Ablative Radiotherapy Research Articles

Stereotactic radiotherapy and the potential role of magnetic resonance-guided adaptive techniques for pancreatic cancer.

BACKGROUNDPancreatic cancer is a malignancy with one of the poorest prognoses amongst all cancers. Patients with unresectable tumours either receive palliative care or undergo various chemoradiotherapy regimens. Conventional techniques are often associated with acute gastrointestinal toxicities, as adjacent critical structures such as the duodenum ultimately limits delivered doses. Stereotactic body radiotherapy (SBRT) is an advanced radiation technique that delivers highly ablative radiation split into several fractions, with a steep dose fall-off outside target volumes. AIMTo discuss the latest data on SBRT and whether there is a role for magnetic resonance-guided techniques in multimodal management of locally advanced, unresectable pancreatic cancer.METHODSWe conducted a search on multiple large databases to collate the latest records on radiotherapy techniques used to treat pancreatic cancer. Out of 1229 total records retrieved from our search, 36 studies were included in this review.RESULTSStudies indicate that SBRT is associated with improved clinical efficacy and toxicity profiles compared to conventional radiotherapy techniques. Further dose escalation to the tumour with SBRT is limited by the poor soft-tissue visualisation of computed tomography imaging during radiation planning and treatment delivery. Magnetic resonance-guided techniques have been introduced to improve imaging quality, enabling treatment plan adaptation and re-optimisation before delivering each fraction.CONCLUSIONTherefore, SBRT may lead to improved survival outcomes and safer toxicity profiles compared to conventional techniques, and the addition of magnetic resonance-guided techniques potentially allows dose escalation and conversion of unresectable tumours to operable cases.

Salvage ablative radiation therapy for loco-regionally recurrent pancreatic ductal adenocarcinoma following surgical resection.

552 Background: Dose escalated radiation therapy for localized pancreatic ductal adenocarcinoma (PDAC) is associated with improved outcomes (Reyngold, JAMA Onc, 2021). Overall survival (OS) and loco-regional failure (LRF) rates with ablative radiation therapy (A-RT) in unresectable PDAC approach those of surgery. Herein, we report outcomes of A-RT as loco-regional salvage after resection. Methods: A prospective database (2016 onward) has been maintained of all patients receiving A-RT at for PDAC. A-RT is defined as a biologically effective dose (BED) ≥96 Gy (α/β = 10). We analyzed consecutive patients from June 2016 through January 2021 who received A-RT for isolated loco-regional recurrences after resection. Survival was calculated using the Kaplan-Meier method. Results: Sixty-nine patients (40 men, 29 women) with median age of 67 received A-RT for loco-regionally recurrent PDAC. At diagnosis of recurrence, median disease-free interval from time of initial resection was 15.6 months (range 6.2–82.7) and median CA 19-9 was 65 U/mL (range < 1–1087). Twenty-one patients (30%) received neoadjuvant chemotherapy prior to surgery: pancreaticoduodenectomy (57 patients, 83%) or distal pancreatectomy (12 patients, 17%). There was a negative resection margin in 55 patients (80%). Most had T1/T2 (61 patients, 88%) and node-positive disease (44 patients, 64%). Radiation fractionation ranged from 5-25 fractions (median 25) to a total dose of 50-75 Gy (median 75). Median follow up was 16.2 months from RT. Median OS was 26.5 months from diagnosis of recurrence and 20.7 months from time of salvage A-RT. Twelve- and 24-month OS were 78.5% (95% CI 66.3–86.7) and 40.3% (25.8–54.3), respectively. In-field local failure was 8.5% (0.3–36.0) at 12 months and 27.5% (5.2–57.0) at 24 months. Respective disease-free survival at 12 and 24 months were 32.9% (21.7–44.1) and 12.3% (5.7–21.6). Grade 3 or greater gastrointestinal bleeding (GIB) occurred in 7 patients (10%), including one grade 4 event while on anticoagulation and one grade 5 event in a patient with portal hypertension. Conclusions: A-RT achieves favorable OS and LRF outcomes in patients with PDAC and an isolated loco-regional recurrence after surgical resection.

Multi-institutional outcomes of patients aged 75 years and older with pancreatic ductal adenocarcinoma treated with ablative 5-fraction stereotactic magnetic resonance image-guided adaptive radiation therapy (SMART).

569 Background: Dose escalated radiation therapy (RT) may improve long-term clinical outcomes compared to standard radiation dose for patients with initially inoperable pancreatic ductal adenocarcinoma (PDAC). Favorable outcomes have recently been reported of ablative stereotactic magnetic resonance image-guided adaptive radiation therapy (SMART) delivered in 5 fractions. The appropriateness of ablative SMART inoperable PDAC patients with advanced age (>75 years) is not well understood. Methods: A retrospective analysis was performed of inoperable non-metastatic PDAC patients aged 75 year or older treated on a 0.35T-MR Linac at two institutions. Patients were excluded who did not have at least 3 months follow up after SMART. Fiducial markers were not used. Treatment delivery was typically in breath hold. Most (65.3%) were treated to gross disease only without elective coverage. On-table adaptive replanning was performed for each fraction if needed, primarily to account for interfraction anatomic changes and ensure all organ-at-risk (OAR) constraints were met. Treatment response was defined using RECIST 1.1 criteria and CTCAE v5 criteria was used to assess toxicity. Results: 49 patients were evaluated with median age of 81 years (range 75-91). ECOG performance status (PS) was 0-1 in 89.8%. PDAC was locally advanced (46.9%), borderline resectable (36.7%), or medically inoperable (16.3%). Median CA19-9 at diagnosis was 235.8 U/mL. Most received induction chemotherapy (83.7%), usually gemcitabine/nab-paclitaxel (63.3%) and rarely FOLFIRINOX (12.2%), for a median 3.2 months. Median prescribed dose was 50 Gy (range, 40-50 Gy). Surgery was performed in 18.4% after a median 10 weeks from SMART, all having negative margins. Median follow-up was 14 months from diagnosis. Median and 1-year local control (LC) was 29 months and 88.9%, respectively. Median and 1-year progression free survival (PFS) was 13 months and 53.8%, respectively. Median and 1-year estimated overall survival (OS) was 23 months and 78.9%, respectively. ECOG PS < 2 was the only significant predictor of improved OS on multivariate analysis with a trend towards significance for induction chemotherapy >3 months. Acute and late grade 3+ toxicity rates were 8.2% and 4.1%, respectively. Conclusions: Ablative 5-fraction SMART is associated with encouraging long-term LC and OS among elderly patients with PDAC. This novel treatment strategy is noninvasive, does not require anesthesia, is remarkably well tolerated among patients with advanced age despite the high prescription dose, and therefore should be strongly considered especially among older patients who have limited treatment options.

Stereotactic body radiotherapy (SBRT) with functional treatment planning in patients with hepatocellular carcinoma (HCC) and advanced hepatic cirrhosis: Survival outcomes and toxicity.

460 Background: To evaluate outcomes and dosimetric parameters of ablative stereotactic body radiotherapy (SBRT) with functional treatment planning for localized hepatocellular carcinoma (HCC) in patients with Child-Pugh B (CP-B) hepatic cirrhosis. Methods: Liver SPECT with 99mTc-sulfur colloid was co-registered to 3D-CT for identification and avoidance of functional hepatic parenchyma during SBRT in patients with advanced cirrhosis. Functional liver volumes (FLV-SPECT) were compared to anatomical liver volumes, as were dosimetric parameters when radiation dose constraints were adapted exclusively to FLV-SPECT. Hepatic function, toxicity, and radiographic response were documented every 4–6 months following SBRT. Results: With a median follow-up of 25 months 37 patients (48 lesions treated) with CP-B cirrhosis received SBRT to a median dose 48 Gy (4–5 fractions). FLV-SPECT volume loss (509 cc or 41.3%, p < 0.001) was observed in all patients, while the functional and anatomical liver volumes matched well in a control group of non-cirrhotic/non-HCC patients. While tumors received ablative irradiation, mean dose to FLV-SPECT was maintained at 1.3 – 16 Gy (median 9.17 Gy), well below the liver threshold tolerance to radiation. Seventeen patients successfully completed liver transplant at a median time to transplant of 6.5 months. The dropout rate from the transplant list was 9 % with intrahepatic progression outside treated tumors. Eight of 10 patients with intrahepatic progression received additional SBRT during follow-up. Overall 2-year survival rate was 65% with no incidence of RILD or CP class migration from B to C was observed at 6+ months post SBRT. Two patients completed liver SBRT on a hybrid linear accelerator combined with MRI scanner (Unity MR-Linac, Elekta) utilizing Super-Paramagnetic Iron Oxide (SPIO) nanoparticle agent as an alternative contrast media for functionally active liver parenchyma. Prolonged SPIO-contrast retention also allowed per fraction treatment plan adaptation and enhanced tumor imaging. Conclusions: SBRT planning with 99mTc sulfur colloid SPECT allows identification and conformal avoidance of residual functionally active hepatic parenchyma in patients with CP-B cirrhosis. We report high local control and low toxicity leading to satisfactory pre- and post-liver transplant outcomes. Prospective clinical trial investigating MRI-SPIO functional treatment planning for liver SBRT is ongoing at our institution.

Liver-Directed Treatment Options Following Liver Tumor Recurrence: A Review of the Literature.

Recurrence following curative-intent hepatectomy for colorectal cancer liver metastasis, hepatocellular carcinoma, or cholangiocarcinoma is unfortunately common with a reported incidence as high as 75%. Various treatment modalities can improve survival following disease recurrence. A review of the literature was performed using PubMed. In addition to systemic therapy, liver-directed treatment options for recurrent liver disease include repeat hepatectomy, salvage liver transplantation, radiofrequency or microwave ablation, intra-arterial therapy, and stereotactic body radiation therapy. Repeat resection can be consider for patients with limited recurrent disease that meets resection criteria, as this therapeutic approach can provide a survival benefit and is potentially curative in a subset of patients. Salvage liver transplantation for recurrent hepatocellular carcinoma is another option, which has been associated with a 5-year survival of 50%. Salvage transplantation may be an option in particular for patients who are not candidates for resection due to underlying liver dysfunction but meet criteria for transplantation. Ablation is another modality to treat patients who recur with smaller tumors and are not surgical candidates due to comorbidity, liver dysfunction, or tumor location. For patients with inoperable disease, transarterial chemoembolization, or radioembolization with Yttrium-90 are liver-directed intra-arterial therapy modalities with relatively low risks that can be utilized. Stereotactic body radiation therapy is another palliative treatment option that can provide a response and local tumor control for smaller tumors.

Randomized trial of intracardiac echocardiography-guided slow pathway ablation.

Radiofrequency (RF) catheter ablation of the slow pathway (SP) in atrioventricular nodal reentry tachycardia (AVNRT) is highly effective; however, it may require prolonged fluoroscopy and RF time. We postulated that visualization of the SP region with intracardiac echocardiography (ICE) could decrease ablation time, minimize radiation exposure, and facilitate SP ablation compared to the standard, fluoroscopy-guided approach. In our study, we randomized 91 patients undergoing electrophysiologic study and SP ablation for AVNRT into 2 groups: fluoroscopy-only (n = 48) or ICE-guided (n = 43) group. Crossover to ICE-guidance was allowed after 8 unsuccessful RF applications. Mapping plus ablation time (mean ± standard deviation: 18.8 ± 16.1min vs 11.6 ± 15.0min, p = 0.031), fluoroscopy time (median [interquartile range]: 4.9 [2.93-8.13] min vs. 1.8 [1.2-2.8] min, p < 0.001), and total ablation time (144 [104-196] s vs. 81 [60-159] s, p = 0.001) were significantly shorter in the ICE group. ICE-guidance was associated with reduced radiation exposure (13.2 [8.2-13.4] mGy vs. 3.7 [1.5-5.8] mGy, p < 0.001). The sum of delivered RF energy (3866 [2786-5656] Ws vs. 2283 [1694-4284] Ws, p = 0.002) and number of RF applications (8 [4.25-12.75] vs. 4 [2-7], p = 0.001) were also lower with ICE-guidance. Twelve (25%) patients crossed over to the ICE-guided group. All were treated successfully thereafter with similar number, time, and cumulative energy of RF applications compared to the ICE group. No recurrence occurred during the follow-up. ICE-guidance during SP ablation significantly reduces mapping and ablation time, radiation exposure, and RF delivery in comparison to fluoroscopy-only procedures. Moreover, early switching to ICE-guided ablation seems to be an optimal choice in challenging cases.

Phase II Trial of Stereotactic Ablative Radiation for Oligoprogressive Metastatic Kidney Cancer

BackgroundPatients with metastatic renal cell carcinoma (mRCC) treated with systemic therapy sometimes progress at limited sites.The best treatment approach for patients with oligoprogression remains unclear. ObjectiveTo determine the ability of stereotactic ablative radiation (SAbR) to extend ongoing systemic therapy in mRCC patients with oligoprogression. Design, setting, and participantsA single-arm phase II clinical trial was conducted at a university medical center and county hospital, including 20 patients with mRCC on first- to fourth-line systemic therapy with three or fewer sites of progression (including new sites) involving ≤30% of all sites. InterventionSAbR to oligoprogressing metastases at outset and longitudinally, while radiated sites remain controlled and overall disease oligoprogressive. Outcome measurements and statistical analysisThe primary objective was to extend ongoing systemic therapy by >6 mo in >40% of patients. Secondary endpoints included overall survival, toxicity, and patient-reported quality of life. Results and limitationsTwenty patients were enrolled. Upfront and sequential SAbR was administered to a total of 37 sites. The local control rate was 100%. At a median follow-up of 10.4 mo (interquartile range: 5.8–16.4), SAbR extended the duration of the ongoing systemic therapy by >6 mo in 14 patients (70%, 95% confidence interval [CI]: 49.9–90.1). The median time from SAbR to the onset of new systemic therapy or death was 11.1 mo (95% CI: 4.5–19.3). The median duration of SAbR-aided systemic therapy was 24.4 mo (95% CI: 15.3–42.2). Median overall survival was not reached. One patient developed grade 3 gastrointestinal toxicity possibly related to treatment. There was no significant decline in quality of life. Limitations include nonrandomized design and a small patient cohort. ConclusionsSAbR extended the duration of the ongoing systemic therapy for patients with oligoprogressive mRCC without undermining quality of life. These data support the evaluation of SAbR for oligoprogressive mRCC in a prospective randomized clinical trial. Patient summaryPatients with metastatic kidney cancer on systemic therapy but progressing at limited sites may benefit from focused radiation to progressive sites. Focused radiation was safe and effective, and extended the duration of the ongoing systemic therapy.

What Is the Optimal Bridging Therapy for Patients with Hepatitis C-associated Hepatocellular Carcinoma Awaiting Liver Transplant? An Analysis of the United States HCC Liver Transplantation Consortium

Introduction: Patients with hepatitis C (HCV)-associated hepatocellular carcinoma (HCC) often receive bridging therapy in the form of liver-directed therapy (LDT) while awaiting liver transplant (LT). The optimal modality of LDT, with respect to both cancer outcomes and response to direct-acting antiviral (DAA) therapy, remains unknown. Methods: The United States HCC Liver Transplantation Consortium was queried for patients with primary HCV-associated HCC within Milan criteria who completed DAA therapy and underwent LT. Primary outcomes were HCC recurrence-free survival (RFS) and overall survival (OS). Secondary outcome was sustained virologic response (SVR) as indicator of efficacy of DAA therapy. Results: Of 857 patients, 753 met inclusion criteria. LDT consisted of radiofrequency ablation (RFA,13.3%,N=100), transarterial chemoembolization (TACE,44.1%,N=332), yttrium-90 (Y90,4.8%,N=36), and stereotactic body radiation therapy (SBRT,2.9%,N=22). Eighty-one(10.8%) patients received no LDT and 182(24.2%) received multiple modalities. SBRT patients had the highest 5-year RFS(100%) followed by those receiving TACE(94%), Y90(91.4%), RFA(89.9%), and multiple therapies(88.2%) (p=0.048, Figure 1A). OS was higher among patients who received SBRT, but not statistically significant (p=0.685, Figure 1B). SVR rate was lower among radiation-based therapy groups (Y90 73.5%, SBRT 78.9%, others≥88%; p=0.046). Conclusions: In a homogeneous population of HCV-associated HCC patients within Milan criteria who received bridging therapy while awaiting LT, SBRT was associated with increased RFS and trended towards increased OS. However, radiation-based therapy was associated with decreased efficacy of DAA as measured by lower SVR rates. The optimal choice of bridging therapy to liver transplant must balance oncologic and virologic outcomes, but these findings seem to favor SBRT.

MArkerless image Guidance using Intrafraction Kilovoltage x-ray imaging (MAGIK): study protocol for a phase I interventional study for lung cancer radiotherapy

IntroductionIn radiotherapy, tumour tracking leads the radiation beam to accurately target the tumour while it moves in a complex and unpredictable way due to respiration. Several tumour tracking techniques require...

Inter- and intrafraction motion assessment and accumulated dose quantification of upper gastrointestinal organs during magnetic resonance-guided ablative radiation therapy of pancreas patients.

Background and purposeStereotactic body radiation therapy (SBRT) of locally advanced pancreatic cancer (LAPC) is challenging due to significant motion of gastrointestinal (GI) organs. The goal of our study was to quantify inter and intrafraction deformations and dose accumulation of upper GI organs in LAPC patients.Materials and methodsFive LAPC patients undergoing five-fraction magnetic resonance-guided radiation therapy (MRgRT) using abdominal compression and daily online plan adaptation to 50 Gy were analyzed. A pre-treatment, verification, and post-treatment MR imaging (MRI) for each of the five fractions (75 total) were used to calculate intra and interfraction motion. The MRIs were registered using Large Deformation Diffeomorphic Metric Mapping (LDDMM) deformable image registration (DIR) method and total dose delivered to stomach_duodenum, small bowel (SB) and large bowel (LB) were accumulated. Deformations were quantified using gradient magnitude and Jacobian integral of the Deformation Vector Fields (DVF). Registration DVFs were geometrically assessed using Dice and 95th percentile Hausdorff distance (HD95) between the deformed and physician’s contours. Accumulated doses were then calculated from the DVFs.ResultsMedian Dice and HD95 were: Stomach_duodenum (0.9, 1.0 mm), SB (0.9, 3.6 mm), and LB (0.9, 2.0 mm). Median (max) interfraction deformation for stomach_duodenum, SB and LB was 6.4 (25.8) mm, 7.9 (40.5) mm and 7.6 (35.9) mm. Median intrafraction deformation was 5.5 (22.6) mm, 8.2 (37.8) mm and 7.2 (26.5) mm. Accumulated doses for two patients exceeded institutional constraints for stomach_duodenum, one of whom experienced Grade1 acute and late abdominal toxicity.ConclusionLDDMM method indicates feasibility to measure large GI motion and accumulate dose. Further validation on larger cohort will allow quantitative dose accumulation to more reliably optimize online MRgRT.

Curative treatment of pancreatic functioning insulinoma with stereotactic ablative radiation therapy: case report

Insulinoma is the most common pancreatic neuroendocrine tumor (NET). It is a rare disease account for 1-2% of pancreatic tumors and affect approximately up to 3 patients per million per year. complete surgical resection or debulking are standard of care option. However, surgery is associated with short and long-term post-operative morbidity and may not be appropriate for all patients. In This case we present management and cure of a case of functioning insulinoma with stereotactic ablative radiosurgery in an unfit patient for surgery.

An analysis of a large multi-institutional database reveals important associations between treatment parameters and clinical outcomes for stereotactic body radiotherapy (SBRT) of oligometastatic colorectal cancer

PurposeIn recent years, stereotactic body radiotherapy (SBRT) has emerged as an effective treatment for oligometastatic cancers. Here, we report radiation treatment parameters and clinical outcomes for patients with oligometastatic colorectal cancer (CRC) treated with SBRT using a large multi-institutional database. MethodsPatients with extra-cranial oligometastatic CRC (≤5 lesions) treated with SBRT at six large academic cancer centers were included. The primary outcome was local recurrence while secondary outcomes included overall survival (OS) progression free survival, oligo-progression, and widespread progression. Survival outcomes were estimated using the Kaplan-Meier method. Univariable and multivariable analyses were performed to determine the relationship between patient and treatment characteristics and clinical outcomes. ResultsWe identified 235 patients with a total of 381 oligometastatic CRC lesions. The 1- and 5-year local recurrence rate was 13.6% and 44.3% respectively. The median OS was 49 months with a 2-and 5-year OS of 76.1% and 35.9%, respectively. On multivariable analysis, a BED10 of ≥120 Gy, and lung versus liver metastases were associated with a reduction in local recurrence. Larger total PTV size (≥17.5 cc) was associated with worse overall survival, progression free survival, and widespread progression. ConclusionThis large multi-institutional analysis found that the use of SBRT for oligometastatic colorectal cancer resulted in favorable overall survival. However, local recurrence is higher than expected for ablative radiation treatment. An increase in BED10 should be considered if feasible and safe.

Positron Emission Tomography–Derived Metrics Predict the Probability of Local Relapse After Oligometastasis-Directed Ablative Radiation Therapy

PurposeEarly positron emission tomography–derived metrics post–oligometastasis radioablation may predict impending local relapses (LRs), providing a basis for a timely ablation. Methods and MaterialsPositron emission tomography data of 623 lesions treated with either 24 Gy single-dose radiation therapy (SDRT) (n = 475) or 3 × 9 Gy stereotactic body radiation therapy (SBRT) (n = 148) were analyzed in a training data set (n = 246) to obtain optimal cutoffs for pretreatment maximum standardized uptake value (SUVmax) and its 3-month posttreatment decline (ΔSUVmax) in predicting LR risk, validated in a data set unseen to testing (n = 377). ResultsAt a median of 21.7 months, 91 lesions developed LRs: 39 of 475 (8.2%) after SDRT and 52 of 148 (35.1%) after SBRT. The optimal cutoff values were 12 for SUVmax and –75% for ΔSUVmax. Bivariate SUVmax/ΔSUVmax permutations rendered a 3-tiered LR risk stratification of dual-favorable (low risk), 1 adverse (intermediate risk) and dual-adverse (high risk). Actuarial 5-year local relapse-free survival rates were 93.9% versus 89.6% versus 57.1% (P < .0001) and 76.1% versus 48.3% versus 8.2% (P < .0001) for SDRT and SBRT, respectively. The SBRT area under the ROC curve was 0.71 (95% CI, 0.61-0.79) and the high-risk subgroup yielded a 76.5% true positive LR prediction rate. ConclusionsThe SBRT dual-adverse SUVmax/ΔSUVmax category LR prediction power provides a basis for prospective studies testing whether a timely ablation of impending LRs affects oligometastasis outcomes.

Benchmarking Outcomes after Ablative Radiotherapy for Molecularly Characterized Intrahepatic Cholangiocarcinoma.

We have previously shown that ablative radiotherapy (A-RT) with a biologically effective dose (BED10) ≥ 80.5 Gy for patients with unresectable intrahepatic cholangiocarcinoma (ICC) is associated with longer survival. Despite recent large-scale sequencing efforts in ICC, outcomes following RT based on genetic alterations have not been described. We reviewed records of 156 consecutive patients treated with A-RT for unresectable ICC from 2008 to 2020. For 114 patients (73%), next-generation sequencing provided molecular profiles. The overall survival (OS), local control (LC), and distant metastasis-free survival (DMFS) were estimated using the Kaplan–Meier method. Univariate and multivariable Cox analyses were used to determine the associations with the outcomes. The median tumor size was 7.3 (range: 2.2–18.2) cm. The portal vein thrombus (PVT) was present in 10%. The RT median BED10 was 98 Gy (range: 81–144 Gy). The median (95% confidence interval) follow-up was 58 (42–104) months from diagnosis and 39 (33–74) months from RT. The median OS was 32 (29–35) months after diagnosis and 20 (16–24) months after RT. The one-year OS, LC, and intrahepatic DMFS were 73% (65–80%), 81% (73–87%), and 34% (26–42%). The most common mutations were in IDH1 (25%), TP53 (22%), ARID1A (19%), and FGFR2 (13%). Upon multivariable analysis, the factors associated with death included worse performance status, larger tumor, metastatic disease, higher CA 19-9, PVT, satellitosis, and IDH1 and PIK3CA mutations. TP53 mutation was associated with local failure. Further investigation into the prognostic value of individual mutations and combinations thereof is warranted.

Stereotactic Body Radiation Therapy (SBRT) vs Stereotactic Ablative Radiation Therapy (SABR): Does Terminology Differentiate Treatment Intent in Metastatic Cancer?

Stereotactic Body Radiation Therapy (SBRT) vs Stereotactic Ablative Radiation Therapy (SABR): Does Terminology Differentiate Treatment Intent in Metastatic Cancer?

P124 - Validation of a robust optimization approach for VMAT treatment planning of stereotactic ablative radiation therapy (SABR) in lung cancer

P124 - Validation of a robust optimization approach for VMAT treatment planning of stereotactic ablative radiation therapy (SABR) in lung cancer

3D-printed patient-specific pelvis phantom for dosimetry measurements for prostate stereotactic radiotherapy with dominant intraprostatic lesion boost.

Developing and assessing the feasibility of using a three-dimensional (3D) printed patient-specific anthropomorphic pelvis phantom for dose calculation and verification for stereotactic ablative radiation therapy (SABR) with dose escalation to the dominant intraprostatic lesions. A 3D-printed pelvis phantom, including bone-mimicking material, was fabricated based on the computed tomography (CT) images of a prostate cancer patient. To compare the extent to which patient and phantom body and bones overlapped, the similarity Dice coefficient was calculated. Modular cylindrical inserts were created to encapsulate radiochromic films and ionization chamber for absolute dosimetry measurements at the location of prostate and at the boost region. Gamma analysis evaluation with 2%/2mm criteria was performed to compare treatment planning system calculations and measured dose when delivering a 10 flattening filter free (FFF) SABR plan and a 10FFF boost SABR plan. Dice coefficients of 0.98 and 0.91 were measured for body and bones, respectively, demonstrating agreement between patient and phantom outlines. For the boost plans the gamma analysis yielded 97.0% of pixels passing 2%/2mm criteria and these results were supported by the chamber average dose difference of 0.47±0.03%. These results were further improved when overriding the bone relative electron density: 97.3% for the 2%/2mm gamma analysis, and 0.05±0.03% for the ionization chamber average dose difference. The modular patient-specific 3D-printed pelvis phantom has proven to be a highly attractive and versatile tool to validate prostate SABR boost plans using multiple detectors.

Account for the Full Extent of Esophagus Motion in Radiation Therapy Planning: A Preliminary Study of the IRV of the Esophagus.

ObjectiveAccounting for esophagus motion in radiotherapy planning is an important basis for accurate assessment of toxicity. In this study, we calculated how much the delineations of the esophagus should be expanded based on three-dimensional (3D) computed tomography (CT), four-dimensional (4D) average projection (AVG), and maximum intensity projection (MIP) scans to account for the full extent of esophagus motion during 4D imaging acquisition.Methods and MaterialsThe 3D and 4D CT scans of 20 lung cancer patients treated with conventional radiotherapy and 20 patients treated with stereotactic ablative radiation therapy (SBRT) were used. Radiation oncologists contoured the esophagus on the 3DCT, AVG, MIP and 25% exhale scans, and the combination of the esophagus in every phase of 4DCT. The union of all 4D phase delineations (U4D) represented the full extent of esophagus motion during imaging acquisition. Surface distances from U4D to 3D, AVG, and MIP volumes were calculated. Distances in the most extreme surface points (1.5 cm most superoinferior, 10% most right/left/anteroposterior) were used to derive margins accounting only for systematic (delineation) errors.ResultsEsophagus delineations on the MIP were the closest to the full extent of motion, requiring only 6.9 mm margins. Delineations on the AVG and 3D scans required margins up to 7.97 and 7.90 mm, respectively. The largest margins were for the inferior, right, and anterior aspects for the delineations on the 3D, AVG, and MIP scans, respectively.ConclusionDelineations on 3D, AVG, or MIP scans required extensions for representing the esophagus’s full extent of motion, with the MIP requiring the smallest margins. Research including daily imaging to determine the random components for the margins and dosimetric measurements to determine the relevance of creating a planning organ at risk volume (PRV) of the esophagus is required.

Dose calculation and reporting with a linear Boltzman transport equation solver in vertebral SABR.

Vertebral Stereotactic ablative body radiotherapy (SABR) involves substantial tumour density heterogeneities. We evaluated the impact of a linear Boltzmann transport equation (LBTE) solver dose calculation on vertebral SABR dose distributions. A sequential cohort of 20 patients with vertebral metastases treated with SABR were selected. Treatment plans were initially planned with a convolution style dose calculation algorithm. The plan was copied and recalculated with a LBTE algorithm reporting both dose to water (Dw) or dose to medium (Dm). Target dose as a function of CT number, and spinal cord dose was compared between algorithms. Compared with a convolution algorithm, there was minimal change in PTV D90% with LBTE. LBTE reporting Dm resulted in reduced GTV D50% by (mean, 95% CI) 2.2% (1.9-2.6%) and reduced Spinal Cord PRV near-maximum dose by 3.0% (2.0-4.1%). LBTE reporting Dw resulted in increased GTV D50% by 2.4% (1.8-3.0%). GTV D50% decreased or increased with increasing CT number with Dm or Dw respectively. LBTE, reporting either Dm or Dw resulted in decreased central spinal cord dose by 8.7% (7.1-10.2%) and 7.2% (5.7-8.8%) respectively. Reported vertebral SABR tumour dose when calculating with an LBTE algorithm depends on tumour density. Spinal cord near-maximum dose was lower when using LBTE algorithm reporting Dm, which may result in higher spinal cord doses being delivered than with a convolution style algorithm. Spinal cord central dose was significantly lower with LBTE, potentially reflecting LBTE transport approximations.

V1r + DIIq is a novel and accurate criterion to predict right vs. left paraseptal accessory pathways

PurposeThe correct estimation of accessory pathway (AP) localization from surface ECG is critical before the procedure. Our study aimed to detect the predictive value of the V1r + DIIq criterion for differentiating right- from left-sided paraseptal APs. MethodsWe retrospectively included 58 patients with (Wolff–Parkinson–White) WPW syndrome and paraseptal APs who underwent successful catheter ablation (37 male, 21 female; mean age 34.4 ± 13.6 years). The V1r + DIIq criterion was calculated using the following formula: V1r + DIIq (mV) = initial r wave amplitude in V1 + q wave amplitude in DII. The combined criterion included V1r + DIIq <2.05 mV and/or no initial r wave in V1. ResultsRight-sided paraseptal APs were detected in 36 patients (62.1%), left-sided paraseptal APs were detected in 21 patients (36.2%), and AP from CS was detected in 1 patient (1.7%). The initial r wave amplitude in V1 (mV), q wave amplitude in DII (mV) and V1r + DIIq criterion (mV) were lower in patients with right-sided paraseptal APs (p < 0.001). The percentage of patients with no initial r wave in V1 (36.1% vs. 0%) and those meeting the combined criterion (91.7% vs. 4.5%) were increased in patients with right-sided paraseptal APs. The cutoff value of the V1r + DIIq criterion obtained by ROC curve analysis was 2.05 mV for predicting right-sided paraseptal APs (sensitivity: 86.1%, specificity: 95.5%). The area under the curve (AUC) was 0.943 (95% CI = 0.881–1.000) (p < 0.001). The sensitivity and specificity values were 36.1% and 100%, respectively, for the no initial r wave criterion and 91.7% and 95.5%, respectively, for the combined criterion. ConclusionThe V1r + DIIq criterion and the combined criterion represent novel and simple electrocardiographic criteria for accurately differentiating right- from left-sided paraseptal APs. This simple ECG measurement can improve the accuracy of detection of paraseptal AP localization and could be beneficial for decreasing ablation duration and radiation exposure.