Accuracy of surveillance serum squamous cell carcinoma antigen for cervical cancer recurrence after definitive chemoradiation.

OBJECTIVE: Recurrence remains a significant clinical problem for patients with cervical cancer, and early detection may improve outcomes. Serum squamous cell carcinoma antigen (SCCA) is a biomarker of prognosis and response to chemoradiotherapy. We hypothesized that elevated serum SCCA during surveillance is sensitive and specific for recurrence. METHODS: Pre-treatment and follow-up serum SCCA from patients treated with definitive-intent radiotherapy were measured via enzyme-linked immunosorbent assay in a Clinical Laboratory Improvement Amendments (CLIA)-certified laboratory and analyzed retrospectively. Follow-up SCCA was defined as the value closest to recurrence, or as last available for patients without recurrence. Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of follow-up SCCA for recurrence was determined for the whole cohort (Cohort 1), for patients with elevated (Cohort 2), and normal pre-treatment SCCA (Cohort 3). Patterns of failure were also evaluated. RESULTS: Of 227 patients in Cohort 1, 23% experienced recurrence, and 17% died of cervical cancer. Mean follow-up SCCA was 0.9 (±2.5) for patients with no recurrence and 6.0 (±18.7) for patients with recurrence (p=0.02). Sensitivity, specificity, PPV, and NPV of follow-up SCCA for recurrence in Cohort 1 were 38.5%, 97.1%, 80%, and 84.2%, and for patients in Cohort 2 were 54.5%, 95%, 78.3%, and 86.5%, respectively. Four of 86 patients in Cohort 3 had an elevated follow-up SCCA, two of these at the time of recurrence. Elevated pre-treatment SCCA and follow-up SCCA were associated with isolated pelvic recurrence. CONCLUSIONS: Surveillance serum SCCA has high specificity and NPV for recurrence, and may be of limited utility in patients with normal pre-treatment SCCA.

Early posttherapy clearance of human papillomavirus and treatment response in cervical carcinoma.

BACKGROUND: Among patients with cervical cancer, little is known about the significance of persistent human papillomavirus (HPV) expression after chemoradiation (CRT). This study evaluated associations between early posttreatment HPV clearance and patient outcomes with an added focus on the value of posttherapy positron emission tomography (PET) imaging. METHODS: Included patients underwent pretreatment testing indicating a high-risk HPV infection and posttreatment testing with a messenger RNA (mRNA)-based genital swab after CRT. Posttherapy responses were stratified on the basis of HPV mRNA detection into an early clearance (EC) group (no mRNA) and a persistent expression (PE) group (detectable mRNA) on the basis of an evaluation at a median of 6 weeks after therapy. The Kaplan-Meier method was used to compare outcomes, and multivariable analysis was used to identify predictors of outcomes. RESULTS: Seventy-two of the 97 eligible patients (74.2%) had EC. The mean follow-up time was 25 months (range, 4-56 months), and 2-year pelvic control (76.9% vs 50.2%; P = .01) and overall survival (OS; 80.9% vs 52.2%; P < .01) were superior among EC patients. In the multivariable analysis, EC predicted for improved survival (hazard ratio [HR] for mortality, 0.46; 95% confidence interval [CI], 0.21-0.96; P = .047), as did a complete response (CR) on posttherapy PET (HR for less than a CR on PET, 6.17; 95% CI, 2.58-14.72; P < .01). In a subset analysis of patients with a posttherapy PET CR, HPV clearance retained prognostic significance (2-year OS, 95.6% with EC vs 66.7% with PE; P = .04), whereas PE patients without a PET CR had the worst survival (35.9%; P < .01 for trend). CONCLUSIONS: Early posttherapy clearance of HPV is associated with improved survival in cervical cancer. Evaluating HPV expression at this 6-week time point provides prognostic information beyond posttherapy PET imaging and may aid in risk stratification and decisions for treatment escalation.

Feasibility and safety assessment of magnetic resonance-guided high-intensity focused ultrasound (MRgHIFU)-mediated mild hyperthermia in pelvic targets evaluated using an in vivo porcine model.

Purpose: To evaluate the feasibility and assess safety parameters of magnetic resonance-guided high-intensity focused ultrasound (MRgHIFU)-mediated hyperthermia (HT; heating to 40-45 °C) in various pelvic targets in a porcine model in vivo.Methods: Thirteen HT treatments were performed in six pigs with a commercial MRgHIFU system (Sonalleve V2, Profound Medical Inc., Mississauga, Canada) to muscle adjacent to the ventral/dorsal bladder wall and uterus to administer 42 °C (±1°) for 30 min (±5%) using an 18-mm target diameter and 100 W power. Feasibility was assessed using accuracy, uniformity, and MR-thermometry performance-based metrics. Safety parameters were assessed for tissues in the targets and beam-path by contrast-enhanced MRI, gross-pathology and histopathology.Results: Across all HT sessions, the mean difference between average temperature (Tavg) and the target temperature within the target region-of-interest (tROI, the cross-section of the heated volume at focal depth) was 0.51 ± 0.33 °C. Within the tROI, the temperature standard deviation averaged 1.55 ± 0.31 °C, the average 30-min Tavg variation was 0.80 ± 0.17 °C, and the maximum difference between Tavg and the 10th- or 90th-percentile temperature averaged 2.01 ± 0.44 °C. The average time to reach ≥41 °C and cool to ≤40 °C within the tROI at the beginning and end of treatment was 47.25 ± 27.47 s and 66.37 ± 62.68 s, respectively. Compared to unheated controls, no abnormally-perfused tissue or permanent damage was evident in the MR images, gross pathology or histological analysis.Conclusions: MRgHIFU-mediated HT is feasible and safety assessment is satisfactory for treating an array of clinically-mimicking pelvic geometries in a porcine model in vivo, implying the technique may have utility in treating pelvic targets in human patients.

Quality of life after high-dose-rate brachytherapy monotherapy for prostate cancer.

PURPOSE: There is little information in the literature on health-related quality of life (HRQOL) changes due to high-dose-rate (HDR) brachytherapy monotherapy for prostate cancer. MATERIALS AND METHODS: We conducted a prospective study of HRQOL changes due to HDR brachytherapy monotherapy for low risk or favorable intermediate risk prostate cancer. Sixty-four of 84 (76 %) patients who were treated between February 2011 and April 2013 completed 50 questions comprising the Expanded Prostate Cancer Index Composite (EPIC) before treatment and 6 and/or 12 months after treatment. RESULTS: Six months after treatment, there was a significant decrease (p <0.05) in EPIC urinary, bowel, and sexual scores, including urinary overall, urinary function, urinary bother, urinary irritative, bowel overall, bowel bother, sexual overall, and sexual bother scores. By one year after treatment, EPIC urinary, bowel, and sexual scores had increased and only the bowel overall and bowel bother scores remained significantly below baseline values. CONCLUSIONS: HDR brachytherapy monotherapy is well-tolerated in patients with low and favorable intermediate risk prostate cancer. EPIC urinary and sexual domain scores returned to close to baseline 12 months after HDR brachytherapy.

Cone-Beam Computed Tomography (CBCT)-Guided Adaptive Boost Radiotherapy for a Patient With Locally Advanced Cervical Cancer Ineligible for Brachytherapy.

Brachytherapy is a critical component of locally advanced cervical cancer treatment, and patients ineligible for brachytherapy historically have poor outcomes. Delivery of boost with stereotactic body radiation therapy (SBRT) has been studied, though toxicity is a concern. Recent case reports have explored adaptive radiation boost, which can adjust plans for inter-fraction motion using magnetic resonance guidance. Herein, we report the first patient with locally advanced cervical cancer ineligible for brachytherapy who was treated with a cone-beam computed tomography (CBCT)-guided adaptive boost following completion of chemoradiation. A 71-year-old female with locally advanced cervical cancer was treated with chemoradiation and was deemed ineligible for a brachytherapy boost due to tumor size, geometry, and a fistula with a tumor in the bladder. She was prescribed a boost to the primary tumor of 25 Gy in five fractions using CBCT-guided adaptive radiation following the completion of chemoradiation. A simulation was performed using a non-contrast CT fused with a mid-chemoradiation magnetic resonance imaging (MRI) scan to create an initial plan. For each treatment fraction, kilovoltage CBCTs were acquired, contours of organs at risk (OARs) were adjusted to reflect anatomy-of-the-day, and an adapted plan was generated. The initial and adapted plans were compared using dose-volume histogram objectives, and the adapted plan was used if it resolved OAR constraint violations or improved target coverage. The use of the initial treatment plan would have resulted in constraint violations for the rectum, sigmoid, and bladder in all fractions. The adapted plans achieved hard constraints in all fractions for all four critical OARs. The mean total treatment time across all five fractions was 58 minutes. This case demonstrates the feasibility of a CBCT-guided adaptive boost approach and the dosimetric benefits of plan adaptation in this setting. Though larger-scale and longer-term data are needed, CBCT-guided adaptive radiation may present a feasible alternative modality to deliver boost doses for brachytherapy-ineligible patients.

Submandibular gland transfer for the prevention of radiation-induced xerostomia in oropharyngeal cancer: Dosimetric impact in the intensity modulated radiotherapy era.

BACKGROUND: Submandibular gland (SMG) transfer decreased radiation-associated xerostomia in the 2/3-dimensional radiotherapy era. We evaluated the dosimetric implications of SMG transfer on modern intensity modulated radiotherapy (IMRT) plans. METHODS: Eighteen oropharynx cancer patients underwent SMG transfer followed by IMRT; reoptimized plans using the baseline SMG location were generated. Mean salivary gland, oral cavity, and larynx doses were compared between clinical plans and reoptimized plans. RESULTS: No statistically significant difference in mean SMG dose (27.53 Gy vs. 29.61 Gy) or total salivary gland dose (26.12 Gy vs. 26.41 Gy) was observed with or without SMG transfer (all p > 0.05). Mean oral cavity and larynx doses were not statistically different. Neither tumor site, target volume crossing midline, stage, nor salivary gland volumes were associated with mean doses. CONCLUSIONS: Salivary gland doses were similar with or without SMG transfer. IMRT likely decreases the benefit of SMG transfer on the risk of radiation-associated xerostomia.

Evaluation of a prospective radiation oncology departmental team review process using standardized simulation directives.

INTRODUCTION: The primary objective of this study is to evaluate the utility and value of an institutional, multi-disciplinary radiation oncology team review process prior to radiotherapy (RT) simulation. METHODS: Over a period of 3 months and through an iterative team-based process, a standardized simulation requisition directive (SSRD) was developed, piloted, modified, and subsequently implemented for all patients treated with external beam RT at a single tertiary care institution from January to December 2020. The SSRDs were reviewed at a daily multi-disciplinary radiation oncology team review conference; modifications consequential to the review were prospectively recorded in a quality database. RESULTS: 1500 consecutive SSRDs were prospectively reviewed for this study. 397 modifications on 290 (19.3%) SSRDs were recorded and parsed into 5 main categories and 18 subcategories. The most common modifications resulted from changes in immobilization device (n = 88, 22.2%), RT care path (n = 56, 14.1%), and arm positioning (n = 43, 10.8%). On univariate analysis, modifications were associated with RT intent, scan parameters, tumor site, and consultation type. An increased rate modifications was observed for patients had telemedicine consults (n = 101, 22.7%) compared to in-person consultations (n = 189, 17.9%) (p = 0.032). Using logistic regression analysis, there was also a statistically significant relationship between postoperative RT delivery and modification rates (OR: 2.913, 95% CI: 1.014-8.372) (p = 0.0126). Overall, only 14 patients (0.9%) needed re-simulation during the entire study period. CONCLUSIONS: Prospective multi-disciplinary radiation oncology team review prior to simulation identifies actionable change in approximately 19% of procedures, and results in an extremely low rate (<1%) of re-simulation. As departmental processes transition to virtual platforms, thorough attention is needed to identify patients at higher risk of simulation modifications.

CT-guided versus MR-guided radiotherapy: Impact on gastrointestinal sparing in adrenal stereotactic body radiotherapy.

BACKGROUND AND PURPOSE: To quantify the indication for adaptive, gated breath-hold (BH) MR-guided radiotherapy (MRgRTBH) versus BH or free-breathing (FB) CT-based image-guided radiotherapy (CT-IGRT) for the ablative treatment of adrenal malignancies. MATERIALS AND METHODS: Twenty adrenal patients underwent adaptive IMRT MRgRTBH to a median dose of 50 Gy/5 fractions. Each patient was replanned for VMAT CT-IGRTBH and CT-IGRTFB on a c-arm linac. Only CT-IGRTFB used an ITV, summed from GTVs of all phases of the 4DCT respiratory evaluation. All used the same 5 mm GTV/ITV to PTV expansion. Metrics evaluated included: target volume and coverage, conformality, mean ipsilateral kidney and 0.5 cc gastrointestinal organ-at-risk (OAR) doses (D0.5cc). Adaptive dose for MRgRTBH and predicted dose (i.e., initial plan re-calculated on anatomy of the day) was performed for CT-IGRTBH and MRgRTBH to assess frequency of OAR violations and coverage reductions for each fraction. RESULTS: The more common VMAT CT-IGRTFB, with its significantly larger target volumes, proved inferior to MRgRTBH in mean PTV and ITV/GTV coverage, as well as small bowel D0.5cc. Conversely, VMAT CT-IGRTBH delivered a dosimetrically superior initial plan in terms of statistically significant (p ≤ 0.02) improvements in target coverage, conformality and D0.5cc to the large bowel, duodenum and mean ipsilateral kidney compared to IMRT MRgRTBH. However, non-adaptive CT-IGRTBH had a 71.8% frequency of predicted indications for adaptation and was 2.8 times more likely to experience a coverage reduction in PTV D95% than predicted for MRgRTBH. CONCLUSION: Breath-hold VMAT radiotherapy provides superior target coverage and conformality over MRgRTBH, but the ability of MRgRTBH to safely provide ablative doses to adrenal lesions near mobile luminal OAR through adaptation and direct, real-time motion tracking is unmatched.

Phase I Trial of Stereotactic MRI-Guided Online Adaptive Radiation Therapy (SMART) for the Treatment of Oligometastatic Ovarian Cancer.

PURPOSE: Stereotactic body radiation therapy is increasingly used to treat a variety of oligometastatic histologies, but few data exist for ovarian cancer. Ablative stereotactic body radiation therapy dosing is challenging in sites like the abdomen, pelvis, and central thorax due to proximity and motion of organs at risk. A novel radiation delivery method, stereotactic magnetic-resonance-guided online-adaptive radiation therapy (SMART), may improve the therapeutic index of stereotactic body radiation therapy through enhanced soft-tissue visualization, real-time nonionizing imaging, and ability to adapt to the anatomy-of-the-day, with the goal of producing systemic-therapy-free intervals. This phase I trial assessed feasibility, safety, and dosimetric advantage of SMART to treat ovarian oligometastases. METHODS AND MATERIALS: Ten patients with recurrent oligometastatic ovarian cancer underwent SMART for oligometastasis ablation. Initial plans prescribed 35 Gy/5 fractions with goal 95% planning target volume coverage by 95% of prescription, with dose escalation permitted, subject to strict organ-at-risk dose constraints. Daily adaptive planning was used to protect organs-at-risk and/or increase target dose. Feasibility (successful delivery of >80% of fractions in the first on-table attempt) and safety of this approach was evaluated, in addition to efficacy, survival metrics, quality-of-life, prospective timing and dosimetric outcomes. RESULTS: Ten women with seventeen ovarian oligometastases were treated with SMART, and 100% of treatment fractions were successfully delivered. Online adaptive plans were selected at time of treatment for 58% of fractions, due to initial plan violation of organs-at-risk constraints (84% of adapted fractions) or observed opportunity for planning target volume dose escalation (16% of adapted fractions), with a median on-table time of 64 minutes. A single Grade ≥3 acute (within 6 months of SMART) treatment-related toxicity (duodenal ulcer) was observed. Local control at 3 months was 94%; median progression-free survival was 10.9 months. Median Kaplan-Meier estimated systemic-therapy-free survival after radiation completion was 11.5 months, with concomitant quality-of-life improvements. CONCLUSIONS: SMART is feasible and safe for high-dose radiation therapy ablation of ovarian oligometastases of the abdomen, pelvis, and central thorax with minimal toxicity, high rates of local control, and prolonged systemic-therapy-free survival translating into improved quality-of-life.

Multi-Institutional Outcomes of Stereotactic Magnetic Resonance Image Guided Adaptive Radiation Therapy With a Median Biologically Effective Dose of 100 Gy10 for Non-bone Oligometastases.

Purpose: Randomized data show a survival benefit of stereotactic ablative body radiation therapy in selected patients with oligometastases (OM). Stereotactic magnetic resonance guided adaptive radiation therapy (SMART) may facilitate the delivery of ablative dose for OM lesions, especially those adjacent to historically dose-limiting organs at risk, where conventional approaches preclude ablative dosing. Methods and Materials: The RSSearch Registry was queried for OM patients (1-5 metastatic lesions) treated with SMART. Freedom from local progression (FFLP), freedom from distant progression (FFDP), progression-free survival (PFS), and overall survival (LS) were estimated using the Kaplan-Meier method. FFLP was evaluated using RECIST 1.1 criteria. Toxicity was evaluated using Common Terminology Criteria for Adverse Events version 4 criteria. Results: Ninety-six patients with 108 OM lesions were treated on a 0.35 T MR Linac at 2 institutions between 2018 and 2020. SMART was delivered to mostly abdominal or pelvic lymph nodes (48.1%), lung (18.5%), liver and intrahepatic bile ducts (16.7%), and adrenal gland (11.1%). The median prescribed radiation therapy dose was 48.5 Gy (range, 30-60 Gy) in 5 fractions (range, 3-15). The median biologically effective dose corrected using an alpha/beta value of 10 was 100 Gy10 (range, 48-180). No acute or late grade 3+ toxicities were observed with median 10 months (range, 3-25) follow-up. Estimated 1-year FFLP, FFDP, PFS, and OS were 92.3%, 41.1%, 39.3%, and 89.6%, respectively. Median FFDP and PFS were 8.9 months (95% confidence interval, 5.2-12.6 months) and 7.6 months (95% confidence interval, 4.5-10.6 months), respectively. Conclusions: To our knowledge, this represents the largest analysis of SMART using ablative dosing for non-bone OM. A median prescribed biologically effective dose of 100 Gy10 resulted in excellent early FFLP and no significant toxicity, likely facilitated by continuous intrafraction MR visualization, breath hold delivery, and online adaptive replanning. Additional prospective evaluation of dose-escalated SMART for OM is warranted.

A Comprehensive Analysis of a Prospective Multidisciplinary Peer Review Process Before Radiation Therapy Simulation.

PURPOSE: Although peer review in radiation oncology (RO) has been recommended to improve quality of care, an analysis of modifications resulting from an RO multidisciplinary presimulation standardized review process has yet to be empirically demonstrated. METHODS AND MATERIALS: A standardized simulation directive was used for patients undergoing simulation for external beam radiation therapy at a single tertiary care institution. The simulation directives were presented, and all aspects were reviewed by representatives from key RO disciplines. Modifications to the original directives were prospectively captured in a quality improvement registry. Association between key variables and the incidence of modifications were performed using Fisher exact test and t test. RESULTS: A registry of 500 consecutive simulations for patients undergoing radiation therapy was reviewed. A median of 105 simulations occurred per month. All simulation directives were entered by a physician a median of 3 days before simulation (range, 1-76 days). The treatment intent was curative for 269 patients (53.8%), palliative for 203 patients (40.6%), and benign for 3 patients (0.6%). Twenty-five (5%) patients did not have a treatment intent selected. Based on RO multidisciplinary review, 105 directives (21%) were modified from the original intent, with 29 (5.8%) requiring more than 1 modification. A total of 149 modifications were made and categorized as changes to patient positioning and immobilization (n = 100, 20%), treatment site and care path (n = 34, 6.8%), simulation coordination activities (n = 6, 1.2%), and treatment technique and planning instructions (n = 9, 1.8%). A higher proportion of modifications occurred at the time of multidisciplinary review in patients receiving more complex treatments (intensity modulated radiation therapy/stereotactic radiosurgery/stereotactic body radiation therapy [IMRT/SRS/SBRT] vs 3-dimensional radiation therapy [3DCRT] radiation therapy, 25% vs 16%, P < .025). CONCLUSIONS: Given the complexity of radiation therapy simulation, standardization of directives with prospective RO multidisciplinary presimulation peer review is critical to optimizing department processes and reducing errors. Approximately 1 in 5 patients benefits from this peer review process, especially patients treated with IMRT/SRS/SBRT.

Eliminating Postoperative Radiation to the Pathologically Node-Negative Neck: Long-Term Results of a Prospective Phase II Study.

PURPOSE: The volume treated with postoperative radiation therapy (PORT) is a mediator of toxicity, and reduced volumes result in improved quality of life (QOL). In this phase II trial, treatment volumes were reduced by omitting PORT to the pathologically negative (PN0) neck in patients with primary head and neck squamous cell carcinoma. METHODS: Patients with head and neck squamous cell carcinoma who underwent surgical resection and neck dissection with a PN0 neck and high-risk features mandating PORT to the primary and/or involved neck were eligible. The primary end point was greater than 90% disease control in the unirradiated neck. QOL was evaluated using the MD Anderson Dysphagia Inventory and the University of Michigan patient-reported xerostomia questionnaire. RESULTS: Seventy-three patients were enrolled, and 72 were evaluable. Median age was 56 years (range, 31 to 81 years); 58 patients were male, and 47 (65%) had a smoking history. Sites included oral cavity (n = 14), oropharynx (n = 37), hypopharynx (n = 4), larynx (n = 16), and unknown primary tumor (n = 1). According to the American Joint Committee on Cancer Staging Manual (7th edition), 67 patients (93%) had stage III/IV disease, and 71% of tumors involved or crossed midline. No patient had contralateral neck PORT. In 17 patients (24%), only the primary site was treated. At a median follow-up of 53 months, two patients experienced treatment failure of the PN0 unirradiated neck; they also experienced treatment failure locally. Unirradiated neck control was 97% (95% CI, 93.4% to 100.0%). Five-year rates of local control, regional control, progression-free survival, and overall survival were 84%, 93%, 60%, and 64%, respectively. QOL measures were not significantly different from baseline at 12 and 24 months post-PORT (P > .05). CONCLUSION: Eliminating PORT to the PN0 neck resulted in excellent control rates in the unirradiated neck without long-term adverse effects on global QOL.

Stereotactic MR-Guided Online Adaptive Radiation Therapy (SMART) for Ultracentral Thorax Malignancies: Results of a Phase 1 Trial.

PURPOSE: Stereotactic body radiation therapy (SBRT) is an effective treatment for oligometastatic or unresectable primary malignancies, although target proximity to organs at risk (OARs) within the ultracentral thorax (UCT) limits safe delivery of an ablative dose. Stereotactic magnetic resonance (MR)-guided online adaptive radiation therapy (SMART) may improve the therapeutic ratio using reoptimization to account for daily variation in target and OAR anatomy. This study assessed the feasibility of UCT SMART and characterized dosimetric and clinical outcomes in patients treated for UCT lesions on a prospective phase 1 trial. METHODS AND MATERIALS: Five patients with oligometastatic (n = 4) or unresectable primary (n = 1) UCT malignancies underwent SMART. Initial plans prescribed 50 Gy in 5 fractions with goal 95% planning target volume (PTV) coverage by 95% of prescription, subject to strict OAR constraints. Daily real-time online adaptive plans were created as needed to preserve hard OAR constraints, escalate PTV dose, or both, based on daily setup MR image set anatomy. Treatment times, patient outcomes, and dosimetric comparisons were prospectively recorded. RESULTS: All initial and daily adaptive plans met strict OAR constraints based on simulation and daily setup MR imaging anatomy, respectively. Four of the 5 patients received ≥1 adapted fraction. Ten of the 25 total delivered fractions were adapted. A total of 30% of plan adaptations were performed to improve PTV coverage; 70% were for reversal of ≥1 OAR violation. Local control by Response Evaluation Criteria in Solid Tumors was 100% at 3 and 6 months. No grade ≥3 acute (within 6 months of radiation completion) treatment-related toxicities were identified. CONCLUSIONS: SMART may allow PTV coverage improvement and/or OAR sparing compared with nonadaptive SBRT and may widen the therapeutic index of UCT SBRT. In this small prospective cohort, we found that SMART was clinically deliverable to 100% of patients, although treatment delivery times surpassed our predefined, timing-based feasibility endpoint. This technique is well tolerated, offering excellent local control with no identified acute grade ≥3 toxicity.

Delineation of a Cardiac Planning Organ-At-Risk Volume Using Real-Time Magnetic Resonance Imaging for Cardiac Protection in Thoracic and Breast Radiation Therapy.

PURPOSE: Cardiac radiation is associated with cardiotoxicity in patients with thoracic and breast malignancies. We conducted a prospective study using cine magnetic resonance imaging (MRI) scans to evaluate heart motion. We hypothesized that cine MRI could be used to define population-based cardiac planning organ-at-risk volumes (PRV). METHODS AND MATERIALS: A total of 16 real-time acquisitions were obtained per subject on a 1.5 Tesla MRI (Philips Ingenia). Planar cine MRI was performed in 4 sequential sagittal and coronal planes at free-breathing (FB) and deep-inspiratory breath hold (DIBH). In-plane cardiac motion was assessed using a scale-invariant feature transformation-based algorithm. Subject-specific pixel motion ranges were defined in anteroposterior (AP), left-right (LR), and superoinferior (SI) planes. Averages of the 98% and 67% of the maximum ranges of pixel displacement were defined by subject, then averaged across the cohort to calculate PRV expansions at FB and DIBH. RESULTS: Data from 20 subjects with a total of 3120 image frames collected per subject in coronal and sagittal planes at DIBH and FB, and 62,400 total frames were analyzed. Cohort averages of 98% of the maximum cardiac motion ranges comprised margin expansions of 12.5 ± 1.1 mm SI, 5.8 ± 1.2 mm AP, and 6.6 ± 1.0 mm LR at FB and 6.7 ± 1.5 mm SI, 4.7 ± 1.3 mm AP, and 5.3 ± 1.3 mm LR at DIBH. Margins for 67% of the maximum range comprised 7.7 ± 0.7 mm SI, 3.2 ± 0.6 mm AP, and 3.7 ± 0.6 mm LR at FB and 4.1 ± 0.9 mm SI, 2.7 ± 0.8 mm AP, and 3.2 ± 0.8 mm LR at DIBH. Subsequently, these margins were simplified to form PRVs for treatment planning. CONCLUSIONS: We implemented scale-invariant feature transformation-based motion tracking for analysis of the cardiac cine MRI scans to quantify motion and create cohort-based cardiac PRVs to improve cardioprotection in breast and thoracic radiation.

A propensity analysis comparing definitive chemo-radiotherapy for muscle-invasive squamous cell carcinoma of the bladder vs. urothelial carcinoma of the bladder using the National Cancer Database.

INTRODUCTION: Squamous cell carcinoma (SqCC) is the second most common histology of primary bladder cancer, but still very limited information is known about its treatment outcomes. Most bladder cancer trials have excluded SqCC, and the current treatment paradigm for localized SqCC is extrapolated from results in urothelial carcinoma (UC). In particular, there is limited data on the efficacy of definitive chemo-radiotherapy (CRT). In this study, we compare overall survival outcomes between SqCC and UC patients treated with definitive CRT. MATERIALS/METHODS: We queried the National Cancer Database (NCDB) for muscle-invasive (cT2-T4 N0 M0) bladder cancer patients diagnosed from 2004 to 2013 who underwent concurrent CRT. Propensity matching was performed to match patients with SqCC to those with UC. OS was analyzed using the Kaplan-Meier survival method, and the log-rank test and Cox regression were used for analyses. RESULTS: 3332 patients met inclusion criteria of which 79 (2.3%) had SqCC. 73.4% of SqCC patients had clinical T2 disease compared to 82.5% of UC patients. Unadjusted median OS for SqCC patients was 15.6 months (95% CI, 11.7-19.6) versus 29.1 months (95% CI, 27.5-30.7) for those with UC (P < 0.0001). On multivariable analysis, factors associated with worse OS included: SqCC histology [HR: 1.53 (95% CI, 1.19-1.97); P = 0.001], increasing age [HR: 1.02 (95% CI, 1.02-1.03); P < 0.0001], increasing clinical T-stage [HR: 1.21 (95% CI, 1.13-1.29); P < 0.0001], and Charlson-Deyo comorbidity index [HR: 1.26 (95% CI, 1.18-1.33); P < 0.0001]. Seventy-seven SqCC patients were included in the propensity-matched analysis (154 total patients) with a median OS for SqCC patients of 15.1 months (95% CI, 11.1-18.9) vs. 30.4 months (95% CI, 19.4-41.4) for patients with UC (P = 0.013). CONCLUSIONS: This is the largest study to-date assessing survival outcomes for SqCC of the bladder treated with CRT. In this study, SqCC had worse overall survival compared to UC patients. Histology had a greater impact on survival than increasing T-stage, suggesting that histology should be an important factor when determining a patient's treatment strategy and that treatment intensification in this subgroup may be warranted.

Cardiac dose is associated with immunosuppression and poor survival in locally advanced non-small cell lung cancer.

PURPOSE: Studies have associated increased radiation therapy (RT) heart dose with cardiac toxicity. Others have correlated RT-related immunosuppression with worsened survival. Given the large vascular volumes irradiated during locally advanced non-small cell lung cancer (LA-NSCLC) treatment, we hypothesized an association between increased heart dose and immunosuppression. METHODS: We identified 400 LA-NSCLC patients treated with definitive RT ±â€¯chemotherapy between 2001 and 2016. Absolute lymphocyte counts (ALC), absolute neutrophil counts (ANC), and neutrophil-to-lymphocyte ratio (NLR = ANC/ALC) were analyzed pre-RT, during RT, and post-RT. Multivariable analysis (MVA) was performed to correlate Clinical factors with both hematologic toxicity and overall survival. An upper tertile threshold to increase specificity of NLR was chosen to dichotomize continuous hematologic variables. RESULTS: Median follow up was 17 months (range 0.2-174 months) in all patients and 46 months (range 0.2-161 months) in survivors. A total of 94% of patients had stage III disease and 77% received concurrent chemo radiation. Two-year overall survival (OS), freedom from local recurrence (FFLR), and freedom from distant metastases (FFDM) was 42%, 60% and 45%, respectively. Median survival was 18 months. On MVA for OS (n = 207), male gender (Hazard Ratio [HR] 1.7; 95% CI 1.2-2.3), RT alone (HR 2.1; 95% CI 1.9-4.0), the percentage of heart receiving ≥50 Gy (V50) (HR 1.02; 95% CI 1.01-1.03), and higher NLR at 4 months (HR 1.02, 95% CI 1.01-1.03) were associated with reduced OS. ALC nadir was not associated with treatment outcomes. NLR >10.5 was associated with decreased OS (p < 0.001) and decreased FFDM (p = 0.04). On MVA evaluating factors associated with hematological toxicity (n = 247), adjuvant chemotherapy (HR 2.6; 95% CI 1.3-5.0; p = 0.006), RT alone (HR 3.6; 95% CI 1.1-12; p = 0.04), and heart V50 >25% (HR 2.0; 95% CI 1.1-3.5; p = 0.02) were associated with a NLR >10.5 4 months post-RT. CONCLUSION: RT related immunosuppression is associated with worse patient outcomes, and may represent a source of increased mortality beyond cardiac toxicity alone.

Quality of life after high-dose-rate brachytherapy monotherapy for prostate cancer

Purpose There is little information in the literature on health-related quality of life (HRQOL) changes due to high-dose-rate (HDR) brachytherapy monotherapy for prostate cancer. Materials and Methods We conducted a prospective study of HRQOL changes due to HDR brachytherapy monotherapy for low risk or favorable intermediate risk prostate cancer. Sixty-four of 84 (76%) patients who were treated between February 2011 and April 2013 completed 50 questions comprising the Expanded Prostate Cancer Index Composite (EPIC) before treatment and 6 and/or 12 months after treatment. Results Six months after treatment, there was a significant decrease (p<0.05) in EPIC urinary, bowel, and sexual scores, including urinary overall, urinary function, urinary bother, urinary irritative, bowel overall, bowel bother, sexual overall, and sexual bother scores. By one year after treatment, EPIC urinary, bowel, and sexual scores had increased and only the bowel overall and bowel bother scores remained significantly below baseline values. Conclusions HDR brachytherapy monotherapy is well-tolerated in patients with low and favorable intermediate risk prostate cancer. EPIC urinary and sexual domain scores returned to close to baseline 12 months after HDR brachytherapy. .