Selective Personalized RadioImmunotherapy for Locally Advanced Non-Small-Cell Lung Cancer Trial (SPRINT).

PURPOSE: Standard therapy for locally advanced non-small-cell lung cancer (LA-NSCLC) is concurrent chemoradiotherapy followed by adjuvant durvalumab. For biomarker-selected patients with LA-NSCLC, we hypothesized that sequential pembrolizumab and risk-adapted radiotherapy, without chemotherapy, would be well-tolerated and effective. METHODS: Patients with stage III NSCLC or unresectable stage II NSCLC and an Eastern Cooperative Oncology Group performance status of 0-1 were eligible for this trial. Patients with a PD-L1 tumor proportion score (TPS) of ≥50% received three cycles of induction pembrolizumab (200 mg, once every 21 days), followed by a 20-fraction course of risk-adapted thoracic radiotherapy (55 Gy delivered to tumors or lymph nodes with metabolic volume exceeding 20 cc, 48 Gy delivered to smaller lesions), followed by consolidation pembrolizumab to complete a 1-year treatment course. The primary study end point was 1-year progression-free survival (PFS). Secondary end points included response rates after induction pembrolizumab, overall survival (OS), and adverse events. RESULTS: Twenty-five patients with a PD-L1 TPS of ≥50% were enrolled. The median age was 71, most patients (88%) had stage IIIA or IIIB disease, and the median PD-L1 TPS was 75%. Two patients developed disease progression during induction pembrolizumab, and two patients discontinued pembrolizumab after one infusion because of immune-related adverse events. Using RECIST criteria, 12 patients (48%) exhibited a partial or complete response after induction pembrolizumab. Twenty-four patients (96%) received definitive thoracic radiotherapy. The 1-year PFS rate is 76%, satisfying our efficacy objective. One- and 2-year OS rates are 92% and 76%, respectively. The most common grade 3 adverse events were colitis (n = 2, 8%) and esophagitis (n = 2, 8%), and no higher-grade treatment-related adverse events have occurred. CONCLUSION: Pembrolizumab and risk-adapted radiotherapy, without chemotherapy, are a promising treatment approach for patients with LA-NSCLC with a PD-L1 TPS of ≥50%.

Exploring causes and consequences of early discontinuation of durvalumab after chemoradiotherapy for non-small cell lung cancer.

Introduction: For most locally advanced non-small cell lung cancer (LA-NSCLC) patients who complete definitive chemoradiotherapy (CRT) and do not experience disease progression, one year of adjuvant durvalumab is recommended. Here, we explore causes and consequences of early durvalumab discontinuation. Materials and Methods: We reviewed patients treated for LA-NSCLC with definitive CRT who began adjuvant durvalumab between 2017 and 2021. Duration of durvalumab receipt and causes for early discontinuation were tabulated. Logistic regression models were utilized to evaluate predictors of early durvalumab discontinuation. Landmark analyses were performed to explore associations between early durvalumab discontinuation and clinical outcomes (progression-free survival (PFS), overall survival (OS)). Results: Fifty-nine patients were included. Forty-one patients (69%) discontinued durvalumab early, most commonly for disease progression (n = 14) or lung toxicity (n = 10). Multivariable analysis revealed mean heart radiotherapy dose (MHD) was associated with risk of durvalumab discontinuation from progression (HR = 2.34 per 10 Gy, p = 0.052), and there was a trend suggesting an association between MHD and risk of durvalumab discontinuation from lung toxicity (HR = 2.16 per 10 Gy, p = 0.126). Median PFS duration following durvalumab initiation was 14 months, and median OS duration was 32 months. Landmark analyses that excluded patients with progression or death within one year of durvalumab initiation demonstrated improved outcomes for patients who completed one year of durvalumab (2-year PFS 100% v. 40%, p < 0.001; 2-year OS 100% v. 67%, p = 0.862). Improved outcomes were observed for patients who received MHD below the cohort median (9.3 Gy) compared to patients with higher MHD (median PFS 32 months v. 8 months, p < 0.001; 2-year OS 69% v. 44%, p = 0.088). Conclusion: For LA-NSCLC patients treated with CRT followed by immunotherapy, extent of cardiac irradiation may be a risk factor for immunotherapy discontinuation, disease recurrence, and death.

Predictors of Financial Toxicity in Patients Receiving Concurrent Radiation Therapy and Chemotherapy.

Purpose: Financial toxicity (FT) is a significant concern for patients with cancer. We reviewed prospectively collected data to explore associations with FT among patients undergoing concurrent, definitive chemoradiation therapy (CRT) within a diverse, urban, academic radiation oncology department. Methods and Materials: Patients received CRT in 1 of 3 prospective trials. FT was evaluated before CRT (baseline) and then weekly using the European Organization for Research and Treatment of Cancer Core Quality of Life Questionnaire Core-30 questionnaire. Patients were classified as experiencing FT if they answered ≥2 on a Likert scale question (1-4 points) asking if they experienced FT. Rate of change of FT was calculated using linear regression; worsening FT was defined as increase ≥1 point per month. χ2, t tests, and logistic regression were used to assess predictors of FT. Results: Among 233 patients, patients attended an average of 9 outpatient and 4 radiology appointments over the 47 days between diagnosis and starting CRT. At baseline, 52% of patients reported experiencing FT. Advanced T stage (odds ratio, 2.47; P = .002) was associated with baseline FT in multivariate analysis. The mean rate of FT change was 0.23 Likert scale points per month. In total, 26% of patients demonstrated worsening FT during CRT. FT at baseline was not associated with worsening FT (P = .98). Hospitalization during treatment was associated with worsening FT (odds ratio, 2.30; P = .019) in multivariate analysis. Conclusions: Most patients reported FT before CRT. These results suggest that FT should be assessed (and, potentially, addressed) before starting definitive treatment because it develops early in a patient's cancer journey. Reducing hospitalizations may mitigate worsening FT. Further research is warranted to design interventions to reduce FT and avoid hospitalizations.

Predictors of prostate bed recurrence on magnetic resonance imaging in patients with rising prostate-specific antigen after radical prostatectomy.

INTRODUCTION: Radical prostatectomy (RP) is a standard treatment modality for localized prostate cancer. Biochemical failure after RP is usually evaluated with whole-body imaging to exclude distant metastatic disease, and pelvic magnetic resonance imaging (MRI) to detect local recurrence in the prostatectomy bed. The goal of this study is to correlate disease characteristics and demographic data in patients with rising prostate-specific antigen (PSA) after RP to determine association with MRI-detected cancer recurrence. METHODS: Sixty-four patients who underwent pelvic MRI for rising PSA after RP and had complete clinical and pathological data available were included. Using Chi-squared testing, we analyzed PSA levels, pathological disease characteristics (prostate cancer risk group, Gleason score, extracapsular extension, positive surgical margin, seminal vesicle involvement, perineural invasion, lymphovascular invasion, and PSA level before MRI), time from surgery to biochemical failure, and patient demographic characteristics as potential predictors of MRI-detected local recurrence. RESULTS: Definite MRI-detected local recurrence was observed in 17/64 patients (27%). Eleven (17%) patients had a suspicious lesion with the differential of scarring, retained seminal vesicle, or recurrent cancer. Thirty-six (56%) patients had no evidence of tumor in the prostate bed or pelvis on MRI. Patient race was associated with likelihood of detecting a prostate nodule on MRI (p=0.04), with African American patients having 82% lower odds of MRI-detected tumor recurrence compared with white patients (p=0.045). No other tumor or patient characteristic was significantly associated with MRI-detected recurrence. CONCLUSIONS: African American patients with biochemical failure after RP are less likely to have MRI-detectable recurrence in the prostate bed compared with white patients.

Who Benefits the Most From Adjuvant Durvalumab After Chemoradiotherapy for Non-small Cell Lung Cancer? An Exploratory Analysis.

PURPOSE: Adjuvant durvalumab is now recommended for most patients with locally advanced non-small cell lung cancer after concurrent chemoradiotherapy. Herein, we explore the clinical factors that may be associated with the benefit from adjuvant durvalumab. METHODS AND MATERIALS: Patients with non-small cell lung cancer who were treated with definitive concurrent chemoradiotherapy at our institution between August 2013 and May 2019 were included in this analysis. Clinical and treatment characteristics were tested for associations with progression-free survival (PFS) in Cox models. Interaction terms were added to the PFS Cox models to explore factors that may modulate the effects of adjuvant durvalumab. PFS and overall survival (OS) rates were estimated using the Kaplan-Meier method, and comparisons between patient subgroups were performed using log rank testing. RESULTS: A total of 105 patients met the eligibility criteria. Thirty-five patients (33%) received adjuvant durvalumab. Treatment with durvalumab was associated with significant improvement in PFS (1-year PFS: 67% vs 39%; log rank P = .006) and OS (1-year OS: 88% vs 76%; log rank P = .041). Exploratory analyses identified the neutrophil-to-lymphocyte ratio (NLR) after radiation therapy (RT) as a factor that may be associated with a benefit from durvalumab. For patients with post-RT NLR exceeding the cohort's median value of 4.3, receipt of adjuvant durvalumab was not associated with a significant PFS improvement (1-year PFS: 45% vs 36%; log rank P = .702). For patients with post-RT NLR <4.3, durvalumab receipt was associated with improved PFS (69% vs 41%; P = .009). High mean RT doses delivered to the heart and esophagus were associated with high post-RT NLR. CONCLUSIONS: We identified low NLR after chemoradiotherapy as a factor that may be associated with a benefit from adjuvant durvalumab. Validation studies are warranted.

Cardiac Irradiation Predicts Activity Decline in Patients Receiving Concurrent Chemoradiation for Locally Advanced Lung Cancer.

PURPOSE: Many patients with lung cancer are inactive due to their disease and underlying comorbidities, and activity levels can decline further during cancer therapy. Here we explore dosimetric predictors of activity decline in a cohort of patients who underwent continuous activity monitoring during definitive concurrent chemoradiotherapy (CRT) for locally advanced lung cancer. METHODS AND MATERIALS: We identified patients who participated in prospective clinical trials involving the use of a commercial fitness tracker throughout the course of CRT. For each patient, we applied linear regression to log-transformed daily step counts to compute the weekly rate of activity change from 1 week before radiation therapy (RT) initiation to 2 weeks after RT completion. Clinical and dosimetric factors were tested as predictors of activity change using linear regressions. RESULTS: Forty-six patient met the eligibility criteria. Median age was 66 years (range, 38-90). Pretreatment Eastern Cooperative Oncology Group performance status was 0, 1, and 2 for 17%, 70%, and 13%, respectively. Mean lung dose ranged from 5.0 to 23.5 Gy, mean esophagus dose from 1.1 to 39.6 Gy, and mean heart dose from 0.6 to 31.5 Gy. Median daily step count average was 5861 (interquartile range, 3540-8282) before RT and 3422 (interquartile range, 2364-5395) 2 weeks after RT completion. Rate of activity change was not significantly associated with age, performance status, or mean RT dose received by lungs or esophagus. In multivariate analysis, mean heart dose was significantly associated with rate of activity decline, with a 3.1% reduction in step count per week for every 10 Gy increase in mean heart dose (95% confidence interval: 0.5-5.7, P = .023). CONCLUSIONS: Extent of cardiac irradiation is associated with the rate of physical activity decline during CRT for lung cancer. Our novel finding contributes to the growing body of evidence that adverse effects of cardiac irradiation may be manifested at early time points.

Daily Step Counts: A New Prognostic Factor in Locally Advanced Non-Small Cell Lung Cancer?

PURPOSE: Here we explore the prognostic value of baseline step count data captured using wearable devices for patients treated with definitive chemoradiation therapy for locally advanced non-small cell lung cancer (NSCLC). METHODS AND MATERIALS: Patients with locally advanced NSCLC wore a commercial fitness tracker during a course of definitive, concurrent chemoradiation therapy as part of a clinical trial. Baseline step count average was defined as the average daily step total from study enrollment until completion of the first week of radiation therapy. Based on data from healthy individuals, study subjects were categorized as inactive (below the 25th percentile), moderately active (25th to 75th percentile), or highly active (above the 75th percentile). Fisher's exact test was used to examine activity level as a predictor of hospitalization during radiation therapy and of completing the planned radiation therapy course without delay exceeding 1 week. Median progression-free survival (PFS) and overall survival (OS) durations were estimated using the Kaplan-Meier method. Inactivity was tested as a predictor of PFS and OS using Cox proportional hazards models. RESULTS: Fifty subjects met eligibility criteria. Nine (18%) were categorized as highly active, 23 (46%) were moderately active, and 18 (36%) were inactive. Inactive subjects were more likely to be hospitalized during the radiation therapy course than other subjects (50% vs 9%, P = .004) and less likely to complete radiation therapy without delay exceeding 1 week (67% vs 97%, P = .006). Median PFS duration was 5.3 months for inactive subjects and 18.3 months for others (hazard ratio for inactivity = 5.10, P < .001). Median OS duration was 15.0 months for inactive subjects and not reached for others (hazard ratio = 3.91, P = .004). Performance status was not a significant predictor of PFS or OS. CONCLUSIONS: Baseline activity level measured using wearable devices may help identify patients with NSCLC who are fit for concurrent chemoradiation therapy and can predict clinical outcomes in this setting.

Pretreatment financial toxicity predicts progression-free survival following concurrent chemoradiotherapy for locally advanced non-small-cell lung cancer.

Aim: Financial toxicity (FT) describes patients' burden from out-of-pocket medical treatment costs. We studied associations between patient-reported pretreatment FT, socioeconomic status and clinical outcomes for locally advanced non-small-cell lung cancer (LA-NSCLC) patients. Methods: Patients received chemoradiotherapy for locally advanced non-small-cell lung cancer and completed the European Organization for the Research and Treatment of Cancer Core Quality of Life Questionnaire (EORTC QLQ-C30) quality of life assessment before treatment. One question asks whether patients experience 'financial difficulties'. We tested FT and socioeconomic status (SES) as predictors of progression-free survival (PFS) and overall survival (OS). Results: A total of 43 patients were included. Median follow-up for surviving patients was 15 months. A total of 19 patients (44%) experienced disease progression and 17 patients (40%) died. Increasing FT was associated with shorter PFS (p = 0.011). FT did not predict overall survival (p = 0.67). Conclusion: Higher pretreatment FT is associated with shorter PFS.

Comparing photon and proton-based hypofractioned SBRT for prostate cancer accounting for robustness and realistic treatment deliverability.

OBJECTIVE: To investigate whether photon or proton-based stereotactic body radiation therapy (SBRT is the preferred modality for high dose hypofractionation prostate cancer treatment. Achievable dose distributions were compared when uncertainties in target positioning and range uncertainties were appropriately accounted for. METHODS: 10 patients with prostate cancer previously treated at our institution (Montefiore Medical Center) with photon SBRT using volumetric modulated arc therapy (VMAT) were identified. MRI images fused to the treatment planning CT allowed for accurate target and organ at risk (OAR) delineation. The clinical target volume was defined as the prostate gland plus the proximal seminal vesicles. Critical OARs include the bladder wall, bowel, femoral heads, neurovascular bundle, penile bulb, rectal wall, urethra and urogenital diaphragm. Photon plan robustness was evaluated by simulating 2 mm isotropic setup variations. Comparative proton SBRT plans employing intensity modulated proton therapy (IMPT) were generated using robust optimization. Plan robustness was evaluated by simulating 2 mm setup variations and 3% or 1% Hounsfield unit (HU) calibration uncertainties. RESULTS: Comparable maximum OAR doses are achievable between photon and proton SBRT, however, robust optimization results in higher maximum doses for proton SBRT. Rectal maximum doses are significantly higher for Robust proton SBRT with 1% HU uncertainty compared to photon SBRT (p = 0.03), whereas maximum doses were comparable for bladder wall (p = 0.43), urethra (p = 0.82) and urogenital diaphragm (p = 0.50). Mean doses to bladder and rectal wall are lower for proton SBRT, but higher for neurovascular bundle, urethra and urogenital diaphragm due to increased lateral scatter. Similar target conformality is achieved, albeit with slightly larger treated volume ratios for proton SBRT, >1.4 compared to 1.2 for photon SBRT. CONCLUSION: Similar treatment plans can be generated with IMPT compared to VMAT in terms of target coverage, target conformality, and OAR sparing when range and HU uncertainties are neglected. However, when accounting for these uncertainties during robust optimization, VMAT outperforms IMPT in terms of achievable target conformity and OAR sparing. Advances in knowledge: Comparison between achievable dose distributions using modern, robust optimization of IMPT for high dose per fraction SBRT regimens for the prostate has not been previously investigated.

Evaluating which plan quality metrics are appropriate for use in lung SBRT.

OBJECTIVE: Several dose metrics in the categories-homogeneity, coverage, conformity and gradient have been proposed in literature for evaluating treatment plan quality. In this study, we applied these metrics to characterize and identify the plan quality metrics that would merit plan quality assessment in lung stereotactic body radiation therapy (SBRT) dose distributions. METHODS: Treatment plans of 90 lung SBRT patients, comprising 91 targets, treated in our institution were retrospectively reviewed. Dose calculations were performed using anisotropic analytical algorithm (AAA) with heterogeneity correction. A literature review on published plan quality metrics in the categories-coverage, homogeneity, conformity and gradient was performed. For each patient, using dose-volume histogram data, plan quality metric values were quantified and analysed. RESULTS: For the study, the radiation therapy oncology group (RTOG) defined plan quality metrics were: coverage (0.90 ± 0.08); homogeneity (1.27 ± 0.07); conformity (1.03 ± 0.07) and gradient (4.40 ± 0.80). Geometric conformity strongly correlated with conformity index (p < 0.0001). Gradient measures strongly correlated with target volume (p < 0.0001). The RTOG lung SBRT protocol advocated conformity guidelines for prescribed dose in all categories were met in ≥94% of cases. The proportion of total lung volume receiving doses of 20 Gy and 5 Gy (V20 and V5) were mean 4.8% (±3.2) and 16.4% (±9.2), respectively. CONCLUSION: Based on our study analyses, we recommend the following metrics as appropriate surrogates for establishing SBRT lung plan quality guidelines-coverage % (ICRU 62), conformity (CN or CIPaddick) and gradient (R50%). Furthermore, we strongly recommend that RTOG lung SBRT protocols adopt either CN or CIPadddick in place of prescription isodose to target volume ratio for conformity index evaluation. Advances in knowledge: Our study metrics are valuable tools for establishing lung SBRT plan quality guidelines.

Positron Emission Tomography-Adjusted Intensity Modulated Radiation Therapy for Locally Advanced Non-Small Cell Lung Cancer.

PURPOSE: To perform a prospective trial examining positron emission tomography (PET)-based, dose-painted intensity modulated radiation therapy (IMRT) in the setting of locally advanced non-small cell lung cancer (NSCLC). METHODS AND MATERIALS: Patients with stage IIB-III NSCLC were treated with 25 fractions of dose-painted IMRT. Tumors or lymph nodes with metabolic tumor volume exceeding 25 cm3 were deemed "high risk" and received 65 Gy. Smaller lesions were treated with 57 Gy or 52.5 Gy (after November 2014). Patients received concurrent weekly carboplatin (area under the curve = 2) and paclitaxel (45 mg/m2). The primary study endpoint was the absence of high residual metabolic activity (maximum standardized uptake value > 6) in treated lesions on PET 12 to 16 weeks after completion of IMRT. RESULTS: Thirty-five subjects with 116 hypermetabolic lesions were eligible for analysis. The primary endpoint was met for 24 of 30 patients (80%) who underwent posttreatment PET, satisfying our efficacy objective. With a median follow-up duration of 23.8 months for living patients, progression in a lesion targeted with radiation therapy has been observed in 5 patients (14%). Treating progression in other sites and death without progression as competing risks, 2-year cumulative incidence rates of local disease progression in high-risk lesions (n=24) and low-risk lesions (n=92) are 9% and 3%, respectively. The actuarial rate of overall survival at 2 years is 52%. CONCLUSIONS: Dose-painted IMRT based on pretreatment PET metrics with concurrent chemotherapy yields high rates of metabolic response and local disease control for locally advanced NSCLC. Future trials should test this approach to maximize the therapeutic ratio of thoracic radiation therapy.

Dosimetric Evaluation of a Flexible Dual Balloon-Constructed Applicator in Treating Anorectal Cancer.

BACKGROUND AND PURPOSE: To assess the dosimetric flexibility of a dual balloon brachytherapy applicator developed for the treatment of anorectal lesions. MATERIALS AND METHODS: Different amounts of water were infused into the inner and outer balloon separately to study the asymmetrical distribution of the catheter, the radial distance of the active source channel to the inner surface of the global target volume , the space between the active source channels, and their dosimetric impact to target tissues and uninvolved rectum. RESULTS: Increasing inner balloon volume directly increased both the space between the active source channels and the radial distance of the active source channel to the inner surface of the global target volume. The space between the active source channels and the percentage of global target volume received 150% or more of the prescribed dose to target had a strong inverse correlation (-0.881/P = .007, -0.976/P = .001, respectively) with the radial distance of the active source channel to the inner surface of the global target volume. Conformity index, dose to 2 cm3 of rectum, and total reference air kerma were strongly correlated with the radial distance of the active source channel to the inner surface of the global target volume, with values of 0.952 (P = .001), 0.833 (P = .015), and 0.922 (P = .002), respectively. Percentage of global target volume received 150% or more of the prescribed dose was significantly correlated with the space between the active source channels (0.81/P = .022), and conformity index was strongly inversely correlated with the space between the active source channels (-0.833/P = .015). CONCLUSION: The dual balloon-constructed Anorectal Applicator offers a flexible way to adjust the distances of the active source positions to the target in relation to uninvolved rectal wall. This flexibility simplifies planning which results in a highly conformal dose distribution to the target lesion while minimizing dose to normal rectal tissue.

Continuous Activity Monitoring During Concurrent Chemoradiotherapy.

PURPOSE: To perform a prospective trial testing the feasibility and utility of acquiring activity data as a measure of health status during concurrent chemoradiotherapy. METHODS AND MATERIALS: Ambulatory patients who were planned for treatment with concurrent chemoradiotherapy with curative intent for cancers of the head and neck, lung, or gastrointestinal tract were provided with activity monitors before treatment initiation. Patients were asked to wear the devices continuously throughout the radiation therapy course. Step count data were downloaded weekly during radiation therapy and 2 and 4 weeks after radiation therapy completion. The primary objective was to demonstrate feasibility, defined as collection of step counts for 80% of the days during study subjects' radiation therapy courses. Secondary objectives included establishing step count as a dynamic predictor of unplanned hospitalization risk. RESULTS: Thirty-eight enrolled patients were treated with concurrent chemoradiotherapy. Primary diagnoses included head and neck cancer (n=11), lung cancer (n=13), and a variety of gastrointestinal cancers (n=14). Step data were collected for 1524 of 1613 days (94%) during patients' radiation therapy courses. Fourteen patients were hospitalized during radiation therapy or within 4 weeks of radiation therapy completion. Cox regression modeling demonstrated a significant association between recent step counts (3-day average) and hospitalization risk, with a 38% reduction in the risk of hospitalization for every 1000 steps taken each day (hazard ratio 0.62, 95% confidence interval 0.46-0.83, P=.002). Inferior quality of life scores and impaired performance status were not associated with increased hospitalization risk. CONCLUSION: Continuous activity monitoring during concurrent chemoradiotherapy is feasible and well-tolerated. Step counts may serve as powerful, objective, and dynamic indicators of hospitalization risk.

18F-Fluorodeoxyglucose/Positron Emission Tomography Predicts Patterns of Failure After Definitive Chemoradiation Therapy for Locally Advanced Non-Small Cell Lung Cancer.

BACKGROUND: We previously reported that pretreatment positron emission tomography (PET) identifies lesions at high risk for progression after concurrent chemoradiation therapy (CRT) for locally advanced non-small cell lung cancer (NSCLC). Here we validate those findings and generate tumor control probability (TCP) models. METHODS: We identified patients treated with definitive, concurrent CRT for locally advanced NSCLC who underwent staging 18F-fluorodeoxyglucose/PET/computed tomography. Visible hypermetabolic lesions (primary tumors and lymph nodes) were delineated on each patient's pretreatment PET scan. Posttreatment imaging was reviewed to identify locations of disease progression. Competing risks analyses were performed to examine metabolic tumor volume (MTV) and radiation therapy dose as predictors of local disease progression. TCP modeling was performed to describe the likelihood of local disease control as a function of lesion size. RESULTS: Eighty-nine patients with 259 hypermetabolic lesions (83 primary tumors and 176 regional lymph nodes) met the inclusion criteria. Twenty-eight patients were included in our previous report, and the remaining 61 constituted our validation cohort. The median follow-up time was 22.7 months for living patients. In 20 patients, the first site of progression was a primary tumor or lymph node treated with radiation therapy. The median time to progression for those patients was 11.5 months. Data from our validation cohort confirmed that lesion MTV predicts local progression, with a 30-month cumulative incidence rate of 23% for lesions above 25 cc compared with 4% for lesions below 25 cc (P=.008). We found no evidence that radiation therapy dose was associated with local progression risk. TCP modeling yielded predicted 30-month local control rates of 98% for a 1-cc lesion, 94% for a 10-cc lesion, and 74% for a 50-cc lesion. CONCLUSION: Pretreatment FDG-PET identifies lesions at risk for progression after CRT for locally advanced NSCLC. Strategies to improve local control should be tested on high-risk lesions, and treatment deintensification for low-risk lesions should be explored.

Model assessment of individual tumor control rate and adverse effects in comparing locally advanced cervical cancer treatment using intracavitary with and without interstitial brachytherapy.

PURPOSE: This study assessed the modeled probability of tumor control and organ at risk toxicities in locally advanced cervical cancer in patients treated by external beam radiation plus brachytherapy using intracavitary combined with interstitial brachytherapy (IC/IS) vs. intracavitary brachytherapy (IC) alone. MATERIAL AND METHODS: Twenty cervical cancer patients with a mean HR-CTV volume of 47.4 cm3 and a mean width of 54 mm were planned with both IC/IS and IC brachytherapy alone. A probit model was utilized to model 3-year (3-yr) local control rate (LC), 3-yr cancer specific survival rate (CSS), and the adverse effect (AE) of the organ at risk by using a modeled data set from multiple institutions. Modeling results were used to estimate the LC, CSS, and AE of the treatments in this study. RESULTS: Using the IC/IS technique, an EQD2 increase of 12.3 Gy to D90 (from 76.1 Gy to 88.3 Gy) of HR-CTV is expected to increase 3-yr LC and 3-yr CSS by 12.5%, and 11.0%, respectively. Comparing IC/IS to IC alone, the expected G2+ AE were 7.7% vs. 7.9% for the bladder, and 5.9% vs. 6.8% for the rectum. CONCLUSIONS: The IC/IS technique improved dose coverage to the HR-CTV without significantly increasing dose to 2 cm3 of the organ at risk (OAR) surrounding it. With different regimens of EBRT combined with BT, IC/IS can be used to increase the probability of LC and CSS, or decrease the risk of AE.

An efficient Volumetric Arc Therapy treatment planning approach for hippocampal-avoidance whole-brain radiation therapy (HA-WBRT).

An efficient and simple class solution is proposed for hippocampal-avoidance whole-brain radiation therapy (HA-WBRT) planning using the Volumetric Arc Therapy (VMAT) delivery technique following the NRG Oncology protocol NRG-CC001 treatment planning guidelines. The whole-brain planning target volume (PTV) was subdivided into subplanning volumes that lie in plane and out of plane with the hippocampal-avoidance volume. To further improve VMAT treatment plans, a partial-field dual-arc technique was developed. Both the arcs were allowed to overlap on the in-plane subtarget volume, and in addition, one arc covered the superior out-of-plane sub-PTV, while the other covered the inferior out-of-plane subtarget volume. For all plans (n = 20), the NRG-CC001 protocol dose-volume criteria were met. Mean values of volumes for the hippocampus and the hippocampal-avoidance volume were 4.1 cm(3) ± 1.0 cm(3) and 28.52 cm(3) ± 3.22 cm(3), respectively. For the PTV, the average values of D(2%) and D(98%) were 36.1 Gy ± 0.8 Gy and 26.2 Gy ± 0.6 Gy, respectively. The hippocampus D(100%) mean value was 8.5 Gy ± 0.2 Gy and the maximum dose was 15.7 Gy ± 0.3 Gy. The corresponding plan quality indices were 0.30 ± 0.01 (homogeneity index), 0.94 ± 0.01 (target conformality), and 0.75 ± 0.02 (confirmation number). The median total monitor unit (MU) per fraction was 806 MU (interquartile range [IQR]: 792 to 818 MU) and the average beam total delivery time was 121.2 seconds (IQR: 120.6 to 121.35 seconds). All plans passed the gamma evaluation using the 5-mm, 4% criteria, with γ > 1 of not more than 9.1% data points for all fields. An efficient and simple planning class solution for HA-WBRT using VMAT has been developed that allows all protocol constraints of NRG-CC001 to be met.

Pre-treatment FDG-PET predicts the site of in-field progression following concurrent chemoradiotherapy for stage III non-small cell lung cancer.

PURPOSE: Locoregional progression following definitive chemoradiotherapy (CRT) for locally advanced non-small cell lung cancer (NSCLC) is common. In this study, we explore the utility of pre-treatment PET for predicting sites of disease progression following CRT. METHODS: We identified patients treated at our institution with definitive, concurrent CRT for stage III NSCLC in the years 2007-2010 who underwent staging FDG-PET/CT. Using a semiautomatic gradient-based tool, visible thoracic hypermetabolic lesions were contoured on each patient's pre-treatment PET. Post-treatment imaging was reviewed to identify specific locations of disease progression. Patients' maximum SUV (SUVmax_pat) and metabolic tumor volume (MTV_pat) were evaluated as predictors of clinical outcomes using logrank testing. Competing risks analysis was performed to examine the relationship between lesion (tumor or lymph node) MTV (MTV_les) and the risk of local disease progression. Patient death and progression in other sites were treated as competing risks. RESULTS: 28 patients with 82 hypermetabolic lesions (27 pulmonary tumors, 55 lymph nodes) met inclusion criteria. Median follow-up was 39.0 months for living patients. Median progression-free survival (PFS) was 12.4 months, and median overall survival (OS) was 31.8 months. Low MTV_pat was associated with improved PFS (median 14.3 months for MTV<60 cc vs. 9.7 months for MTV>60 cc, p=0.039). MTV_les was strongly associated with the risk of local disease progression. The 2-year cumulative incidence rate (CIR) for progression in lesions larger than 25 cc was 45%, compared to 5% for lesions under 25 cc (p<0.001). CONCLUSION: Pre-treatment PET can be used to identify specific lesions at high risk for treatment failure following definitive CRT for locally advanced NSCLC. Selective treatment intensification to high-risk lesions should be studied as a strategy to improve clinical outcomes in this patient population.

Day to day treatment variations of accelerated partial breast brachytherapy using a multi-lumen balloon.

PURPOSE: To evaluate the variations of multi-lumen balloon (MLB)-based brachytherapy from simulation day to treatment day and their dosimetric impacts during accelerated partial breast irradiation (APBI). MATERIAL AND METHODS: A total of 42 CT images scanned from seven patients were evaluated with regards to daily variation due to of: 1) internal uncertainty: size and shape of balloon, seroma volume; 2) geometrical uncertainty-random: length of each catheter was measured for each fraction (total 70); 3) geometrical uncertainty-systematic: virtual systematic errors were tested by offsetting dwell positions. The original plans (as group A) had a mean value of 96.8% on V95 of the PTV_Eval. Plans were rerun (as group B) such that the mean value of the V95 was relaxed to 90.4%. By applying the reference plan to each daily CT image, variations of target coverage under different sources of error were evaluated. RESULTS: Shape and size of the balloon had means of < 1 mm decreased in diameter and < 0.4 cm(3) decreased in volume; the mean seroma volume increased by 0.2 cm(3). This internal variation has a mean of < 1% difference for both V90 and V95. The geometrical uncertainty made a mean deviation of 2.7 mm per root of sum of square. It caused the degradations of V90 and V95 by mean values of 1.0% and 1.2%, respectively. A systematic error of 3 mm and 4 mm would degrade both of V90 and V95 by 4% and 6%, respectively. The degradations on target coverage of the plans in group A were statistically the same as those in group B. CONCLUSIONS: Overall, APBI treatments with MLB based brachytherapy are precise from day to day. However, minor variation due to daily treatment uncertainties can still degrade tumor bed coverage to an unacceptable coverage when V95 of the original plan is close to 90%.

Prostate-specific antigen bounce predicts for a favorable prognosis following brachytherapy: a meta-analysis.

PURPOSE: Controversy exists whether the prostate-specific antigen (PSA) bounce phenomenon following definitive radiation for prostate cancer has prognostic significance. Here, we perform a meta-analysis to determine the association between PSA bounce and biochemical control after brachytherapy alone. MATERIAL AND METHODS: We reviewed Medline, EMBASE, and CENTRAL citations through February 2012. Studies that recorded biochemical failure rates in bouncers and non-bouncers were included. Hazard ratios describing the impact of bounce on biochemical failure were extracted directly from the studies or calculated from survival curves. Pooled estimates were obtained using the inverse variance method. A random effects model was used in cases of significant effect heterogeneity (p < 0.10 using Q test). RESULTS: The final analysis included 3011 patients over 6 studies treated with brachytherapy. Meta-analysis revealed that patients experiencing PSA bounce after brachytherapy, conferred a decreased risk of biochemical failure (random effects model HR = 0.42, 95% CI: 0.30-0.59; p < 0.001). CONCLUSIONS: Our meta-analysis determined that PSA bounce predicts for improved biochemical control following brachytherapy. To our knowledge, this is the first study describing this effect.