Gy EQD2 Research Articles

Feasibility and safety of definite volumetric modulated arc therapy with simultaneous integrated boost to the dominant intraprostatic lesion in patients with unfavorable intermediate to high-risk prostate cancer.

BackgroundThe most common site of recurrence of prostate cancer after definite radiation therapy is the dominant intraprostatic lesion (DIL). This study aimed to investigate the feasibility and safety of definite volumetric modulated arc therapy (VMAT) with simultaneous integrated boost (SIB) to the DIL in patients with unfavorable intermediate to high-risk prostate cancer.Materials and methodsIn this prospective uncontrolled clinical trial, patients were delivered VMAT at a dose of 87.75 Gy in 39 fractions or 70 Gy in 20 fractions to the DIL in combination with androgen deprivation therapy. Genitourinary (GU) and rectal toxicity, International Prostate Symptom Score (IPSS) and IPSS quality of life (IPSS-QOL) score were collected.ResultsForty-five patients with a median follow-up of 20 months were analyzed. The cumulative incidence of acute grade ≥ 2 GU and rectal toxicity was 33.1% and 9.5%, respectively. Regarding late toxicity, the cumulative incidence of grade ≥ 2 GU and rectal toxicity was 12.6% and 2.8%, respectively. During treatment, the mean increase of IPSS was +7.4 ± 4.2 and the mean increase of IPSS-QOL was +1.7 ± 1.3. However, both IPSS and IPSS-QOL scores returned to their baseline levels by 3-months post-treatment. No significant correlation between baseline characteristics and grade ≥ 2 GU or rectal toxicity was found.ConclusionFocal SIB to the DIL of ≥ 90 Gy EQD2 in unfavorable intermediate to high-risk prostate cancer patients resulted in tolerable toxicity profiles. The mean IPSS and IPSS-QOL scores both worsened during treatment; however, both scores returned to baseline level by 3 months after treatment.

Dose to the Left Anterior Descending Artery Correlates With Cardiac Events After Irradiation for Breast Cancer

Although global heart dose has been associated with late cardiac toxic effects in patients who received radiation therapy for breast cancer, data detailing the clinical significance of cardiac substructure dosimetry are limited. We investigated whether dose to the left anterior descending artery (LAD) correlates with adverse cardiac events. We identified 375 consecutively treated female patients from 2012 to 2018 who received left-sided breast or chest wall irradiation (with or without regional nodal irradiation). Medical records were queried to identify cardiac events after radiation therapy. Mean and maximum LAD and heart doses (LAD Dmean, LAD Dmax, heart Dmean, and heart Dmax) were calculated and converted to 2-Gy equivalent doses (EQD2). Univariate and multivariable Cox regression analyses were performed to determine association with cardiac toxic effects. Potential dose thresholds for each of the 4 dose parameters were identified by receiver operating characteristic (ROC) curve analysis, after which Kaplan-Meier analysis was performed to compare cardiac event-free survival based on these constraints. Median follow-up time was 48 months. Thirty-six patients experienced a cardiac event, and 23 patients experienced a major cardiac event. On univariate and multivariable analyses, increased LAD Dmean, LAD Dmax, and heart Dmean were associated with increased risk of any cardiac event and a major cardiac event. ROC curve analysis identified a threshold LAD Dmean EQD2 of 2.8 Gy (area under the ROC curve, 0.69), above which the risk for any cardiac event was higher (P=.001). Similar results were seen when stratifying by LAD Dmax EQD2 of 6.7 Gy (P=.005) and heart Dmean EQD2 of 0.8 Gy (P=.01). Dose to the LAD correlated with adverse cardiac events in this cohort. Contouring and minimizing dose to the LAD should be considered for patients receiving radiation therapy for left-sided breast cancer.

BAIRDA: a novel in vitro setup to quantify radiobiological parameters for cervical cancer brachytherapy dose estimations

Objective. Brachytherapy (BT) dose prescriptions for locally advanced cervical cancer are made with account for the radiobiological parameters, α/β ratio and halftime of repair (T 1/2 ). However, a wide range of parameter values has been reported which can challenge commonly held equivalencies between dose prescriptions. This is the first reported study that aims to develop an in vitro experimental technique using clinical high-dose-rate (HDR) and pulsed-dose-rate (PDR) Ir-192 brachytherapy afterloaders to quantify these parameters in vitro and to contextualize findings within contemporary practice. Approach. To efficiently quantify α/β and T 1/2 , in vitro experiments more reflective of clinical BT practice than traditional clonogenic survival assays were developed and applied to four squamous cell carcinoma cell lines (CaSki, C-33A, SiHa, and SW756). Radiation was delivered using single acute and fractionated dose treatments with a conventional irradiator and clinical HDR and PDR BT afterloaders. For the latter, a novel brachytherapy afterloader in vitro radiation delivery apparatus (BAIRDA) was developed. Main Results. The α/β and T 1/2 values determined using BAIRDA and the conventional irradiator showed close agreement, validating the novel apparatus and technique. For CaSki, C-33A, SiHa, and SW756, the BAIRDA-measured α/β ratios (5.2 [4.6–5.8], 5.6 [4.5–6.6], 6.3 [4.9–7.7], and 5.3 [4.7–6.0] Gy, respectively) were consistently smaller, while the T 1/2 (3.3 [2.7–3.9], 2.7 [2.0–3.3], 2.8 (2.4–3.1], and 4.8 [4.1–5.4] hours) larger, than the widely accepted values in clinical practice (α/β = 10 Gy; T 1/2 = 1.5 h). Significance. In vitro experiments using BAIRDA provided evidence for differences between the conventionally selected and experimentally determined α/β ratio and T 1/2 . Treatment regimens using HDR-BT and PDR-BT, designed to deliver equivalent radiobiological doses based on conventional values, were shown to differ by up to 27 Gy EQD2 – an effect that could impact treatment outcomes in cervical cancer. Furthermore, with BAIRDA, we have developed a novel method for radiobiological research in BT.

Toxicity and Survival Outcomes From Intensity Modulated Proton Therapy-Based Re-Irradiation in Patients With Non-Small Cell Lung Cancer

<h3>Purpose/Objective(s)</h3> Cumulative radiation doses to organs-at-risk is the primary limiting factor when delivering thoracic reirradiation (reRT). Intensity-modulated proton therapy (IMPT) offers a unique dosimetric advantage allowing for dose-escalation while limiting normal tissue irradiation. Given the limited published data, we analyzed toxicity and survival outcomes of non-small cell lung cancer (NSCLC) patients with prior radiation history undergoing IMPT-based definitive reRT. <h3>Materials/Methods</h3> A single-institution retrospective IRB-approved analysis was conducted of 62 consecutive patients treated with IMPT-reRT between from 2016-2020. Median dose of prior RT was 60.2 Gy EQD2 (range 30-126 Gy EQD2). Median time between initial and reirradiation courses was 30 months (range 3.5 – 562 months). Median IMPT-reRT dose was 62.2 Gy (RBE) EQD2 (range 40.1 – 99.7 Gy RBE EQD2). Patients received conventionally fractioned (n=37), twice-daily (n=6), or hypofractionated (n=19) reirradiation. The majority had full overlap with the previous radiation field (N=49, 79%), were centrally located (N=42, 58%), and involved nodal irradiation (N=47, 76%). Concurrent chemotherapy was delivered in 27 (44%) patients. Treatment related toxicities were analyzed in relationship to re-RT dosimetric parameters in 30 patients whose initial RT plan was available. Kaplan-Meier method and Cox Proportional Hazard was used to estimate overall survival (OS) and freedom from local progression (FFLP) calculated from the start of reRT. <h3>Results</h3> Grade 3 acute toxicities were seen in 6 (9%) patients (pulmonary [N=3], esophageal/skin/fatigue [N=1 each]). With a median follow-up from the start of reirradiation of 12.5 months, 8 (13%) patients experienced a grade 3 late toxicity (esophageal [N=4], pulmonary [N=3] and cardiac [N=1]). Two (3%) grade 5 toxicities were observed. None of the analyzed dosimetric parameters (lung, heart, esophageal, target) correlated with grade 3 or more toxicity. CTV size greater than 150 cm³ exhibited a trend of association with grade 3+ toxicity HR = 3.2 (95% CI: 0.88 – 12.1; p=0.08). Median FFLP was not reached and median OS was 22.6 months (95% CI, 16.5 – 22.1 months). On univariate analysis variables associated with improved OS were higher reirradiation dose, cumulative radiation dose >135 Gy, and smaller CTV (< 150 cc). However, on MVA only CTV size retained statistical significance (HR = 3.56; 95% CI, 1.10 – 11.48; p=0.03). <h3>Conclusion</h3> This is the largest series to date reporting outcomes for NSCLC patients treated with IMPT-reRT which demonstrated acceptable risk (<15%) of grade 3 or higher late toxicity with durable local control and prolonged survival. In contrast to limited published literature, no specific dosimetric parameters were significantly correlated with risk of toxicity.

Combined intra-cavitary and interstitial image-guided adaptative brachytherapy for cervical stump carcinomas: technical and clinical results of six patients.

PurposeAccording to European guidelines for cervix cancers, the management of cervical stump cancers should follow recommendations for patients without previous sub-total hysterectomy, but may require adaptation of radiotherapy modalities, especially brachytherapy (BT). However, data with modern BT technics are very scarce.Material and methodsFrom May 2013 to March 2020, 6 patients (age range, 71-88 years) with cervical stump squamous cell carcinoma (previously treated by sub-total hysterectomy) have been treated with external beam radiotherapy (intensity-modulated radiation therapy – IMRT, 45 Gy in 25 fractions, 5 patients, or 50.4 Gy in 28 fractions, 1 patient), with concomitant chemotherapy in 2 patients, followed by image-guided adaptive brachytherapy with pulsed-dose-rate in 5 patients or high-dose-rate in 1 patient. We used Utrecht BT applicator (Elekta®), with the implant of interstitial needles within the parametrium (unilaterally in 3 and bilaterally in 3 patients), and/or within the residual cervix (3 patients). Dosimetry was based on GEC-ESTRO recommendations.ResultsThe median high-risk (HR) and intermediate-risk (IR) clinical target volumes (CTV) were 14.5 cc (range, 12-35 cc) and 40 cc (range, 31-62 cc), respectively. The median dose (D90) delivered to HR and IR CTVs were 81.2 (range, 78.2-89.8) and 68.95 (range, 64.3-72.3) Gy EQD2, respectively. With a 26.5 months median follow-up (range, 10-92 months), we did not observe any local or distant recurrence. No grade 2 or more acute or late toxicities were reported.ConclusionsCervix brachytherapy with Utrecht applicator using interstitial needle is safe and effective in cervical stump cancer patients.

Dosimetric feasibility and clinical outcome of image guided interstitial brachytherapy using two different fractionation schedule in carcinoma cervix

Background: In advanced cervical cancer, external beam radiotherapy along with concurrent chemotherapy followed by brachytherapy is the treatment of choice. There are various dose fractionation regimes for template-based high dose rate (HDR) interstitial brachytherapy (ISBT) following external beam radiotherapy (EBRT) for cancer cervix with consideration of the normal-tissue EQD2 3Gy dose limits and recommended D90 goal between 85 and 95 Gy EQD2 10Gy for the high risk clinical target volume (HR-CTV). Materials and methods: 60 patients were accrued between 2014–2017 and treated with ISBT using Syed–Neblett Template by iridium 192 with Gamma Med plus HDR after loader unit. They were allotted in 2 arms (n = 30) and received 9 Gy ×2# and 7 Gy ×3 #, respectively. All patients received 50 Gy/25# whole pelvis EBRT by Theratron 780C. Coverage index (CI), dose homogeneity index (DHI), overdose index (OI), dose non-uniformity ratio (DNR), D90 Target and 2 cc EQD2 of OARs were calculated and correlated with toxicity, locoregional control and survival. Unpaired t-test and χ 2 test were used. Progression-free survival (PFS) and overall survival (OS) were calculated and a log-rank test was used for comparison. Results: Mean equivalent dose in 2 Gy fractions (EQD2) for the bladder (77.33 vs. 80.24 Gy) and rectum (69.12 vs. 69.87) along with D90 (9.12 Gy vs. 7.20 Gy) were comparable. With a median follow up period of 38 months, 3-year local control rate was 56.6% vs. 46.60% (p = 0.72) and 3-year OS was also similar: 83% vs. 80% (p = 0.8). Conclusions: In a developing country like India, 9 Gy ×2 # is a reasonably good alternative for treating locally advanced carcinoma cervix, keeping the patient compliance and convenience in mind.

Associations between cardiac irradiation and survival in patients with non-small cell lung cancer: Validation and new discoveries in an independent dataset

IntroductionIn ‘IDEAL-6′ patients (N = 78) treated for locally-advanced non-small-cell lung cancer using isotoxically dose-escalated radiotherapy, overall survival (OS) was associated more strongly with VLAwall-64-73-EQD2, the left atrial (LA) wall volume receiving 64–73 Gy equivalent dose in 2 Gy fractions (EQD2), than with whole-heart irradiation measures. Here we test this in an independent cohort ‘OX-RT’ (N = 64) treated routinely. MethodsUsing Cox regression analysis we assessed how strongly OS was associated with VLAwall-64-73-EQD2, with whole-heart volumes receiving 64–73 Gy EQD2 or doses above 10-to-70 Gy thresholds, and with principal components of whole-heart dose-distributions. Additionally, we tested associations between OS and volumes of cardiac substructures receiving dose-ranges described by whole-heart principal components significantly associated with OS. ResultsIn univariable analyses of OX-RT, OS was associated more strongly with VLAwall-64-73-EQD2 than with whole-heart irradiation measures, but more strongly still with VAortV-29-38-EQD2, the volume of the aortic valve region receiving 29–38 Gy EQD2. The best multivariable OS model included LA wall and aortic valve region mean doses, and the aortic valve volume receiving ≥38 Gy EQD2, VAortV-38-EQD2. In a subsidiary analysis of IDEAL-6, the best multivariable model included VLAwall-64-73-EQD2, VAortV-29-38-EQD2, VAortV-38-EQD2 and mean aortic valve dose. ConclusionWe propose reducing heart mean doses to the lowest levels possible while meeting protocol dose-limits for lung, oesophagus, proximal bronchial tree, cord and brachial plexus. This in turn achieves large reductions in VAortV-29-38-EQD2 and VLAwall-64-73-EQD2, and we plan to closely monitor patients with values of these measures still >0% (their median value in OX-RT) following reduction.

In-Field Failures in Patients Undergoing Bridging Radiotherapy for CD19-Directed Chimeric Antigen Receptor (CAR) T-Cell Therapy for Recurrent/Refractory Large B-Cell Lymphomas

In-Field Failures in Patients Undergoing Bridging Radiotherapy for CD19-Directed Chimeric Antigen Receptor (CAR) T-Cell Therapy for Recurrent/Refractory Large B-Cell Lymphomas

Safety of Dose Escalation for Pancreatic Cancer Using a Uni-Directional, Pd-103 Implantable Radiation Device: Results of a Phase I Trial

Pancreatic cancer is a challenging disease to treat with approximately 30% local recurrence following surgery. A uni-directional 103palladium (Pd-103) device implanted at the time of surgery during tumor resection may decrease the local recurrence rate. We performed a dose escalation study to determine the maximum tolerable dose (MTD) for the implantable device.A Phase I/II Clinical Trial to implant the Pd-103 device in pancreatic cancer patients with borderline resectable/locally advanced disease is ongoing. All patients received at least 8 weeks of combination chemotherapy prior to enrollment. Patients were prescribed neoadjuvant radiation with a median dose of 50.4 Gy (range 30-55). Phase I investigated 25 Gy and 35 Gy EQD2 (37.8 Gy and 50.4 Gy physical dose) dose levels, prescribed to 5 mm depth. 11 patients were treated with a device consisting of a matrix of Pd-103 radiation sources on a bio-absorbable membrane with a gold shield embedded in each source to attenuate radiation in one direction from the device. Primary endpoint was vascular toxicity at 2 months. Secondary endpoints included additional operating room time, source migration, and disease recurrence at 3 months follow up.Median age was 64.1 (range 47-79) and 7 of 11 patients were male. Sources were implanted successfully in 11 patients during surgery with radiation sources directed toward the retroperitoneal margin. For the first 5 patients, implants were prescribed to deliver 25 Gy EQD2. 1 of 5 patients suffered a pneumothorax immediately following surgery judged to be unrelated to the device. For the next 6 patients, prescription dose was increased to 35 Gy EQD2. 1 of 6 had an SMV thrombosis possibly related to the device. Device placement added 23 min (range 8-37 min). No sources migrated during the 3-month follow up period. Two of 11 patients developed metastasis: one hepatic metastasis, and another pulmonary metastasis. There was no local disease recurrence within the follow up period.Patients tolerated the device well with only one adverse event possibly related to study treatment. A MTD of 35 Gy EQD2 was determined to be safe for this patient population and is being prescribed in the phase II portion of the study. The permanently implantable, uni-directional, Pd-103 device delivers a targeted dose boost to the surgical margin in this difficult to treat patient population. The ongoing phase II protocol is currently enrolling additional subjects to evaluate local control at 1 year.

Impact of High DosE rAdioTherapy (HEAT) in Localized Prostate Cancer: An Individual Patient Data (IPD) Meta-Analysis of 15 Randomized Trials

<h3>Purpose/Objective(s)</h3> Radiotherapy (RT) dose escalation for localized prostate cancer has not demonstrated improvement in overall survival (OS) from individual trials. It is unclear if the use of androgen deprivation therapy (ADT) effects the potential benefit of dose escalation. Therefore, to achieve sufficient power to answer this question, we performed a meta-analysis of randomized trials evaluating the benefit of RT dose escalation in localized prostate cancer. <h3>Materials/Methods</h3> The Meta-Analysis of Randomized clinical trials in Cancer of the Prostate (MARCAP) Consortium was formed to obtain IPD from multiple randomized controlled trials. Patients were categorized based on RT dose and use and duration of ADT. Short-term ADT (STADT) was defined as ≤6 months, long-term ADT (LTADT) as 18-36 months, and low and high dose RT as < or ≥74 Gy EQD2. IPD from 15 trials (n = 13,864 patients) were used. The primary endpoint of all analyses was OS, with metastasis-free survival (MFS) and the incidence of biochemical recurrence (BCR) as secondary endpoints. Sensitivity analyses using only trials with direct and relevant randomization (10 trials; n = 9,775 patients) were used to perform a network meta-analysis (NMA). <h3>Results</h3> The median follow-up was 8.5 years (IQR 5.6-11.2). Escalating dose in the absence of ADT did not improve OS (HR 0.92, 95% CI 0.79-1.08) or MFS (HR 0.91, 95% CI 0.78-1.07). In the presence of STADT, high dose RT significantly improved OS (HR 0.79, 95% CI 0.67-0.94) and MFS (HR 0.80, 95% CI 0.68-0.94), as well as in the presence of LTADT for OS (HR 0.64, 95% CI 0.50-0.82) and MFS (HR 0.71, 95% CI 0.57-0.89). On sensitivity analysis using the NMA, dose escalation did not significantly improve outcomes in the absence of ADT (OS: HR 1.00, 95% CI 0.75-1.34; MFS: HR 0.97, 95% CI 0.67-1.41) or in the presence of STADT (OS: HR 0.95, 95% CI 0.54-1.67; MFS: HR 0.89, 95% CI 0.46-1.70) or LTADT (OS: HR 0.75, 95% CI 0.38-1.47; MFS: HR 0.78, 95% CI 0.36-1.67). In both the pooled comparison and the NMA, dose escalation improved BCR without ADT (NMA HR 0.53, 95% CI 0.32-0.88) in the presence of STADT (NMA HR 0.37, 95% CI 0.16-0.84), but not in the presence of LTADT (NMA HR 0.46, 95% CI 0.18-1.21). <h3>Conclusion</h3> Dose-escalation alone does not improve MFS or OS. In the presence of STADT or LTADT, the impact of dose-escalation differed when pooling non-randomized comparisons (which is prone to selection bias) versus performing an NMA restricted to only direct randomized comparisons (which is affected by limited network connectivity). BCR was more consistently improved. Given the uncertain impact on survival and the potential for increased toxicity, future studies using biomarker selection are needed to better personalize which patients benefit most from dose escalation.

Variation of optimization techniques for high dose rate brachytherapy in cervical cancer treatment

High dose rate (HDR) brachytherapy treatment planning usually involves optimization methods to deliver uniform dose to the target volume and minimize dose to the healthy tissues. Four optimizations were used to evaluate the high-risk clinical target volume (HRCTV) coverage and organ at risk (OAR). Dose-volume histogram (DVH) and dosimetric parameters were analyzed and evaluated. Better coverage was achieved with PGO (mean CI = 0.95), but there were no significant mean CI differences than GrO (p = 0.03322). Mean EQD2 doses to HRCTV (D90) were also superior for PGO with no significant mean EQD2 doses than GrO (p = 0.9410). The mean EQD2 doses to bladder, rectum, and sigmoid were significantly higher for NO plan than PO, GrO, and PGO. PO significantly reduced the mean EQD2 doses to bladder, rectum, and sigmoid but compromising the conformity index to HRCTV. PGO was superior in conformity index (CI) and mean EQD2 doses to HRCTV compared with the GrO plan but not statistically significant. The mean EQD2 doses to the rectum by PGO plan slightly exceeded the limit from ABS recommendation (mean EQD2 dose = 78.08 Gy EQD2). However, PGO can shorten the treatment planning process without compromising the CI and keeping the OARs dose below the tolerance limit.

Single Application Multifractionated Image Guided Adaptive High-Dose-Rate Brachytherapy for Cervical Cancer: Dosimetric and Clinical Outcomes

A prospective phase 2 study was conducted to evaluate the feasibility and safety of single-application multifractionated (SA-MF), high-dose-rate (HDR), image guided adaptive brachytherapy (IGABT) for cervical cancer. Patients (N=41) with International Federation of Gynaecology and Obstetrics 2009 stage IIB-IVA disease recruited between 2017 and 2019 underwent SA-MF. After completion of external beam radiation therapy of 50 Gy in 25 fractions, patients received magnetic resonance IGABT. The IGABT protocol consisted of a single brachytherapy (BT) application and treatment with 3 fractions of HDR (9 Gy on day 1; 2 fractions of 7 Gy with a minimum 6-hour gap on day 2) after achieving planning aims of the high-risk clinical target volume (HRCTV) receiving >84 Gy EQD2 and 2 cm3 of the bladder and rectum/sigmoid receiving ≤85 Gy and <71 Gy, respectively. Interfraction variation was addressed by performing computed tomography planning and coregistration using a mutual information-based coordinate system on day 2 before the second fraction. Organ at risk contouring was done on computed tomography, and doses were re-evaluated and reoptimized if required. Thirty-eight patients were treated as per the protocol. All patients underwent Intracavitary + Interstitial BT with needles (median, 4; range, 3-11). The mean ± standard deviation HRCTV volume was 41 ± 21 cm3 and HRCTV D90 dose was 87.2 ± 3.6Gy. The 0.1 cm3 and 2 cm3 to bladder, rectum, and sigmoid were -103.2 ± 10.6 Gy and -84.6 ± 6.8 Gy, 82.2 ± 9.5 Gy and -68.3 ± 5.7 Gy, and 83.5 ± 9.8 Gy and -69.5 ± 5.9 Gy, respectively. Six patients required reoptimization before the second fraction to meet planning aims. Mean overall treatment time was 47 ± 6 days. With a median follow up of 22 months (range, 2-37), 2-year local control and disease-free and overall survival were 90.1%, 85%, and 94.5%, respectively. So far 1 patient with grade II and 2 patients with grade III rectal toxicities have been reported. Magnetic resonance IGABT with SA-MF BT was feasible in 95% of patients. The dosimetric parameters and clinical results achieved so far look promising.

Use of deformable image registration techniques to estimate dose to organs at risk following prostate external beam radiation therapy and high-dose-rate brachytherapy.

PurposeThe purpose of this investigation was to examine differences in estimates of accumulated rectal dose when using deformable image registration (DIR) compared with rigid image registration (RIR) methods, and parameter addition methods for combined transrectal ultrasound (TRUS)-based high-dose-rate brachytherapy (HDR-BT) and external beam radiation therapy (EBRT) treatments of prostate cancer.Material and methodsIn this retrospective study, data from 10 patients who had previously received HDR-BT in one 15 Gy fraction, followed by 46 Gy EBRT in twenty-three fractions were used. To estimate total combined dose to the rectum, dose accumulation using both DIR and RIR methods were compared with parameter addition methods, which assume the same region of rectal anatomy receives the maximum dose from both treatment modalities. For both rigid and deformable image registration techniques, the quality of image registration was evaluated through metrics, including mean distance to agreement and dice similarity coefficient of prostate contours. Total D1cc and D2cc for the rectum was calculated and compared using each method.ResultsThe parameter addition methods predicted the highest accumulated dose to the rectum. On average, the predicted D2cc dose was higher than that calculated by the DIR method by 6.59 Gy EQD2 (range, –3.03 to 13.68 Gy EQD2) for partial parameter addition (PPA), and 4.88 Gy EQD2 (range, –3.41 to 11.97 Gy EQD2) for the full parameter addition (FPA) methods. Similarly, RIR predicted higher average doses compared with DIR, with a difference of 3.46 Gy EQD2 (range, –5.50 to 7.90 Gy EQD2). The results showed a significant difference between DIR and parameter addition methods for dose estimation.ConclusionsThis retrospective study demonstrates significant differences in accumulated rectal dose prediction using different image registration methods. Each method has limitations in its application, and when used with real-time HDR-BT dose planning, awareness of these limitations is essential.

An audit of high dose-rate prostate brachytherapy treatment planning at six Swedish clinics.

PurposeHigh dose-rate prostate brachytherapy has been implemented in Sweden in the late 1980s and early 1990s in six clinics using the same schedule: 20 Gy in two fractions combined with 50 Gy in 25 fractions with external beam radiation therapy. Thirty years have passed and during these years, various aspects of the treatment process have developed, such as ultrasound-guided imaging and treatment planning system. An audit was conducted, including a questionnaire and treatment planning, which aimed to gather knowledge about treatment planning methods in Swedish clinics.Material and methodsA questionnaire and a treatment planning case (non-anatomical images) were sent to six Swedish clinics, in which high-dose-rate prostate brachytherapy is performed. Treatment plans were compared using dosimetric indices and equivalent 2 Gy doses (EQD2). Treatment planning system report was used to compare dwell positions and dwell times.ResultsFor all the clinics, the planning aim for the target was 10.0 Gy, but the volume to receive the dose differed from 95% to 100%. Dose constraints for organs at risk varied with up to 2 Gy. The dose to 90% of target volume ranged from 10.0 Gy to 11.1 Gy, equivalent to 26.0 Gy EQD2 and 31.3 Gy EQD2, respectively. Dose non-homogeneity ratio differed from 0.18 to 0.32 for clinical target volume (CTV) in treatment plans and conformity index ranged from 0.52 to 0.59 for CTV.ConclusionsDose constraints for the organs at risk are showing a larger variation than that reflected in compared treatments plans. In all treatment plans in our audit, at least 10 Gy was administered giving a total treatment of 102 Gy EQD2, which is in the upper part of the prescription doses published in the GEC/ESTRO recommendations.

Re-Irradiation for Recurrent Glioblastoma Multiforme.

Patients requiring re-irradiation for recurrent glioblastoma multiforme (GBM) may benefit from individualized therapy. This study aimed to identify predictors of survival and contribute to treatment personalization. In 28 patients with recurrent GBM, nine factors were analyzed for associations with survival: Main location and type of recurrence, Karnofsky performance score (KPS), age, gender, interval between primary radiotherapy and recurrence, gross total resection (GTR), equivalent dose in 2-Gy fractions (EQD2) of re-irradiation and cumulative EQD2 of primary and re-irradiation. On univariate analyses, GTR (p=0.047), EQD2 ≥30 Gy (p=0.029) and cumulative EQD2 ≥90 Gy (p=0.023) were significantly associated with better survival; frontal location (p=0.119) and KPS 80-100% (p=0.067) showed trends. In multivariate analyses, frontal location (p=0.032) and cumulative EQD2 ≥90 Gy (p=0.038) were significant; KPS 80-100% (p=0.110) and EQD2 ≥30 Gy (p=0.083) showed trends. Predictors of survival after re-irradiation for recurrent GBM were identified that can help when designing personalized treatments. Use of irradiation with EQD2 ≥30 Gy appeared superior to lower doses.

Vaginal Dose Surface Maps and Morbidity in Cervical Cancer Brachytherapy

To develop a methodology for generating vagina dose-surface maps (DSMs) in cervix cancer patients. To investigate the association of dose level and spatial distribution with vaginal stenosis (St) and mucositis (Muc). A mono-institutional series of 31 patients, enrolled in the EMBRACE I study, with no vaginal St/Muc (CTCAE v3) at baseline were selected for this analysis. Patients were divided in 3 morbidity groups: 16 had St/Muc G0/1, 8 had St G≥2 (3 also had Muc G≥2), 10 had Muc G≥2 (3 also had St G≥2) within 24 months after treatment. 16 patients had vaginal involvement at diagnosis and 10 at BT. Patients received EBRT and 2 insertions and 4 fractions of HDR BT using tandem and ovoids. DSMs were generated from delineated contours of the vagina surface (VS). VS contours were unfolded by cutting them anteriorly through the urethra and inferiorly through the posterior–inferior border of the symphysis (PIBS). DSMs of EBRT and each BT fraction, converted to Gy EQD2 (α/β = 3), were added based on a system of homologous points, to generate cumulative DSMs. Dose D20cm2 (Gy), surface S60Gy (%), including their spatial location on the VS, rectovaginal (ICRU-RV) point dose, vaginal lateral 5 mm point dose and vagina length (VL measured from the vagina top to the PIBS) were compared between morbidity groups. Average/difference VS DSMs and one-way ANOVA statistical testing were used to compare between groups. A total of 96 DSMs (31 EBRT and 62 BT) were generated. Table shows mean/difference values for each parameter, according to morbidity groups. Patients in the St G≥2 and Muc G≥2 groups had significantly higher D20cm2 and ICRU-RV point doses compared to St/Muc G0/1 group. Moreover, average/difference DSMs showed that the most irradiated 20 cm2 in the St G≥2 group (mean dose 103 Gy EQD23) was spatially distributed over entire upper 1-2 cm VS circumference. St G≥2 vs St/Muc G0/1 patients had also larger S60Gy (by 27%) and shorter VL (by 9 mm). Muc G≥2 vs St/Muc G0/1 patients had significantly higher vaginal lateral 5mm point doses (by 14 Gy EQD23), while average/difference DSMs showed significant dose differences mainly in the latero-posterior area of the VS. Vaginal dose reporting is currently based on dose points. A novel method was developed to generate vaginal DSMs that incorporate 3D spatial information and new spatial dose descriptors for a more comprehensive view on vaginal doses and correlation with morbidity. St G≥2 patients had significantly higher doses over the whole VS circumference. Muc G≥2 patients showed higher D20cm2, ICRU-RV point and vagina lateral 5mm point doses. Generally, ventral vagina received lower dose than the dorsal and lateral vagina, in the majority of patients.Tabled 1Abstract 3029; TableSt/Muc G0/1 MeanSt G≥2 MeanMuc G≥2 MeanSt G≥2 - St/Muc G0/1Muc G≥2 - St/Muc G0/1Diff.pDiff.pD20cm2 (Gy)7910396240.0000*170.0031*S60Gy (%)376451270.0018*140.0176*ICRU-RV Point (Gy)637678130.0041*150.0015*Vag LAT-5mm (Gy)85909850.2465140.0085*VL (mm)595053-90.0501-60.1427 Open table in a new tab

Application of hypoglossal nerve constraint in definitive radiotherapy for nasopharyngeal carcinoma: A dosimetric feasibility study

Purpose: Radiation-induced hypoglossal nerve palsy is an infrequent but debilitating late complication after definitive radiotherapy for head and neck cancers. D1cc < 74 Gy (equivalent dose in 2 Gy fractions, EQD2) has been proposed as a potential dose constraint that limits 8-year palsy risk to < 5%. This study sets to perform detailed dosimetric assessments on the applicability of this novel dose constraint in advanced nasopharyngeal carcinoma (NPC). Materials and methods: This is a retrospective single-institution dosimetry study. NPC radiotherapy plans were identified from an institutional database, with an aim to select 10 eligible cases. Bilateral hypoglossal nerves were retrospectively contoured following a standard atlas. Cases with either one, or both, hypoglossal nerves D1cc exceeded 74 Gy EQD2 were included. Dosimetry of hypoglossal nerves, planning target volumes (PTV) and normal structures before and after application of the new hypoglossal nerve constraint were compared and analyzed. Results: Ten NPC cases were replanned. All hypoglossal nerve contours overlapped with high-dose PTV, predominantly at regions of gross nodal diseases. D1cc in 15 out of 20 hypoglossal nerves exceeded 74G y EQD2 at initial plans. All nerves fulfilled the pre-specified constraint of 74Gy EQD2 after re-plan. Median hypoglossal nerve D1cc reduced from 74.8Gy (range, 74.1 to 77.4Gy) to 73.5Gy (range, 72.4 to 74.0Gy) (p < 0.001), corresponded to a projected reduction in 8-year palsy risk from 5%-14% to 3%-5%. PTV V100 was maintained above 95% in all cases. Dose increments in near-maximum (D2) and decrements in near-minimum (D98) were < 1 Gy. Safety dosimetric parameters of standard head and neck organs-at-risk showed no significant changes. Conclusions: Hypoglossal nerve D1cc < 74 Gy EQD2 is a dosimetrically feasible constraint in definitive radiotherapy for NPC. Tumor target coverage and normal organ dosimetry were not compromised with its usage. Its routine application should be considered in definitive radiotherapy for head and neck cancers.

Preliminary survey of 3D image-guided brachytherapy for cervical cancer at representative hospitals in Asian countries

3D image-guided brachytherapy (3D-IGBT) has become a standard therapy for cervical cancer. However, the use of 3D-IGBT is limited in East and Southeast Asia. This study aimed to clarify the current usage patterns of 3D-IGBT for cervical cancer in East and Southeast Asia. A questionnaire-based survey was performed in 11 countries within the framework of the Forum for Nuclear Cooperation in Asia. The questionnaire collected the treatment information of patients with cervical cancer who underwent 3D-IGBT. The cumulative external beam radiotherapy and 3D-IGBT doses were summarized and normalized to a biological equivalent dose of 2 Gy per fraction (EQD2) using a linear-quadratic model. Of the 11 institutions representing the participating countries, six (55%) responded to the questionnaire. Overall, data of 36 patients were collected from the six institutions. Twenty-one patients underwent whole-pelvic irradiation and 15 underwent whole-pelvic irradiation with central shielding. Patients received a median of four treatment sessions of 3D-IGBT (range, 2–6). All 3D-IGBT sessions were computed tomography (CT)-based and not magnetic resonance image-based. The median doses to the high-risk clinical target volume D90, bladder D2cc, rectum D2cc and sigmoid colon D2cc were 80.9 Gy EQD2 (range, 58.9–105.9), 77.7 Gy EQD2 (range, 56.9–99.1), 68.0 Gy EQD2 (range, 48.6–90.7) and 62.0 Gy EQD2 (range, 39.6–83.7), respectively. This study elucidated the current patterns of 3D-IGBT for the treatment of cervical cancer in East and Southeast Asia. The results indicate the feasibility of observational studies of CT-based 3D-IGBT for cervical cancer in these countries.

Nodal recurrence patterns on PET/CT after RTOG-based nodal radiotherapy for prostate cancer

PurposeBiochemical failure after external beam radiotherapy (RT) for node-positive prostate cancer (PCN+) frequently involves nodal recurrences, in most cases out of field. This raises the question if current RTOG-based elective nodal fields can still be considered optimal. Modern diagnostic tools like PSMA PET/CT and choline PET/CT can visualize nodal recurrences with unprecedented accuracy. We evaluated recurrence patterns on PET/CT after RT for PCN+, with the aim to explore options for improved nodal target definition. Methods and materialsData of all patients treated with curative intent EBRT for PCN+ in NKI-AVL from 2008 to 2018 were retrospectively reviewed. EBRT comprised 70 Gy to the prostate or 66–70 Gy to the prostate bed, 60 Gy to involved nodes, and 52,5–56 Gy (46 Gy EQD2) to RTOG-based elective nodal fields, in 35 fractions. Locations of recurrences on PET/CT were noted, and nodal locations were correlated with the applied EBRT fields. Results42 patients received PSMA (28) or choline (14) PET/CT at biochemical recurrence. 35 patients (83%) had a positive scan. At their first positive scan 17 patients had nodal metastasis, in some cases together with a local recurrence or distant disease. In-field nodal recurrences were uncommon (n = 3). Out-field nodal recurrences occurred more frequently (n = 14), with the majority (n = 12) just above the elective nodal field. These nodes were the single area of detectable failure in 6 patients (14%). ConclusionsCurrent RT with RTOG-based nodal fields for PCN+ provides good in-field tumour control, but frequent out-field nodal recurrences suggest missed microscopic locations. Expanding elective fields to include the aorta bifurcation may prolong recurrence-free survival. Future research must address whether the potential benefits of this strategy outbalance additional toxicity.

Diminishing Returns From Ultrahypofractionated Radiation Therapy for Prostate Cancer

More than a decade of randomized controlled trials in prostate cancer has established a positive radiation dose response at moderate doses and a consistently low α/β ratio in the linear quadratic model for moderate hypofractionation. The recently published large randomized trial of ultrahypofractionated prostate cancer radiation therapy adds substantially to our current knowledge of dose response and fractionation sensitivity. Randomized trials of dose escalation and hypofractionation of radiation therapy were meta-analyzed to yield the overall best estimate of the α/β ratio. Additionally, a putative saturation of dose effect previously reported at approximately 80 Gy EQD2 was investigated by mapping the relative effectiveness assessed at 5 years onto a single reference dose-response curve. Meta-analysis of 14 randomized trials including 13,384 patients yielded a best estimate of α/β = 1.6 Gy (95% confidence interval, 1.3-2.0 Gy) but with highly significant heterogeneity (I2 = 70%, P = .0005). Further analysis indicated an association between increasing dose per fraction in the experimental arm and increasing α/β ratio (slope, 0.6 Gy increase in α/β per Gy increase in fraction size; P = .017). This deviation from the linear quadratic model could, however, also be explained by biochemical control maxing out at doses above approximately 80 Gy. Biochemical control data from randomized controlled trials of dose-per-fraction escalation in prostate cancer radiation therapy are inconsistent with the presence of a constant fractionation sensitivity in the linear-quadratic model and/or a monotonic dose response for biochemical control beyond 80 Gy equivalent dose. These observations have a potential effect on the optimal doses in future trials and the interpretation of ongoing trials of ultrahypofractionation.