Cardiac stereotactic radiation therapy for refractory ventricular arrhythmias in patients with left ventricular assist devices.

Left ventricular assist device (LVAD) implantation is an established treatment for patients with advanced heart failure refractory to medical therapy. However, the incidence of ventricular arrhythmias (VAs) is high in this population, both in the acute and delayed phases after implantation. About one-third of patients implanted with an LVAD will experience sustained VAs, predisposing these patients to worse outcomes and complicating patient management. The combination of pre-existing myocardial substrate and complex electrical remodeling after LVAD implantation account for the high incidence of VAs observed in this population. LVAD patients presenting VAs refractory to antiarrhythmic therapy and catheter ablation procedures are not rare. In such patients, treatment options are extremely limited. Stereotactic body radiation therapy (SBRT) is a technique that delivers precise and high doses of radiation to highly defined targets, reducing exposure to adjacent normal tissue. Cardiac SBRT has recently emerged as a promising alternative with a growing number of case series reporting the effectiveness of the technique in reducing the VA burden in patients with arrhythmias refractory to conventional therapies. The safety profile of cardiac SBRT also appears favorable, even though the current clinical experience remains limited. The use of cardiac SBRT for the treatment of refractory VAs in patients implanted with an LVAD are even more scarce. This review summarizes the clinical experience of cardiac SBRT in LVAD patients and describes technical considerations related to the implementation of the SBRT procedure in the presence of an LVAD.

A phase I study of the combination of atezolizumab, tiragolumab, and stereotactic body radiation therapy in patients with metastatic multiorgan cancer.

BACKGROUND: Immunotherapy targeting the PD-1/PD-L1 pathway is a standard of care in a number of metastatic malignancies, but less than a fifth of patients are expected to respond to ICIs (Immune Checkpoint Inhibitors). In a clinical trial, combining the anti-TIGIT (T cell immunoreceptor with Ig and ITIM domains) Mab (monoclonal antibody) tiragolumab with atezolizumab improved outcomes in non-small cell lung cancer. In preclinical models, SBRT (Stereotactic Body Radiation Therapy) could increase expression levels of the inhibitory co-receptors TIGIT and PD-L1. We aim to assess the combination of tiragolumab with atezolizumab and SBRT in metastatic, previously treated by ICIs, non-small cell lung cancer, head and neck cancer, bladder cancer, and renal cell cancer. METHODS: This phase I study (ClinicalTrials.gov NCT05259319) will assess the efficacy and safety of the combination of atezolizumab with tiragolumab and stereotactic body radiation therapy in patients with histologically proven metastatic non-small cell lung cancer, renal cell cancer, bladder cancer, and head and neck cancer previously treated. First part: 2 different schedules of SBRT in association with a fixed dose of atezolizumab and tiragolumab will be investigated only with metastatic non-small cell lung cancer patients (cohort 1). The expansion cohorts phase will be a multicentric, open-label study at the recommended scheme of administration and enroll additional patients with metastatic bladder cancer, renal cell cancer, and head and neck cancer (cohort 2, 3 and 4). Patients will be treated until disease progression, unacceptable toxicity, intercurrent conditions that preclude continuation of treatment, or patient refusal in the absence of progression or intolerance. The primary endpoint of the first phase is the safety of the combination in a sequential or concomitant scheme and to determine the expansion cohorts phase recommended scheme of administration. The primary endpoint of phase II is to evaluate the efficacy of tiragolumab + atezolizumab + SBRT in terms of 6-month PFS (Progression-Free Survival). Ancillary analyses will be performed with peripheral and intratumoral immune biomarker assessments. TRIAL REGISTRATION: This study is registered on ClinicalTrials.gov: NCT05259319, since February 28th, 2022.

Predictive value of health-related quality of life on radiotherapy-related toxicities in patients with head and neck cancer.

PURPOSE: Little is known about whether baseline health-related quality of life (HRQoL) scores also could predict occurrence radiotherapy-related toxicities, which we aim to assess in this study. METHODS: This study analyzed data from 200 patients enrolled in randomized study investigating the utility of HRQoL. HRQOL was assessed at baseline and during follow up using QLQ-C30 questionnaire and major toxicity was considered as adverse event ≥ 3 according to NCI-CTCAE classification. Cox regressions adjusting for clinical and sociodemographic data were used to assess prognostic significance of HRQOL scores. RESULTS: In multivariable analyses adjusted on clinical and sociodemographic data, every 10-point improvement in physical (HR = 0.74), role (HR = 0.87) and social (HR = 0.88) functioning was associated with 24%, 13% and 12% lower hazard of occurrence of major toxicity respectively while every 10 point-increase in dyspnea (HR = and loss appetite was associated with 15% and 16% increased hazard of major toxicity. CONCLUSION: Certain baseline HRQoL scores were found to be significantly associated with the occurrence of major toxicity.

Salvage extended field or involved field nodal irradiation in 18F-fluorocholine PET/CT oligorecurrent nodal failures from prostate cancer.

PURPOSE: The concept of metastasis-directed therapy for nodal oligorecurrences with stereotactic body radiotherapy is increasingly accepted. Hence, the comparison between salvage extended field radiotherapy (s-EFRT) and salvage involved field radiotherapy (s-IFRT) in patients with 18F-fluorocholine (FCH) PET/CT+ nodal oligorecurrences from prostate cancer is worthy of investigation. METHODS: Patients with oligorecurrent nodes on FCH PET/CT treated with salvage radiotherapy between 2009 and 2017 in a single tertiary cancer centre were selected for this study. Patients treated with s-IFRT were compared with those treated with s-EFRT. Toxicities and times to failure (TTF) were compared between the two groups. RESULTS: The study included 62 patients with positive lymph nodes only who underwent FCH PET/CT for a rising PSA level after radical prostatectomy or radiotherapy. Of these patients, 35 had s-IFRT and 27 had s-EFRT. After a median follow-up of 41.8 months (range 5.9-108.1 months), no differences were observed in acute or late gastrointestinal and genitourinary toxicities of grade 2 or more between the two groups. The 3-year failure rates were 55.3% (95% CI 37.0-70.3%) in the s-IFRT group and 88.3% (95% CI 66.9-96.1%) in the s-EFRT group (p = 0.0094). In multivariate analysis of TTF, an interval of >5 years was significantly correlated with better outcomes (HR = 0.33, 95% CI 0.13-0.86, p = 0.023). There was a strong trend toward better outcomes with s-EFRT even after adjusting for concomitant androgen-deprivation therapy (HR = 0.38, 95% CI 0.12-1.27, p = 0.116). CONCLUSION: FCH PET-positive node-targeted s-EFRT is feasible with low rates of toxicity and longer TTF, suggesting that oligorecurrent nodal disease diagnosed on FCH PET is unlikely.

A Phase 2 Randomized Open-label Study of Oral Darolutamide Monotherapy Versus Androgen Deprivation Therapy in Men with Hormone-sensitive Prostate Cancer (EORTC-GUCG 1532).

BACKGROUND AND OBJECTIVE: Darolutamide is an androgen receptor inhibitor that increases overall survival in combination with androgen deprivation therapy (ADT) in patients with metastatic hormone-sensitive and nonmetastatic castration-resistant prostate cancer (PCa). This phase 2 study assessed the efficacy and safety of darolutamide as monotherapy without ADT in patients with eugonadal testosterone levels. METHODS: This was a 24-wk, open-label, randomized study of patients with hormone-sensitive, histologically confirmed PCa requiring gonadotropin-releasing hormone (GnRH); an Eastern Cooperative Oncology Group performance status score of 0/1; and life expectancy >1 yr. All patients received darolutamide 600 mg bid or a commercially available GnRH analog. The primary endpoint is a prostate-specific antigen (PSA) response, defined as a ≥80% decline at week 24 relative to baseline in the darolutamide study arm. The GnRH arm is used as an internal control. The secondary endpoints included changes in T levels, safety/tolerability, and quality of life. KEY FINDINGS AND LIMITATIONS: Among 61 men enrolled, the median (range) age was 72 yr (53-86 yr); 42.6% of them had metastases. In the darolutamide arm, the evaluable population with available PSA values at baseline and week 24 consisted of 23 patients. Twenty-three (100%) evaluable darolutamide patients achieved a PSA decline of >80% at week 24 (primary endpoint), with a median (range) decrease of -99.1% (-91.9%, -100%). Serum T levels increased by a median (range) of 44.3 (5.7-144.0) at week 24, compared with baseline. In the darolutamide arm, 48.4% of men reported drug-related adverse events (AEs; mostly grade 1 or 2). The most frequent treatment-emergent AEs included gynecomastia (35.5%), fatigue (12.9%), hot flush (12.9%), and hypertension (12.9%). Health-related quality of life measures are descriptive, and GnRH arm results will be presented as an internal reference. CONCLUSIONS AND CLINICAL IMPLICATIONS: Darolutamide monotherapy was associated with a significant PSA response in nearly all men with hormone-naïve PCa. Testosterone-level changes and most common AEs (gynecomastia, fatigue, hypertension, and hot flush) were consistent with potent androgen receptor inhibition. PATIENT SUMMARY: In this study, we report the first use of darolutamide, a novel antiandrogen, as monotherapy without androgen deprivation therapy (ADT). The study shows that darolutamide induce a profound suppression of prostate-specific antigen in all patients, with a safety profile different from that of ADT.

Salvage Involved-Field and Extended-Field Radiation Therapy in Positron Emission Tomography-Positive Nodal Recurrent Prostate Cancer: Outcomes and Patterns of Failure.

Purpose: The optimal salvage pelvic treatment for nodal recurrences in prostate cancer is not yet clearly defined. We aimed to compare outcomes of salvage involved-field radiation therapy (s-IFRT) and salvage extended-field radiation therapy (s-EFRT) for positron emission tomography/computed tomography-positive nodal-recurrent prostate cancer and to analyze patterns of progressions after salvage nodal radiation therapy. Methods and Materials: Patients with 18F-fluorocholine or 68Ga prostate-specific membrane antigen ligand positron emission tomography/computed tomography-positive nodal-recurrent prostate cancer and treated with s-IFRT or s-EFRT were retrospectively selected. Time to biochemical failure, time to palliative androgen deprivation therapy (ADT), and distant metastasis-free survival were analyzed. Results: Between 2009 and 2019, 86 patients were treated with salvage nodal radiation therapy: 38 with s-IFRT and 48 with s-EFRT. After a median follow-up of 41.9 months (5.4-122.1 months), 47 patients presented a further relapse: 31 after s-IFRT and 16 after s-EFRT, with only 1 in-field relapse. The median time to palliative ADT was 24.8 months (95% confidence interval [CI], 13.3-93.5 months) in the s-IFRT group and not yet reached (95% CI, 40.3 months to not yet reached) in the s-EFRT group (P = .010). The 3-year biochemical failure-free rate was 70.2% (95% CI, 51.5%-82.9%) with s-IFRT and 73.9% (95% CI, 55.4%-85.7%) with s-EFRT (P = .657). The 3-year distant metastasis-free survival was 74.1% (95% CI, 56.0%-85.7%) with s-IFRT and 82.0% (95% CI, 63.0%-91.8%) with s-EFRT (P = .338). Conclusions: s-EFRT and s-IFRT for positron emission tomography-positive nodal-recurrent prostate cancer provide excellent local control. Time to palliative ADT was longer following s-EFRT than following s-IFRT.

Elevated Baseline Neutrophil Count Correlates with Worse Outcomes in Patients with Muscle-Invasive Bladder Cancer Treated with Chemoradiation.

BACKGROUND: The role of inflammation in the development and prognosis of bladder cancer (BC) is now established. We evaluated the significance of neutrophil-to-lymphocyte ratio (NLR) and neutrophil count (PNN) in patients with localized BC treated with chemoradiation. METHODS: Clinical characteristics and baseline biological data were retrospectively collected. We tested the association between NLR, PNN, and overall survival (OS) and progression-free survival (PFS). RESULTS: One hundred and ninety-four patients were included. Median PNN was 4000.0/mm3 [1500.0-16,858.0] and median NLR was 2.6 [0.6-19.2]. In patients with NLR > 2.6, median OS and PFS were lower (OS: 25.5 vs. 58.4 months, p = 0.02; PFS: 14.1 vs. 26.7 months, p = 0.07). Patients with PNN > 4000/mm3 had significantly lower OS (21.8 vs. 70.1 months, p < 0.001) and PFS (13.7 vs. 38.8 months, p < 0.001). Contrary to NLR, PNN > 4000/mm3 was associated with shorter OS and PFS in multivariate analysis. CONCLUSIONS: Elevated PNN at baseline was associated with worse OS and PFS. NLR was not an independent prognostic factor.

Outcomes following brachytherapy boost for intermediate- and high-risk prostate cancer: A retrospective bicenter study by the SFRO brachytherapy group.

INTRODUCTION: Radiotherapy dose escalation improves biochemical control in intermediate- or high-risk prostate cancer. Brachytherapy boost was shown to further improve biochemical control compared to radiotherapy alone in three randomized trials. The SFRO brachytherapy group sought to evaluate the efficacy and toxicity of BT-boost for intermediate and high-risk prostate cancer in real life, and to determine prognostic factors for efficacy and toxicity. MATERIAL AND METHOD: A retrospective study was conducted, including all patients with intermediate- or high-risk prostate cancer treated with a combination of external beam radiotherapy (EBRT) and high dose-rate brachytherapy boost (HDR-BB), from 2006 until December 2019 at two centers. Patient characteristics, initial disease, treatment and follow-up were collected. RESULTS: 709 patients from two centers were analyzed given a short follow-up in the other centers. Out of those, 277 were intermediate risk (170 favorable and 107 unfavorable) and 432 were high risk. The median EBRT and HDR-BB doses were 46 Gy (35-50) and 14 Gy (10-20). After a median follow-up of 62 months, biochemical control at 5 years was 87.5 % for the overall population, 91 % and 85 % for intermediate- and high-risk cancers, respectively. At 5 years, biochemical and clinical relapse-free survival, metastasis-free survival and local control rates were 83 %, 90 % and 97 % respectively. 5-years overall survival was 94 %. Late grade 2 or higher GU or GI toxicity was found in 36 patients (5 %) and 9 patients (1.3 %). CONCLUSION: This bicenter analysis shows the efficacy and tolerability of HDR-BB as a complement to external radiotherapy. Further improvements such as combination with new hormonal agents or new brachytherapy-radiotherapy fractionation regimens are warranted to improve further the outcomes and therapeutic ratio.

The Safety and Efficacy of Salvage Stereotactic Radiation Therapy in Patients with Intraprostatic Tumor Recurrence After Previous External Radiation Therapy: Phase 1 Results from the GETUG-AFU 31 Study.

BACKGROUND: There is no consensus on the best local salvage treatment for prostate cancer recurrence after primary external beam radiotherapy. Prospective data on stereotactic body radiation therapy (SBRT) are very scarce. OBJECTIVE: To determine the optimal dose regimen for salvage SBRT. DESIGN, SETTING, AND PARTICIPANTS: The present report concerns the phase 1 part of the GETUG-AFU 31 multicenter open-label study. The main inclusion criteria were histologically proven biochemical recurrence, clinical stage T1-T2 upon relapse, multiparametric magnetic resonance imaging data, prostate-specific antigen (PSA) level ≤10 ng/ml prior to salvage SBRT, PSA doubling time >10 mo, and an International Prostate Symptom Score of ≤12. INTERVENTION: Five or six fractions of 6 Gy were delivered using focal SBRT. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Dose-limiting toxicity (DLT) was defined as grade ≥3 gastrointestinal or genitourinary tract toxicity, or any grade 4 toxicity (according to the National Cancer Institute Common Terminology Criteria for Adverse Events version 4.03) occurring in the first 18 wk following treatment initiation. A time-to-event continual reassessment method was used to select the dose regimen. RESULTS AND LIMITATIONS: Twenty-one patients were treated (median [interquartile range] age: 76.8 yr [72.2-80.8]), including 12 at 6 × 6 dose level. No DLT was observed. The acute grade 2 genitourinary tract toxicity rate was 19%. With a median follow-up of 12.3 mo, the estimated cumulative incidence of late grade 2 genitourinary toxicity was 41.2% (95% confidence interval: 18.1-63.1%). No grade >2 genitourinary toxicity and no grade ≥2 gastrointestinal toxicity were reported. All treated patients were alive and relapse free at the last follow-up. CONCLUSIONS: A 6 × 6 Gy dose regimen was selected for our phase 2 study of salvage SBRT. With a short follow-up period, the level of toxicity appears to be acceptable. PATIENT SUMMARY: There is no consensus on the best local treatment for patients with local relapse after radiotherapy for prostate cancer. Prospective data are very scarce. Our early phase trial allowed us to recommend six fractions of 6 Gy using high-precision radiotherapy for further studies.

Randomized phase II trial in prostate cancer with hormone-sensitive OligometaSTatic relapse: Combining stereotactic ablative radiotherapy and durvalumab (POSTCARD GETUG P13): Study protocol.

Background: As in other solid tumors, increasing evidence indicates that patients diagnosed with a limited number of prostate cancer metastases, so-called oligometastases, have a better prognosis than patients with extensive metastatic disease. Stereotactic body radiotherapy (SBRT) is now considered an option in this population.Programmed death-1 (PD-1) and its ligands (PD-L1) are targeted by immune checkpoint inhibitors. Preclinical studies have shown that the tumor immune microenvironment changes when combining radiotherapy with immunotherapy, especially with hypofractionated radiotherapy.The oligometastatic setting appears to be the most relevant clinical situation for evaluating the immune response generated by radiotherapy and immune checkpoint inhibitors in patients with an intact immune system.We hypothesize that durvalumab will enhance the immune response following SBRT targeting oligometastatic lesions. Our purpose is to demonstrate, via a randomized 2:1 phase II trial, that SBRT (3 fractions) with durvalumab in oligometastatic hormone-sensitive prostate cancer patients would improve progression-free survival in patients with prostate cancer with up to 5 metastases compared to patients who exclusively received SBRT. Methods: This is a multicentric randomized phase II study in French academic hospitals. Patients with prostate cancer and up to 5 metastases (lymph node and/or bone) were randomized into a 2:1 ratio between Arm A (experimental group), corresponding to durvalumab and SBRT to the metastases, and Arm B (control group), corresponding to SBRT alone to the metastases. The study aims to accrue a total of 96 patients within 3 years. The primary endpoint is two-year progression-free survival and secondary endpoints include androgen deprivation therapy-free survival, quality of life, toxicity, prostate cancer specific survival, overall survival, and immune response. Discussion: The expected benefit for the patients in the experimental arm is longer life expectancy with acceptable toxicity. We also expect our study to provide data for better understanding the synergy between immunotherapy and radiotherapy in oligometastatic prostate cancer.

Clinical adoption patterns of 0.35 Tesla MR-guided radiation therapy in Europe and Asia.

BACKGROUND: Magnetic resonance-guided radiotherapy (MRgRT) utilization is rapidly expanding, driven by advanced capabilities including better soft tissue imaging, continuous intrafraction target visualization, automatic triggered beam delivery, and the availability of on-table adaptive replanning. Our objective was to describe patterns of 0.35 Tesla (T)-MRgRT utilization in Europe and Asia among early adopters of this novel technology. METHODS: Anonymized administrative data from all 0.35T-MRgRT treatment systems in Europe and Asia were extracted for patients who completed treatment from 2015 to 2020. Detailed treatment information was analyzed for all MR-linear accelerators (linac) and -cobalt systems. RESULTS: From 2015 through the end of 2020, there were 5796 completed treatment courses delivered in 46,389 individual fractions. 23.5% of fractions were adapted. Ultra-hypofractionated (UHfx) dose schedules (1-5 fractions) were delivered for 63.5% of courses, with 57.8% of UHfx fractions adapted on-table. The most commonly treated tumor types were prostate (23.5%), liver (14.5%), lung (12.3%), pancreas (11.2%), and breast (8.0%), with increasing compound annual growth rates (CAGRs) in numbers of courses from 2015 through 2020 (pancreas: 157.1%; prostate: 120.9%; lung: 136.0%; liver: 134.2%). CONCLUSIONS: This is the first comprehensive study reporting patterns of utilization among early adopters of a 0.35T-MRgRT system in Europe and Asia. Intrafraction MR image-guidance, advanced motion management, and increasing adoption of on-table adaptive RT have accelerated a transition to UHfx regimens. MRgRT has been predominantly used to treat tumors in the upper abdomen, pelvis and lungs, and increasingly with adaptive replanning, which is a radical departure from legacy radiotherapy practices.

Randomized Trial Assessing the Impact of Routine Assessment of Health-Related Quality of Life in Patients with Head and Neck Cancer.

The impact of routine assessment of health-related quality of life (HRQoL) on satisfaction with care and the HRQoL of patients with head and neck cancer (HNC) treated with radiotherapy was assessed. Patients with HNC were randomly assigned to two arms, with stratification on sex, cancer localization, and stage of the disease. In the intervention arm, the patients completed the EORTC QLQ-C30 and EORTC QLQ-H&N35 questionnaires first before randomization, then before each medical appointment during radiotherapy (7 weeks), and then every 3 months until 1 year and at 2 years thereafter. In the control arm, the EORTC QLQ-C30 and EORTC QLQ-H&N35 questionnaires were completed before randomization and at 1 year and 2 years thereafter. The primary endpoint was mean change in HRQoL at score at 2 years from baseline assessed by EQ VAS from the EuroQol questionnaire. The secondary endpoint was mean change in satisfaction with care at 2 years from baseline assessed by QLQ-SAT32. Two hundred patients with head and neck cancers were involved in this study (mean age, 58.83 years (range, 36.56-87.89)), of whom 100 were assigned to the intervention arm and 100 to the control arm. Patients in the intervention arm were reported to have a statistically significant increase in EQ VAS at 2 years (p < 0.0001) and exceeded the minimal clinically important difference (mean change at 2 years from baseline = 10.46). In the two arms, mean differences between arms were not statistically significant, but minimal clinically important differences in favor of the intervention arm were found for EQ VAS (mean change difference (MD) = 5.84), satisfaction with care, in particular waiting times (MD = 10.85) and satisfaction with accessibility (MD = 6.52). Routine assessment of HRQoL improves HRQoL and satisfaction with care for patients with HNC treated with radiotherapy.

Patterns of Bone Failure in Localized Prostate Cancer Previously Irradiated: The Preventive Role of External Radiotherapy on Pelvic Bone Metastases.

Introduction: External beam radiation therapy (EBRT) can cure localized prostate cancer (PCa) by sterilizing cancer cells in the prostate gland and surrounding tissues at risk of microscopic dissemination. We hypothesized that pelvic EBRT for localized PCa might have an unexpected prophylactic impact on the occurrence of pelvic bone metastases. Material and Methods: We reviewed the data of 332 metastatic PCa patients. We examined associations between the number (≤5 vs. >5) and the location of bone metastases (in-field vs. out-of-field), which occurred at first relapse, and a previous history of EBRT for PCa (EBRT vs. No-EBRT). Results: One hundred and ten patients M0 at baseline were eligible. Fifty-six patients (51%) were in the No-EBRT group, and 54 patients (49%) in the EBRT group. The proportion of patients who developed >5 bone metastases in the bony pelvis was higher in the No-EBRT group vs. the EBRT group: 10 patients (18%) vs. 2 patients (4%), respectively (p = 0.02). By multivariate analysis EBRT was associated with a lesser occurrence of patients who had >5 bone metastases in the bony pelvis (OR = 0.17 [95%CI, 0.04-0.87], p = 0.03). Time to occurrence of bone metastases ≥5 years (OR = 0.10 [95%CI, 0.05-0.19], p < 0.01), prior curative prostate treatment (OR = 0.58 [95%CI, 0.36-0.91], p = 0.02), >5 bone metastases in bony pelvis (OR = 2.61 [95%CI, 1.28-5.31], p < 0.01), >5 bone metastases out of bony pelvis (OR = 1.73 [95%CI, 1.09-2.76], p = 0.02) were all predictive of overall survival. Conclusion: Previous pelvic EBRT for PCa is associated with a lower number of pelvic bone metastases, which is associated with better overall survival.

Impact of rectal distension on prostate CBCT-based positioning assessed with 6 degrees-of-freedom couch.

INTRODUCTION: Prostate requires a daily correction of its 3-dimensional position in relation with rectal distension. In this study, we sought to determine whether rectal distension with respect to the rectal behavior might have an impact on prostate translations and/or rotations during prostate image guided radiation therapy using a 6 degrees-of-freedom (DOF) couch. METHODS AND MATERIALS: We reviewed the data from 39 patients with localized prostate cancer treated with protracted external radiation therapy using a 6 DOF couch. Before each fraction, a kilovoltage cone beam computed tomography (kV-CBCT) scan was performed. The automatic fusion algorithm was set to fuse on soft tissue and allowed correction for translations in 3 dimensions and rotations in the longitudinal axis ("roll") and lateral axis ("pitch"). After contouring the rectum on each kV-CBCT, we determined the cross-sectional area (CSA) and relative CSA (CSArel) by dividing with the CSA of planning CT. The standard deviation of CSArel per patient was used to classify the patients in 2 groups: patients with a stable rectum and patients with an unstable rectum. The CSArel was compared between these 2 groups with a linear mixed model with group as fixed effect and patient as random effect. RESULTS: A total of 616 kV-CBCT were analyzed, and 2 subgroups of patients could be defined a posteriori: 19 patients had a stable rectum, mean CSArel (1.06 ± 0.08); the other 20 patients had an unstable rectum, mean CSArel (1.43 ± 0.08). The average pitch in the group with a stable rectum was 0.36° (±0.21) versus 0.40° (±0.20) (P = .898). The pitch was not correlated with the CSArel (P = -.065, r = 0.119). The average roll in the group with a stable rectum was 0.27° (±0.16) versus 0.05° (±0.16) (P = .137). The roll was not correlated with the CSA (P = .094, r = 0.068). The average CSArel was higher (P = .0013) and more variable (P = .035) in the unstable group. CONCLUSION: Rectal distension had no impact on the pitch or on the roll, which suggest that a 6 DOF couch has little interest in daily practice for prostate image guided radiation therapy.

Inferring postimplant dose distribution of salvage permanent prostate implant (PPI) after primary PPI on CT images.

PURPOSE: To evaluate the dose distribution of additional radioactive seeds implanted during salvage permanent prostate implant (sPPI) after a primary permanent prostate implant (pPPI). METHODS AND MATERIALS: Patients with localized prostate cancer were primarily implanted with iodine-125 seeds and had a dosimetric assessment based on day 30 postimplant CT (CT1). After an average of 6 years, these patients underwent sPPI followed by the same CT-based evaluation of dosimetry (CT2). Radioactive seeds on each CT were detected. The detected primary seeds on CT1 and CT2 were registered and then removed from CT2 referred as a modified CT2 (mCT2). Dosimetry evaluations (D90 and V100) of sPPI were performed with dedicated planning software on CT2 and mCT2. Indeed, prostate volume, D90, and V100 differences between CT2 and either CT1 or mCT2 were calculated, and values were expressed as mean (standard deviation). RESULTS: The mean prostate volume difference between sPPI and pPPI over the 6 patients was 9.85 (7.32) cm3. The average D90 and V100 assessed on CT2 were 486.5 Gy (58.9) and 100.0% (0.0), respectively, whereas it was 161.3 Gy (47.5) and 77.3% (25.2) on mCT2 (p = 0.031 each time). The average D90 the day of sPPI [145.4 Gy (11.2)] was not significantly different from that observed on mCT2 (p = 0.56). CONCLUSION: Postimplant D90 and V100 of sPPI after pPPI can be estimated on CT images after removing the primary seeds.

Focal or whole-gland salvage prostate brachytherapy with iodine seeds with or without a rectal spacer for postradiotherapy local failure: How best to spare the rectum?

PURPOSE: Salvage prostate permanent implant (sPPI) for postradiation local failure provides high rates of biochemical control. The cumulative dose delivered to the prostate and the rectum is still unknown. METHODS AND MATERIALS: We reviewed the postimplant CT-based dosimetry of 18 selected patients who underwent sPPI with (125)I seeds for isolated biopsy-proven local failure several years after external beam radiation therapy. Ten patients had whole-prostate sPPI, and 8 patients had multiparametric MRI-based focal sPPI. In 8 patients, hyaluronic acid (HA) gel was injected into the prostate-rectum space. RESULTS: The median cumulative biological effective dose after EBRT + sPPI for the prostate and the rectum was higher in patients treated with whole-gland sPPI than in patients treated with focal sPPI (313.5 Gy2 vs. 174.4 Gy2; p = 0.06 and 258.1 Gy3 vs. 172.6 Gy3; p < 0.01, respectively). The median D0.1cc for the rectum was significantly lower in patients who had HA gel: 63.3 Gy (29.0-78.3) vs. 83.9 Gy (34.9-180.0) (p = 0.04). CONCLUSIONS: Cumulative prostate and rectum biological effective doses were lower with focal sPPI. D0.1cc delivered to the rectum was significantly lower with HA gel, while there was no difference between focal or whole-gland plans.

Impact of waiting time on nodal staging in head and neck squamous-cell carcinoma treated with radical intensity modulated radiotherapy.

BACKGROUND AND PURPOSE: To evaluate the influence of delays for radiotherapy on survival, recurrence and upstaging for head and neck squamous-cell carcinoma (HNSCC) with no nodal involvement treated with intensity modulated radiotherapy (IMRT). MATERIAL AND METHODS: This retrospective study included 63 consecutive patients with HNSCC located in the pharynx and larynx and treated with exclusive IMRT with or without chemotherapy. Survival, loco-regional or distant failure and upstaging were analyzed according to the waiting time. RESULTS: Mean waiting time for treatment was 62.5 days for the hypopharynx subgroup (range = 37-102), 63 days for the larynx subgroup (range = 19-128) and 58.5 days for the oropharynx subgroup (range = 29-99) (p = 0.725). Nine patients (14%) experienced upstaging. Loco-regional or distant failure occurred in 18 patients. Beyond a delay of 50 days, 19% of patients had local failure, 17% nodal recurrence and 11% distant failure. Within a delay of 50 days, no nodal or distant failure was observed and only 1 patient experienced local recurrence. Upstaging and overall survival were not significantly affected by an increased waiting time. CONCLUSION: For N0 patients treated with IMRT for HNSCC, waiting time around 50 days after the diagnosis was not significantly associated with an excessive risk of upstaging or recurrence.

Multiparametric MRI and post implant CT-based dosimetry after prostate brachytherapy with iodine seeds: The higher the dose to the dominant index lesion, the lower the PSA bounce.

PURPOSE: To determine whether post-implant MRI-based dosimetry of the Dominant Intra-prostatic Lesion (DIL) could best predict the occurrence of PSA bounce after prostate brachytherapy. METHODS AND MATERIALS: We selected 66 patients with a low risk prostate cancer treated with (125)I prostate brachytherapy as monotherapy. Post-implant dosimetry based on day 30 CT-scan and multiparametric MRI co-registration was generated: planned D90, D95, V100, V150 values were calculated for each DIL. Bounce was defined as a PSA elevation ⩾ 0.2 ng/mL from the previous baseline value followed by a decrease to or below the prior nadir with no additional treatment. RESULTS: After a median follow-up of 35.5 months (range 13.2-72.5), a PSA bounce occurred in 24 (36.4%) patients. The mean planned D90 of the DIL was significantly lower in bouncers: 196 ± 61 Gy vs. 234 ± 62 Gy, p = 0.018. The mean planned V150 of the DIL was 56 ± 32% for bouncers while it was 75 ± 30% for non-bouncers, p = 0.026. CONCLUSION: A lower planned D90 or V150 in the DIL were predictive of PSA bounce after prostate brachytherapy. PSA bounce could be caused by delayed cell death related to sublethal damage accumulation in the tumor.

Mapping of failures after radiochemotherapy in patients with non-metastatic esophageal cancer: A posteriori analysis of the dose distribution in the sites of loco-regional relapse.

BACKGROUND AND PURPOSE: We aimed to evaluate the patterns of loco-regional failure (LRF) after exclusive chemoradiotherapy (eCRT) for esophageal cancer with respect to planned dose and/or the incidental (unplanned) dose outside target volumes. MATERIALS AND METHODS: Co-image registration of CT or (18)F-FDG PET-CT at the time of failure (tf) and at the time of CRT (t0) was performed in 34 patients with LRF. Dosimetric parameters with regard to local failure (LF), nodal failure (NF) and involved nodal stations (NS) were derived. RESULTS: Twenty-two patients (64.7%) had LF, the majority of which (95.5%) were located at the epicenter of the GTV of the primary tumor. The mean doses recalculated to the NS at tf were more likely to be lower than the planned dose delivered to the PTV at t0: Dmean=33.9 ± 20.8 Gy vs 52.2 ± 8.5 Gy (p=0.0009), D95%=27.5 ± 21 Gy vs 46.1 ± 4.8 Gy (p=0.004). Among the 12 patients with NF outside the elective nodal irradiation (ENI) volume, Dmean of NS outside the ENI was significantly lower (19.4 ± 21.4 Gy) than the Dmean of NS with failure within the ENI (45.1 ± 6.1 Gy, p=0.01). CONCLUSION: Loco-regional failure after exclusive chemoradiotherapy for esophageal cancer may be due to an inadequately low dose.