Guided Intensity Modulated Radiation Therapy Research Articles

Prospective evaluation of dose-escalated preoperative concurrent chemo-radiation with image-guided intensity modulated radiation therapy in locally advanced rectal cancers.

155 Background: The paradigm of locally advanced (T3/4; T1-4N1-2) rectal cancers (LARC) requires an intensified treatment for better pathological outcomes. Treatment intensification may be done by radiation dose escalation of long course neoadjuvant chemoradiation therapy (NACRT) by image guided Intensity Modulated Radiation Therapy (IG-IMRT) to increase downstaging with potentially higher local control rates. We aimed to analyze the efficacy and safety of NACRT with dose escalated IG-IMRT in LARC. Methods: 20 patients of LARC were recruited in this prospective interventional phase-II study treated by IG-IMRT with 45 Gray/25 fractions to elective nodal volumes and concomitant boost of 55 Gray/25 fractions to gross primary and nodal disease with concurrent capecitabine (825 mg/m2 twice a day on radiation days). All were planned to undergo definitive surgery 6-8 weeks post completion of NACRT with Total mesorectal excision by Low anterior resection (LAR) or Abdominoperineal resection (APR) followed by 6-8 cycles of adjuvant chemotherapy. Post operative response assessment was assessed by Modified Ryan’s scheme for regression and by tumor downstaging. Primary end point was acute toxicity assessment and secondary end points were pathological complete response (pCR) and loco-regional control (LRC). Results: Of 20 patients, 18 underwent definitive surgery and received full course adjuvant chemotherapy (90%). Median follow up was 15.1 months. 2 patients refused surgery, had complete clinical response (cCR) on assessment and were on follow up. Tumor downstaging was achieved in 14 (77.7%) patients and nodal downstaging was achieved in 15/18 (83.3%) patients. In 4 patients (22.2%) pCR was achieved and overall complete response (OCR defined as pCR and nearCR, including 2 patients with cCR) in 10 patients (50%). 4 patients planned for APR underwent LAR achieving a sphincter preservation rate of 22%. Grade 3 toxicities were observed in 2 patients which resolved on first follow up. No Grade 4 acute toxicities were reported. No loco-regional relapses were found and all patients are disease free at the time of last follow up. Conclusions: Dose escalation with IG-IMRT offers higher rates of pCR and OCR with acceptable toxicity profile and excellent short term locoregional control. [Table: see text]

Long-Term Outcomes of a Phase I Trial of Weekly Docetaxel, Total Androgen Blockade, and Image Guided Intensity Modulated Radiation Therapy for Localized High-Risk Prostate Adenocarcinoma

PurposeOur purpose was to describe the long-term outcomes seen with the addition of concurrent weekly docetaxel to high-dose intensity modulated radiation (IMRT) to the prostate and androgen deprivation therapy in patients with high-risk nonmetastatic adenocarcinoma of the prostate. Methods and MaterialsNineteen patients with high-risk, localized prostate cancer were treated in a phase I trial with concurrent docetaxel at doses of 10 to 30 mg/m2, in a dose-escalated scheme, in addition to IMRT (77.4 Gy/43 fx) and neoadjuvant and concurrent combined androgen blockade (gonadotropin-releasing hormone agonist and antiandrogen). A gonadotropin-releasing hormone agonist was continued for an additional 24 months post radiation. Kaplan-Meier analysis was used to estimate the survival probabilities. ResultsAt a median follow-up of 10.5 years, 5-year and 10-year overall survival were found to be 89.5% and 68.4%, respectively. The median metastasis-free survival and progression-free survival were determined to be 11.3 years and 9.0 years, respectively. ConclusionsThis regimen produced a 10-year overall survival of 68% with a 10-year metastasis-free survival of 58%. Grade >2 toxicity was minimal. These limited data suggest that the addition of concurrent weekly docetaxel to high-dose IMRT for high-risk prostate cancer warrants further investigation.

Phase 1 Trial of Concurrent Gemcitabine and Cisplatin with Image Guided Intensity Modulated Radiation Therapy for Locoregionally Advanced Cervical Carcinoma

The use of concurrent doublet chemotherapy with radiation for locoregionally advanced cervical cancer (LACC) is limited by gastrointestinal and hematologic toxicity. By reducing radiation dose to bowel and bone marrow, image guided intensity modulated radiation therapy (IG-IMRT) may improve chemotherapy tolerance. The goal of this study was to determine whether IG-IMRT could lead to improved tolerance to concurrent cisplatin and gemcitabine for LACC. We conducted an open-label, nonrandomized, prospective phase 1 dose escalation trial at a tertiary academic cancer center (ClinicalTrials.gov identifier: NCT01554410). We enrolled patients with stage IB-IVA cervical cancer, with either an intact cervix or posthysterectomy with residual/recurrent pelvic or paraortic nodal involvement, undergoing radical pelvic or extended field chemoradiation therapy. Treatment consisted of chemoradiation with IG-IMRT (45-47.6 Gy, 25-28 fractions to the pelvis ± paraortic nodes with simultaneous nodal boost to 53.2-59.4 Gy, 28 fractions) plus 5 cycles of concurrent weekly cisplatin 40 mg/m2 with escalating doses of gemcitabine (50, 75, 100, or 125 mg/m2). Cohorts were separated preregistration according to whether the patient received pelvic or extended field IG-IMRT and whether gemcitabine followed (CG) or preceded (GC) cisplatin delivery. Dose-limiting toxicity (DLT) events were monitored up to 30 days after chemoradiation therapy. The primary endpoint was maximum tolerated dose (MTD) resulting in DLT probability ≤20%. Between February 2011 and June 2019, 35 patients were registered. Overall, 7 patients (20.0%) experienced DLTs. For the pelvic field cohort, the estimated MTD was 100 mg/m2 with GC sequencing, which is higher than the previously reported MTD for this regimen. The extended field cohort was closed after 2 of 3 patients experienced a DLT at the first dose level. IG-IMRT can permit higher doses of concurrent gemcitabine with cisplatin and pelvic radiation for LACC. However, acute toxicity remains a factor with this regimen, depending on radiation volume and chemotherapy sequencing.

Phase I Trial of Intensity-Modulated Hyperfractionated Radiotherapy Boost with Concurrent Chemotherapy Immediately Following Standard Chemoradiotherapy in Patients Primarily with Advanced Intra-thoracic/Cervical Esophageal Squamous Cell Carcinomas

Local persistence and relapse of disease in the gross tumor volume (GTV) account for the majority of treatment failures after standard chemoradiation therapy. The primary objective of this phase 1 trial was to define the maximum tolerated dose (MTD) of a hyperfractionated radiation therapy (HFRT) boost to the GTV with concurrent weekly paclitaxel and carboplatin after standard-dose chemoradiation therapy, using image guided intensity modulated radiation therapy techniques. Eligible patients were given weekly doses of paclitaxel (45mg/m2) and carboplatin (area under the curve 1.5) for 5 weeks with concurrent radiation therapy (50 Gy), immediately followed by an HFRT boost to the GTV with the same chemotherapy regimen. The boost doses were escalated in increments of 7.2 Gy delivered in 6 twice-daily fractions of 1.2 Gy using a modified Fibonacci design. Once the MTD was established, additional patients were treated at that dose to determine the safety. Thirty-one patients fulfilled the inclusion criteria. The incidence of dose-limiting toxicity was 0 of 3, 0 of 3, 0 of 3, 1 of 6 (grade 4 esophagitis), 0 of 3, and 2 of 3 (1 case each of grade 5 esophageal fistula and grade 3 pneumotitis) at 7.2, 14.4, 21.6, 28.8, 36, and 43.2 Gy, respectively, indicating an MTD of 36 Gy. Ten patients treated with this MTD showed no dose-limiting toxicities. The most common acute grade 3 or greater toxicities were esophagitis (26%) and neutropenia (19%). Late toxicity of grade 2 esophageal stricture occurred in 4 patients. The overall response rate was 84% (95% confidence interval, 42%-93%) in the entire cohort. The 1-year local control rate was 100% among those receiving a cumulative dose of the MTD or greater. The MTD of the HFRT boost after standard chemoradiation therapy in the setting of concurrent chemotherapy was 36 Gy, resulting in the cumulative tumor dose of 86 Gy in patients primarily with advanced intrathoracic/cervical esophageal squamous cell carcinomas and not adenocarcinomas of the gastroesophageal junction. A phase 2 study to further evaluate this regimen is underway.

Tumour volume reduction following PET guided intensity modulated radiation therapy and temozolomide in IDH mutated anaplastic glioma

The role of maximal surgical debulking in isocitrate dehydrogenase (IDH) mutated anaplastic glioma prior to adjuvant radiation therapy remains uncertain. This study assessed the reduction in tumour volume following intensity modulated radiation therapy (IMRT) and temozolomide in this favourable and more responsive tumour pathology. 56 patients were managed from 2011 to 2014 and 53 had residual disease. To assess radiological response, tumour volumes were created on representative T1/T2Flair MRI sequences using identical slice-levels in three planes for pre-IMRT, month + 3 and month + 12 post-IMRT scans. Change in volumes was assessed between time periods. Progression-free survival (PFS) was calculated from start of radiotherapy.Median follow-up for survivors is 48.2 months. Pathology was anaplastic oligodendroglioma (AOD) and anaplastic astrocytoma IDH-mutated (AAmut) in 32 and 21 patients respectively. 93% received sequential chemotherapy. The median residual disease on T1 and T2Flair imaging was 9.7 cm3 and 20.6 cm3. 17 patients relapsed for projected 5 year PFS of 74.9%; with 8 isolated relapses within initial surgical site. On MRI at month + 3, the median volume for T1 and T2Flair reduced by 69.4% and 67.3% respectively; which further decreased to 82.4% and 81.3% at month + 12. By month + 12, 69.2% and 62.2% of patients had >75% volume reduction. Patients with AOD had superior reduction at month + 3 compared with AAmut (p = 0.02); but equivalent reduction at month + 12 (p = 0.14). Thus, in patients with anaplastic glioma harbouring an IDH mutation, where an attempt at near-total resection may be associated with unacceptable morbidity, this data suggests that the radiation therapy may provide effective cytoreduction of residual disease.

Less Than Whole Uterus Irradiation for Locally Advanced Cervical Cancer Maintains Locoregional Control and Decreases Radiation Dose to Bowel

ObjectiveThis study aimed to evaluate whether our institutional standard of less-than-whole-uterus irradiation affects locoregional control in patients with locally advanced cervical cancer. Methods and MaterialsWe retrospectively reviewed 53 patients with stage IB to IVB cervical carcinoma who were treated with image guided intensity modulated radiation therapy and brachytherapy. The entire uterus was not included in the clinical target volume, as per our institutional standard. Dosimetric parameters were obtained, including positron emission tomography gross tumor volume (GTV), uterus volume excluding GTV, proportion of uterus included in the planning target volume (PTV; percentage), volume of overlap between uterus and prescription dose (cm3), minimum and mean dose to the uterus, and bowel V40 and D200cc. Local, regional, and distant failure and death were recorded. ResultsThe median proportion of the uterus included in the PTV was 66%. With a median follow-up of 44 months, no patient experienced isolated local recurrence, and 2-year locoregional failure was 10.9%. Positron emission tomography GTV correlated significantly with increased chance of any failure (P = .049; 95% confidence interval, 1.000-1.018). Compared with patients who had ≥90% of the uterus included in the PTV (n = 12), patients who had <90% (n = 41) of the uterus included in the PTV had significantly lower bowel V40 (P = .049) and D200cc (P = .006). ConclusionsLess-than-whole-uterus irradiation for locally advanced cervical cancer does not compromise locoregional control and reduces bowel V40 and D200cc. Further investigation is required to evaluate whether this reduction in bowel dose translates to a clinically significant reduction in bowel toxicity and whether modifications should be made to the recommended definitive cervix intensity modulated radiation therapy volumes.

Successful Management of Diffuse Large B-Cell Lymphoma Involving the Mesentery with Volumetric Image Guided Intensity Modulated Radiation Therapy

Due to the potential for unpredictable motion of mesenteric masses, there may be reluctance to administer radiation therapy (RT) for diffuse large B- cell lymphoma (DLBCL) with mesenteric nodal involvement. We report the outcome of patients treated with RT to mesenteric adenopathy with involved site radiation therapy (ISRT), intensity modulated radiation therapy (IMRT) and daily CT image guidance. Patients treated for DLBCL with RT to the mesentery between 2011-2017 were reviewed. Eligible patients had RT for consolidation or definitive treatment targeting all sites of evident disease. Clinical and treatment characteristics were analyzed for an association with local control (LC), progression free survival (PFS) and overall survival (OS). Twenty-four patients were eligible for analysis. At diagnosis, the median age was 52 years (39-77), and 54% (n=13) had stage I/II DLBCL. All patients received frontline chemotherapy (ChT) (R-CHOP, n=20; dose adjusted R-EPOCH, n=4) with a median of 6 cycles. Salvage ChT for refractory DLBCL was given prior to RT in 46% (n=11) and autologous stem cell transplantation was administered in 13% (n=3) before RT. At the time of RT, PET-CT imaging revealed 5PS of 1-3 in 46% (n=11), 5PS of 4 in 12% (n=3) and 5PS of 5 in 42% (n=10). All patients received IMRT, daily CT imaging and ISRT. The median RT dose was 40 Gy. After RT, relapse or progression occurred in 22% (n=5). Two patients progressed, 2 relapsed, and one had a residual avid mass in-field that has been followed for 12 months without additional therapy. Disease relapse/progression occurred locally (within field) for 2 patients, distant (outside of the abdomen) in 1 patient, and combined distant and local in 2 patients. The median time to local failure, PFS, and OS were not reached. At a median follow up of 37 months, the 3-year LC, PFS and OS rates were 81%, 76% and 96% respectively. Among patients treated with consolidative RT after successful frontline ChT (n=9), 3-year PFS was 100%, compared to 64% for patients with a history of chemorefractory DLBCL (n=16, p=0.07). Comparing patients with 5PS 1-3 after ChT to those with 5PS 4-5, there was no difference in time to local recurrence, PFS, or OS (p= 0.27, 0.31, 0.10). 4 of the 5 relapses occurred in patients with 5PS of 5 prior to RT. Patients with 5PS of 5 (n=10) had a median of 3 lines of ChT prior to RT and 3-year PFS of 56%, compared to 1 prior line of ChT and 3-year PFS of 92% for those with 5PS of 1-4 (n=14, p=0.098). Two deaths occurred due to DLBCL (n=1) or myelodysplastic syndrome (n=1). Patients with DLBCL involving the mesentery can be successfully treated with image-guided IMRT and ISRT. Outcomes for patients treated with combined modality therapy for chemosensitive disease are excellent. Even among patients with highly refractory and heavily pretreated DLBCL with a 5PS of 5, RT offers disease control in roughly half of patients.

Simultaneous Integrated Boost for Radiation Dose Escalation to the Gross Tumor Volume With Intensity Modulated (Photon) Radiation Therapy or Intensity Modulated Proton Therapy and Concurrent Chemotherapy for Stage II to III Non-Small Cell Lung Cancer: A Phase 1 Study

To establish, in the phase 1 portion of a prospective phase 1/2 study, the maximum tolerated dose of image guided intensity modulated radiation therapy (IMRT) or proton therapy (IMPT), both with a simultaneous integrated boost (SIB), for patients with stage II to IIIB non-small cell lung cancer receiving concurrent chemoradiation therapy. Patients had pathologically proven non-small cell lung cancer, either unresectable stage II to IIIB disease or recurrent disease after surgical resection, and could tolerate concurrent chemoradiation. Radiation doses were selectively escalated to the SIB volume (internal gross tumor volume+5-mm margin), and the dose to the planning target volume (internal gross tumor volume+8-mm margin for clinical target volume+5mm) was kept at 60Gy [cobalt gray equivalent (CGE)] over 30 fractions. Patients were randomized between the IMRT and IMPT groups if slots were available on the treatment machines for both groups. Otherwise, patients were allocated to IMRT or IMPT, whichever had an open treatment slot on the machine without randomization. Fifteen patients (6 IMRT, 9 IMPT) were enrolled. The highest doses to the SIB were 72Gy in the IMRT group and 78Gy(CGE) in the IMPT group. Nine patients (6 IMRT, 3 IMPT) received an SIB dose of 72Gy(CGE) [biologically effective dose=89.3Gy(CGE)], and 6 patients (IMPT) received an SIB dose of 78Gy(CGE) [biologically effective dose=98.3Gy(CGE)]. Dose-limiting (grade ≥3) toxicity (esophagitis) developed in 1 of the 9 patients given 72Gy(CGE) SIB. Grade ≥3 pneumonitis developed in 2 of the 6 patients treated to 78Gy(CGE) IMPT SIB: 1 (grade 3) at 3months after treatment and the other (grade 5, possibly related to treatment) at 2months after treatment. Only 1 patient developed a marginal tumor recurrence with a median follow-up of 25months (range, 4.3-47.4months). We recommend that an SIB dose of 72Gy(CGE) be used as the highest SIB dose for the planned randomized phase 2 study.

Toxicity After Post Prostatectomy Image-Guided Intensity-Modulated Radiation Therapy Using Australian Guidelines

Australian post prostatectomy radiotherapy (PPRT) contouring and treatment guidelines are in use in clinical practice, but late toxicity outcomes have not been published and concern over toxicity may contribute to underutilization. In addition, there are no reports of late toxicity for patients treated with image-guidance using implanted fiducial markers. This study reports single institution toxicity outcomes after post prostatectomy radiotherapy (PPRT) via image guided intensity modulated radiation therapy (IG-IMRT) using the national eviQ guidelines. Baseline, acute and late toxicity data are reported both using incidence and prevalence which will help to inform radiation oncologists, patients and referring clinicians regarding the expected patterns of genitourinary, gastrointestinal and sexual toxicity before, during and after post prostatectomy radiotherapy. Prospectively collected toxicity data using Common Terminology Criteria for Adverse Events version 4 was reviewed for 293 men who underwent 64-66Gy IG-IMRT to the prostate bed between 2007 and 2015. Image-guidance was achieved via implanted fiducial markers. Median follow up after PPRT was 39 months. Baseline grade ≥ 2 genitourinary (GU), gastrointestinal (GI) and sexual toxicity was 20.5%, 2.7% and 43.7% respectively, reflecting ongoing toxicity after radical prostatectomy. Incidence of new (compared to baseline) acute grade ≥ 2 GU and GI toxicity was 5.8% and 10.6% respectively. New late grade ≥ 2 GU, GI and sexual toxicity occurred in 19.1%, 4.7% and 20.2% respectively, however many patients also experienced improvements in toxicities. For this reason, prevalence of grade ≥ 2 GU, GI and sexual toxicities four years after PPRT was similar to or lower than baseline (21.7%, 2.6% and 17.4% respectively). Baseline and acute grade ≥ 2 GU and sexual toxicity predicted respective late toxicities, while salvage intent predicted late grade ≥ 2 GU toxicity. There were no grade ≥ 4 toxicities. Post prostatectomy IG-IMRT using Australian contouring guidelines appears to have tolerable acute and late toxicity. The four year prevalence of grade ≥ 2 GU and GI toxicity was virtually unchanged compared to baseline, and sexual toxicity improved over baseline. This should reassure radiation oncologists following these guidelines. Late toxicity rates of surgery and PPRT are higher than following definitive IG-IMRT, and this should be taken into account if patients are considering surgery and likely to require PPRT.

Salvage image guided radiation therapy to the prostate after cryotherapy failure

PurposeCryotherapy is an option for the primary treatment of localized prostate cancer, along with radical prostatectomy, external beam radiation therapy, and brachytherapy. Although it is known that local recurrence can occur in >20% of patients treated with primary cryotherapy, unfortunately there is a paucity of data on later salvage treatments. The use of external beam radiation therapy is an attractive option after cryotherapy failure, but there is little data on its efficacy and toxicity. We evaluated the biochemical control and complication rates of salvage dose-escalated image guided intensity modulated radiation therapy (IG-IMRT) after cryotherapy failure. Methods and materialsPatients who were treated at our institution from 2005 to 2016 were reviewed for those who underwent cryotherapy as initial treatment followed by salvage IGRT. Patients were treated with dose-escalated IG-IMRT using standard treatment margins of 3 mm posterior and 7 mm in all other directions and daily cone beam computed tomography or kv imaging to implanted fiducial markers. Biochemical progression was defined in accordance with the Phoenix consensus conference definition. ResultsEight patients were identified as having received post-cryotherapy salvage radiation within the study period. The median total dose was 77.7 Gy (range, 75.6-81.0 Gy). Median follow-up was 55 months (range, 6-88 months). Six patients remained biochemically controlled at the latest follow-up. One patient developed distant metastases after 22 months and one experienced biochemical failure at 30 months with no evidence of distant metastases. No patients experienced acute gastrointestinal toxicities of grade 2 or higher. There were no cases of late gastrointestinal or genitourinary toxicity. ConclusionsHigh-dose IG-IMRT results in high rates of salvage and extremely low rates of serious late toxicity for patients with locally recurrent prostate cancer after cryotherapy. Although the results are encouraging, given the small number of patients in this and other series, we remain cautious with regard to this treatment and believe the use of salvage radiation therapy after cryotherapy warrants further study.

A Prospective Study of an Offline Matching Protocol for Head and Neck Cancer on Helical Tomotherapy: The F5 Study

Daily online matching is the default standard for image guided intensity modulated radiation therapy on the helical tomotherapy platform, but requires more time and involves higher imaging dose. Following a hypothesis that carefully performed offline protocols like the No-action-level (NAL) protocol may be appropriate for head and neck cancers where appropriate immobilization is possible, we had first performed a retrospective audit on 100 head and neck cancer patients spanning 2,858 daily online images revealing that offline imaging may be performed safely if the PTV margin was 5 mm (Clin Oncol (R Coll Radiol). 2016;28(3):178-84). In this study, we aimed to prospectively verify these findings and determine the savings in time and imaging dose associated with offline imaging. A cohort of 62 head and neck cancer patients planned for radiation therapy with curative intent on helical tomotherapy were identified prospectively. Patients underwent daily online image verification for the first 5 fractions, and the mean shift in each translational axis was then implemented for all subsequent fractions prior to treatment. The residual errors (RE) with this method was verified and tabulated by daily imaging as part of study. These were used for a recursive verification PTV margin (PTVverif) calculation. For every patient, the time taken to do daily setup, verification imaging and correction and treatment delivery were measured. Imaging dose at central axis of a cheese phantom for a 15 cm scan length at different scan resolutions were measured. Anatomical primary sites comprised nasopharynx 10 (16.1%); oropharynx 7 (11.3%); oral cavity 20 (32.3%); larynx/hypopharynx 21 (33.9%) and others 4 (6.4%). The treatment intent was radical in 38 (61.3%) and adjuvant in 24 (38.7%). Data from a total of 1853 treatment fractions were analyzed. RE were small, with >5 mm deviations seen in 51 (3.3%), 25 (1.6%) and 83(5.4%) fractions in the X (lateral), Y (craniocaudal) and Z (anteroposterior) axes respectively. The systematic errors were 1.1, 0.8, and 1.3 mm, while the random errors were 2.1, 1.8, and 2.2 mm in these axes. Based on the RE, the PTVverif margins in these axes were 4.3, 3.3, and 4.7 mm, confirming that 5 mm PTV margins are safe with this offline protocol. The mean time for daily imaging verification imaging and correction was 4.3 mins corresponding to 32.3% of in-room time. The daily imaging dose was 3.2 cGy, 1.6 cGy and 1.1 cGy for fine, normal, and coarse imaging modes, corresponding to reduction of imaging dose by 64 cGy, 32 cGy, 22 cGy per treatment course (assuming imaging avoidance in 20 of 30 fractions). To our knowledge, this is the only prospective study verifying the application of offline imaging during head and neck cancer IMRT on helical tomotherapy. Our results suggest that with PTV margins of 5 mm, an offline F5 NAL protocol could be performed safely and could lead to substantial savings in time and imaging dose.

Outcomes and toxicity of 313 prostate cancer patients receiving helical tomotherapy after radical prostatectomy

PurposeThere are limited long-term data on patients treated with image guided intensity modulated radiation therapy (IG-IMRT) for prostate cancer recurrence or high-risk disease features after radical prostatectomy. We report single-institution results for patients treated with IG-IMRT and identify variables associated with outcome. Methods and materialsThis is a retrospective chart review consisting of 313 consecutive patients who were treated with adjuvant or salvage IG-IMRT from 2004 to 2013. Cox proportional hazards analysis was used to identify factors related to survival and toxicity. Toxicity was graded using the Common Terminology Criteria for Adverse Events Version 4.0. ResultsThe median follow-up was 55 months (range, 6-131 months). The median pre-radiation therapy (RT) prostate-specific antigen (PSA) was 0.3 ng/mL (range, <0.01-55.4). The vast majority of patients (87%) received elective pelvic nodal irradiation (median dose: 45 Gy). Androgen deprivation therapy (ADT) was given to 39% of patients for a median of 9 months. Five-year biochemical progression-free survival and distant metastasis-free survival were 59% (95% confidence interval, 53%-66%) and 89% (95% confidence interval, 85%-93%), respectively. On multivariate analysis, higher pre-RT PSA (>0.2 ng/mL), biopsy Gleason score (≥7 [4+3]), and duration of ADT (>6 months) were significantly associated (P < .05) with biochemical progression-free survival. Actuarial late grade 3 genitourinary and gastrointestinal toxicities at 5 years were 10% and 2%, respectively. ConclusionOur results suggest that lower pre-RT PSA level and longer duration of ADT are associated with improved biochemical control. The incidence of late grade 3 gastrointestinal toxicity was low, but late grade 3 genitourinary toxicity was higher than anticipated.

Three-Dimensional Dosimetric Validation of a Magnetic Resonance Guided Intensity Modulated Radiation Therapy System

To validate the dosimetric accuracy of a commercially available magnetic resonance guided intensity modulated radiation therapy (MRgIMRT) system using a hybrid approach: 3-dimensional (3D) measurements and Monte Carlo calculations. We used PRESAGE radiochromic plastic dosimeters with remote optical computed tomography readout to perform 3D high-resolution measurements, following a novel remote dosimetry protocol. We followed the intensity modulated radiation therapy commissioning recommendations of American Association of Physicists in Medicine Task Group 119, adapted to incorporate 3D data.Preliminary tests ("AP" and "3D-Bands") were delivered to 9.5-cm usable diameter cylindrical PRESAGE dosimeters to validate the treatment planning system (TPS) for nonmodulated deliveries; assess the sensitivity, uniformity, and rotational symmetry of the PRESAGE dosimeters; and test the robustness of the remote dosimetry protocol. Following this, 4 clinical MRgIMRT plans ("MultiTarget," "Prostate," "Head/Neck," and "C-Shape") were measured using 13-cm usable diameter PRESAGE dosimeters. For all plans, 3D-γ (3% or 3mm global, 10% threshold) passing rates were calculated and 3D-γ maps were examined.Point doses were measured with an IBA-CC01 ionization chamber for validation of absolute dose. Finally, by use of an in-house-developed, GPU-accelerated Monte Carlo algorithm (gPENELOPE), we independently calculated dose for all 6 Task Group 119 plans and compared against the TPS. For PRESAGE measurements, 3D-γ analysis yielded passing rates of 98.7%, 99.2%, 98.5%, 98.0%, 99.2%, and 90.7% for AP, 3D-Bands, MultiTarget, Prostate, Head/Neck, and C-Shape, respectively. Ion chamber measurements were within an average of 0.5% (±1.1%) from the TPS dose. Monte Carlo calculations demonstrated good agreement with the TPS, with a mean 3D-γ passing rate of 98.5%±1.9% using a stricter 2%/2-mm criterion. We have validated the dosimetric accuracy of a commercial MRgIMRT system using high-resolution 3D techniques. We have demonstrated for the first time that hybrid 3D remote dosimetry is a comprehensive and feasible approach to commissioning MRgIMRT. This may provide better sensitivity in error detection compared with standard 2-dimensional measurements and could be used when implementing complex new magnetic resonance guided radiation therapy technologies.

Continued Benefit to Rectal Separation for Prostate Radiation Therapy: Final Results of a Phase III Trial

SpaceOAR, a Food and Drug Administration-approved hydrogel intended to create a rectal-prostate space, was evaluated in a single-blind phase III trial of image guided intensity modulated radiation therapy. A total of 222 men were randomized 2:1 to the spacer or control group and received 79.2Gy in 1.8-Gy fractions to the prostate with or without the seminal vesicles. The present study reports the final results with a median follow-up period of 3years. Cumulative (Common Terminology Criteria for Adverse Events, version 4.0) toxicity was evaluated using the log-rank test. Quality of life (QOL) was examined using the Expanded Prostate Cancer Index Composite (EPIC), and the mean changes from baseline in the EPIC domains were tested using repeated measures models. The proportions of men with minimally important differences (MIDs) in each domain were tested using repeated measures logistic models with prespecified thresholds. The 3-year incidence of grade ≥1 (9.2% vs 2.0%; P=.028) and grade ≥2 (5.7% vs 0%; P=.012) rectal toxicity favored the spacer arm. Grade ≥1 urinary incontinence was also lower in the spacer arm (15% vs 4%; P=.046), with no difference in grade ≥2 urinary toxicity (7% vs 7%; P=0.7). From 6months onward, bowel QOL consistently favored the spacer group (P=.002), with the difference at 3years (5.8 points; P<.05) meeting the threshold for a MID. The control group had a 3.9-point greater decline in urinary QOL compared with the spacer group at 3years (P<.05), but the difference did not meet the MID threshold. At 3years, more men in the control group than in the spacer group had experienced a MID decline in bowel QOL (41% vs 14%; P=.002) and urinary QOL (30% vs 17%; P=.04). Furthermore, the control group were also more likely to have experienced large declines (twice the MID) in bowel QOL (21% vs 5%; P=.02) and urinary QOL (23% vs 8%; P=.02). The benefit of a hydrogel spacer in reducing the rectal dose, toxicity, and QOL declines after image guided intensity modulated radiation therapy for prostate cancer was maintained or increased with a longer follow-up period, providing stronger evidence for the benefit of hydrogel spacer use in prostate radiation therapy.

Long-Term Outcomes of a Phase 2 Trial of Moderate Hypofractionated Image Guided Intensity Modulated Radiation Therapy (IG-IMRT) for Localized Prostate Cancer

Long-Term Outcomes of a Phase 2 Trial of Moderate Hypofractionated Image Guided Intensity Modulated Radiation Therapy (IG-IMRT) for Localized Prostate Cancer

Narrow-Margin Image Guided Intensity Modulated Radiation Therapy for Head and Neck Cancer: Can We Afford Not to Adaptively Replan?

Narrow-Margin Image Guided Intensity Modulated Radiation Therapy for Head and Neck Cancer: Can We Afford Not to Adaptively Replan?

Interim Acute Toxicity Analysis and Surgical Outcomes of Neoadjuvant Gemcitabine/nab-Paclitaxel and Hypofractionated Image Guided Intensity Modulated Radiation Therapy in Resectable and Borderline Resectable Pancreatic Cancer (ANCHOR) Study

Interim Acute Toxicity Analysis and Surgical Outcomes of Neoadjuvant Gemcitabine/nab-Paclitaxel and Hypofractionated Image Guided Intensity Modulated Radiation Therapy in Resectable and Borderline Resectable Pancreatic Cancer (ANCHOR) Study

Long-Term Decision Regret After Postprostatectomy Image Guided Intensity Modulated Radiation Therapy

Long-Term Decision Regret After Postprostatectomy Image Guided Intensity Modulated Radiation Therapy

Hypofractionated image guided radiation therapy followed by prostate seed implant boost for men with newly diagnosed intermediate and high risk adenocarcinoma of the prostate: Preliminary results of a phase 2 prospective study

PurposeA phase 2 protocol was designed and implemented to assess the toxicity and efficacy of hypofractionated image guided intensity modulated radiation therapy (IG-IMRT) combined with low-dose rate 103Pd prostate seed implant for treatment of localized intermediate- and high-risk adenocarcinoma of the prostate. Methods and materialsThis is a report of an interim analysis on 24 patients enrolled on an institutional review board–approved phase 2 single-institution study of patients with intermediate- and high-risk adenocarcinoma of the prostate. The median pretreatment prostate-specific antigen level was 8.15 ng/mL. The median Gleason score was 4 + 3 = 7 (range, 3 + 4 = 7 - 4 + 4 = 8), and the median T stage was T2a. Of the 24 patients, 4 (17%) were high-risk patients as defined by the National Comprehensive Cancer Network criteria, version 2016. The treatment consisted of 2465 cGy in 493 cGy/fraction of IG-IMRT to the prostate and seminal vesicles. This was followed by a 103Pd transperineal prostate implant boost (prescribed dose to 90% of the prostate volume of 100 Gy) using intraoperative planning. Five patients received neoadjuvant, concurrent, and adjuvant androgen deprivation therapy. ResultsThe median follow-up was 18 months (range, 1-42 months). The median nadir prostate-specific antigen was 0.5 ng/mL and time to nadir was 16 months. There was 1 biochemical failure associated with distant metastatic disease without local failure. Toxicity (acute or late) higher than grade 3 was not observed. There was a single instance of late grade 3 genitourinary toxicity secondary to hematuria 2 years and 7 months after radiation treatment. There were no other grade 3 gastrointestinal or genitourinary toxicities. ConclusionsEarly results on the toxicity and efficacy of the combination of hypofractionated IG-IMRT and low-dose-rate brachytherapy boost are favorable. Longer follow-up is needed to confirm safety and effectiveness.

Late Side Effects After Image Guided Intensity Modulated Radiation Therapy Compared to 3D-Conformal Radiation Therapy for Prostate Cancer: Results From 2 Prospective Cohorts

Technical developments in the field of external beam radiation therapy (RT) enabled the clinical introduction of image guided intensity modulated radiation therapy (IG-IMRT), which improved target conformity and allowed reduction of safety margins. Whether this had an impact on late toxicity levels compared to previously applied three-dimensional conformal radiation therapy (3D-CRT) is currently unknown. We analyzed late side effects after treatment with IG-IMRT or 3D-CRT, evaluating 2 prospective cohorts of men treated for localized prostate cancer to investigate the hypothesized reductions in toxicity. Patients treated with 3D-CRT (n=189) or IG-IMRT (n=242) to 78Gy in 39 fractions were recruited from 2 Dutch randomized trials with identical toxicity scoring protocols. Late toxicity (>90days after treatment) was derived from self-assessment questionnaires and case report forms, according to Radiation Therapy Oncology Group/European Organization for Research and Treatment of Cancer (RTOG-EORTC) scoring criteria. Grade ≥2 endpoints included gastrointestinal (GI) rectal bleeding, increased stool frequency, discomfort, rectal incontinence, proctitis, and genitourinary (GU) obstruction, increased urinary frequency, nocturia, urinary incontinence, and dysuria. The Cox proportional hazards regression model was used to compare grade ≥2 toxicities between both techniques, adjusting for other modifying factors. The 5-year cumulative incidence of grade ≥2 GI toxicity was 24.9% for IG-IMRT and 37.6% following 3D-CRT (adjusted hazard ratio [HR]: 0.59, P=.005), with significant reductions in proctitis (HR: 0.37, P=.047) and increased stool frequency (HR: 0.23, P<.001). GU grade ≥2 toxicity levels at 5years were comparable with 46.2% and 36.4% following IG-IMRT and 3D-CRT, respectively (adjusted HR: 1.19, P=.33). Other strong predictors (P<.01) of grade ≥2 late toxicity were baseline complaints, acute toxicity, and age. Treatment with IG-IMRT reduced the risk of late grade ≥2 complications, whereas GU toxicities remained comparable. This clinically relevant observation demonstrates that IMRT and image-guidance should therefore be the preferred treatment option, provided that margin reduction is implemented with caution.