAC) group consensus guidelines for risk-adapted delineation of the elective clinical target volume in anal cancer

Background: To date, anal cancer patients are treated with radiotherapy to similar volumes despite a marked difference in risk profile based on tumor location and stage. A more individualized approach to delineation of the elective clinical target volume (CTVe) could potentially provide better oncological outcomes as well as improved quality of life. The aim of the present work was to establish Nordic Anal Cancer (NOAC) group guidelines for delineation of the CTVe in anal cancer. Methods: First, 12 radiation oncologists reviewed the literature in one of the following four areas: (1) previous delineation guidelines; (2) patterns of recurrence; (3) anatomical studies; (4) common iliac and para-aortic recurrences and delineation guidelines. Second, areas of controversy were identified and discussed with the aim of reaching consensus. Results: We present consensus-based recommendations for CTVe delineation in anal cancer regarding (a) which regions to include, and (b) how the regions should be delineated. Some of our recommendations deviate from current international guidelines. For instance, the posterolateral part of the inguinal region is excluded, decreasing the volume of irradiated normal tissue. For the external iliac region and the cranial border of the CTVe, we agreed on specifying two different recommendations, both considered acceptable. One of these recommendations is novel and risk-adapted; the external iliac region is omitted for low-risk patients, and several different cranial borders are used depending on the individual level of risk. Conclusion: We present NOAC consensus guidelines for delineation of the CTVe in anal cancer, including a risk-adapted strategy.

Automated Robust Planning for IMPT in Oropharyngeal Cancer Patients Using Machine Learning

The aim of this study was to evaluate an automated treatment planning method for robustly optimized intensity modulated proton therapy (IMPT) plans for oropharyngeal carcinoma patients and to compare the results with manually optimized robust IMPT plans. An atlas regression forest based machine learning (ML) model for dose prediction was trained on CT scans, contours and dose distributions of robust IMPT plans of 88 oropharyngeal cancer patients (OCP). The ML model was combined with a robust voxel and dose volume histogram based dose mimicking optimization algorithm for 21 perturbed scenarios to generate a machine deliverable plan from the predicted dose distribution. Machine learning optimization (MLO) configuration was performed using a cross-validation approach with 3 × 8 tuning patients and comprised of adjustments to the mimicking optimization, to generate higher quality MLO plans. Independent testing of the MLO algorithm was performed with another 25 patients. Plan quality of clinical and MLO plans was evaluated by the clinical target volume (D98% voxel-wise minimum dose >94%), organ at risk (OAR) doses and the normal tissue complication probability (NTCP) (sum (Σ) of grade-2 and grade-3 dysphagia and xerostomia). Adequate robust target coverage was achieved in 24/25 clinical plans and in 23/25 MLO plans in the primary clinical target volume (CTV). In the elective CTV, 22/25 clinical plans and 24/25 MLO plans passed the robust target coverage evaluation threshold. The MLO average Σgrade 2 and Σgrade 3 NTCPs were comparable to the clinical plans (Σgrade 2 NTCPs: clinical 47.5% vs MLO 48.4%, Σgrade 3 NTCPs: clinical 11.9% vs MLO 12.3%). Significant increases in OAR average doses in MLO plans were found in the pharynx constrictor muscles (163 cGy, p=0.002) and cervical esophagus (265 cGy, p=0.002). The MLO plans were created within 45 min. This study showed that automated MLO planning is able to generate robustly optimized MLO plans with quality comparable to clinical plans in OCP.

Defining high-risk elective contralateral neck radiation volumes for oropharynx cancer.

To define the location of the initial contralateral lymph node (LN) metastasis in patients with oropharynx cancer. The location of the LN centroids from patients with oropharynx cancer and a single radiographically positive contralateral LN was defined. A clinical target volume (CTV) inclusive of all LN centroids was created, and its impact on dose to organs at risk was assessed. We identified 55 patients of which 49/55 had a single contralateral LN in level IIA, 4/55 in level III, 1/55 in level IIB, and 1/55 in the retropharynx. Mean radiation dose to the contralateral parotid gland was 15.1 and 21.0Gy, (p <0.001) using the modeled high-risk elective CTV and a consensus CTV, respectively. We present a systematic approach for identifying the contralateral nodal regions at highest risk of harboring subclinical disease in patients with oropharynx cancer that warrants prospective clinical study.

Refining Elective Contralateral Neck Radiation Volumes for Oropharynx Cancer

<h3>Purpose/Objective(s)</h3> Judicious reduction in elective nodal volumes for patients with oropharyngeal squamous cell carcinoma (OPSCC) has the potential to reduce acute and long term toxicity while maintaining high rates of regional control. We postulated that the contralateral N0 neck region at highest risk for containing occult microscopic lymph node (LN) metastases in patients with OPSCC could be best defined by the location of the initial positive ipsilateral LN. We sought to identify and target this N0 elective neck region and assess impact on dose to organs at risk compared to using a consensus-defined contralateral elective nodal volume. <h3>Materials/Methods</h3> We performed a retrospective review to identify patients with OPSCC and N2c disease as defined by a single radiographically positive LN. LN centroids were used to define the anatomic boundaries of the novel contralateral elective clinical target volume (ceCTV). Factors associated with LN centroid locations were assessed by the Fisher exact test. We used an external testing cohort to evaluate the robustness of ceCTV. The dosimetric impact of ceCTV compared to consensus elective nodal clinical target volumes (conCTV) was assessed with the t-test. <h3>Results</h3> We identified 25 patients that fit the selection criteria of which 84% had a single contralateral LN in level II and 16% in level III. We did not identify factors associated with LN centroid location. In the external data set, 97% (33/34) of the LN centroids were located within the novel elective contralateral target volume. Mean radiation dose to the contralateral parotid gland was 15.1 Gy (range 13.0-17.0 Gy) versus 21.0 Gy (range 18.0-24.0 Gy), <i>P</i> < 0.001 using the novel versus consensus elective contralateral nodal clinical target volumes, respectively. <h3>Conclusion</h3> We present a systematic approach for considering the contralateral nodal regions at highest risk of harboring subclinical disease in patients with oropharyngeal squamous cell carcinoma. These data support clinical study to evaluate this novel contralateral elective clinical target volume in patients with oropharyngeal squamous cell carcinoma who warrant elective contralateral neck radiotherapy.

A hidden Markov model for lymphatic tumor progression in the head and neck

Currently, elective clinical target volume (CTV-N) definition for head and neck squamous cell carcinoma (HNSCC) is mostly based on the prevalence of nodal involvement for a given tumor location. In this work, we propose a probabilistic model for lymphatic metastatic spread that can quantify the risk of microscopic involvement in lymph node levels (LNL) given the location of macroscopic metastases and T-category. This may allow for further personalized CTV-N definition based on an individual patient’s state of disease. We model the patient's state of metastatic lymphatic progression as a collection of hidden binary random variables that indicate the involvement of LNLs. In addition, each LNL is associated with observed binary random variables that indicate whether macroscopic metastases are detected. A hidden Markov model (HMM) is used to compute the probabilities of transitions between states over time. The underlying graph of the HMM represents the anatomy of the lymphatic drainage system. Learning of the transition probabilities is done via Markov chain Monte Carlo sampling and is based on a dataset of HNSCC patients in whom involvement of individual LNLs was reported. The model is demonstrated for ipsilateral metastatic spread in oropharyngeal HNSCC patients. We demonstrate the model's capability to quantify the risk of microscopic involvement in levels III and IV, depending on whether macroscopic metastases are observed in the upstream levels II and III, and depending on T-category. In conclusion, the statistical model of lymphatic progression may inform future, more personalized, guidelines on which LNL to include in the elective CTV. However, larger multi-institutional datasets for model parameter learning are required for that.

Patterns of pathologic lymph nodes in anal cancer: a PET-CT-based analysis with implications for radiotherapy treatment volumes

BackgroundThis study investigates the patterns of PET-positive lymph nodes (LNs) in anal cancer. The aim was to provide information that could inform future anal cancer radiotherapy contouring guidelines.MethodsThe baseline [18F]-FDG PET-CTs of 190 consecutive anal cancer patients were retrospectively assessed. LNs with a Deauville score (DS) of ≥3 were defined as PET-positive. Each PET-positive LN was allocated to a LN region and a LN sub-region; they were then mapped on a standard anatomy reference CT. The association between primary tumor localization and PET-positive LNs in different regions were analyzed.ResultsPET-positive LNs (n = 412) were identified in 103 of 190 patients (54%). Compared to anal canal tumors with extension into the rectum, anal canal tumors with perianal extension more often had inguinal (P < 0.001) and less often perirectal (P < 0.001) and internal iliac (P < 0.001) PET-positive LNs. Forty-two patients had PET-positive LNs confined to a solitary region, corresponding to first echelon nodes. The most common solitary LN region was inguinal (25 of 42; 60%) followed by perirectal (26%), internal iliac (10%), and external iliac (2%). No PET-positive LNs were identified in the ischiorectal fossa or in the inguinal area located posterolateral to deep vessels. Skip metastases above the bottom of the sacroiliac joint were quite rare. Most external iliac PET-positive LNs were located posterior to the external iliac vein; only one was located in the lateral external iliac sub-region.ConclusionsThe results support some specific modifications to the elective clinical target volume (CTV) in anal cancer. These changes would lead to reduced volumes of normal tissue being irradiated, which could contribute to a reduction in radiation side-effects.

PH-0161: Elective clinical target volumes for rectal IMRT delivery – moving towards a UK wide consensus

PH-0161: Elective clinical target volumes for rectal IMRT delivery – moving towards a UK wide consensus

Deep learning for elective neck delineation: More consistent and time efficient

Background/purposeDelineation of the lymph node levels of the neck for irradiation of the elective clinical target volume in head and neck cancer (HNC) patients is time consuming and prone to interobserver variability (IOV), although international consensus guidelines exist. The aim of this study was to develop and validate a 3D convolutional neural network (CNN) for semi-automated delineation of all nodal neck levels, focussing on delineation accuracy, efficiency and consistency compared to manual delineation. Material/methodsThe CNN was trained on a clinical dataset of 69 HNC patients. For validation, 17 lymph node levels were manually delineated in 16 new patients by two observers, independently, using international consensus guidelines. Automated delineations were generated by applying the CNN and were subsequently corrected by both observers separately as needed for clinical acceptance. Both delineations were performed two weeks apart and blinded to each other. IOV was quantified using Dice similarity coefficient (DSC), mean surface distance (MSD) and Hausdorff distance (HD). To assess automated delineation accuracy, agreement between automated and corrected delineations were evaluated using the same measures. To assess efficiency, the time taken for manual and corrected delineations were compared. In a second step, only the clinically relevant neck levels were selected and delineated, once again manually and by applying and correcting the network. ResultsWhen all lymph node levels were delineated, time taken for correcting automated delineations compared to manual delineations was significantly shorter for both observers (mean: 35 vs 52 min, p < 10−5). Based on DSC, automated delineation agreed best with corrected delineation for lymph node levels Ib, II–IVa, VIa, VIb, VIIa, VIIb (DSC >85%). Manual corrections necessary for clinical acceptance were 1.4 mm MSD on average and were especially low (<1mm) for levels II–IVa, VIa, VIIa and VIIb. IOV was significantly smaller with automated compared to manual delineations (MSD: 1.4 mm vs 2.5 mm, p < 10−11). When delineating only the clinically relevant neck levels, the correction time was also significantly shorter (mean: 8 vs 15 min, p < 10−5). Based on DSC, automated delineation agreed very well with corrected delineation (DSC > 87%). Manual corrections necessary for clinical acceptance were 1.3 mm MSD on average. IOV was significantly smaller with automated compared to manual delineations (MSD: 0.8 mm vs 2.3 mm, p < 10−3). ConclusionThe CNN developed for automated delineation of the elective lymph node levels in the neck in HNC was shown to be more efficient and consistent compared to manual delineation, which justifies its implementation in clinical practice.

Patterns of inguinal lymph node metastases in anal canal cancer and recommendations for elective clinical target volume (CTV) delineation

PurposeOptimal clinical target volume (CTV) for inguinal lymph node irradiation in anal cancer remains uncertain. This study documents the location of radiographically involved inguinal lymph nodes and proposes guidelines for CTV delineation. Materials and MethodsPatients with anal canal squamous cell carcinoma with inguinal lymph node metastases were identified. Criteria for lymph node involvement included: >15 mm short axis or suspicious morphology on CT or MRI, increased avidity on 18-FDG-PET, or positive biopsy. Distances from center of involved nodes to femoral vessels and inferior pubic symphysis were measured. ResultsForty patients with 79 inguinal lymph nodes were included. Relative to right femoral vessels, nodes were located: 12:00 (n = 6); 1:00 (n = 28); 2:00 (n = 35), 3:00 (n = 5); 4:00 (n = 1); 10:00 (n = 1); 11:00 (n = 3). No nodes were identified lateral or posterior to vessels. Published AGITG guidelines covered 68% of nodes anteriorly and 85% medially. Margins from nearest femoral vessel to cover 95% of nodes were 30 mm anteriorly and 26 mm medially. Inferior margin to cover 95% of nodes was 14 mm below inferior pubic symphysis. Proposed borders include cranial, where external iliac vessels leave bony pelvis; caudal, 14 mm below inferior pubic symphysis; posterior, posterior border of femoral vessels; lateral, lateral border of femoral vessels; anterior, 30 mm margin on femoral vessels and medial, 26 mm margin on femoral vessels, including radiographically suspicious nodes. ConclusionsPublished guidelines for inguinal CTV in anal cancer may result in inadequate coverage of high risk areas. Updated guidelines based on this study ensure coverage of at-risk areas.

What is the Best Way to Plan Rectum Three-Dimensional Conformal Radiotherapy in Prone Position—Classic Anatomical Landmark, Three Dimensional Fitting the Planning Target Volume, or Volumetric Modulated Arc?

BackgroundTraditionally, rectal cancer radiation therapy uses bony landmark fields to cover common lymphatic drainage sites, including the internal iliac, presacral, and perirectal lymph nodes. We aimed to investigate if bony landmark borders sufficiently cover the internal iliac nodes and to compare tumor volume and normal tissue avoidance using classic bony landmarks (c3DCRT), contoured elective clinical target volume (f3DCRT), and volumetric modulated arc therapy (VMAT) planning in locally advanced rectal cancer. MethodsComputed tomography datasets of 11 patients with locally advanced rectal cancer who had completed treatment in the prone position on a bellyboard in c3DCRT technique. The elective clinical target volumes and organs at risk were contoured, and a f3DCRT VMAT plan generated for all patients. Planning target volume, gross tumor volume, and normal tissue dose limits were evaluated. ResultsThe mean planning target volume 95% coverages were significantly lower for c3DCRT plans, and the lymph node coverage was better for f3DCRT. No differences were found in PTV coverages between f3DCRT and volumetric modulated arc therapy plans. No significant differences among all techniques were found for organs-at-risk constraints. The bladder dosage was higher in the VMAT plan. The c3DCRT technique missed coverage of the internal iliac lymph nodes and exposed smaller bowel, compared with the other methods. Discussion and ConclusionTumor volume coverage was improved by f3DCRT planning, without significant differences in doses to critical structures compared with c3DCRT and was noninferior to VMAT planning. It is recommended that f3DCRT be used in routine clinical practice in radiotherapy treatments for locally advanced rectal cancer.

Dosimetric comparison of organs at risk using different contouring guidelines for definition of the clinical target volume in anal cancer

BackgroundThere are different contouring guidelines for definition of the clinical target volume (CTV) for intensity-modulated radiation therapy (IMRT) of anal cancer (AC). We conducted a planning comparison study to evaluate and compare the dose to relevant organs at risk (OARs) while using different CTV definitions.MethodsTwelve patients with a primary diagnosis of anal cancer, who were treated with primary chemoradiation (CRT), were selected. We generated four guideline-specific CTVs and subsequently planned target volumes (PTVs) on the planning CT scan of each patient. An IMRT plan for volumetric arc therapy (VMAT) was set up for each PTV. Dose parameters of the planned target volume (PTV) and OARs were evaluated and compared, too.ResultsThe mean volume of the four PTVs ranged from 2138 cc to 2433 cc. The target volumes contoured by the authors based on the recommendations of each group were similar in the pelvis, while they differed significantly in the inguinal region. There were no significant differences between the four target volumes with regard to the dose parameters of the cranially located OARs. Conversely, some dose parameters concerning the genitals and the skin varied significantly among the different guidelines.ConclusionThe four contouring guidelines differ significantly concerning the inguinal region. In order to avoid inguinal recurrence and to protect relevant OARs, further investigations are needed to generate uniform standards for definition of the elective clinical target volume in the inguinal region.

A Retrospective Study of the Dosimetric Parameters and Duodenal Toxicity in Patients With Upper Gastrointestinal and Gynaecological Cancers Treated With Radiation Therapy

AimsThe duodenum is a critical organ at risk while planning radiation for gastrointestinal cancers or para-aortic nodes from gynaecological cancers due to the close proximity to the target volumes. The aim of this study was to assess the dosimetric parameters of the duodenum received during radiotherapy to upper gastrointestinal and gynaecological malignancies and their correlation with clinical toxicity. Materials and methodsAll adult patients who were treated with radiotherapy for primary upper gastrointestinal cancers (liver, stomach, pancreas, gall bladder) and patients with gynaecological cancers who were treated with extended fields in view of para-aortic nodal involvement from 1 January 2010 to 31 July 2015 were considered for the study. The radiation dose prescription was 45 Gy to the elective clinical target volume and 52.5–60 Gy to the gross nodal volume. The planning computed tomography scan was retrieved and the dose–volume histogram parameters for the duodenum were extracted. The relative volumes of duodenum receiving a dose from 40 to 55 Gy in increments of 5 Gy (V40Gy, V45Gy, V50Gy, V55Gy) were also noted. ResultsOf the 258 patients assessed, 30 patients (12.1%) were detected to have grade 2–4 toxicities related to the duodenum as detected on endoscopy. Most had grade 3 toxicity – 18 patients were diagnosed with grade 3 toxicity and four patients had grade 4 toxicity. The most common toxicity noted was duodenal ulceration seen in 16 patients. The other toxicities were duodenal stricture in eight patients, duodenal perforation in five patients and one patient was reported to have duodenal fistula. The patients with duodenum receiving V55Gy ≥ 1 cm3 (7.7% versus 3.8%, P = 0.014) and V50Gy ≥ 4 cm3 (7.7% versus 3.8%, P = 0.014) had higher grade ≥2 duodenal toxicity. ConclusionA threshold level of V55Gy ≥ 1 cm3 and V50Gy ≥ 4 cm3 for the duodenum is predictive of clinically significant grade 2 and higher toxicity and could serve as valid dose constraints for the duodenum.

Robustness of elective lymph node target coverage with shrinking Planning Target Volume margins in external beam radiotherapy of locally advanced cervical cancer.

Background and purposeImage-Guidance decreases set-up uncertainties, which may allow for Planning Target Volume (PTV) margins reduction. This study evaluates the robustness of the elective lymph node target coverage to translational and rotational set-up errors in combination with shrinking PTV margins and determines the gain for the Organs At Risk (OARs).Material and methodsTen cervix cancer patients who underwent external beam radiotherapy with 45 Gy/25Fx were analysed. Daily Image-Guidance was based on bony registration of Cone Beam CT (CBCT) to planning CT (pCT) and daily couch correction (translation and yaw). On each pCT, four Volumetric Modulated Arc Therapy dose-plans were generated with PTV margins of 0, 3, 5 and 8 mm. The elective clinical target volume (CTV-E) was propagated from daily CBCTs to the pCT to evaluate daily CTV-E dose. Additional systematic translational isocenter shifts of 2 mm were simulated. D98% (dose received by 98% of the volume of interest) and D99.9% were extracted from each CTV-E for all dose-plans and scenarios. Total dose was accumulated by Dose-Volume Histogram addition. The dosimetric impact of PTV margin reduction on the OARs was evaluated through V30Gy (volume included within the 30 Gy isodose), V40Gy and body V43Gy.ResultsWhen decreasing the PTV margin from 5 to 0 mm, bowel V30Gy was decreased by 13% (from 247 cm3 to 214 cm3), body V43Gy by 19% (from 1462 cm3 to 1188 cm3) and PTV by 39% (from 1416 to 870 cm3). The dosimetric impact of combined systematic shifts and residual rotations on the elective target with a 0 mm PTV margin was a decrease of D98% (mean ± SD) from 44.1 Gy ± 0.4 Gy to 43.7 Gy ± 0.8 Gy and a minimum of 42.4 Gy.ConclusionPTV margin reduction from 5 to 0 mm induced significant OARs dosimetric gains while elective target coverage remained robust to positioning uncertainties.

Importance of Technique, Target Selection, Contouring, Dose Prescription, and Dose-Planning in External Beam Radiation Therapy for Cervical Cancer: Evolution of Practice From EMBRACE-I to II

To describe the evolution of external beam radiation therapy (EBRT) from EMBRACE-I (general guidelines for EBRT) to the initial phase of the EMBRACE-II study (detailed protocol for EBRT). EMBRACE-I enrolled 1416 locally advanced cervical cancer patients treated with chemoradiation including image-guided adaptive brachytherapy during 2008 to 2015. From March 2016 until March 2018, 153 patients were enrolled in the ongoing EMBRACE-II study, which involves a comprehensive detailed strategy and accreditation procedure for EBRT target contouring, treatment planning, and image guidance. EBRT planning target volumes (PTVs), treated volumes (V43Gy), and conformity index (CI; V43Gy/PTV) were evaluated in both studies and compared. For EMBRACE-I, conformal radiation therapy (60% of patients) or intensity-modulated radiation therapy (IMRT) and volumetric arc therapy (VMAT; 40%) was applied with 45 to 50Gy over 25 to 30 fractions to the elective clinical target volume (CTV). For pelvic CTVs (82%), median PTV and V43 Gy volumes were 1549 and 2390mL, respectively, and CI was 1.54. For pelvic plus paraortic nodal (PAN) CTVs (15%), median PTV and V43Gy volumes were 1921 and 2895mL, and CI was 1.51. For pelvic CTVs treated with 45 to 46Gy, the use of conformal radiation therapy was associated with a median V43Gy volume that was 546mL larger than with IMRT/VMAT. For pelvic CTVs treated with IMRT, the use of a dose prescription ≥48Gy was associated with a median V43 Gy volumes that was 428mL larger than with a dose prescription of 45 to 46Gy. For EMBRACE-II, all patients were treated with: IMRT/VMAT, daily IGRT, 45Gy over 25 fractions for the elective CTV, and simultaneously integrated boost for pathologic lymph nodes. For pelvic CTVs (61%), median PTV and V43Gy volumes were 1388 and 1418mL, and CI was 1.02. For pelvic plus PAN CTVs (32%), median PTV and V43Gy volumes were 1720 and 1765mL, and CI was 1.03. From EMBRACE-I to initial II, median V43Gy was decreased by 972mL (41%) and 1130mL (39%), and median CI decreased from 1.54 to 1.02 and 1.51 to 1.03 for pelvic and pelvic plus PAN irradiation, respectively. Application of IMRT/VMAT, IGRT, and a 45-Gy dose provides the potential of higher conformality inducing significant reduction of treated volume. Adherence to a detailed protocol including comprehensive accreditation, as in EMBRACE-II, reduces considerably V43Gy and V50Gy and improves conformality and interinstitutional consistency.

Comparison of different treatment planning approaches for intensity-modulated proton therapy with simultaneous integrated boost for pancreatic cancer

BackgroundNeoadjuvant radio(chemo)therapy of non-metastasized, borderline resectable or unresectable locally advanced pancreatic cancer is complex and prone to cause side-effects, e.g., in gastrointestinal organs. Intensity-modulated proton therapy (IMPT) enables a high conformity to the targets while simultaneously sparing the normal tissue such that dose-escalation strategies come within reach. In this in silico feasibility study, we compared four IMPT planning strategies including robust multi-field optimization (rMFO) and a simultaneous integrated boost (SIB) for dose-escalation in pancreatic cancer patients.MethodsFor six pancreatic cancer patients referred for adjuvant or primary radiochemotherapy, four rMFO-IMPT-SIB treatment plans each, consisting of two or three (non-)coplanar beam arrangements, were optimized. Dose values for both targets, i.e., the elective clinical target volume [CTV, prescribed dose Dpres = 51Gy(RBE)] and the boost target [Dpres = 66Gy(RBE)], for the organs at risk as well as target conformity and homogeneity indexes, derived from the dose volume histograms, were statistically compared.ResultsAll treatment plans of each strategy fulfilled the prescribed doses to the targets (Dpres(GTV,CTV) = 100%, D95%,(GTV,CTV) ≥ 95%, D2%,(GTV,CTV) ≤ 107%). No significant differences for the conformity index were found (p > 0.05), however, treatment plans with a three non-coplanar beam strategy were most homogenous to both targets (p < 0.045). The median value of all dosimetric results of the large and small bowel as well as for the liver and the spinal cord met the dose constraints with all beam arrangements. Irrespective of the planning strategies, the dose constraint for the duodenum and stomach were not met. Using the three-beam arrangements, the dose to the left kidney could be significant decreased when compared to a two-beam strategy (p < 0.045).ConclusionBased on our findings we recommend a three-beam configuration with at least one non-coplanar beam for dose-escalated SIB with rMFO-IMPT in advanced pancreatic cancer patients achieving a homogeneous dose distribution in the target while simultaneously minimizing the dose to the organs at risk. Further treatment planning studies on aspects of breathing and organ motion need to be performed.

Patterns of Inguinal Lymph Node Metastases in Anal Cancer: Recommendations for Elective Clinical Target Volume (CTV) Delineation

In the era of conformal radiotherapy for anal cancer, the optimal CTV for inguinal lymph node irradiation remains uncertain. The purpose of this study was to document the location of radiographically involved inguinal lymph nodes in patients with anal canal cancer and to propose guidelines for elective inguinal CTV delineation. Patients with squamous cell carcinoma of the anal canal with inguinal lymph node metastases presenting to our institution between 2003 and 2017 were identified from a departmental database. Inguinal lymph nodes were considered involved based on at least one of the following: >1.5 cm on computed tomography (CT) or magnetic resonance imaging (MRI), FDG avidity greater than background liver on positron emission tomography (PET), or positive histology from lymph node biopsy. Distances from the center of the involved lymph node to the closest adjacent femoral vessel and to the inferior extent of the primary tumor were measured on a pre-treatment diagnostic imaging study. Position of lymph nodes relative to the right femoral vessels was recorded on a clock face with 12:00 anterior, 3:00 medial, 6:00 posterior, and 9:00 lateral. The anatomic location of each lymph node was transferred onto a representative CT scan of a patient in treatment position and compared to the inguinal lymph node CTV in the Australasian Gastrointestinal Trials Group (AGITG) consensus guidelines for intensity-modulated radiotherapy for anal cancer. We identified 41 patients with 81 positive inguinal lymph nodes. Median lymph node size was 16.1 mm (range 7-59 mm) in short axis and 21.4 mm (range 10-65 mm) in long axis. Median distances from the nearest femoral artery and vein were 19.8 mm (range 8-40 mm) and 17.1 mm (range 8-46 mm), respectively. Median distance from the inferior aspect of the primary tumor was 47.9 mm (range 4-108 mm). Relative to the femoral vessels, lymph nodes were located at 12:00 (n=7); 1:00 (n=28); 2:00 (n=35), 3:00 (n=5); 4:00 (n=1); 10:00 (n=1); 11:00 (n=4). No lymph nodes were identified in the 5:00-9:00 positions (lateral or posterior to the vessels). Volumes contoured according to AGITG consensus guidelines covered 70% of lymph nodes anteriorly and 85% of lymph nodes medially. Margins from the nearest femoral vessel required to cover 90% and 95% of lymph nodes were 29 mm and 30 mm anteriorly and 25 mm and 26 mm medially, respectively. Inferior borders of the inguinal CTV required to cover 90% and 95% of lymph nodes were 18 mm and 12 mm, respectively, from the inferior aspect of the primary tumor. Published guidelines for CTV delineation of the inguinal lymph node region in anal cancer may result in inadequate coverage of high-risk areas. Updated contouring guidelines based on the present study would ensure coverage of areas at high risk for harboring metastatic disease and may reduce toxicity by sparing low-risk areas.

Elective Management of the Neck in Parotid Tumours

AimsManagement of the clinically node-negative (cN0) neck for parotid tumours remains controversial. Options include observation, elective neck dissection (END) or elective nodal irradiation (ENI). We reviewed the evidence for ENI on a background of current practice among UK clinical oncologists. Materials and methodsWe carried out a systematic search of PubMed between 1 January 1980 and 31 December 2016. Articles on patients treated with parotidectomy and either END or ENI, and studies on nodal patterns of disease, were included. UK clinical oncologists were asked to complete an online questionnaire regarding their use of neck radiotherapy in this setting. ResultsFrom 96 references, 20 studies met the inclusion criteria: 11 reported on END, five on ENI and two on both. Eight studies reported on nodal patterns of disease. The prevalence of occult nodal metastases after END ranged from 0 to 45%. Five year locoregional control was variable (range 64–100%). For ENI, 5 year locoregional control varied from 74 to 100%. High-grade and T3/T4 tumours were factors for nodal relapse after END or ENI, which most commonly occurred in levels I–III. For the survey, 33/50 (66%) of cancer centres responded. Fourteen (42%) centres had guidelines for ENI. Most centres considered high-grade tumours (96%), T3/T4 disease (80%) and lymphovascular invasion (88%) as indications for ENI. Twelve centres (36%) irradiated levels Ib–IV electively; the remaining centres treated other various combinations of nodal levels. ConclusionThere is heterogeneity in the use and indications for ENI in the UK. ENI is a reasonable alternative to END as elective management for the cN0 neck in patients with high-grade tumours or T3/T4 disease. The elective clinical target volume should at least encompass nodal levels I–III.

The impact of contour variation on tumour control probability in anal cancer

BackgroundWhile intensity modulated radiotherapy (IMRT) has been widely adopted for the treatment of anal cancer (AC), the added contour complexity poses potential risks. This study investigates the impact of contour variation on tumour control probability (TCP) when using IMRT for AC.MethodsNine Australian centres contoured a single computed tomography dataset of a patient with AC. The same optimised template-based IMRT planning protocol was applied to each contour set to generate nine representative treatment plans and their corresponding dose volume histograms. A geometric analysis was performed on all contours. The TCP was calculated for each plan using the linear quadratic and logitEUD model.ResultsThe median concordance index (CI) for the bladder, head and neck of femur, bone marrow, small bowel and external genitalia was 0.94, 0.88, 0.84, 0.65 and 0.65, respectively. The median CI for the involved nodal, primary tumour and elective clinical target volumes were 0.85, 0.77 and 0.71, respectively. Across the nine plans, the TCP was not significantly different. Variation in TCP between plans increased as tumour cell load increased or radiation dose decreased.ConclusionsWhen using IMRT for AC, contour variations generated from a common protocol within the limits of minor deviations do not appear to have a significant impact on TCP. Contouring variations may be more critical with increasing tumour cell load or reducing radiotherapy dose.

Modeling tumor control probability for spatially inhomogeneous risk of failure based on clinical outcome data

PurposeObjectives of this work are (1) to derive a general clinically relevant approach to model tumor control probability (TCP) for spatially variable risk of failure and (2) to demonstrate its applicability by estimating TCP for patients planned for photon and proton irradiation. Methods and MaterialsThe approach divides the target volume into sub-volumes according to retrospectively observed spatial failure patterns. The product of all sub-volume TCPi values reproduces the observed TCP for the total tumor. The derived formalism provides for each target sub-volume i the tumor control dose (D50,i) and slope (γ50,i) parameters at 50% TCPi. For a simultaneous integrated boost (SIB) prescription for 45 advanced head and neck cancer patients, TCP values for photon and proton irradiation were calculated and compared. The target volume was divided into gross tumor volume (GTV), surrounding clinical target volume (CTV), and elective CTV (CTVE). The risk of a local failure in each of these sub-volumes was taken from the literature. ResultsConvenient expressions for D50,i and γ50,i were provided for the Poisson and the logistic model. Comparable TCP estimates were obtained for photon and proton plans of the 45 patients using the sub-volume model, despite notably higher dose levels (on average +4.9%) in the low-risk CTVE for photon irradiation. In contrast, assuming a homogeneous dose response in the entire target volume resulted in TCP estimates contradicting clinical experience (the highest failure rate in the low-risk CTVE) and differing substantially between photon and proton irradiation. ConclusionsThe presented method is of practical value for three reasons: It (a) is based on empirical clinical outcome data; (b) can be applied to non-uniform dose prescriptions as well as different tumor entities and dose-response models; and (c) is provided in a convenient compact form. The approach may be utilized to target spatial patterns of local failures observed in patient cohorts by prescribing different doses to different target regions. Its predictive power depends on the uncertainty of the employed established TCP parameters D50 and γ50 and to a smaller extent on that of the clinically observed pattern of failure risk.