Evaluating outcomes and toxicities for a newly implemented MRI-based brachytherapy program for cervical cancer.

OBJECTIVE: We report an updated analysis of the outcomes and toxicities of MRI-based brachytherapy for locally advanced cervical cancer from a U.S. academic center. METHODS: A retrospective review was performed on patients treated with MRI-based brachytherapy for cervical cancer. EBRT was standardly 45 Gy in 25 fractions with weekly cisplatin. MRI was performed with the brachytherapy applicator in situ. Dose specification was most commonly 7 Gy for 4 fractions with optimization aim of D90 HR-CTV EQD2 of 85-95 Gyα/ß=10 Gy in 2 implants each delivering 2 fractions. RESULTS: Ninety-eight patients were included with median follow up of 24.5 months (IQR 11.9-39.8). Stage IIIA-IVB accounted for 31.6% of cases. Dosimetry results include median GTV D98 of 101.0 Gy (IQR 93.3-118.8) and HR-CTV D90 of 89 Gy (IQR 86.1-90.6). Median D2cc bladder, rectum, sigmoid, and bowel doses were 82.1 Gy (IQR 75.9-88.0), 65.9 Gy (IQR 59.6-71.2), 65.1 Gy (IQR 57.7-69.6), and 55 Gy (IQR 48.9-60.9). Chronic grade 3+ toxicities were seen in the bladder (8.2%), rectosigmoid (4.1%), and vagina (1.0%). Three-year LC, PFS, and OS were estimated to be 84%, 61.7%, and 76.1%, respectively. CONCLUSION: MRI-based brachytherapy demonstrates excellent local control and acceptable rates of high-grade morbidity. These results are possible in our population with relatively large volume primary tumors and extensive local disease.

Prevalence of trauma history and symptoms in patients who have received vaginal brachytherapy as part of their endometrial cancer treatment.

OBJECTIVE: Vaginal brachytherapy (VBT) is an essential component of curative intent treatment for many patients with endometrial cancer. The prevalence of trauma history in this population is unknown and important to understand considering VBT requires patients to have an instrument vaginally inserted while in the vulnerable lithotomy position. We aim to identify patients treated with intracavitary VBT and collect survey data to assess trauma endpoints. METHODS: We retrospectively identified patients with endometrial cancer who underwent intracavitary VBT at our institution between 01/2017 and 08/2022. Patients were mailed and/or electronically mailed a survey that included demographics, psychosocial background, and validated trauma surveys to be filled out as they relate to their trauma experiences prior to VBT and again considering any trauma symptomatology related to VBT. Electronic medical record review was performed. Descriptive statistics as well as multivariate analysis were performed. RESULTS: 206 patients met inclusion criteria, 66 (32.1%) of whom returned the survey and were included for analysis. Thirty-two percent of patients self-reported a personal history of any prior mental health diagnosis. Eighty-eight percent of patients screened positive for a history of trauma exposure, 23% endorsed symptoms of PTSD related to their VBT experience, and 5% screened positive for a likely PTSD diagnosis from VBT. CONCLUSION: A majority of included patients had a history of trauma exposure prior to VBT. In a subset of patients, VBT re-induced trauma and was considered to be an independent traumatic event. This study highlights the importance of practicing trauma informed care, particularly in this patient population.

Thoracic Reirradiation with Stereotactic Body Radiation Therapy (SBRT) for Recurrent Advanced Non-Small Cell Lung Cancer (NSCLC).

PURPOSE: Non-small cell lung cancer (NSCLC) local control remains suboptimal with rates around 75%. Stereotactic body radiation therapy (SBRT) is an option for isolated local recurrences of small-volume recurrences. This study investigates the safety and efficacy of 60 Gy in 8 fractions in large-volume local recurrences. METHODS AND MATERIALS: We conducted a retrospective chart review of patients treated with salvage SBRT for NSCLC lung parenchymal recurrence between July 2013 and February 2020. Reirradiation prescribed dose was 60 Gy in 8 fractions using the SBRT technique. The primary endpoint was local control at most recent follow-up or death. Secondary endpoints included overall survival, disease-free interval, cancer-specific survival, and treatment related toxicities. RESULTS: Seven patients met inclusion criteria. Median follow up time was 38 months (18.1-72.4). Median age was 67 years (63-80). Median time to reirradiation was 18.2 months (7.3-28.6). Retreatment median ITV was 57.9 cc (15.8-344.6), and PTV median was 113.6 cc (38.3-506.9). Local control was maintained in 4 of 7 patients (57.1%). Two of the 7 patients (28.6%) remained alive. Median disease-free interval was 22.5 months (11-65). Three of 7 patients (42.9%) had grade 2 toxicities. One patient (14.3%) had a grade 3 rib/chest wall toxicity with concurrent disease recurrence invading the chest wall. CONCLUSION: This study reports that SBRT of 60 Gy in 8 fractions was delivered safely and effectively to large volume recurrent NSCLC previously treated with radiation therapy. The disease-free interval of nearly 2 years is meaningful for patients' quality of life and duration of time off systemic therapy.

Bombarding Oligoprogression: Oncologic Outcomes After Radiation to Patients With Oligoprogressive Non-Small Cell Lung Cancer on Maintenance Systemic Therapy.

OBJECTIVES: This study aims to evaluate the efficacy and toxicity of radiotherapy (RT) to oligoprogressive metastatic non-small cell lung cancer (NSCLC). METHODS: This is a retrospective analysis of 23 patients with metastatic NSCLC on maintenance systemic therapy, developed oligoprogression (1 to 5 sites), and all oligoprogressive sites amenable to and treated with RT. The primary endpoints included progression-free survival (PFS) and median time to start next-line therapy (MTT). Kaplan-Meier survival analysis and log-rank testing were performed using R-Studio software. RESULTS: Twenty-three patients met the inclusion criteria. The median overall survival for the entire cohort was 31.3 months (interquartile range [IQR]: 17.86 to 45.4). The median event-free survival for the entire cohort was 8.3 months (IQR: 2.7 to 12). Patients with no prior radiation had longer median event-free survival of 11.9 months (IQR: 8.4 to 18.2) compared with patients with a history of prior radiation at 4.1 months (IQR: 2.7 to 12; P = 0.041). The local control rate for the treated lesions was 97.5%. At 12 months follow-up, 6 (43%) of 14 living patients maintained systemic therapy without initiating next-line therapy. The median PFS for the entire cohort was 8.4 months (IQR: 4.1 to 17.5). Patients who did not receive prior radiation had longer median PFS of 11.9 months (IQR: 8.4 to 18.2) compared with patients who received prior radiation 6.2 months (IQR: 2.7 to 8.5; P = 0.018). Two patients (9%) had grade 3 chronic toxicity related to RT and were medically managed. CONCLUSION: We identified that in patients with oligoprogressive metastatic NSCLC, targeted RT to all progressive sites yielded high LC and favorable rates of PFS and MTT.

F-SHARP: a Phase I/II trial of focal salvage high-dose-rate brachytherapy for Radiorecurrent prostate cancer.

BACKGROUND: Intraprostatic local radiorecurrence (LRR) after definitive radiation is being increasingly identified due to the implementation of molecular positron emission tomography (PET)/computed tomography (CT) imaging for the evaluation of biochemical recurrence. Salvage high-dose rate (HDR) brachytherapy offers a promising local therapy option, with encouraging toxicity and efficacy based on early series. Furthermore, the incorporation of advanced imaging allows for focal HDR to further reduce toxicity to maximise the therapeutic ratio. The objectives of the 'focal salvage HDR brachytherapy for locally recurrent prostate cancer in patients treated with prior radiotherapy' (F-SHARP) trial are to determine the acute and late toxicity and efficacy outcomes of focal salvage HDR brachytherapy for LRR prostate cancer. STUDY DESIGN: The F-SHARP is a multi-institutional two-stage Phase I/II clinical trial of salvage focal HDR brachytherapy for LRR prostate cancer enrolling patients at three centres. ENDPOINTS: The primary endpoint is the acute radiation-related Grade ≥3 Common Terminology Criteria for Adverse Events (CTCAE, version 4.03) genitourinary (GU) and gastrointestinal (GI) toxicity rate, defined as within 3 months of brachytherapy. Secondary endpoints include acute and late CTCAE toxicity, biochemical failure, patterns of clinical progression, disease-specific and overall survival, and health-related quality of life, as measured by the International Prostate Symptom Score and 26-item Expanded Prostate Cancer Index Composite instruments. PATIENTS AND METHODS: Key eligibility criteria include: biopsy confirmed LRR prostate adenocarcinoma after prior definitive radiation therapy using any radiotherapeutic modality, no evidence of regional or distant metastasis, and cT1-3a Nx or N0 prostate cancer at initial treatment. All patients will have multiparametric magnetic resonance imaging and molecular PET/CT imaging if possible. In Stage 1, seven patients will be accrued. If there are two or more GI or GU Grade ≥3 toxicities, the study will be stopped. Otherwise, 17 additional patients will be accrued (total of 24 patients). For Stage 2, the cohort will expand to 62 subjects to study the efficacy outcomes, long-term toxicity profile, quality of life, and compare single- vs multi-fraction HDR. Transcriptomic analysis of recurrence biopsies will be performed to identify potential prognostic and predictive biomarkers.

A practical guide to hybrid interstitial/intracavitary brachytherapy for locally-advanced cervical cancer.

PURPOSE: In select cases of locally advanced cervical cancer, a hybrid brachytherapy (HBT) approach consisting of a combined intracavitary (IC)/insterstitial (IS) implant can yield improved target coverage and/or decreased organ at risk dose compared to IC techniques while limiting invasiveness compared to IS techniques. METHODS AND MATERIALS: The technique involves placement of transvaginal and/or perineal needles in addition to the tandem and ring/ovoids using either a specialized applicator or free-hand placement. Following applicator and needle placement, brachytherapy may then be planned using principles similar to IC or IS techniques. During treatment planning, it can be helpful to obtain both MRI and CT imaging, as plastic MRI-compatible needles do not show up well on MRI. RESULTS: In patients where acceptable target coverage cannot be achieved using IC alone or doses to nearby OAR are too high, HBT should be evaluated. HBT can improve both dose to target and OAR while sparing patients the morbidity of perineal template-based interstitial brachytherapy. Specific scenarios where HBT may be preferred include bulky residual primary tumor especially with poor response to EBRT, extension into the lateral parametrium, vaginal extension of tumor, and an asymmetric target. Use of HBT can typically permit extension of dose coverage by an additional 1-2 cm beyond what can be achieved with an IC alone technique. CONCLUSION: HBT allows for improved therapeutic ratio by improving target volume coverage and/or lowering doses to OARs. Brachytherapists should be trained on the practical aspects of administering HBT to be able to offer a less invasive and impactful treatment option when appropriate.

Prostate segmentation accuracy using synthetic MRI for high-dose-rate prostate brachytherapy treatment planning.

Objective. Both computed tomography (CT) and magnetic resonance imaging (MRI) images are acquired for high-dose-rate (HDR) prostate brachytherapy patients at our institution. CT is used to identify catheters and MRI is used to segment the prostate. To address scenarios of limited MRI access, we developed a novel generative adversarial network (GAN) to generate synthetic MRI (sMRI) from CT with sufficient soft-tissue contrast to provide accurate prostate segmentation without MRI (rMRI).Approach. Our hybrid GAN, PxCGAN, was trained utilizing 58 paired CT-MRI datasets from our HDR prostate patients. Using 20 independent CT-MRI datasets, the image quality of sMRI was tested using mean absolute error (MAE), mean squared error (MSE), peak signal-to-noise ratio (PSNR) and structural similarity index (SSIM). These metrics were compared with the metrics of sMRI generated using Pix2Pix and CycleGAN. The accuracy of prostate segmentation on sMRI was evaluated using the Dice similarity coefficient (DSC), Hausdorff distance (HD) and mean surface distance (MSD) on the prostate delineated by three radiation oncologists (ROs) on sMRI versus rMRI. To estimate inter-observer variability (IOV), these metrics between prostate contours delineated by each RO on rMRI and the prostate delineated by treating RO on rMRI (gold standard) were calculated.Main results. Qualitatively, sMRI images show enhanced soft-tissue contrast at the prostate boundary compared with CT scans. For MAE and MSE, PxCGAN and CycleGAN have similar results, while the MAE of PxCGAN is smaller than that of Pix2Pix. PSNR and SSIM of PxCGAN are significantly higher than Pix2Pix and CycleGAN (p < 0.01). The DSC for sMRI versus rMRI is within the range of the IOV, while the HD for sMRI versus rMRI is smaller than the HD for the IOV for all ROs (p ≤ 0.03).Significance. PxCGAN generates sMRI images from treatment-planning CT scans that depict enhanced soft-tissue contrast at the prostate boundary. The accuracy of prostate segmentation on sMRI compared to rMRI is within the segmentation variation on rMRI between different ROs.

Dosimetric and workflow impact of synthetic-MRI use in prostate high-dose-rate brachytherapy.

PURPOSE: Target and organ delineation during prostate high-dose-rate (HDR) brachytherapy treatment planning can be improved by acquiring both a postimplant CT and MRI. However, this leads to a longer treatment delivery workflow and may introduce uncertainties due to anatomical motion between scans. We investigated the dosimetric and workflow impact of MRI synthesized from CT for prostate HDR brachytherapy. METHODS AND MATERIALS: Seventy-eight CT and T2-weighted MRI datasets from patients treated with prostate HDR brachytherapy at our institution were retrospectively collected to train and validate our deep-learning-based image-synthesis method. Synthetic MRI was assessed against real MRI using the dice similarity coefficient (DSC) between prostate contours drawn using both image sets. The DSC between the same observer's synthetic and real MRI prostate contours was compared with the DSC between two different observers' real MRI prostate contours. New treatment plans were generated targeting the synthetic MRI-defined prostate and compared with the clinically delivered plans using target coverage and dose to critical organs. RESULTS: Variability between the same observer's prostate contours from synthetic and real MRI was not significantly different from the variability between different observer's prostate contours on real MRI. Synthetic MRI-planned target coverage was not significantly different from that of the clinically delivered plans. There were no increases above organ institutional dose constraints in the synthetic MRI plans. CONCLUSIONS: We developed and validated a method for synthesizing MRI from CT for prostate HDR brachytherapy treatment planning. Synthetic MRI use may lead to a workflow advantage and removal of CT-to-MRI registration uncertainty without loss of information needed for target delineation and treatment planning.

Multi-institutional Development and Validation of Contouring Guidelines for Para-aortic Elective Nodal Irradiation in Prostate Cancer Based on Patterns of Involvement on Targeted Molecular Imaging Positron Emission Tomography/Computed Tomography.

PURPOSE: Molecular imaging better identifies anatomic regions of metastatic spread of prostate cancer compared with conventional imaging, resulting in para-aortic (PA) nodal metastases being increasingly identified. Consequently, some radiation oncologists electively treat the PA lymph node region in patients with gross or high risk of PA nodal involvement. The anatomic locations of at-risk PA lymph nodes for prostate cancer are unknown. Our objective was to use molecular imaging to develop guidelines for the optimal delineation of the PA clinical target volume (CTV) in patients with prostate cancer. METHODS AND MATERIALS: We conducted a multi-institutional retrospective cohort study of patients with prostate cancer undergoing 18F-fluciclovine or 18F-DCFPyL prostate-specific membrane antigen positron emission tomography (PET)/computed tomography (CT). Images of patients with PET-positive PA nodes were imported into the treatment planning system, avid nodes were contoured, and measurements were taken in relation to anatomic landmarks. A contouring guideline that encompassed the location of ≥95% of PET-positive PA nodes was created using descriptive statistics and then validated in an independent data set. RESULTS: Five hundred fifty-nine patients had molecular PET/CT imaging in the development data set (78% 18F-fluciclovine, 22% prostate-specific membrane antigen). Seventy-six patients (14%) had evidence of PA nodal metastasis. We determined that expanding the CTV to 1.8 cm left of the aorta, 1.4 cm right of the inferior vena cava (IVC), 7 mm posterior to the aorta/IVC or to the vertebral body, and superiorly to the T11/T12 vertebral interface, with the anterior border 4 mm anterior to the aorta/IVC and inferior border at the bifurcation of the aorta/IVC, resulted in coverage of ≥95% of PET-positive PA nodes. When the guideline was used in the independent validation data set (246 patients with molecular PET/CT imaging, of whom 31 had PA nodal metastasis), 97% of nodes were encompassed, thereby validating our guideline. CONCLUSIONS: We used molecular PET/CT imaging to determine the anatomic locations of PA metastases to develop contouring guidelines for creating a prostate cancer PA CTV. Although the optimal patient selection and clinical benefits of PA radiation therapy remain uncertain, our results will aid in delineating the optimal target when PA radiation therapy is pursued.

Dosimetric Evaluation of Organs at Risk From SAVE Protocol.

PURPOSE: The objective of this work was to evaluate dosimetric characteristics to organs at risk (OARs) from short-course adjuvant vaginal cuff brachytherapy (VCB) in early endometrial cancer compared with standard of care (SOC) in a multi-institutional prospective randomized trial. METHODS AND MATERIALS: SAVE (Short Course Adjuvant Vaginal Brachytherapy in Early Endometrial Cancer Compared to Standard of Care) is a prospective, phase 3, multisite randomized trial in which 108 patients requiring VCB were randomized to an experimental short-course arm (11 Gy × 2 fractions [fx] to surface) and SOC arm. Those randomized to the SOC arm were subdivided into treatment groups based on treating physician discretion as follows: 7 Gy × 3 fx to 5 mm, 5 to 5.5 Gy × 4 fx to 5 mm, and 6 Gy × 5 fx to surface. To evaluate doses to OARs of each SAVE cohort, the rectum, bladder, sigmoid, small bowel, and urethra were contoured on planning computed tomography, and doses to OARs were compared by treatment arm. Absolute doses for each OAR and from each fractionation scheme were converted to 2 Gy equivalent dose (EQD23). Each SOC arm was compared with the experimental arm separately using 1-way analysis of variance, followed by pairwise comparisons using Tukey's honestly significant difference test. RESULTS: The experimental arm had significantly lower doses for rectum, bladder, sigmoid, and urethra compared with the 7 Gy × 3 and 5 to 5.5 Gy × 4 fractionation schemes; however, the experimental arm did not differ from the 6 Gy × 5 fractionation scheme. For small bowel doses, none of the SOC fractionation schemes were statistically different than the experimental. The highest EQD23 doses to the examined OARs were observed to come from the most common dose fractionation scheme of 7 Gy × 3 fx. With a short median follow-up of 1 year, there have been no isolated vaginal recurrences. CONCLUSIONS: Experimental short-course VCB of 11 Gy × 2 fx to the surface provides a comparable biologically effective dose to SOC courses. Experimental short-course VCB was found to reduce or be comparable to D2cc and D0.1cc EQD23 doses to rectum, bladder, sigmoid, small bowel, and urethra critical structures. This may translate into a comparable or lower rate of acute and late adverse effects.

Effect of scattered megavoltage x-rays on markerless tumor tracking using dual energy kilovoltage imaging.

PURPOSE: To determine the effect of megavoltage (MV) scatter on the accuracy of markerless tumor tracking (MTT) for lung tumors using dual energy (DE) imaging and to consider a post-processing technique to mitigate the effects of MV scatter on DE-MTT. METHODS: A Varian TrueBeam linac was used to acquire a series of interleaved 60/120 kVp images of a motion phantom with simulated tumors (10 and 15 mm diameter). Two sets of consecutive high/low energy projections were acquired, with and without MV beam delivery. The MV field sizes (FS) ranged from 2 × 2 cm2 -6 × 6 cm2 in steps of 1 × 1 cm2 . Weighted logarithmic subtraction was performed on sequential images to produce soft-tissue images for kV only (DEkV ) and kV with MV beam on (DEkV+MV ). Wavelet and fast Fourier transformation filtering (wavelet-FFT) was used to remove stripe noise introduced by MV scatter in the DE images ( DE kV + MV Corr ${\rm{DE}}_{{\rm{kV}} + {\rm{MV}}}^{{\rm{Corr}}}$ ). A template-based matching algorithm was then used to track the target on DEkV, DEkV+MV , and DE kV + MV Corr ${\rm{DE}}_{{\rm{kV}} + {\rm{MV}}}^{{\rm{Corr}}}$ images. Tracking accuracy was evaluated using the tracking success rate (TSR) and mean absolute error (MAE). RESULTS: For the 10 and 15 mm targets, the TSR for DEkV images was 98.7% and 100%, and MAE was 0.53 and 0.42 mm, respectively. For the 10 mm target, the TSR, including the effects of MV scatter, ranged from 86.5% (2 × 2 cm2 ) to 69.4% (6 × 6 cm2 ), while the MAE ranged from 2.05 mm to 4.04 mm. The application of wavelet-FFT algorithm to remove stripe noise ( DE kV + MV Corr ${\rm{DE}}_{{\rm{kV}} + {\rm{MV}}}^{{\rm{Corr}}}$ ) resulted in TSR values of 96.9% (2 × 2 cm2 ) to 93.4% (6 × 6 cm2 ) and subsequent MAE values were 0.89 mm to 1.37 mm. Similar trends were observed for the 15 mm target. CONCLUSION: MV scatter significantly impacts the tracking accuracy of lung tumors using DE images. Wavelet-FFT filtering can improve the accuracy of DE-MTT during treatment.

Embracing a future of progress in gynecologic brachytherapy.

In the last 20 years, gynecologic brachytherapy has made tremendous advancements, most prominently evidenced by the evolution of cervical cancer brachytherapy. In its 20 year history, Brachytherapy has become known as a journal of science, education, and advocacy for our specialty and for our patients. In this review, we celebrate the 25 most impactful manuscripts in gynecologic brachytherapy in the journal's history.

Radiation Therapy for Endometrial Cancer: An American Society for Radiation Oncology Clinical Practice Guideline.

PURPOSE: With the results of several recently published clinical trials, this guideline informs on the use of adjuvant radiation therapy (RT) and systemic therapy in the treatment of endometrial cancer. Updated evidence-based recommendations provide indications for adjuvant RT and the associated techniques, the utilization and sequencing of adjuvant systemic therapies, and the effect of surgical staging techniques and molecular tumor profiling. METHODS: The American Society for Radiation Oncology convened a multidisciplinary task force to address 6 key questions that focused on the adjuvant management of patients with endometrial cancer. The key questions emphasized the (1) indications for adjuvant RT, (2) RT techniques, target volumes, dose fractionation, and treatment planning aims, (3) indications for systemic therapy, (4) sequencing of systemic therapy with RT, (5) effect of lymph node assessment on utilization of adjuvant therapy, and (6) effect of molecular tumor profiling on utilization of adjuvant therapy. Recommendations were based on a systematic literature review and created using a predefined consensus-building methodology and system for quality of evidence grading and strength of recommendation. RESULTS: The task force recommends RT (either vaginal brachytherapy or external beam RT) be given based on the patient's clinical-pathologic risk factors to reduce risk of vaginal and/or pelvic recurrence. When external beam RT is delivered, intensity modulated RT with daily image guided RT is recommended to reduce acute and late toxicity. Chemotherapy is recommended for patients with International Federation of Gynecology and Obstetrics (FIGO) stage I to II with high-risk histologies and those with FIGO stage III to IVA with any histology. When sequencing chemotherapy and RT, there is no prospective data to support an optimal sequence. Sentinel lymph node mapping is recommended over pelvic lymphadenectomy for surgical nodal staging. Data on sentinel lymph node pathologic ultrastaging status supports that patients with isolated tumor cells be treated as node negative and adjuvant therapy based on uterine risk factors and patients with micrometastases be treated as node positive. The available data on molecular characterization of endometrial cancer are compelling and should be increasingly considered when making recommendations for adjuvant therapy. CONCLUSIONS: These recommendations guide evidence-based best clinical practices on the use of adjuvant therapy for endometrial cancer.

GEC-ESTRO (ACROP)-ABS-CBG Consensus Brachytherapy Target Definition Guidelines for Recurrent Endometrial and Cervical Tumors in the Vagina.

PURPOSE: Representatives from the Gynecologic Groupe European de Curietherapie-European Society for Radiation Therapy and Oncology (GYN GEC-ESTRO), the American Brachytherapy Society (ABS), and the Canadian Brachytherapy Group (CBG) met to develop international consensus recommendations for target definitions for image-guided adaptive brachytherapy for vaginal recurrences of endometrial or cervical cancer. METHODS AND MATERIALS: Seventeen radiation oncologists and 2 medical physicists participated. Before an in-person meeting each participant anonymously contoured 3 recurrent endometrial/cervical cancer cases. Participants contoured the residual gross primary tumor volume (GTV-Tres), a high-risk clinical target volume (CTV-THR), and an intermediate-risk clinical target volume (CTV-TIR), on T2-weighted magnetic resonance images (MRIs). All contours were drawn using Falcon EduCase. Contours were reviewed at an in-person meeting during which a consensus document was created defining agreed-upon target definitions (Trial 1). After establishing these definitions, the group was sent one of the cases again (recurrent cervical cancer vaginal recurrence) and asked to contour the targets again (Trial 2). The Computerized Environment for Radiation Research (CERR) software (The Mathworks, Natwick, MA) was used to analyze the contours. Kappa statistics were generated to assess level of agreement between contours. A conformity index (CI), defined as the ratio between the intersection and union volume of a given pair of contours, was calculated. A simultaneous truth and performance level estimation (STAPLE) contour was created for the CTV-THR and CTV-TIR for the postmeeting case. RESULTS: Consensus definitions for GTV-Tres, CTV-THR, and CTV-TIR were established. Kappa statistics (Trial 1/Trial 2) for GTV-Tres, CTV-THR, and CTV-TIR were 0.536/0.583, 0.575/0.743 and 0.522/0.707. Kappa statistics for Trial 2 for the CTV-THR and CTV-TIR showed "substantial" agreement while the GTV-Tres remained at moderate agreement. CONCLUSIONS: This consensus provides recommendations to facilitate future collaborations for MRI-guided adaptive brachytherapy target definitions in endometrial/cervical vaginal recurrences.

Effect of different noise reduction techniques and template matching parameters on markerless tumor tracking using dual-energy imaging.

PURPOSE: To evaluate the impact of various noise reduction algorithms and template matching parameters on the accuracy of markerless tumor tracking (MTT) using dual-energy (DE) imaging. METHODS: A Varian TrueBeam linear accelerator was used to acquire a series of alternating 60 and 120 kVp images (over a 180° arc) using fast kV switching, on five early-stage lung cancer patients. Subsequently, DE logarithmic weighted subtraction was performed offline on sequential images to remove bone. Various noise reduction techniques-simple smoothing, anticorrelated noise reduction (ACNR), noise clipping (NC), and NC-ACNR-were applied to the resultant DE images. Separately, tumor templates were generated from the individual planning CT scans, and band-pass parameter settings for template matching were varied. Template tracking was performed for each combination of noise reduction techniques and templates (based on band-pass filter settings). The tracking success rate (TSR), root mean square error (RMSE), and missing frames (percent unable to track) were evaluated against the estimated ground truth, which was obtained using Bayesian inference. RESULTS: DE-ACNR, combined with template band-pass filter settings of σlow  = 0.4 mm and σhigh  = 1.6 mm resulted in the highest TSR (87.5%), RMSE (1.40 mm), and a reasonable amount of missing frames (3.1%). In comparison to unprocessed DE images, with optimized band-pass filter settings of σlow  = 0.6 mm and σhigh  = 1.2 mm, the TSR, RMSE, and missing frames were 85.3%, 1.62 mm, and 2.7%, respectively. Optimized band-pass filter settings resulted in improved TSR values and a lower missing frame rate for both unprocessed DE and DE-ACNR as compared to the use previously published band-pass parameters based on single energy kV images. CONCLUSION: Noise reduction strategies combined with the optimal selection of band-pass filter parameters can improve the accuracy and TSR of MTT for lung tumors when using DE imaging.

Executive summary of the American Radium Society appropriate use criteria for management of uterine clear cell and serous carcinomas.

BACKGROUND: Uterine clear cell and serous carcinomas have a high propensity for locoregional and distant spread, tend to be more advanced at presentation, and carry a higher risk of recurrence and death than endometrioid cancers. Limited prospective data exist to guide evidence-based management of these rare malignancies. OBJECTIVE: The American Radium Society sought to summarize evidence-based guidelines developed by a multidisciplinary expert panel that help to guide the management of uterine clear cell and serous carcinomas. METHODS: The American Radium Society Appropriate Use Criteria presented in this manuscript were developed by a multidisciplinary expert panel using an extensive analysis of current published literature from peer-reviewed journals. A well-established methodology (modified Delphi) was used to rate the appropriate use of diagnostic and therapeutic procedures for the management of uterine clear cell and serous carcinomas. RESULTS: The primary treatment for non-metastatic uterine clear cell and serous carcinomas is complete surgical staging, with total hysterectomy, salpingo-oophorectomy, omentectomy, and lymph node staging. Even in early-stage disease, patients with uterine clear cell and serous carcinomas have a worse prognosis than those with type I endometrial cancers, warranting consideration for adjuvant therapy regardless of the stage. Given the aggressive nature of these malignancies, and until further research determines the most appropriate adjuvant therapy, it may be reasonable to counsel patients about combined-modality treatment with systemic chemotherapy and radiotherapy. CONCLUSION: Patients diagnosed with uterine clear cell and serous carcinomas should undergo complete surgical staging. Multimodal adjuvant therapies should be considered in the treatment of both early-stage and advanced-stage disease. Further prospective studies or multi-institutional retrospective studies are warranted to determine optimal sequencing of therapy and appropriate management of patients based on their unique risk factors. Long-term surveillance is indicated due to the high risk of locoregional and distant recurrence.

Lymphocyte sparing normal tissue effects in the clinic (LymphoTEC): A systematic review of dose constraint considerations to mitigate radiation-related lymphopenia in the era of immunotherapy.

BACKGROUND: Radiation-related lymphopenia has been associated with suboptimal tumor control rates leading to inferior survival outcomes. To date, no standardized dose constraints are available to limit radiation dose to resident and circulating lymphocyte populations. We undertook this systemic review of the literature to provide a synopsis of the dosimetric predictors of radiation-related lymphopenia in solid malignancies. METHODOLOGY: A systematic literature review of PubMed (National Institutes of Health), Cochrane Central (Cochrane collaboration), and Google Scholar was conducted with the following keywords: "radiation", "lymphopenia", "cancer", "dosimetric predictors" with an inclusion deadline of May 31, 2022. Studies that met prespecified inclusion criteria were designated either Good, Fair, or Poor Quality based on the Newcastle-Ottawa quality assessment. The dosimetric parameters derived from Good Quality studies were tabulated as LymphoTEC dose constraints. Dosimetric parameters derived from Fair and Poor-quality studies were grouped as optional. RESULTS: An initial systematic search of the literature yielded 1,632 articles. After screening, a total of 48 studies met inclusion criteria and were divided into the following categories: central nervous system (CNS, 6), thoracic (11), gastrointestinal (26), gynecologic (2), head and neck, breast, and genitourinary (one each) cancers. Lung mean dose, heart mean dose, brain V25, spleen mean dose, estimated dose to immune cells, and bone marrow V10 were among the strongest predictors for severe lymphopenia related to radiotherapy. CONCLUSION: Optimizing the delivery of radiation therapy to limit dose to lymphocyte-rich structures may curb the negative oncologic impact of lymphocyte depletion. The dose constraints described herein may be considered for prospective validation and future use in clinical trials to limit risk of radiation-related lymphopenia and possibly improve cancer-associated outcomes.

A Review of Concurrent Chemo/Radiation, Immunotherapy, Radiation Planning, and Biomarkers for Locally Advanced Non-small Cell Lung Cancer and Their Role in the Development of ECOG-ACRIN EA5181.

ECOG-ACRIN EA5181 is a current prospective, randomized trial that is investigating whether the addition of concomitant durvalumab to standard chemo/radiation followed by 1 year of consolidative durvalumab results in an overall survival benefit over standard chemo/radiation alone followed by 1 year of consolidative durvalumab in patients with locally advanced, unresectable non-small cell lung cancer (NSCLC). Because multiple phase I/II trials have shown the relative safety of adding immunotherapy to chemo/radiation and due to the known synergism between chemotherapy and immunotherapy, it is hoped that concomitant durvalumab can reduce the relatively high incidence of local failure (38%-46%) as seen in recent prospective, randomized trials of standard chemo/radiation in this patient population. We will review the history of radiation for LA-NSCLC and discuss the role of induction, concurrent and consolidative chemotherapy as well as the concerns for late cardiac and pulmonary toxicities associated with treatment. Furthermore, we will review the potential role of next generation sequencing, PD-L1, ctDNA and tumor mutation burden and their possible impact on this trial.