Technical evaluation of the cone-beam computed tomography imaging performance of a novel, mobile, gantry-based X-ray system for brachytherapy.

PURPOSE: A novel, mobile cone-beam computed tomography (CBCT) system for image-guided adaptive brachytherapy was recently deployed at our hospital as worldwide first site. Prior to the device's clinical operation, a profound characterization of its imaging performance was conducted. This was essential to optimize both the imaging workflow and image quality for achieving the best possible clinical outcomes. We present the results of our investigations. METHODS: The novel CBCT-system features a ring gantry with 121 cm clearance as well as a 43.2 × 43.2 cm2 flat-panel detector, and is controlled via a tablet-personal computer (PC). For evaluating its imaging performance, the geometric reproducibility as well as imaging fidelity, computed tomography (CT)-number accuracy, uniformity, contrast-noise-ratio (CNR), noise characteristics, and spatial resolution as fundamental image quality parameters were assessed. As dose metric the weighted cone-beam dose index (CBDIw ) was measured. Image quality was evaluated using standard quality assurance (QA) as well as anthropomorphic upper torso and breast phantoms. Both in-house and manufacturer protocols for abdomen, pelvis, and breast imaging were examined. RESULTS: Using the in-house protocols, the QA phantom scans showed altogether a high image quality, with high CT-number accuracy (R2  > 0.97) and uniformity (<12 Hounsfield Unit (HU) cupping), reasonable noise and imaging fidelity, and good CNR at bone-tissue transitions of up to 28:1. Spatial resolution was strongly limited by geometric instabilities of the device. The breast phantom scans fulfilled clinical requirements, whereas the abdomen and pelvis scans showed severe artifacts, particularly at air/bone-tissue transitions. CONCLUSION: With the novel CBCT-system, achieving a high image quality appears possible in principle. However, adaptations of the standard protocols, performance enhancements in image reconstruction referring to artifact reductions, as well as the extinction of geometric instabilities are imperative.

Chemoradiotherapy with and without deep regional hyperthermia for squamous cell carcinoma of the anus.

PURPOSE: To compare results after chemoradiotherapy with and without deep regional hyperthermia in patients with anal cancer. METHODS: Between 2000 and 2015, a total of 112 consecutive patients with UICC stage I-IV anal cancer received chemoradiotherapy with 5­fluororuracil and mitomycin C (CRT). In case of insufficient tumor response 4-6 weeks after chemoradiotherapy, patients received an interstitial pulsed-dose-rate brachytherapy boost. Additionally, 50/112 patients received hyperthermia treatments (HCRT). RESULTS: Median follow-up was 41 (2-165) months. After 5 years follow-up, overall (95.8 vs. 74.5%, P = 0.045), disease-free (89.1 vs. 70.4%, P = 0.027), local recurrence-free (97.7 vs. 78.7%, P = 0.006), and colostomy-free survival rates (87.7 vs. 69.0%, P = 0.016) were better for the HCRT group. Disease-specific, regional failure-free, and distant metastasis-free survival rates showed no significant differences. The adjusted hazard ratios for death were 0.25 (95% CI, 0.07 to 0.92; P = 0.036) and for local recurrence 0.14 (95% CI, 0.02 to 1.09; P = 0.06), respectively. Grades 3-4 early toxicities were comparable with the exception of hematotoxicity, which was higher in the HCRT group (66 vs. 43%, P = 0.032). Incidences of late side effects were similar with the exception of a higher telangiectasia rate in the HCRT group (38.0 vs. 16.1%, P = 0.009). CONCLUSION: Additional regional hyperthermia improved overall survival, local control, and colostomy rates. Its potential beneficial role has to be confirmed in a prospective randomized setting. Therefore, the HyCAN trial has already been established by our group and is currently recruiting patients (Clinicaltrials.gov identifier: NCT02369939).

Quality-of-life results for accelerated partial breast irradiation with interstitial brachytherapy versus whole-breast irradiation in early breast cancer after breast-conserving surgery (GEC-ESTRO): 5-year results of a randomised, phase 3 trial.

BACKGROUND: Previous results from the GEC-ESTRO trial showed that accelerated partial breast irradiation (APBI) using multicatheter brachytherapy in the treatment of early breast cancer after breast-conserving surgery was non-inferior to whole-breast irradiation in terms of local control and overall survival. Here, we present 5-year results of patient-reported quality of life. METHODS: We did this randomised controlled phase 3 trial at 16 hospitals and medical centres in seven European countries. Patients aged 40 years or older with 0-IIA breast cancer were randomly assigned (1:1) after breast-conserving surgery (resection margins ≥2 mm) to receive either whole-breast irradiation of 50 Gy with a boost of 10 Gy or APBI using multicatheter brachytherapy. Randomisation was stratified by study centre, tumour type, and menopausal status, with a block size of ten and an automated dynamic algorithm. There was no masking of patients or investigators. The primary endpoint of the trial was ipsilateral local recurrence. Here, we present 5-year results of quality of life (a prespecified secondary endpoint). Quality-of-life questionnaires (European Organisation for Research and Treatment of Cancer QLQ-C30, breast cancer module QLQ-BR23) were completed before radiotherapy (baseline 1), immediately after radiotherapy (baseline 2), and during follow-up. We analysed the data according to treatment received (as-treated population). Recruitment was completed in 2009, and long-term follow-up is continuing. The trial is registered at ClinicalTrials.gov, number NCT00402519. FINDINGS: Between April 20, 2004, and July 30, 2009, 633 patients had accelerated partial breast irradiation and 551 patients had whole-breast irradiation. Quality-of-life questionnaires at baseline 1 were available for 334 (53%) of 663 patients in the APBI group and 314 (57%) of 551 patients in the whole-breast irradiation group; the response rate was similar during follow-up. Global health status (range 0-100) was stable in both groups: at baseline 1, APBI group mean score 65·5 (SD 20·6) versus whole-breast irradiation group 64·6 (19·6), p=0·37; at 5 years, APBI group 66·2 (22·2) versus whole-breast irradiation group 66·0 (21·8), p=0·94. The only moderate, significant difference (difference of 10-20 points) between the groups was found in the breast symptoms scale. Breast symptom scores were significantly higher (ie, worse) after whole-breast irradiation than after APBI at baseline 2 (difference of means 13·6, 95% CI 9·7-17·5; p<0·0001) and at 3-month follow-up (difference of means 12·7, 95% CI 9·8-15·6; p<0·0001). INTERPRETATION: APBI with multicatheter brachytherapy was not associated with worse quality of life compared with whole-breast irradiation. This finding supports APBI as an alternative treatment option after breast-conserving surgery for patients with early breast cancer. FUNDING: German Cancer Aid.

Reirradiation for recurrent head and neck cancer with salvage interstitial pulsed-dose-rate brachytherapy: Long-term results.

PURPOSE: To assess the long-term results of protocol-based interstitial pulsed-dose-rate (PDR) brachytherapy as reirradiation combined with simultaneous chemotherapy and interstitial hyperthermia in selected patients with recurrent head and neck tumors. MATERIALS AND METHODS: A total of 104 patients with biopsy-proven recurrent head and neck cancer were treated with interstitial PDR brachytherapy. Salvage surgery had also been undergone by 53/104 (51%) patients (R1 or R2 resection in > 80% of patients). Salvage brachytherapy alone was administered in 81 patients (78%), with a median total dose of 56.7 Gy. Salvage brachytherapy in combination with external beam radiotherapy (EBRT) was performed in 23/104 patients (32%), using a median total dose of DREF = 24 Gy. Simultaneously to PDR brachytherapy, concomitant chemotherapy was administered in 58/104 (55.8%) patients. A single session of interstitial hyperthermia was also used to treat 33/104 (31.7%) patients. The analysis was performed after a median follow-up of 60 months. RESULTS: Calculated according to Kaplan-Meier, local tumor control rates after 2, 5, and 10 years were 92.5, 82.4, and 58.9%, respectively. Comparing results of salvage PDR brachytherapy with or without simultaneous chemotherapy, the 10-year local control rates were 76 vs. 39% (p = 0014), respectively. No other patient- or treatment-related parameters had a significant influence on treatment results. Soft tissue necrosis or bone necrosis developed in 18/104 (17.3%) and 11/104 (9.6%) patients, respectively, but only 3% of patients required surgical treatment. CONCLUSION: PDR interstitial brachytherapy with simultaneous chemotherapy is a very effective and, in experienced hands, also a safe treatment modality in selected patients with head and neck cancer in previously irradiated areas.

Radiation therapy and simultaneous chemotherapy for recurrent cervical carcinoma.

PURPOSE: To evaluate the efficacy and toxicity in patients with recurrence of cervical cancer treated with radiotherapy and simultaneous chemotherapy. PATIENTS AND METHODS: Between 1987 and 2001, 24 patients with recurrent cervical carcinoma were treated with concurrent chemoradiotherapy. Nine patients had incomplete tumor resection prior to radiation therapy. Irradiation was delivered to a total dose of 60 Gy, in three patients with central recurrences supplemented by brachytherapy. One patient was treated with brachytherapy alone. Simultaneous chemotherapy was done as a combined therapy of 5-fluorouracil-(5-FU, 600 mg/m(2)/d1-5, 29-33) and cisplatin (20 mg/m(2)/d1-5, 29-33; 16/24 patients) or of 5-FU (1,000 mg/m(2)/d1-5, 29-33) and mitomycin C (10 mg/m(2)/d2, 30; 1/24 patients). Cisplatin alone (25 mg/m(2)/d1-5) and carboplatin alone (800 mg/m(2)/d1-5) were administered in 5/24 patients (21%) and 2/24 patients (8%). RESULTS: The 5-year local recurrence-free survival rate was 37%, disease-free survival 33%, and overall survival 34%. Grade 3 toxicity (NCI-CTC grade 3) occurred mainly as diarrhea (38%), leukopenia (33%), and nausea (21%). Severe toxicity (grade 4) was not seen in any of the patients. CONCLUSION: Radiation therapy with simultaneous chemotherapy for recurrences of cervical cancer is an effective treatment with acceptable toxicity.

The role of pulsed-dose-rate brachytherapy in previously irradiated head-and-neck cancer.

PURPOSE: The purpose of this prospective study was to analyze the value of interstitial pulsed-dose-rate (PDR) brachytherapy (iBT) with regard to local control and the incidence of side effects in patients with head-and-neck cancer in a previously irradiated area. METHODS AND MATERIALS: From October 1997 to September 2001, 43 patients with head-and-neck cancer in a previously irradiated area (31 patients with recurrent cancer) were treated with iBT alone or in combination with external beam radiation. Thirty-four of 43 patients received interstitial PDR brachytherapy (DREF=20-60 Gy) as part of their curative treatment regimen alone or in combination with external radiation. Nine patients were implanted for palliative purposes. The pulses were delivered 24 h/day with a time interval of 1 h between two pulses. The dose per pulse (dp) ranged from 0.4-0.7 Gy. Sixteen of 43 (37%) patients also received cisplatin or carboplatin with 5-fluorouracil during the time of the iBT. Additionally 20/43 (47%) patients were treated with interstitial hyperthermia. Thirteen of 43 (30%) patients received external beam radiation in a dose range from 20-67 Gy. A follow-up of all patients was done to analyze local control and survival, and acute and delayed toxicity. This analysis was performed after a median follow-up of 24 months (6-48 months). RESULTS: Local tumor control was achieved in 34 of a total of 43 patients (79%) and in 30/34 patients (88%) treated for curative intention. Distant metastases were observed in 5/43 (12%) patients. The 2-year local recurrence-free survival rates, disease-free survival rates, and overall survival rates according to the Kaplan-Meier method for all patients were 68%, 62%, and 49%, respectively, and for patients treated with curative intention they were 80%, 77% and 66%, respectively. There was no statistical difference in the probability of local recurrence in patients subgrouped by recurrent tumor vs. secondary primary, tumor size, grading and lymphangiosis. The application of chemotherapy or hyperthermia did not have significant influence on the therapy results. Soft tissue necrosis was the only serious side effect seen in 2/43 patients (4.7%). No other serious side effects were observed. CONCLUSIONS: Interstitial pulsed-dose-rate brachytherapy for patients with previously irradiated head-and-neck cancer is an effective therapy with minimal toxicity. The role of chemotherapy and hyperthermia in these patients remains unclear. Further randomized studies with larger patient numbers are necessary to draw a definite conclusion.

Pulsed-dose rate brachytherapy with concomitant chemotherapy and interstitial hyperthermia in patients with recurrent head-and-neck cancer.

PURPOSE: We attempted in our clinic to evaluate the efficacy and feasibility of a simultaneous application of a cis-platinum-based chemotherapy and interstitial hyperthermia to interstitial pulsed-dose rate (PDR) brachytherapy in patients with recurrent head-and-neck cancer. METHODS AND MATERIALS: Between April 1999 and September 2001, 15 patients with recurrent head-and-neck cancer were treated with PDR brachytherapy, chemotherapy, and interstitial hyperthermia. All patients had received prior radiation therapy. A dose per pulse of 0.46 to 0.55 Gy was given up to a median total dose of 55 Gy. Simultaneously to the PDR brachytherapy, chemotherapy was given with cis-platinum 20 mg/m2 as a short i.v. infusion each day and 5-fluorouracil 800 mg/m2 by continuous infusion from Day 1 to Day 5. After the PDR brachytherapy was finished, all patients were treated with a single session of interstitial hyperthermia. RESULTS: All the patients could receive the whole treatment. After treatment, only mild oral mucositis occurred. One patient developed soft tissue ulceration. None of the patients developed osteoradionecrosis. After a median follow-up of 6 months, the local tumor control rate was 80% (12 of 15), and the 2-year overall survival was 67% (10 of 15). CONCLUSIONS: The intensification of the interstitial PDR brachytherapy with chemotherapy and hyperthermia is feasible and safe, and the preliminary results are encouraging.