Validation of Fully Automated Robust Multicriterial Treatment Planning for Head and Neck Cancer IMPT.

PURPOSE: Our purpose was to compare robust intensity modulated proton therapy (IMPT) plans, automatically generated with wish-list-based multicriterial optimization as implemented in Erasmus-iCycle, with manually created robust clinical IMPT plans for patients with head and neck cancer. METHODS AND MATERIALS: Thirty-three patients with head and neck cancer were retrospectively included. All patients were previously treated with a manually created IMPT plan with 7000 cGy dose prescription to the primary tumor (clinical target volume [CTV]7000) and 5425 cGy dose prescription to the bilateral elective volumes (CTV5425). Plans had a 4-beam field configuration and were generated with scenario-based robust optimization (21 scenarios, 3-mm setup error, and ±3% density uncertainty for the CTVs). Three clinical plans were used to configure the Erasmus-iCycle wish-list for automated generation of robust IMPT plans for the other 30 included patients, in line with clinical planning requirements. Automatically and manually generated IMPT plans were compared for (robust) target coverage, organ-at-risk (OAR) doses, and normal tissue complication probabilities (NTCP). No manual fine-tuning of automatically generated plans was performed. RESULTS: For all automatically generated plans, voxel-wise minimum D98% values for the CTVs were within clinical constraints and similar to manual plans. All investigated OAR parameters were favorable in the automatically generated plans (all P < .001). Median reductions in mean dose to OARs went up to 667 cGy for the inferior pharyngeal constrictor muscle, and median reductions in D0.03cm3 in serial OARs ranged up to 1795 cGy for the spinal cord surface. The observed lower mean dose in parallel OARs resulted in statistically significant lower NTCP for xerostomia (grade ≥2: 34.4% vs 38.0%; grade ≥3: 9.0% vs 10.2%) and dysphagia (grade ≥2: 11.8% vs 15.0%; grade ≥3: 1.8% vs 2.8%). CONCLUSIONS: Erasmus-iCycle was able to produce IMPT dose distributions fully automatically with similar (robust) target coverage and improved OAR doses and NTCPs compared with clinical manual planning, with negligible hands-on planning workload.

Corrigendum to "Harmonization of breast cancer radiotherapy treatment planning in the Netherlands" [Tech. Innov. Patient Support Radiat. Oncol. 19 (2021) 26-32].

[This corrects the article DOI: 10.1016/j.tipsro.2021.06.004.].

Harmonization of breast cancer radiotherapy treatment planning in the Netherlands.

PURPOSE: The aim was to reach consensus in The Netherlands on which parameters should be used to evaluate breast cancer radiotherapy (RT) plans. MATERIALS AND METHODS: A Benchmark Case with delineated planning target volumes (PTVs) and Organs At Risk (OARs) was sent to all Dutch radiotherapy centres in combination with a questionnaire, with the request to generate RT plans prescribing 15 times 2.67 Gy for four different treatment indications according to the institutional irradiation technique. The plans and accompanying questionnaire answers were analysed using descriptive statistics. These results, together with a harmonisation proposal, were sent to all centres. The proposal was discussed at a meeting of the Dutch Society of Radiation Oncology breast cancer platform. Distinct parameters were accepted if consensus on them was reached. RESULTS: 19 out of 20 Dutch departments participated in this study. PTV coverage varied considerably, with D98% between 63% and 99% for the breast and between 37% and 97% for the internal mammary nodes (IMN). Also substantial OAR dose differences were observed, with e.g. mean heart doses ranging between 1.85 Gy and 5.42 Gy in case the IMN were included in the PTV. For evaluation of the PTVs D98%, D2% and Dmean were chosen to report on, with target values of ≥ 95% (90% for the PTV_IMN), ≤ 107%, and 99-101%, respectively. For OARs, consensus was reached on the parameters to be evaluated, without target values: Dmean of the heart, Dmean and V5% of the lungs, and in case of periclavicular radiotherapy V30Gy of the thyroid gland. For patients younger than 40 years a contralateral mean breast dose of ≤ 1 Gy was agreed upon. CONCLUSION: A new Dutch consensus guideline for evaluation of breast cancer RT plans has been established.

Automatic generation of three-dimensional dose reconstruction data for two-dimensional radiotherapy plans for historically treated patients.

Performing large-scale three-dimensional radiation dose reconstruction for patients requires a large amount of manual work. We present an image processing-based pipeline to automatically reconstruct radiation dose. The pipeline was designed for childhood cancer survivors that received abdominal radiotherapy with anterior-to-posterior and posterior-to-anterior field set-up. First, anatomical landmarks are automatically identified on two-dimensional radiographs. Second, these landmarks are used to derive parameters to emulate the geometry of the plan on a surrogate computed tomography. Finally, the plan is emulated and used as input for dose calculation. For qualitative evaluation, 100 cases of automatic and manual plan emulations were assessed by two experienced radiation dosimetrists in a blinded comparison. The two radiation dosimetrists approved 100%/100% and 92%/91% of the automatic/manual plan emulations, respectively. Similar approval rates of 100% and 94% hold when the automatic pipeline is applied on another 50 cases. Further, quantitative comparisons resulted in on average < 5 mm difference in plan isocenter/borders, and < 0.9 Gy in organ mean dose (prescribed dose: 14.4 Gy) calculated from the automatic and manual plan emulations. No statistically significant difference in terms of dose reconstruction accuracy was found for most organs at risk. Ultimately, our automatic pipeline results are of sufficient quality to enable effortless scaling of dose reconstruction data generation.

Dosimetric Benefits of Midposition Compared With Internal Target Volume Strategy for Esophageal Cancer Radiation Therapy.

PURPOSE: Both midposition (MidP) and internal target volume (ITV) strategies can take the respiration-induced target motion into account. This study aimed to compare these 2 strategies in terms of clinical target volume (CTV) coverage and dose to organs at risk (OARs) for esophageal cancer radiation therapy (RT). METHODS AND MATERIALS: Fifteen patients with esophageal cancer were included retrospectively for neoadjuvant RT planning. Per patient, a 10-phase, 4-dimensional (4D) computed tomography (CT) scan (4D-CT) was acquired with CTV and OARs delineated on the 20% phase. The MidP-CT scan was reconstructed based on deformable image registration between the 20% phase and the other 9 phases; thereby, the CTV and OARs delineations were propagated and an ITV was constructed. Both MidP and ITV strategies were used for treatment planning, yielding the planned dose. Next, these plans were applied to the 10-phase 4D-CT to calculate the dose distribution for each phase of the 4D-CT. On the basis of the deformable image registration, these calculated dose distributions were warped and averaged to yield the accumulated 4D dose. Subsequently, we compared, in terms of CTV coverage and dose to OARs, the planned dose with the accumulated 4D dose and the MidP strategy with the ITV strategy. RESULTS: The differences between the planned dose and the accumulated 4D dose were limited and clinically irrelevant. In 14 patients, both MidP and ITV strategies showed V95% > 98% for the CTV. Compared with the ITV strategy, the MidP strategy showed a significant reduction of approximately 10% in the dose-volume histogram parameters for the lungs, heart, and liver (P < .001, Wilcoxon signed-rank test). CONCLUSIONS: Compared with the ITV strategy, the MidP strategy in treatment planning can lead to a reduction of approximately 10% in the dose to OARs, with an adequate CTV coverage for esophageal cancer RT.

Re­irradiation plus hyperthermia for recurrent pediatric sarcoma; a simulation study to investigate feasibility.

Recurrent pediatric tumors pose a challenge since treatment options may be limited, particularly after previous irradiation. Positive results have been reported for chemotherapy and hyperthermia, but the combination of re­irradiation and hyperthermia has not been investigated thus far, although it is a proven treatment strategy in adults. The theoretical feasibility of re­irradiation plus hyperthermia was investigated for infield recurrent pediatric sarcoma in the pelvic region and the extremities. A total of 46 recurrent pediatric sarcoma cases diagnosed at the Academic Medical Center (Amsterdam, The Netherlands) between 2002 and 2017 were evaluated. Patients not previously irradiated, outfield recurrences and locations other than the pelvis and extremities were excluded, ultimately yielding four eligible patients: Two with sarcomas in the pelvis and two in an extremity. Re­irradiation and hyperthermia treatment plans were simulated for 23x2 Gy treatment schedules and weekly hyperthermia. The radiosensitizing effect of hyperthermia was quantified using biological modelling with a temperature­dependent change in the parameters of the linear­quadratic model. The possible effectiveness of re­irradiation plus hyperthermia was estimated by calculating the equivalent radiotherapy dose distribution. Treatment planning revealed that tumors located in the pelvis and the extremities can be effectively heated in children. Equivalent dose distributions indicated that hyperthermic radiosensitization can be quantified as a target­selective additional D95% of typically 10 Gy, thereby delivering a possibly curative dose of 54 Gy, without substantially increasing the equivalent dose to the organs at risk. Therefore, re­irradiation plus hyperthermia is a theoretically feasible and possibly effective treatment option for recurrent pediatric sarcoma in the pelvic region and the extremities, and its clinical feasibility is worthy of evaluation.

Density override in treatment planning to mitigate the dosimetric effect induced by gastrointestinal gas in esophageal cancer radiation therapy.

PURPOSE: To investigate the dosimetric effect of variable gas volume in esophageal cancer radiation therapy (RT) and whether a density override (DO) in treatment planning can effectively mitigate this dosimetric effect. MATERIAL AND METHODS: Nine patients with gastrointestinal gas pockets in the planning computed tomography (pCT) were retrospectively included. Per patient, the intensity-modulated RT (IMRT) and volumetric-modulated arc therapy (VMAT) plans associated with no DO, DO = 0.5, and DO = 1 in the gas pockets were made. Initial and follow-up gas volumes were assessed from the pCTs and cone-beam CTs (CBCTs), respectively. Fractional CTs were created based on the pCT and CBCTs to calculate the fractional doses using all six plans. We then investigated for all six plans the correlation between the gas volume difference (relative to initial gas volume) and the dose difference (relative to planned dose). We also calculated and compared the accumulated dose by summing the fractional doses using two strategies: single-plan strategy (i.e. using each of the six plans separately) and plan-selection strategy (i.e. selecting one of the three plans depending on the fractional gas volume for IMRT and VMAT planning separately). RESULTS: The dose difference was approximately linearly correlated to the gas volume difference. Underdoses of >3.5% and overdoses of >7% were found for gas volume decreases >160 mL/330 mL and increases >260 mL/370 mL for IMRT/VMAT planning, respectively. Moreover, for most patients, the single-plan strategy with the use of DO = 0.5 resulted in neither undesired underdose nor much overdose. The plan-selection strategy, however, can always ensure sufficient target coverage and minimize high dose regions to the most extent. CONCLUSIONS: The variation in gas volume during the treatment course can result in clinically undesired underdose or overdose. The DO-based plan-selection strategy can effectively mitigate the gas-induced underdose and minimize the overdose for esophageal cancer RT.

Comparing the dosimetric impact of interfractional anatomical changes in photon, proton and carbon ion radiotherapy for pancreatic cancer patients.

Radiotherapy using charged particles is characterized by a low dose to the surrounding healthy organs, while delivering a high dose to the tumor. However, interfractional anatomical changes can greatly affect the robustness of particle therapy. Therefore, we compared the dosimetric impact of interfractional anatomical changes (i.e. body contour differences and gastrointestinal gas volume changes) in photon, proton and carbon ion therapy for pancreatic cancer patients. In this retrospective planning study, photon, proton and carbon ion treatment plans were created for 9 patients. Fraction dose calculations were performed using daily cone-beam CT (CBCT) images. To this end, the planning CT was deformably registered to each CBCT; gastrointestinal gas volumes were delineated on the CBCTs and copied to the deformed CT. Fraction doses were accumulated rigidly. To compare planned and accumulated dose, dose-volume histogram (DVH) parameters of the planned and accumulated dose of the different radiotherapy modalities were determined for the internal gross tumor volume, internal clinical target volume (iCTV) and organs-at-risk (OARs; duodenum, stomach, kidneys, liver and spinal cord). Photon plans were highly robust against interfractional anatomical changes. The difference between the planned and accumulated DVH parameters for the photon plans was less than 0.5% for the target and OARs. In both proton and carbon ion therapy, however, coverage of the iCTV was considerably reduced for the accumulated dose compared with the planned dose. The near-minimum dose ([Formula: see text]) of the iCTV reduced with 8% for proton therapy and with 10% for carbon ion therapy. The DVH parameters of the OARs differed less than 3% for both particle modalities. Fractionated radiotherapy using photons is highly robust against interfractional anatomical changes. In proton and carbon ion therapy, such changes can severely reduce the dose coverage of the target.

Plan selection strategy for rectum cancer patients: An interobserver study to assess clinical feasibility.

BACKGROUND AND PURPOSE: In radiotherapy for rectum cancer, the target volume is highly deformable. An adaptive plan selection strategy can mitigate the effect of these variations. The purpose of this study was to evaluate the feasibility of an adaptive strategy by assessing the interobserver variation in CBCT-based plan selection. MATERIAL AND METHODS: Eleven patients with rectum cancer, treated with a non-adaptive strategy, were selected. Five CBCT scans were available per patient. To simulate the plan selection strategy, per patient three PTVs were created by varying the anterior upper mesorectum margin. For each CBCT scan, twenty observers selected the smallest PTV that encompassed the target volume. After this initial baseline measurement, the gold standard was determined during a consensus meeting, followed by a second measurement one month later. Differences between both measurements were assessed using the Wilcoxon signed-rank test. RESULTS: In the baseline measurement, the concordance with the gold standard was 69% (range: 60-82%), which improved to 75% (range: 60-87%) in the second measurement (p=0.01). For the second measurement, 10% of plan selections were smaller than the gold standard. CONCLUSION: With a plan selection consistency between observers of 75%, a plan selection strategy for rectum cancer patients is feasible.

Dosimetric advantages of proton therapy compared with photon therapy using an adaptive strategy in cervical cancer.

Background Image-guided adaptive proton therapy (IGAPT) can potentially be applied to take into account interfraction motion while limiting organ at risk (OAR) dose in cervical cancer radiation therapy (RT). In this study, the potential dosimetric advantages of IGAPT compared with photon-based image-guided adaptive RT (IGART) were investigated. Material and methods For 13 cervical cancer patients, full and empty bladder planning computed tomography (CT) images and weekly CTs were acquired. Based on both primary clinical target volumes (pCTVs) [i.e. gross tumor volume (GTV), cervix, corpus-uterus and upper part of the vagina] on planning CTs, the pretreatment observed full range primary internal target volume (pITV) was interpolated to derive pITV subranges. Given corresponding ITVs (i.e. pITVs including lymph nodes), patient-specific photon and proton plan libraries were generated. Using all weekly CTs, IGART and IGAPT treatments were simulated by selecting library plans and recalculating the dose. For each recalculated IGART and IGAPT fraction, CTV (i.e. pCTV including lymph nodes) coverage was assessed and differences in fractionated substitutes of dose-volume histogram (DVH) parameters (V15Gy, V30Gy, V45Gy, Dmean, D2cc) for bladder, bowel and rectum were tested for significance (Wilcoxon signed-rank test). Also, differences in toxicity-related DVH parameters (rectum V30Gy, bowel V45Gy) were approximated based on accumulated dose distributions. Results In 92% (96%) of all recalculated IGAPT (IGART) fractions adequate CTV coverage (V95% >98%) was obtained. All dose parameters for bladder, bowel and rectum, except the fractionated substitute for rectum V45Gy, were improved using IGAPT. Also, IGAPT reduced the mean dose to bowel, bladder and rectum significantly (p < 0.01). In addition, an average decrease of rectum V30Gy and bowel V45Gy indicated reductions in toxicity probabilities when using IGAPT. Conclusion This study demonstrates the feasibility of IGAPT in cervical cancer using a plan-library based plan-of-the-day approach. Compared to photon-based IGART, IGAPT maintains target coverage while significant dose reductions for the bladder, bowel and rectum can be achieved.