Image-guided Intensity-modulated Radiotherapy Research Articles

Hitting a Moving Target: Successful Management of Diffuse Large B-cell Lymphoma Involving the Mesentery With Volumetric Image-guided Intensity Modulated Radiation Therapy

IntroductionWe report successful treatment of mesenteric diffuse large B-cell lymphoma (DLBCL) using localized involved site radiation therapy (ISRT), intensity modulated radiation therapy (IMRT), and daily computed tomography (CT)-image guidance. Patients and MethodsPatients with mesenteric DLBCL treated with RT between 2011 and 2017 were reviewed. Clinical and treatment characteristics were analyzed for an association with local control, progression-free survival (PFS), and overall survival. ResultsTwenty-three patients were eligible. At diagnosis, the median age was 52 years (range, 38-76 years), and 57% (n = 13) had stage I/II DLBCL. All patients received frontline chemotherapy (ChT) (R-CHOP [rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone], n = 19; dose-adjusted R-EPOCH [rituximab, etoposide, prednisone, vincristine, cyclophosphamide, and doxorubicin], n = 4) with median 6 cycles. Prior to RT, salvage ChT for refractory DLBCL was given to 43% (n = 10) and autologous stem cell transplantation was administered in 13% (n = 3). At the time of RT, positron emission tomography-CT revealed 5-point scale of 1 to 3 (48%; n = 11), 4 (9%; n = 2), and 5 (44%; n = 10). All patients received IMRT, daily CT imaging, and ISRT. The median RT dose was 40 Gy (range, 16.2-49.4 Gy). Relapse or progression occurred in 22% (n = 5). At a median follow-up of 37 months, the 3-year local control, PFS, and overall survival rates were 80%, 75%, and 96%, respectively. Among patients treated with RT after complete metabolic response to frontline ChT (n = 8), the 3-year PFS was 100%, compared with 61% for patients with a history of chemorefractory DLBCL (n = 15; P = .055). Four of the 5 relapses occurred in patients with 5-point scale of 5 prior to RT (P = .127). ConclusionMesenteric involvement of DLBCL can be successfully targeted with localized ISRT fields using IMRT and daily CT-image guidance.

Quality Improvements of Veterans Health Administration Radiation Oncology Services Through Partnership for Accreditation With the ACR

Approximately 20,000 US veterans receive radiation oncology services at a Veterans Healthcare Administration (VHA) medical facility each year. They currently have access to advanced technologies, which include image-guided intensity-modulated radiotherapy, stereotactic radiosurgery, and stereotactic body radiation therapy. Although this provides access to cancer therapies that are modern, safe, and efficient, the technical complexities of these treatments and clinical decision making that goes into the patient selection and prescriptions demand quality assurances at each VHA practice. To meet the challenges of this need, the VHA established a partnership in 2008 with the ACR’s Radiation Oncology Practice Accreditation Program (ACR-ROPA). This report summarizes the experience of this ongoing partnership and demonstrates the combined impact of the VHA’s mandate for ACR-ROPA accreditation and internal monitoring of all identified corrective actions at each of its radiation oncology practices.

Comparison of Image-Guided Intensity-Modulated Radiotherapy and Low-dose Rate Brachytherapy with or without External Beam Radiotherapy in Patients with Localized Prostate Cancer

To compare the outcome of low-dose rate brachytherapy (LDR-BT) and image-guided intensity-modulated radiotherapy (IG-IMRT) for localized prostate cancer, we examined 488 LDR-BT and 269 IG-IMRT patients. IG-IMRT treated older and advanced disease with more hormonal therapy than LDR-BT, which excluded T3b–T4 tumor and initial PSA > 50 ng/ml. The actuarial five-year biochemical failure-free survival rate was 88.7% and 96.7% (p = 0.0003) in IG-IMRT and LDR-BT, respectively; it was 88.2% (85.1% for IG-IMRT and 94.9% for LDR-BT, p = 0.0578) for the high-risk group, 95.2% (91.6% and 97.0%, p = 0.3361) for the intermediate IG-IMRT and 96.8% (95.7% and 97%, p = 0.8625) for the low-risk group. Inverse probability of treatment weighting (IPTW) involving propensity scores was used to reduce background selection bias. IPTW showed a statistically significant difference between LDR-BT and IG-IMRT in high risk (p = 0.0009) and high risk excluding T3-4/initial PSA > 50 ng/ml group (p = 0.0073). IG-IMRT showed more gastrointestinal toxicity (p = 0.0023) and less genitourinary toxicity (p < 0.0001) than LDR-BT. LDR-BT and IG-IMRT showed equivocal outcome in low- and intermediate-risk groups. For selected high-risk patients, LDR-BT showed more potential to improve PSA control rate than IG-IMRT.

Setup margin for head-and-neck cancer patients receiving 2D-2D and 3D image-guided intensity-modulated radiation therapy

Image-guided intensity-modulated radiation therapy is essential for oncology treatment of head-and-neck cancer patients. MV-kV and CBCT modalities were compared in case of IGRT treatment for head-and-neck cancer patients. Setup error, setup margin (SM), imaging and evaluation times and imaging doses were analyzed. Eight patients' elective treatment was evaluated, 66 orthogonal MV-kV images and 66 CBCT series were acquired. Setup error measurement was based on bony manual image registration in three translational directions. Normality test and F-test were performed followed by the comparison with independent-samples T-test (p<0,05). The necessary target volume setup margin was calculated based on Van Herk's equation. Imaging time and setup error determination time were measured. Imaging doses were estimated based on the literature. No statistically significant difference was found between setup errors determined by MV-kV and CBCT (VRT: 0.5mm, SD = 1.9 vs. 0.4mm, SD = 2.1, p = 0.371; LNG: 0.2mm, SD = 2.2 vs. -0.1mm, SD = 2.2, p = 0.188; LAT: 0.2mm, SD = 2.2 vs. 0.3mm, SD = 2.1, p = 0.41). SM values were: VRT: 2.7mm vs. 2.5mm; LNG: 2.1mm vs. 1.3mm; LAT: 2.2mm vs. 2.3mm. Mean imaging time was 0.65min (MV-kV) vs. 2.29 min (CBCT). Mean setup error determination time was 2.41min for both modalities. Estimated imaging doses were 6.88mGy (MV-kV) vs. 17.2mGy (CBCT) per fraction. The bony anatomy derived image registration based translational setup error determination results in similar values either by MV-kV or by CBCT. Using 3mm setup margin in all the directions might be adequate. Imaging time is less by MV-kV, significant difference in imaging doses did not appear. Using CBCT is generally suggested. MV-kV might be an alternative in case of need for shortened imaging time. Orv Hetil. 2018; 159(29): 1193-1200.

Rectal radiation dose-reduction techniques in prostate cancer: a focus on the rectal spacer.

Prostate cancer is the most common cancer in men. External beam radiotherapy by a variety of methods is a standard treatment option with excellent disease control. However, acute and late rectal side effects remain a limiting concern in intensification of therapy in higher-risk patients and in efforts to reduce treatment burden in others. A number of techniques have emerged that allow for high-radiation dose delivery to the prostate with reduced risk of rectal toxicity, including image-guided intensity-modulated radiation therapy, endorectal balloons and various forms of rectal spacers. Image-guided radiation therapy, either intensity-modulated radiation therapy or stereotactic ablative radiation therapy, in conjunction with a rectal spacer, is an efficacious means to reduce acute and long-term rectal toxicity.

Effectiveness of tomotherapy vs linear accelerator image-guided intensity-modulated radiotherapy for localized pharyngeal cancer treated with definitive concurrent chemoradiotherapy: a Taiwanese population-based propensity score-matched analysis.

This study used a population-based propensity score (PS)-matched analysis to compare the effectiveness of tomotherapy-based image-guided intensity-modulated radiotherapy (referred to as T-IMRT) with that of linear accelerator based (referred to as L-IMRT) for clinically localized pharyngeal cancer (LPC, divided into nasopharyngeal cancer and non-nasopharyngeal cancer) with definitive concurrent chemoradiotherapy (CCRT). Eligible LPC patients diagnosed between 2007 and 2014 were identified among all citizens in Taiwan from the Health and Welfare Data Science Center database. A PS-matched sample based on the PS estimated from the covariables of interest was constructed to compare the effectiveness of T-IMRT with L-IMRT. In the primary analysis, overall survival (OS) was compared for assessment of effectiveness. We also evaluated freedom from local regional recurrence and pharyngeal cancer-specific survival and performed supplementary analyses. The study population included 960 patients equally divided into two groups. OS did not differ significantly between the T-IMRT and L-IMRT groups (hazard ratio for death: 0.82, p = 0.15, 5-year OS rate: 79 and 74% for T-IMRT and L-IMRT, respectively), and there were no significant differences in the other endpoints or supplementary analyses. For LPC patients treated with definitive CCRT, we found no significant difference in disease control or survival between the T-IMRT and L-IMRT groups. However, further studies, especially randomized trials or studies focusing on other dimensions, such as quality of life, are needed. Advances in knowledge: We provide the first population-based study, as well as the largest study, on the clinical effectiveness of T-IMRT compared with L-IMRT in conjunction with CCRT in LPC patients.

A prospective pilot study on early toxicity from a simultaneously integrated boost technique for canine sinonasal tumours using image-guided intensity-modulated radiation therapy.

In order to overcome the common local treatment failure of canine sinonasal tumours, integrated boost techniques were tried in the cobalt/orthovoltage era, but dismissed because of unacceptable early (acute) toxicity. Intriguingly, a recent calculation study of a simultaneously integrated boost (SIB) technique for sinonasal irradiation using intensity-modulated radiation therapy (IMRT) predicted theoretical feasibility. In this prospective pilot study we applied a commonly used protocol of 10 × 4.2 Gy to the planning target volume (PTV) with a 20%-SIB dose to the gross tumour volume (GTV). Our hypothesis expected this dose escalation to be clinically tolerable if applied with image-guided IMRT. We included 9 dogs diagnosed with sinonasal tumours without local/distant metastases. For treatment planning, organs at risk were contoured according to strict anatomical guidelines. Planning volume extensions (GTV/CTV/PTV) were standardized to minimize interplanner variability. Treatments were applied with rigid patient positioning and verified daily with image guidance. After radiation therapy, we set focus on early ophthalmologic complications as well as mucosal and cutaneous toxicity. Early toxicity was evaluated at week 1, 2, 3, 8 and 12 after radiotherapy. Only mild ophthalmologic complications were found. Three patients (33%) had self-limiting moderate to severe early toxicity (grade 3 mucositis) which was managed medically. No patient developed ulcerations/haemorrhage/necrosis of skin/mucosa. The SIB protocol applied with image-guided IMRT to treat canine sinonasal tumours led to clinically acceptable side effects. The suspected increased tumour control probability and the risk of late toxicity with the used dose escalation of 20% has to be further investigated.

"Give me five" ultra-hypofractionated radiotherapy for localized prostate cancer: non-invasive ablative approach.

Ultra-hypofractionated radiotherapy (RT) is given over a shorter time with larger doses with respect to conventional fractionation in patients with localized prostate cancer (PCa). The use of hypofractionation is supported both from the radiobiological point of view (the low α/β-ratio in PCa and dose escalation) and from the rising number of clinical evidences. The aim of this study is to review our data regarding oncological outcomes, namely biochemical progression-free survival (b-PFS) and clinical progression-free survival (c-PFS), acute and long-term toxicities in patients treated with a ultra-hypofractionated RT. A series of 194 patients with clinically localized PCa treated primarily with ultra-hypofractionated RT using image-guided intensity modulated RT (IG-IMRT) at our Institute from 2012 to 2015 was included in this analysis. According to NCCN risk group classification, 65 (33.5%) patients were low risk, 101 (52.1%) intermediate risk, and 28 (14.4%) high risk. Androgen deprivation therapy (ADT) was given to 61 patients (31.4%). A 169 patients (87.1%) received 35Gy in 5 fractions, while 25 patients (13%) received 32.5Gy in 5 fractions (usually given in patients with comorbidity). The median duration of the treatment was 10 days (IQR 9-12). Biochemical relapse was defined as a rise of prostate specific antigen (PSA) > 2ng/ml above nadir. b-PFS, c-PFS, and freedom from gastro-intestinal (GI) and genito-urinary (GU) toxicity curves were calculated by the Kaplan-Meier method. Log-rank test and multivariate Cox models were used to investigate the role RT dose and heterogeneity by NCCN risk groups adjusting for prognostic factors. Data on acute and late term toxicities were collected according to RTOG/EORTC grading system. With a median follow-up of 30 months, 17 patients experienced PSA failure (9%). The 3-year b-PFS was 87% for all patients and rates stratified for the NCCN risk were 94, 82, and 66% for low-, intermediate-, and high-risk groups, respectively. Log-rank tests indicate that biochemical progression was significantly greater for patients with initial PSA (iPSA) greater than 7ng/ml (P = 0.04), high- and intermediate-risk groups (P = 0.002), low total dose (P = 0.02) and Gleason score (GS) equal or greater than 7 (P = 0.04). No statistically significant association was found with T stage nor ADT. In multivariate analyses, total dose (P = 0.03) and risk groups (P = 0.03) remained significantly associated with recurrence. Acute and late GI and GU toxicity were acceptable. The toxicity of ultra-hypofractionated IG-IMRT in a large clinical cohort of PCa patients was tolerable and confirmed that this treatment is safe and offers excellent tumor control. Moreover, the hypofractionated RT allows to deliver the whole RT over 10 days with a sensible impact in patients' quality of life and potential overall health system and social benefits.

The ongoing challenge of large anal cancers: prospective long term outcomes of intensity-modulated radiation therapy with concurrent chemotherapy.

PurposePatterns of failure and long term outcomes were prospectively evaluated following tumor factors-stratified radiation dose for anal/perianal cancer.MethodsBetween 2008–2013, patients with anal/perianal squamous cell carcinoma were accrued to an institutional REB-approved prospective study. All patients were treated with image-guided intensity-modulated radiation therapy (IG-IMRT). Radiation dose selection (27–36 Gy for elective target, and 45–63 Gy for gross target) was based on tumor clinico-pathologic features. Chemotherapy regimen was 5-fluorouracil/mitomycin-C (weeks 1&5). Local [LF], regional failure [RF], distant metastasis [DM], overall- [OS], disease-free [DFS], colostomy-free survival [CFS] and late toxicity were analyzed.ResultsOverall, 101 patients were evaluated; median follow-up: 56.5 months; 49.5% male; 34.7% T3/4-category, and 35.6% N+. Median radiation dose was 63 Gy. The most common acute grade ≥3 toxicities were skin (41.6%) and hematological (30.7%). Five-year OS, DFS, CFS, LF, RF, DM rates were 83.4%, 75.7%, 74.7, 13.9%, 4.6% and 5% respectively. Five-year LF for patients with T1-2 and T3-4 disease were 0% and 39.2% respectively. All LF (n = 14, after 63 Gy, in tumors ≥5 cm) were in the high dose volume except one marginal to the high dose volume. All RF (n = 4) were within elective dose volume except one within the high dose volume. On multivariable analysis, T3/4-category predicted for poor DFS, CFS and OS. The overall late grade ≥3 toxicity was 36.2% (mainly anal [20%]).ConclusionsIndividualized radiation dose selection using IG-IMRT resulted in good long term outcomes. However, central failures remain a problem for locally advanced tumors even with high dose radiation (63 Gy/7weeks).

EP-1289: ABPI with 3D-CRT and image-guided IMRT – 6 year results of a phase II trial

EP-1289: ABPI with 3D-CRT and image-guided IMRT – 6 year results of a phase II trial

Pilot study of moderately-hypofractionated intensity-modulated radiation therapy over 3 weeks for localized prostate cancer.

8 Background: The purpose of this trial was to prospectively evaluate the short-term outcomes of moderately hypofractionated intensity-modulated radiation therapy (MH-IMRT) for localized prostate cancer. Methods: In November 2013, we started a pilot study of MH-IMRT for prostate cancer. Eligible patients were 50 to 80 years old and had D’Amico’s low- or intermediate-risk disease. Fifty-four Gy in 15 fractions (3.6 Gy per fraction), in which the equivalent total dose in 2-Gy fractions to prostate cancer was estimated about 78 Gy, were delivered over 3 weeks using image-guided IMRT based on daily cone beam CT without intraprostatic fiducial markers. Neoadjuvant androgen deprivation therapy was given 4 to 8 months before the start of IMRT. The primary endpoint was incidence rates of acute toxicities, and the secondary endpoints were incidence rates of late toxicities at 2 years and biochemical relapse free survival (BRFS) at 2 years. Acute toxicities were evaluated based on the Common Terminology Criteria for Adverse Events version 4.0 criteria. Late toxicities were evaluated based on RTOG/EORTC Late Radiation Morbidity Scoring Schema. Biochemical relapse was defined according to the Phoenix definition (absolute nadir + 2 ng/ml). The planned sample size was 25 patients. Results: Twenty-five patients were enrolled in this trial. Twenty-four patients were treated with MH-IMRT, and 1 patient was treated with conventionally fractionated IMRT because his small intestine was close to the target. The median age in the cohort was 71 years old, and median follow-up period was 31 months (range 24-42). Four patients (17%) had low- and 20 (83%) had intermediate-risk disease. No grade ≥3 acute toxicity was observed and the incidence rates of grade 2 acute genitourinary and gastrointestinal toxicities were 21% and 4%, respectively. So far no grade ≥2 late toxicity has been observed and the 2-year BRFS is 95.8%. Transient PSA elevation over 0.4 ng/ml was observed in 11 patients (46%) and in 5 patients (21%) PSA rose ≥1.0 ng/ml above nadir. Conclusions: Sort-term outcome of MH-IMRT delivering 54 Gy in 15 fractions over 3 weeks for prostate cancer was comparable to that of conventionally fractionated IMRT. Clinical trial information: UMIN000012057.

Fitting NTCP models to bladder doses and acute urinary symptoms during post-prostatectomy radiotherapy

BackgroundTo estimate the radiobiological parameters of three popular normal tissue complication probability (NTCP) models, which describe the dose-response relations of bladder regarding different acute urinary symptoms during post-prostatectomy radiotherapy (RT). To evaluate the goodness-of-fit and the correlation of those models with those symptoms.MethodsNinety-three consecutive patients treated from 2010 to 2015 with post-prostatectomy image-guided intensity modulated radiotherapy (IMRT) were included in this study. Patient-reported urinary symptoms were collected pre-RT and weekly during treatment using the validated Prostate Cancer Symptom Indices (PCSI). The assessed symptoms were flow, dysuria, urgency, incontinence, frequency and nocturia using a Likert scale of 1 to 4 or 5. For this analysis, an increase by ≥2 levels in a symptom at any time during treatment compared to baseline was considered clinically significant. The dose volume histograms of the bladder were calculated. The Lyman-Kutcher-Burman (LKB), Relative Seriality (RS) and Logit NTCP models were used to fit the clinical data. The fitting of the different models was assessed through the area under the receiver operating characteristic curve (AUC), Akaike information criterion (AIC) and Odds Ratio methods.ResultsFor the symptoms of urinary urgency, leakage, frequency and nocturia, the derived LKB model parameters were: 1) D50 = 64.2Gy, m = 0.50, n = 1.0; 2) D50 = 95.0Gy, m = 0.45, n = 0.50; 3) D50 = 83.1Gy, m = 0.56, n = 1.00; and 4) D50 = 85.4Gy, m = 0.60, n = 1.00, respectively. The AUC values for those symptoms were 0.66, 0.58, 0.64 and 0.64, respectively. The differences in AIC between the different models were less than 2 and ranged within 0.1 and 1.3.ConclusionsDifferent dose metrics were correlated with the symptoms of urgency, incontinence, frequency and nocturia. The symptoms of urinary flow and dysuria were poorly associated with dose. The values of the parameters of three NTCP models were determined for bladder regarding four acute urinary symptoms. All the models could fit the clinical data equally well. The NTCP predictions of urgency showed the best correlation with the patient reported outcomes.

Long-term Outcomes of a Dose-reduction Trial to Decrease Late Gastrointestinal Toxicity in Patients with Prostate Cancer Receiving Soft Tissue-matched Image-guided Intensity-modulated Radiotherapy.

We experienced an unexpected high incidence of gastrointestinal (GI) toxicity in patients undergoing image-guided intensity-modulated radiotherapy (IG-IMRT) using helical tomotherapy in our initial 2.2 Gy/fraction schedule for prostate cancer; hence, a dose-reduction trial from 2.2 Gy to 2 Gy/fraction was conducted using modified planning target volume (PTV) contouring. We compared 130 patients treated using 2.2 Gy/fraction (Group A) and 144 treated using the 2 Gy/fraction (Group B) with modified PTV (excluding rectal volume) with a median follow-up period of 62 months. Prescribed dose was 72.6-74.8 Gy in 33-34 fractions (Group A) and 72-74 Gy in 36-37 fractions (Group B). Patients in Group B had a reduced rectal and bladder V10-V70 and were irradiated at the maximal dose. Their cumulative incidence of grade ≤2 GI toxicity at 5 years improved from 10.1% [95% confidence interval (CI), 4.9-15.3%] to 1.4% (0-3.3%). Grade 2≤ urinary toxicity also decreased from 5.5% (1.5-9.4%) in Group A to 1.4% (0-3.3%, p=0.0167) in Group B. The biochemical failure-free 5-year survival rate was 89.1% (95%CI=83.6-95.4%) and 87.5% (82.0-92.9%, p=0.75) in groups A and B, respectively. The reduced dose fraction schedule decreased the incidence of late GI toxicity without compromising prostate-specific antigen control. Careful target volume definition and fraction size are important even for IG-IMRT.

A comparative analysis of quality of life after postoperative intensity-modulated radiotherapy or three-dimensional conformal radiotherapy for cervical cancer

The aim of this study is to compare the quality of life (QOL) between adjuvant three-dimensional conformal radiotherapy (3DCRT) or intensity-modulated radiotherapy (IMRT) for cervical cancer. QOL assessment was done at the baseline and then longitudinally after completing (chemo) radiation. All patients completed EORTC QLQ-C30 and EORTC QLQ Cx-24 modules. Independent-sample t-test was used to compare the mean scores between the two groups. Analysis of variance was used to compare differences in QOL measures over the six time points (baseline, post-RT, 3, 6, 9, and 12 months after treatment) and between treatment groups (3DCRT vs. IMRT). Linear mixed model was also performed to account for attrition. Overall, 64 patients (image-guided IMRT, n = 40 and 3DCRT, n = 24) completed QOL assessment. The median age and follow-up period were 48 years and 15.5 months, respectively. General QOL domains such as emotional (at 12 months, P = 0.04) and social (at 3 months, P = 0.02 and 12 months, P = 0.03) were better with IMRT. Pain (12 months, P = 0.03); fatigue (12 months, P = 0.05); nausea and vomiting (12 months, P = 0.03); insomnia (post-RT, P = 0.05 and 12 months, P = 0.03); appetite loss (post-RT and 12 months, P = 0.04); and diarrhea (6 months, P = 0.02 and 12 months, P = 0.003) scores were significantly better with IMRT. On linear mixed model analysis, there was a significant interaction between treatment cohort and assessment intervals for physical, emotional, and social functioning, appetite loss, diarrhea, lymphedema, and menopausal symptom scores were significantly better with IMRT. Treatment technique (IMRT vs. 3DCRT) impacts early QOL in undergoing adjuvant radiation for cervical cancer.

Efficacy and toxicity of image-guided intensity-modulated radiation therapy combined with dose-escalated brachytherapy for stage IIB cervical cancer.

Considering internal organ motion and tumor regression, it is controversial to use intensity-modulated radiation therapy (IMRT) in definitive radiotherapy for cervical cancer. In this study, we evaluated the efficacy and toxicity of IMRT combined with dose-escalated intracavitary brachytherapy (ICBT) for cervical cancer. In total, 373 consecutive FIGO-stage-IIB cervical cancer patients treated with IMRT combined with ICBT and concurrent chemotherapy were included in this study. A dose of 50.4 Gy in 28 fractions was delivered to the pelvis for IMRT. Weekly cone-beam computed tomography or daily megavoltage computed tomography was used for image guiding. For ICBT, 30–36 Gy in five to seven fractions were prescribed to point A. All patients received concurrent chemotherapy. The median follow-up duration was 32.5 months (range, 3.1–119.8 months). The three-year overall survival, disease-free survival and local control rates were 87.5%, 82.2% and 92.5%, respectively. Sixty patients (16.1%) experienced treatment failure, including 23 patients (6.2%) with pelvic relapse. The incidences of ≥grade 3 chronic gastrointestinal and genitourinary toxicity were 2.7% and 2.4%, respectively. These findings indicate that image-guided IMRT combined with dose-escalated ICBT results in good survival with acceptable toxicity in stage IIB cervical cancer 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.

MS 03.05 SBRT Experience

MS 03.05 SBRT Experience

Interfractional Rectal Displacement Requiring Repeated Precaution Did Not Correlate to Biochemical Control and Rectal Toxicity in Patients with Prostate Cancer Treated with Image-guided Intensity-modulated Radiation Therapy

To investigate the correlation between frequency of action level of interfractional rectal displacement requiring repeated precaution in patients with prostate cancer and late toxicity from image-guided intensity-modulated radiation therapy (IG-IMRT) using helical tomotherapy. We examined 264 patients who underwent IG-IMRT during 2007-2011. Megavoltage computed tomographic (MVCT) images were acquired before radiation therapy and was examined with soft-tissue matching by comparing treatment planning images within 9,345 fractions. Displacement of the anterior rectal region larger than 5 mm, requiring repeated precaution, was defined as the level of rectal displacement requiring action (ARD). ARD was identified in 815 (7.7%) out of 9,345 fractions and at least once in 82% (216/264) of patients. The highest incidence of ARD (11%) was found during the initial week of treatment (first five and next five fractions), after which the incidence decreased to 6% (p<0.0001). Patients with lean body (lower body mass index (BMI) tended to have a higher incidence of ARD. We identified 16 (6%) cases of gastrointestinal toxicity and 12 (4.5%) genitourinary toxicities as a late adverse reaction (3 months or later after IG-IMRT). There was no correlation between ARD and late toxicity. Prostate-specific antigen (PSA) control was also similar (p=0.12) between those with ARD (96% at 5 year) and those without ARD (88%). ARD occurred predominantly in lean patients, during the initial week of treatment and became less likely over time. ARD was not correlated to late toxicity and PSA control, therefore, IG-IMRT technique was able to adequately control error due to interfractional prostate and rectal motion.

Long-term Tumor Control and Late Toxicity in Patients with Prostate Cancer Receiving Hypofractionated (2.2 Gy) Soft-tissue-matched Image-guided Intensity-modulated Radiotherapy.

We report the long-term tumor control and toxicity outcomes of patients undergoing hypofractionated (2.2 Gy) image-guided intensity-modulated radiotherapy (IG-IMRT) using tomotherapy for clinically localized prostate cancer. We examined the cases of 138 consecutive patients with stage T1-T3 prostate cancer that were treated with IG-IMRT from June 2007 to July 2009. The median follow-up time was 79 months (range=31-96 months). The planning target volume received a dose of 72.6-74.8 Gy in 33-34 fractions (2.2 Gy/fraction). Megavoltage computed tomographic (CT) scans were performed before each treatment and corrected to the registered positions on the planning CT scans using prostate soft-tissue matching. The 5-year biochemical and clinical relapse-free survival rates were 95% for the low-risk group, 92% for the intermediate-risk group, and 77% for the high-risk group. The 5-year incidence rates of grade 2 and 3 late gastrointestinal toxicities were 6.3% and 3.1%, respectively, and those of grade 2 and 3 late genitourinary toxicities were 7.9% and 0%, respectively. Multivariate analysis indicated that T-stage is a prognostic factor for biochemical relapse-free survival rates. This report involved the longest followed-up cohort of patients to have received hypofractionated (2.2 Gy) soft tissue-matched IG-IMRT using tomotherapy. The findings of this study indicate that hypofractionated IMRT is well tolerated and is associated with good long-term tumor-control outcomes in patients with localized prostate cancer.

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.