Impact of total marrow/lymphoid irradiation dose to the intestine on graft-versus-host disease in allogeneic hematopoietic stem cell transplantation for hematologic malignancies.

Background and purpose: Graft-versus-host disease (GvHD) is a leading cause of non-relapse mortality in patients undergoing allogeneic hematopoietic stem cell transplantation. The Perugia Bone Marrow Transplantation Unit designed a new conditioning regimen with total marrow/lymphoid irradiation (TMLI) and adaptive immunotherapy. The present study investigated the impact of radiotherapy (RT) doses on the intestine on the incidence of acute GvHD (aGvHD) in transplant recipients, analyzing the main dosimetric parameters. Materials and methods: Between August 2015 and April 2021, 50 patients with hematologic malignancies were enrolled. All patients underwent conditioning with TMLI. Dosimetric parameters (for the whole intestine and its segments) were assessed as risk factors for aGvHD. The RT dose that was received by each intestinal area with aGvHD was extrapolated from the treatment plan for each patient. Doses were compared with those of the whole intestine minus the affected area. Results: Eighteen patients (36%) developed grade ≥2 aGvHD (G2 in 5, G3 in 11, and G4 in 2). Median time to onset was 41 days (range 23-69 days). The skin was involved in 11 patients, the intestine in 16, and the liver in 5. In all 50 TMLI patients, the mean dose to the whole intestine was 7.1 Gy (range 5.07-10.92 Gy). No patient developed chronic GvHD (cGvHD). No dosimetric variable emerged as a significant risk factor for aGvHD. No dosimetric parameter of the intestinal areas with aGvHD was associated with the disease. Conclusion: In our clinical setting and data sample, we have found no clear evidence that current TMLI dosages to the intestine were linked to the development of aGvHD. However, due to some study limitations, this investigation should be considered as a preliminary assessment. Findings need to be confirmed in a larger cohort and in preclinical models.

Feasibility of a Novel Sparse Orthogonal Collimator-Based Preclinical Total Marrow Irradiation for Enhanced Dosimetric Conformality.

Total marrow irradiation (TMI) has significantly improved radiation conditioning for hematopoietic cell transplantation in hematologic diseases by reducing conditioning-induced toxicities and improving survival outcomes in relapsed/refractory patients. Recently, preclinical three-dimensional image-guided TMI has been developed to enhance mechanistic understanding of the role of TMI and to support the development of experimental therapeutics. However, a dosimetric comparison between preclinical and clinical TMI reveals that the preclinical TMI treatment lacks the ability to reduce the dose to some of the vital organs that are very close to the skeletal system and thus limits the ability to evaluate radiobiological relevance. To overcome this limit, we introduce a novel Sparse Orthogonal Collimator (SOC)-based TMI and evaluate its ability to enhance dosimetric conformality. The SOC-TMI-based dose modulation technique significantly improves TMI treatment planning by reducing radiation exposures to critical organs that are close to the skeletal system that leads to reducing the gap between clinical and preclinical TMI.

Tomotherapy-based moderate hypofractionation for localized prostate cancer: a mono-institutional analysis.

Background: To date, few studies have been published on image-guided helical tomotherapy (HT) in a moderate hypofractionation of localized PCa. We report outcome and toxicity of localized PCa patients treated with HT-based moderate hypofractionated radiotherapy. Materials and methods: 76 patients were retrospectively analyzed. A total dose of 60 Gy (20 × 3 Gy) or 67.5 Gy (25 × 2.7 Gy) was prescribed. The χ2 test was used to analyze associations between toxicity and dosimetric and clinical parameters. The Cox proportional hazard regression model was used for multivariate analysis. Kaplan-Meier method was used for survival analysis. Results: median follow-up was 42.26 months [interquartile (IQR), 23-76). At 4-year, overall survival (OS) and metastasis-free survival (MFS) were 91% and 89%, respectively. At multivariate analysis, smoking habitude was associated with MFS [hazard ratio (HR) 7.32, 95% CI: 1.57-34.16, p = 0.011]. Acute and late grade ≥ 2 gastro-intestinal (GI) toxicity was observed in 6.5% and 2.6% of patients, respectively. Acute and late grade ≥ 2 genito-urinary (GU) toxicity were 31.5% and 3.9%. Four-year late GI and GU grade ≥ 2 toxicity were 3% and 7%, respectively. Acute GI toxicity was associated with statins medication (p = 0.04) and androgen deprivation therapy (p = 0.013). Acute GU toxicity was associated with the use of anticoagulants (p = 0.029) and antiaggregants (p = 0.013). Conclusions: HT-based moderate hypofractionation shows very low rates of toxicity. Smoking habitude is associated with the risk of developing metastases after radical treatment for localized PCa.

High-dose-rate brachytherapy with surface applicator in penile cancer.

PURPOSE: An alternative to surgery for penile cancer is radiation therapy which is administered with external beam techniques and/or brachytherapy (BT) either interstitial or using a surface applicator. Here we report our experience in penile cancer patients treated with high-dose-rate (HDR)-BT with the surface technique, analyzing dosimetric parameters and clinical outcomes. METHODS AND MATERIALS: Between June 2016 and December 2019, 7 patients with squamous cell carcinoma of the penis received HDR-BT by means of customized applicators that were constructed using a 3D printer or thermoplastic mask. The total dose was 57 Gy in 19 fractions. RESULTS: Median clinical target volume percentage receiving 95%, 125%, and 150% of the prescribed dose were 93.1% (range 92.2-98.5), 12% (range 7.4-32.2), and 0.24% (range 0-10.8), respectively. Median urethral volumes receiving 90% and 115% of the prescribed dose were 40.2% (range 21.0-83.8) and 0% (range 0-1), respectively. All patients achieved complete remission. No patient developed G3 or G4 acute or late toxicities. No patient experienced urethral stenosis. CONCLUSIONS: Surface HDR-BT in penile cancer is feasible and is associated with a high tolerance profile and good outcomes.

Haploidentical age-adapted myeloablative transplant and regulatory and effector T cells for acute myeloid leukemia.

Allogeneic hematopoietic stem cell transplantation (HSCT) is the most effective treatment in eradicating high-risk acute myeloid leukemia (AML). Here, we present data from a novel HLA-haploidentical HSCT protocol that addressed the 2 remaining major unmet medical needs: leukemia relapse and chronic graft-versus-host disease (cGVHD). Fifty AML patients were enrolled in the study. The conditioning regimen included total body irradiation for patients up to age 50 years and total marrow/lymphoid irradiation for patients age 51 to 65 years. Irradiation was followed by thiotepa, fludarabine, and cyclophosphamide. Patients received an infusion of 2 × 106/kg donor regulatory T cells on day -4 followed by 1 × 106/kg donor conventional T cells on day -1 and a mean of 10.7 × 106 ± 3.4 × 106/kgpurified CD34+ hematopoietic progenitor cells on day 0. No pharmacological GVHD prophylaxis was administered posttransplantation. Patients achieved full donor-type engraftment. Fifteen patients developed grade ≥2 acute GVHD (aGVHD). Twelve of the 15 patients with aGVHD were alive and no longer receiving immunosuppressive therapy. Moderate/severe cGVHD occurred in only 1 patient. Nonrelapse mortality occurred in 10 patients. Only 2 patients relapsed. Consequently, at a median follow-up of 29 months, the probability of moderate/severe cGVHD/relapse-free survival was 75% (95% confidence interval, 71%-78%). A novel HLA-haploidentical HSCT strategy that combines an age-adapted myeloablative conditioning regimen with regulatory and conventional T-cell adoptive immunotherapy resulted in an unprecedented cGVHD/relapse-free survival rate in 50 AML patients with a median age of 53 years. This trial was registered with the Umbria Region Institutional Review Board Public Registry as identification code 02/14 and public registry #2384/14 and at www.clinicaltrials.gov as #NCT03977103.

Fractionated Stereotactic Sequential Boost in a Selected Cohort of Glioblastoma Patients: A Mono-institutional Analysis.

AIM: To retrospectively assess toxicity and survival in 15 selected Glioblastoma patients treated with a sequential fractionated stereotactic radiotherapy (FSRT) boost after chemo-radiotherapy (CHT-RT) and compare their survival outcomes with a control group. PATIENTS AND METHODS: Toxicity was assessed with the CTCAE 3.0 scale. The Kaplan-Meier method was used to design survival curves, log-rank test for bivariate analysis and Cox proportional hazard regression model for multivariate analysis. RESULTS: The median follow-up was 16 months (range=5-60). One case of headache and one of radionecrosis (RN) occurred. Median overall survival (OS) was 25 months in the boost group vs. 14 in the no-boost group (p=0.004). Median progression-free survival (PFS) was 15 months in the boost group versus 8 in the no-boost group (p=0.046). At multivariate analysis FSRT boost resulted significantly associated with OS and PFS. CONCLUSION: In our series a sequential FSRT boost resulted in safe outcomes and significantly associated with survival.

Multi-institutional evaluation of MVCT guided patient registration and dosimetric precision in total marrow irradiation: A global health initiative by the international consortium of total marrow irradiation.

PURPOSE: Total marrow irradiation (TMI) is a highly conformal treatment of the human skeleton structure requiring a high degree of precision and accuracy for treatment delivery. Although many centers worldwide initiated clinical studies using TMI, currently there is no standard for pretreatment patient setup. To this end, the accuracy of different patient setups was measured using pretreatment imaging. Their impact on dose delivery was assessed for multiple institutions. METHODS AND MATERIALS: Whole body imaging (WBI) or partial body imaging (PBI) was performed using pretreatment megavoltage computed tomography (MVCT) in a helical Tomotherapy machine. Rigid registration of MVCT and planning kilovoltage computed tomography images were performed to measure setup error and its effect on dose distribution. The entire skeleton was considered the planning target volume (PTV) with five sub regions: head/neck (HN), spine, shoulder and clavicle (SC), and one avoidance structure, the lungs. Sixty-eight total patients (>300 images) across six institutions were analyzed. RESULTS: Patient setup techniques differed between centers, creating variations in dose delivery. Registration accuracy varied by anatomical region and by imaging technique, with the lowest to the highest degree of pretreatment rigid shifts in the following order: spine, pelvis, HN, SC, and lungs. Mean fractional dose was affected in regions of high registration mismatch, in particular the lungs. CONCLUSIONS: MVCT imaging and whole body patient immobilization was essential for assessing treatment setup, allowing for the complete analysis of 3D dose distribution in the PTV and lungs (or avoidance structures).

Potential skin morbidity reduction with intensity-modulated proton therapy for breast cancer with nodal involvement.

Background: Different modern radiation therapy treatment solutions for breast cancer (BC) and regional nodal irradiation (RNI) have been proposed. In this study, we evaluate the potential reduction in radiation-induced skin morbidity obtained by intensity modulated proton therapy (IMPT) compared with intensity modulated photon therapy (IMXT) for left-side BC and RNI. Material and Methods: Using CT scans from 10 left-side BC patients, treatment plans were generated using IMXT and IMPT techniques. A dose of 50 Gy (or Gy [RBE] for IMPT) was prescribed to the target volume (involved breast, the internal mammary, supraclavicular, and infraclavicular nodes). Two single filed optimization IMPT (IMPT1 and IMPT2) plans were calculated without and with skin optimization. For each technique, skin dose-metrics were extracted and normal tissue complication probability (NTCP) models from the literature were employed to estimate the risk of radiation-induced skin morbidity. NTCPs for relevant organs-at-risk (OARs) were also considered for reference. The non-parametric Anova (Friedman matched-pairs signed-rank test) was used for comparative analyses. Results: IMPT improved target coverage and dose homogeneity even if the skin was included into optimization strategy (HIIMPT2 = 0.11 vs. HIIMXT = 0.22 and CIIMPT2 = 0.96 vs. CIIMXT = 0.82, p < .05). A significant relative skin risk reduction (RR = NTCPIMPT/NTCPIMXT) was obtained with IMPT2 including the skin in the optimization with a RR reduction ranging from 0.3 to 0.9 depending on the analyzed skin toxicity endpoint/model. Both IMPT plans attained significant OARs dose sparing compared with IMXT. As expected, the heart and lung doses were significantly reduced using IMPT. Accordingly, IMPT always provided lower NTCP values. Conclusions: IMPT guarantees optimal target coverage, OARs sparing, and simultaneously minimizes the risk of skin morbidity. The applied model-based approach supports the potential clinical relevance of IMPT for left-side BC and RNI and might be relevant for the setup of cost-effectiveness evaluation strategies based on NTCP predictions, as well as for establishing patient selection criteria.

Acute Toxicity Profiles of Hypofractionated Adjuvant and Salvage Radiation Therapy After Radical Prostatectomy: Results of a Prospective Study.

PURPOSE: Hypofractionated radiation therapy (RT) is controversial after radical prostatectomy (RP). In this interim analysis, our prospective observational study assessed acute genitourinary (GU) and gastrointestinal (GI) toxicity after hypofractionated adjuvant and salvage RT, as delivered by helical tomotherapy (HT), in patients with prostate cancer. METHODS AND MATERIALS: After undergoing RP with or without pelvic lymph node dissection, 112 patients were enrolled. Hypofractionated adjuvant RT (2.25 Gy daily for 29 fractions; total 65.25 Gy) was administered to 40 patients with high-risk features. Hypofractionated salvage RT (2.25 Gy daily for 32 or 33 fractions; total 72-74.25 Gy) was prescribed for 72 patients (24 with biochemical relapse, 48 with local relapse). Toxicity was graded according to the Common Terminology Criteria for Adverse Events version 4.02. The impact of RT on urinary flow was assessed by uroflowmetry. RESULTS: Acute GU toxicity occurred in 41 of 112 patients (36%) (G1 31, G2 10). Acute GI toxicity was observed in 55 (49%) patients (G1 44, G2 11). Uroflowmetry showed that only salvage RT reduced maximum flow significantly (maximum, 68 vs 50 mL/s; P = .003), perhaps because a higher RT dose had been administered. CONCLUSIONS: After RP, moderate hypofractionated adjuvant and salvage RT were associated with acceptable incidences of slight-to-moderate acute GU and GI toxicity and had little impact on urinary flow. Prospective trials are warranted with longer follow-up in larger cohorts to confirm these findings.

Skin toxicity after chest wall/breast plus level III-IV lymph nodes treatment with helical tomotherapy.

INTRODUCTION: To evaluate the incidence of toxicity in breast cancer with helical tomotherapy (HT). MATERIALS AND METHODS: 51 patients with breast cancer were assigned to postoperative radiotherapy by means of HT to the chest wall/breast plus draining nodes. During HT treatment, toxicity was monitored and were assessed using the Common Terminology Criteria for Adverse Events 4.0 scale. RESULTS: Acute skin G3 toxicity observed in 1.9% cases. No acute or late G4 toxicity was observed. At a median follow-up of 21 months 2 patients have late G1 toxicity. CONCLUSIONS: HT was associated with a low incidence of low-grade skin toxicity.

Is volumetric modulated arc therapy with constant dose rate a valid option in radiation therapy for head and neck cancer patients?

BACKGROUND: Intensity-modulated radiotherapy (IMRT) improves dose distribution in head and neck (HN) radiation therapy. Volumetric-modulated arc therapy (VMAT), a new form of IMRT, delivers radiation in single or multiple arcs, varying dose rates (VDR-VMAT) and gantry speeds, has gained considerable attention. Constant dose rate VMAT (CDR-VMAT) associated with a fixed gantry speed does not require a dedicated linear accelerator like VDR-VMAT. The present study explored the feasibility, efficiency and delivery accuracy of CDR-VMAT, by comparing it with IMRT and VDR-VMAT in treatment planning for HN cancer. METHODS AND MATERIALS: Step and shoot IMRT (SS-IMRT), CDR-VMAT and VDR-VMAT plans were created for 15 HN cancer patients and were generated by Pinnacle3 TPS (v 9.8) using 6 MV photon energy. Three PTVs were defined to receive respectively prescribed doses of 66 Gy, 60 Gy and 54 Gy, in 30 fractions. Organs at risk (OARs) included the mandible, spinal cord, brain stem, parotids, salivary glands, esophagus, larynx and thyroid. SS-IMRT plans were based on 7 co-planar beams at fixed gantry angles. CDR-VMAT and VDR-VMAT plans, generated by the SmartArc module, used a 2-arc technique: one clockwise from 182° to 178° and the other one anti-clockwise from 178° to 182°. Comparison parameters included dose distribution to PTVs (Dmean, D2%, D50%, D95%, D98% and Homogeneity Index), maximum or mean doses to OARs, specific dose-volume data, the monitor units and treatment delivery times. RESULTS: Compared with SS-IMRT, CDR-VMAT significantly reduced the maximum doses to PTV1 and PTV2 and significantly improved all PTV3 parameters, except D98% and D95%. It significantly spared parotid and submandibular glands and was associated with a lower Dmean to the larynx. Compared with VDR-VMAT, CDR-VMAT was linked to a significantly better Dmean, to the PTV3 but results were worse for the parotids, left submandibular gland, esophagus and mandible. Furthermore, the Dmean to the larynx was also worse. Compared with SS-IMRT and VDR-VMAT, CDR-VMAT was associated with higher average monitor unit values and significantly shorter average delivery times. CONCLUSIONS: CDR-VMAT appeared to be a valid option in Radiation Therapy Centers that lack a dedicated linear accelerator for volumetric arc therapy with variable dose-rates and gantry velocities, and are unwilling or unable to sanction major expenditure at present but want to adopt volumetric techniques.

Comparing four radiotherapy techniques for treating the chest wall plus levels III-IV draining nodes after breast reconstruction.

OBJECTIVE: To compare the dosimetric outcomes of four radiotherapy (RT) techniques for treating the chest wall plus draining nodes after mastectomy and breast reconstruction. METHODS: Three-dimensional conformal radiotherapy, linac-based intensity modulated RT, helical tomotherapy (HT) and direct tomotherapy treatments were planned for 40 breast cancer patients. Dose prescription was 50 Gy. Plans were compared in terms of doses to the planning target volume, organs at risk and the homogeneity index. The non-parametric Friedman test for paired data and the Conover post hoc analysis were used for data analysis. RESULTS: HT provided the highest D90 and D98% and the lowest HI, V107% and D2%. HT was associated with the lowest D2% and V25 Gy to the heart in left-sided treatments but the mean cardiac dose was highest. HT provided the highest V5 Gy and V20 Gy to the ipsilateral lung, but the V30 Gy was lower. The contralateral breast and lung were more exposed with HT. CONCLUSION: The present dosimetric study together with daily use of CT-MV image guided RT have led us to opt for HT after mastectomy and breast reconstruction and to draw up a suitable protocol for treating the chest wall and levels III and IV draining nodes. Advances in knowledge: HT is a suitable for treating the chest wall and levels III and IV draining nodes.

Comparison of Helical Tomotherapy and Direct Tomotherapy in Bilateral Whole Breast Irradiation in a Case of Bilateral Synchronous Grade 1 and Stage 1 Breast Cancer.

BACKGROUND Synchronous bilateral breast cancer is rare. A case is presented where whole breast irradiation (WBI) was planned after breast conserving surgery in a patient with synchronous bilateral breast cancer. A comparison was made between the feasibility of helical tomotherapy and direct tomotherapy. CASE REPORT A 60-year-old woman was found to have bilateral breast nodules on routine mammographic screening, resulting in bilateral lumpectomy and sentinel lymph node biopsy. Histopathology showed a 6 mm diameter invasive ductal carcinoma in the right breast (Grade 1, hormone receptor positive, HER2 negative) and an 8mm diameter tubular carcinoma in the left breast (Grade 1, hormone receptor positive, HER2 negative). Lymph node biopsy and histology, chest X-ray, abdominal ultrasound scan, and bone scintigraphy were negative for metastases (both tumors were Stage 1). Adjuvant therapy with commenced with anastrozole, but no chemotherapy was given. Clinical target volumes (CTVs) were contoured on computed tomography (CT) images. For planning target volumes (PTVs), CTVs were expanded by 1 cm in all directions, except for the medial 5 mm. Since dose constraints to organs at risk (OARs) were beyond established limits, CTVs were expanded by 5 mm. For PTVs, OAR doses and homogeneity indices for helical tomotherapy and direct tomotherapy were compared. Helical tomotherapy provided better target volume coverage and OAR sparing than direct tomotherapy. CONCLUSIONS In a case of bilateral synchronous Stage 1 and Grade 1 breast cancer, helical tomotherapy appeared more suitable than direct tomotherapy.

Partial breast irradiation with interstitial multi-catheter high-dose-rate brachytherapy. Long-term results of a phase II prospective study.

PURPOSE: We report the long-term results of phase II prospective study with accelerated partial breast irradiation (APBI) using interstitial multi-catheter high-dose-rate brachytherapy. METHODS: 240 patients received APBI (4Gy, twice daily; total dose 32Gy). RESULTS: Median follow-up was 96months. Recurrences in the treated breast developed in 8 patients (3.3%) at a median of 73months after APBI. The 5- and 10-year cumulative incidences were respectively, 1.8% (95%CI: 0.6-4.3) and 6.6% (95%CI: 2.7-12.9). Regional recurrences developed in 5 patients (2%) at a median of 28months and distant metastases in 8 (3.3%) at a median of 32.5months. Breast cancer specific mortality occurred in 6 patients (2.5%) at a median of 60months. Acute toxicity developed in 71 (29.6%) patients (G1 in 60 and G2 in 11). Almost all were skin toxicity and hematomas. Late toxicity was observed in 90 patients (37.5%), G1 in 97 cases and G2 in 11. Some patients presented with more than one type of toxicity. Teleangectasia and fibrosis were the most common (48 and 44 cases respectively), followed by fat necrosis (in 18 patients) Tamoxifen emerged as the only risk factor for breast fibrosis (p=0.007). Cosmetic results were judged by the physicians as excellent in 174 (83.7%) patients, good in 25 (12%) fair in 8 (3.8%) and poor in 1 (0.5%); 174 patients (83.7%) judged outcomes as excellent, 26 (12.4%) as good, 7 (3.4%) as fair and 1 (0.5%) as poor. Physician/patient agreement was good (weighted k-value 0.72). CONCLUSIONS: APBI with interstitial multi-catheter brachytherapy was associated with good outcomes, low relapse and toxicity rates. Few events during this long-term follow-up preclude identifying specific features of patients at risk of relapse and illustrate the need for a large data-base.

Helical tomotherapy for duodenal adenocarcinoma in an elderly patient: A case report.

To evaluate the efficacy and feasibility of external beam radiotherapy (EBRT) for duodenal adenocarcinoma in an 84-year-old female who underwent EBRT (2.2 Gy/d for a total dose of 46.2 Gy) using helical tomotherapy (HT). Toxicity was evaluated on the National Cancer Institute's common toxicity criteria (CTCAE 3.0). The patient completed the treatment without G3-G4 toxicity. After 22-mo follow-up, she is alive and well, in complete remission with no late side effects. HT seems to be feasible and effective for duodenal adenocarcinoma in old to very old patients.

Recurrences and toxicity after adjuvant vaginal brachytherapy in Stage I-II endometrial cancer: A monoinstitutional experience.

PURPOSE: To evaluate the incidences of vaginal recurrence and toxicity after vaginal brachytherapy in Stage I-II endometrial cancer. METHODS AND MATERIALS: Between 2003 and 2012, 150 high-intermediate-risk Stage I and 7 Stage II patients, median age 64 years, underwent surgery, with or without lymphadenectomy, and 3D brachytherapy: 7 Gy, at 5 mm depth from applicator surface, for 3-week fractions. The effects of age, grading, number of excised lymph nodes and pathologic stage on loco-regional relapse (LRR), metastases, and tumor-related death were investigated. Vaginal toxicity was evaluated during followup visits. RESULTS: At 83 months of median followup, 144 patients were disease free, 2 in relapse, 7 deceased from disease, and 4 from other causes. One vaginal (0.6%), five nodal (3.2%), three pelvic over the vaginal cuff (1.9%), and one distant recurrences were seen (0.6%). The 5-year probability of LRR-free, distant metastasis-free and cause-specific survivals for all patients were 93.6% (95% confidence interval [CI]: 88.1-96.7), 97.8% (95% CI: 93.2-99.3), and 96.5% (95% CI: 93.5-99.5) and for Stage I 95.7% (95% CI: 92.2-9.1), 99.3% (95% CI: 98.0-100), and 97.7% (95% CI: 95.2-100), respectively. At multivariate analysis, Stage II disease and more than 12 lymph nodes sampled were associated with LRR (hazard ratio [HR]: 3.88; 95% CI: 1.390-10.878; p = 0.010 and HR: 6.952; 95% CI: 1.591-30.385; p = 0.010) and Stage II with metastasis and tumor-related death (HR: 23.057; 95% CI: 2.296-231.485; p = 0.008 and HR: 4.324; 95% CI: 1.223-15.290; p = 0.023). Vaginal acute and chronic toxicity was 16% and 55.4%, respectively, all only Grades 1-2. CONCLUSIONS: For high-to-intermediate-risk Stage I endometrial cancer, 3D vaginal brachytherapy achieved good local control and low toxicity. In Stage II, patients brachytherapy could be administered after complete surgical staging.

Radiotherapy for early-stage prostate cancer in men under 70 years of age.

AIMS: To demonstrate that radiotherapy (RT) is a valid alternative to surgery in men ≤70 years old with localized prostate cancer. METHODS: From 1988 to 2009, 214 patients with T1-2 N0 M0 prostate cancer were treated with RT. The effects of patient- and treatment-related risk factors on toxicity were investigated. RESULTS: Median follow-up was 105 months (range 14.2-180). The 5-, 10-, and 15-year biochemical relapse-free survival for all 214 patients was 80%, 61.9%, and 57.5%, respectively. In bivariate analysis, age (≤65 vs 65-70 years) was not a significant factor for biochemical relapse, while radiation dose was (p = 0.05) in multivariate analysis. Cancer-specific survival rates at 5, 10, and 15 years were 98.4%, 93.2%, and 69.7%, respectively. Median overall survival (OS) was 167 months (95% confidence interval 147.3-186.7). The OS rates at 5, 10, and 15 years were 91.8%, 75.8%, and 42.5%, respectively. Acute genitourinary (GU) and gastrointestinal (GI) toxicities occurred in 105 (49%) and 98 patients (45.8%), respectively, with only 2 cases of grade III GI toxicity. Late GU and GI toxicities occurred in 17 (7.9%) and 20 (9.3%) patients, respectively, with 1 grade III GI toxicity and 2 grade III GU toxicities. Risk factors for late toxicity were age and RT dose and technique, which were unrelated to acute toxicity. CONCLUSIONS: Age ≤70 years does not consistently confer a negative prognosis for localized prostate cancer. Radiotherapy appears to be a viable alternative to surgery, offering excellent long-term cancer control.

Prostate cancer: contouring target and organs at risk by kilovoltage and megavoltage CT and MRI in patients with and without hip prostheses.

OBJECTIVE: In radiotherapy treatment, planning target volume and organs at risk are contoured on kilovoltage CT (kVCT) images. Unlike MR images, kVCT does not provide precise information on target volume extension. Since neither kVCT nor MRI may be suitable for contouring in patients with ferrous hip prostheses, this study evaluated whether megavoltage CT (MVCT) reduced interobserver variability. METHODS: Two patients without hip prostheses and one patient (Patient 3) with hip prostheses were enrolled. Six radiation oncologists contoured prostate, rectum and bladder on kVCT (Patients 1 and 3), MRI (Patient 2) and MVCT images (Patient 3). MVCT was acquired with fine, normal and coarse modalities. Interobserver variability for each organ was analysed using conformity index (CI) and coefficient of variation (CV). RESULTS: In patients without hip prostheses, CIs were higher in prostate contouring with MRI than with kVCT, indicating lower interobserver variability with MRI. Very slight variations were seen in rectum and bladder contouring. In the patient with hip prostheses (Patient 3), contouring on kVCT lowered CI and increased CV in the prostate, bladder and rectum. The differences were more marked in the prostate. Only fine modality MVCT reduced interobserver variability and only for the prostate. CONCLUSION: Even though greater noise and less soft-tissue contrast increase contouring variability with MVCT than with kVCT, lack of artefacts on MVCT could provide better image definition by this modality in hip prosthesis patients in whom MRI is precluded. ADVANCES IN KNOWLEDGE: We recommend the fine modality MVCT for contouring hip prostheses patients.

Does ultrasound provide any added value in breast contouring for radiotherapy after conserving surgery for cancer?

BACKGROUND: Whole breast irradiation after conserving surgery for breast cancer requires precise definition of the target volume. The standard approach uses computed tomography (CT) images. However, since fatty breast and non-breast tissues have similar electronic densities, difficulties in differentiating between them hamper breast volume delineation. To overcome this limitation the breast contour is defined by palpation and then radio-opaque wire is put around it before the CT scan. To optimize assessment of breast margins in the cranial, caudal, medial, lateral and posterior directions, the present study evaluated palpation and CT and determined whether ultrasound (US) provided any added value. METHODS: Twenty consecutive patients were enrolled after they had provided informed consent to participating in this prospective study which was approved by the Regional Public Health Ethics Committee. Palpation and US defined breast margins and each contour was marked and outlined with a fine plastic wire. Breasts were then contoured on axial CT images using the breast window width (WW) and window level (WL) (401 and 750 Hounsfield Units -HU- respectively), at which setting the plastic wires were invisible. Then, the lung window function (WW 1601 HU; WL -300 HU) was inserted to visualize the plastic wires which were used as guidelines to contour the palpable and US breast volumes. As each wire had a different diameter, both volumes were easily defined on CT slices. Results were analyzed using descriptive statistics, percentage overlap and reproducibility measures (agreement and reliability). RESULTS: Volumes: US gave the largest and palpation the smallest. Agreement was best between palpation and CT. Reliability was almost perfect in all correlations. Extensions: Cranial and posterior were highest with US and smallest with palpation. Agreement was best between palpation and CT in all extensions except the cranial. Since strong to almost perfect agreement emerged for all comparisons, reliability was high. CONCLUSIONS: US may be useful in defining the cranial and posterior extensions, mainly when tumours are localized there. This study demonstrates that the now standard radio-opaque wires around the palpable breast may not be needed in breast contouring.

Outcome of a phase II prospective study on partial breast irradiation with interstitial multi-catheter high-dose-rate brachytherapy.

BACKGROUND AND PURPOSE: Partial breast irradiation (PBI) is an alternative to whole-breast irradiation after breast-conserving surgery in selected patients. Until the results of randomized phase III studies are available, phase II studies inform about PBI. We report the 5 year results of a phase II prospective study with PBI using interstitial multi-catheter high-dose-rate brachytherapy (ClinicalTrials.gov Identifier: NCT00499057). METHODS: Hundred patients received PBI (4 Gy, twice a day for 4 days, until 32 Gy). Inclusion criteria were: age ≥ 40years, infiltrating carcinoma without lobular histology, ductal in situ carcinoma, tumor size ≤ 2.5 cm, negative surgical margins and axillary lymph nodes. RESULTS: At a median follow-up of 60 months late toxicity occurred in 25 patients; the 5-year probability of freedom from late toxicity was 72.6% (95% CI: 63.7-81.7). Tamoxifen was the only significant risk factor for late toxicity. Cosmetic results, judged by physicians and patients, were good/excellent in 98 patients. Three local relapses (1 true, 2 elsewhere) and 1 regional relapse occurred. The 5-year probability of local or regional relapse-free survival was 97.7% (95% CI: 91.1-99.4) and 99.0% (95% CI: 92.9-99.8), respectively. CONCLUSION: PBI with interstitial multi-catheter brachytherapy is associated with low relapse and late toxicity rates.