Use of a two-dimensional ionization chamber array for quality assurance in medical linear accelerators

Two-dimensional dosimetry measurements are an important tool of Quality Assurance in modern radiotherapy techniques, such as the Intensity Modulated Radiation Therapy (IMRT). Common procedures are usually based on the use of films or semiconductor arrays as dosimeters. This paper presents our experience with a two-dimensional ionization-chamber array. The methods presented here allow the daily use of the array for a constancy check of the accelerator. It is also shown that the position of the individual leafs of the multi-leaf collimator (MLC) can be verified to within +/- 1 mm of their calibration. A procedure for the measurements is described and discussed.     

Clinical Review of the Japanese Experience with Boron Neutron Capture Therapy and A Proposed Strategy Using Epithermal Neutron Beams

Our concept of boron neutron capture therapy (BNCT) is selective destruction of tumor cells using the heavy-charged particles yielded through ¹⁰ B(n, )⁷ Li reactions. To design a new protocol that employs epithermal neutron beams in the treatment of glioma patients, we examined the relationship between the radiation dose, histological tumor grade, and clinical outcome. Since 1968, 183 patients with different kinds of brain tumors were treated by BNCT; for this retrospective study, we selected 105 patients with glial tumors who were treated in Japan between 1978 and 1997. In the analysis of side effects due to radiation, we included all the 159 patients treated between 1977 and 2001.With respect to the radiation dose (i.e. physical dose of boron n-alpha reaction), the new protocol prescribes a minimum tumor volume dose of 15Gy or, alternatively, a minimum target volume dose of 18Gy. The maximum vascular dose should not exceed 15Gy (physical dose of boron n-alpha reaction) and the total amount of gamma rays should remain below 10Gy, including core gamma rays from the reactor and capture gamma in brain tissue.The outcomes for 10 patients who were treated by the new protocol using a new mode composed of thermal and epithermal neutrons are reported.     

The Combined Effect of Electroporation and Borocaptate in Boron Neutron Capture Therapy for Murine Solid Tumors

¹⁰B-Enriched borocaptate (BSH) was administered intraperitoneally to SCCVII tumor-bearing C3H/He mice. Electroporation (EP) was conducted by using a tweezers-type electrode. The ¹⁰B contents in tumors were measured by prompt γ-ray spectrometry. The colony formation assay was applied to investigate the antitumor effects of boron neutron capture therapy (BNCT) and thereby to estimate the intratumor localization of BSH. The ¹⁰B concentrations in tumors decreased with time following BSH administration, falling to 5.4(±0.1) ppm at 3 h, whereas EP treatment (3 repetitions) 15 min after BSH injection delayed the clearance of BSH from tumors, and the ¹⁰B level remained at 19.4(±0.9) ppm at 3 h. The effect of BNCT increased with the ¹⁰B concentration in tumors, and the combination with EP showed a remarkably large cell killing effect even at 3 h after BSH injection. The effect of BNCT, i.e., slope coefficient of the cell survival curve of tumors, without EP was proportional to tumor ¹⁰B level ( r =0.982), and that of BSH-BNCT combined with EP lay close to the same correlation line. However, tumors subjected to EP after BSH injection did not show high radiosensitivity when irradiated after conversion to a single cell suspension by enzymatic digestion. This indicates that the increase of the BNCT effect by EP was a consequence of enclosure of BSH in the interstitial space of tumor tissue and not within tumor cells. This is different from a previous in vitro study. The combination of EP and BNCT may be clinically useful, if a procedure to limit EP to the tumor region becomes available or if an alternative similar method is employed.     

Quality assurance and quality control for radiotherapy/medical oncology in Europe: Guideline development and implementation

The past two decades have brought tremendous changes to the practice of radiation oncology and medical oncology. To manage all the complexities related to the new technologies and the new drugs, the radiation and medical oncologists have to enhance their clinical action and professional skill profile. To accomplish this they have to find reliable tools in the quality of their medical practice and in future research activities. Quality assurance (QA) and quality control (QC) for radiation and medical oncologists mean to clarify the different components of the clinical decision, to supervise with proper methodology the required steps needed to accomplish the agreed outcomes and to control them. Quality for radiation and medical oncology means to supervise each clinical and technical component of the whole process to guarantee that all steps together will arrive at the final and best possible outcome. Key components are guidelines, specialization and a multidisciplinary approach. The research of global quality could represent a further complexity, but it is the best tool to give a perspective and a chance to further improvements of our disciplines and to promote better outcome in all cancer patients.     

In vivo quality assurance of volumetric modulated arc therapy for ano-rectal cancer with thermoluminescent dosimetry and image-guidance

Objective

To assess in vivo dose distribution using cone-beam computed tomography scans (CBCTs) and thermoluminescent dosimeters (TLDs) in patients with anal or rectal cancer treated with volumetric modulated arc therapy (VMAT).

Methods

Intracavitary (IC) in vivo dosimetry (IVD) was performed in 11 patients using adapted endorectal probes containing TLDs, with extra measurements at the perianal skin (PS) for anal margin tumors. Measured doses were compared to calculated ones obtained from image fusion of CBCT with CT treatments plans.

Results

A total of 55 IC and 6 PS measurements were analyzed. IC TLD median planned and measured doses were 1.81 Gy (range, 0.25–2.02 Gy) and 1.82 Gy (range, 0.19–2.12 Gy), respectively. In comparison to the planned doses all IC TLD dose measurements differed by a median dose of 0.02 Gy (range, −0.11/+0.19 Gy, p = 0.102) (median difference of 1.1%, range −6.1%/+10.6%). Overall, 95% of IC measurements were within ±7.7% of the expected percentage doses and only 1 value was above +10%. For PS measurements, only one was not within ±7.7% of expected values (i.e., −8.9%).

Conclusions

Image guidance using CBCT for IVD with TLDs is helpful to validate the delivered doses in patients treated with VMAT for ano-rectal tumors.     

Responses of Total and Quiescent Cell Populations in Solid Tumors to Boron and Gadolinium Neutron Capture Reaction Using Neutrons with Two Different Energy Spectra

In neutron capture therapy, whose effectiveness depends on the tumor distribution of neutron capture compound and the neutron energy distribution, controlling quiescent tumor cells with clonogenic potential is critical for therapeutic gain, as is the case in conventional radio- and chemotherapy. Tumor-bearing mice were continuously given 5-bromo-2'-deoxyuridine (BrdU) to label all proliferating cells. After administration of sodium borocaptate-¹⁰B (BSH), dl-p -boronophenylalanine-¹⁰B (BPA) or gadodiamide hydrate (Omniscan), the tumors were irradiated with neutrons of different cadmium (Cd) ratio, and then isolated and incubated with cytochalasin-B (a cytokinesis blocker). The micronucleus (MN) frequency in cells without BrdU labeling (quiescent cells) was determined using immunofluorescence staining for BrdU, and that for total cells was obtained from tumors not pretreated with BrdU. Without drugs, quiescent cells showed lower MN frequencies than total cells, but neutron irradiation reduced gamma-ray sensitivity difference between the two. Relative biological effectiveness (RBE) of neutrons compared with gamma-rays was greater in quiescent cells than in total cells, and low Cd ratio neutrons tended to exhibit large RBE values. With neutron capture compounds, MN frequency for each cell population was increased, especially when high Cd ratio neutrons were used. BPA increased the MN frequency for total cells to a greater extent than BSH. However, the sensitivity of quiescent cells treated with BPA was lower than that in BSH-treated quiescent cells. This tendency was clearly observed in high Cd ratio neutrons. Omniscan only slightly increased the MN frequency in both cell populations, compared with irradiation alone, without drugs. From the viewpoint of increasing the quiescent cell sensitivity, tumors should be irradiated with high Cd ratio neutrons after BSH administration.     

闪烁体探测器在质子重离子治疗质控中的应用

目的:采用自制二维闪烁体探测器对主动式点扫描质子重离子加速器放疗系统进行质控检测,为质子重离子束的质量(束斑位置、束斑大小、虚源、深度分布曲线及射程等)提供快速检测方法和参考。方法:探测系统由硫氧化钆闪烁体荧光屏、不锈钢板和光学数码相机组成。将质子重离子束垂直入射到闪烁体荧光屏转化为可见光,经不锈钢镜面反射至相机成像仪...     

A multileaf collimator phantom for the quality assurance of radiation therapy planning systems and CT simulators

PURPOSE: The evolution of three-dimensional conformal radiation treatment has led to the use of multileaf collimators (MLCs) in intensity-modulated radiation therapy (IMRT) and other treatment techniques to increase the conformity of the dose distribution. A new quality assurance (QA) phantom has been designed to check the handling of MLC settings in treatment planning and delivery. METHODS AND MATERIALS: The phantom consists of a Perspex block with stepped edges that can be rotated in all planes. The design allows for the assessment of several MLC and micro-MLC types from various manufacturers, and is therefore applicable to most radiation therapy institutions employing MLCs. The phantom is computed tomography (CT) scanned as is a patient, and QA assessments can be made of field edge display for a variety of shapes and orientations on both radiation treatment planning systems (RTPS) and computed tomography simulators. RESULTS: The dimensions of the phantom were verified to be physically correct within an uncertainty range of 0-0.7 mm. Errors in leaf position larger than 1 mm were easily identified by multiple observers. CONCLUSIONS: The MLC geometry phantom is a useful tool in the QA of radiation therapy with application to RTPS, CT simulators, and virtual simulation packages with MLC display capabilities.     

A peer comparison program for the quality assurance of human papillomavirus DNA detection using the Digene Hybrid Capture II/SurePath method shows excellent analytic interlaboratory correlation

BACKGROUND: Interlaboratory peer comparison programs are quality-assurance activities mandated by the Clinical Laboratory Improvement Amendments of 1988. No commercial program is available currently that was designed for cytology laboratories performing only human papillomavirus (HPV) DNA testing. In this report, the authors provide the results from a self-developed program between 2 cytology laboratories. METHODS: Between 4 and 11 SurePath liquid-based cervical cytology samples were selected at each of the 2 participating laboratories each quarter and exchanged without accompanying patient information. Samples were selected to test both positive and negative high-risk HPV DNA results in roughly equivalent numbers. Samples were run with the Hybrid Capture II method using each laboratory's standard procedure. The result obtained was compared with the originating laboratory's result. Correlation was compared on an ongoing basis as a method to assess analytic performance. RESULTS: Over a 3-year period, 12 exchanges took place, constituting 113 total specimens. Overall, there were 9 exchanges of 76 specimens that had 100% correlation, and 3 exchanges in which 4 of 37 specimens had discordant results. Overall, this represented a 97% correlation (109 of 113 specimens) of results between laboratories. All 4 discordant cases were reported as negative by the original laboratory and positive by the exchange laboratory (2 in each direction). CONCLUSIONS: The interlaboratory peer comparison result of 97% concordance demonstrated excellent analytic agreement between the HPV DNA-detection procedures of each laboratory. All discordant cases were "negative to positive" and were distributed equally by originating laboratory. The procedure was easily set up and provided assurance to each laboratory of ongoing performance for the detection of the HPV DNA analyte.     

Boron Neutron Capture Therapy (BNCT) in an oral precancer model: therapeutic benefits and potential toxicity of a double application of BNCT with a six-week interval

Given the clinical relevance of locoregional recurrences in head and neck cancer, we developed a novel experimental model of premalignant tissue in the hamster cheek pouch for long-term studies and demonstrated the partial inhibitory effect of a single application of Boron Neutron Capture Therapy (BNCT) on tumor development from premalignant tissue. The aim of the present study was to evaluate the effect of a double application of BNCT with a 6 week interval in terms of inhibitory effect on tumor development, toxicity and DNA synthesis. We performed a double application, 6 weeks apart, of (1) BNCT mediated by boronophenylalanine (BPA-BNCT); (2) BNCT mediated by the combined application of decahydrodecaborate (GB-10) and BPA [(GB-10 + BPA)-BNCT] or (3) beam-only, at RA-3 nuclear reactor and followed the animals for 8 months. The control group was cancerized and sham-irradiated. BPA-BNCT, (GB-10 + BPA)-BNCT and beam-only induced a reduction in tumor development from premalignant tissue that persisted until 8, 3, and 2 months respectively. An early maximum inhibition of 100% was observed for all 3 protocols. No normal tissue radiotoxicity was detected. Reversible mucositis was observed in premalignant tissue, peaking at 1 week and resolving by the third week after each irradiation. Mucositis after the second application was not exacerbated by the first application. DNA synthesis was significantly reduced in premalignant tissue 8 months post-BNCT. A double application of BPA-BNCT and (GB-10 + BPA)-BNCT, 6 weeks apart, could be used therapeutically at no additional cost in terms of radiotoxicity in normal and dose-limiting tissues.     

Design and implementation of an anthropomorphic quality assurance phantom for intensity-modulated radiation therapy for the Radiation Therapy Oncology Group

PURPOSE: To design, construct, and evaluate an anthropomorphic phantom for evaluation of intensity-modulated radiation therapy (IMRT) dose planning and delivery, for protocols developed by the Radiation Therapy Oncology Group (RTOG) and other cooperative groups. METHODS AND MATERIALS: The phantom was constructed from a plastic head-shaped shell and water-equivalent plastics. Internal structures mimic planning target volumes and an organ at risk. Thermoluminescent dosimeters (TLDs) and radiochromic film were used to measure the absolute dose and the dose distribution, respectively. The reproducibility of the phantom's dosimeters was verified for IMRT treatments, and the phantom was then imaged, planned, and irradiated by 10 RTOG institutions. RESULTS: The TLD results from three identical irradiations showed a percent standard deviation of less than 1.6%, and the film-scanning system was reproducible to within 0.35 mm. Data collected from irradiations at 10 institutions showed that the TLD agreed with institutions' doses to within +/-5% standard deviation in the planning target volumes and +/-13% standard deviation in the organ at risk. Shifts as large as 8 mm between the treatment plan and delivery were detected with the film. CONCLUSIONS: An anthropomorphic phantom using TLD and radiochromic film can verify dose delivery and field placement for IMRT treatments.     

Quality assurance in medical oncology within the EORTC. European Organisation for Research and Treatment of Cancer

Quality assurance (QA) lately arrived in the medical arena in comparison to other fields. EORTC focused initially its attention on the aspects related to clinical trial data handling. In the late 1980s, the EORTC appointed a Quality Control Committee (QCC) with the remit to expand the QA activities to the main disciplines involved in cancer treatment. From 1990 to 1996, two projects supported by the European Commission enabled the QCC to address, amongst others, specific questions related to medical oncology. Both projects focused on the practices of chemotherapy delivery and the quality of data reporting. Following these projects, the QCC developed standard guidelines to advise on chemotherapy delivery and also a systemic chemotherapy checklist to enable an easy collection of essential data onto the patient's files. More recently, the EORTC QA Committee proposed a minimal set of quality control procedures to be implemented by all EORTC groups.     

Comparison of efficacy,safety, and quality of life between sorafenib and sunitinib as first-line therapy for Chinese patients with metastatic renal cell carcinoma

Background: Sorafenib and sunitinib are widely used as first-line targeted therapy for metastatic renal cell carcinoma (mRCC) in China. This study aimed to compare the efficacy, safety, and quality of life (QoL) in Chinese mRCC patients treated with sorafenib and sunitinib as first-line therapy. Methods: Clinical data of patients with mRCC who received sorafenib (400 mg twice daily; 4 weeks) or sunitinib (50 mg twice daily; on a schedule of 4 weeks on treatment followed by 2 weeks off) were retrieved. Primary outcomes were overall survival (OS), progression-free survival (PFS), adverse events (AEs), and QoL (SF-36 scores), and secondary outcomes were associations of clinical characteristics with QoL. Results: Medical records of 184 patients (110 in the sorafenib group and 74 in the sunitinib group) were reviewed. PFS and OS were comparable between the sorafenib and sunitinib groups (bothP > 0.05). The occurrence rates of leukocytopenia, thrombocytopenia, and hypothyroidism were higher in the sunitinib group (36.5％ vs. 10.9％, P < 0.001; 40.5％ vs. 10.9％,P < 0.001; 17.6％ vs. 3.6％,P= 0.001), and that of diarrhea was higher in the sorafenib group (62.7％ vs. 35.2％,P < 0.001). There was no significant difference in SF-36 scores between the two groups. Multivariate analysis indicated that role-physical and bodily pain scores were associated with the occurrence rate of grade 3 or 4 AEs (P= 0.017 and 0.005). Conclusions: Sorafenib has comparable efficacy and lower toxicity profile than sunitinib as first-line therapy for mRCC. Both agents showed no significant impact on QoL of patients.     

Boron neutron capture therapy for the treatment of oral cancer in the hamster cheek pouch model.

We have proposed and validated the hamster cheek pouch model of oral cancer for boron neutron capture therapy (BNCT) studies and shown that boronophenylalanine delivers potentially therapeutic 36.9 +/- 17.5 ppm boron to tumor tissue with tumor:normal tissue and tumor:blood ratios of 2.4:1 and 3.2:1, respectively. Here we report the first evidence of the usefulness of BNCT for the treatment of oral cancer in an experimental model. We assessed the response of hamster cheek pouch tumors, precancerous tissue, and normal oral tissue to boronophenylalanine-mediated BNCT using the thermalized epithermal beam of the RA-6 Reactor at the Bariloche Atomic Center. BNCT leads to complete remission by 15 days posttreatment in 78% of tumors and partial remission in an additional 13% of tumors with virtually no damage to normal tissue.     

The use of in vivo thermoluminescent dosimeters in the quality assurance programme for the START breast fractionation trial.

BACKGROUND AND PURPOSE: The use of in vivo dosimetry for patient measurement is recommended in many publications. It provides an additional check to verify that the dose delivered to the patient corresponds to the prescribed dose. In the context of a clinical trial investigating the effects of different fractionation regimens, it is imperative that the dose given is that prescribed to ensure that noise in the data between centres does not mask the results of the trial. The methodology for in vivo measurement in a clinical trial of breast radiotherapy was developed and verified. MATERIALS AND METHODS: A cohort of patients in the STAndardisation of breast RadioTherapy (START) trial was monitored using postal thermoluminescent dosimeters chips (TLD). All TLD were processed and analysed at Mount Vernon Hospital. Patients for in vivo measurements were identified at randomisation as a random 1 in 9 samples for the first 2500 patients randomised (282 TLD) increasing to 1 in 3 thereafter. The TLD were left in place for the duration of the tangential field treatment and thus a composite entrance and exit dose was recorded. RESULTS: TLD measurements were performed on 429 patients from 33 hospitals. The average ratio of dose measured using TLD to that prescribed was 0.99+/-0.04. Eight patients had initial measurements more than 10% different to the prescribed dose. The mean TLD results for a given centre correlated well with dose measurements performed using an ionisation chamber in a breast shaped phantom at that centre as part of the START trial audit. CONCLUSION: Thermoluminescence dosimetry has provided useful quality assurance information on the doses received by patients in centres participating in the START trial.     

Comparison of efficacy and safety between pembrolizumab combined with chemotherapy and simple chemotherapy in neoadjuvant therapy for esophageal squamous cell carcinoma

BackgroundImmunotherapy can activate the recognition of tumor antigen, build immune memory, and more and more clinical trials have taken the scheme of immunochemotherapy or immunoradiotherapy as a treatment strategy for esophageal squamous cell carcinoma (ESCC). Our objective was to compare the efficacy and safety between pembrolizumab combined with the chemotherapy group and simple chemotherapy in neoadjuvant therapy of ESCC.MethodsFifty-four ESCC patients with stage II–IVa were enrolled at the Fifth Affiliated Hospital of Sun Yat-sen University between January 2018 and December 2020, including 23 in the pembrolizumab combined with chemotherapy group (combined group), and 31 in the simple chemotherapy group. All patients received radical surgical treatment after two cycles of neoadjuvant therapy.ResultsThe pathological complete response (pCR) and objective response rate (ORR) in the combined group were significantly higher than that of the simple chemotherapy group (30.4% vs. 9.7%, P=0.048; 86.9% vs. 95.7%, P=0.017) as well as the score of tumor regression ≥2 (80.7% vs. 50.0%, P=0.013). And the complete rate of esophagectomy and R0 /R1 resection rate in the two groups were not statistically significant. Otherwise, the incidence of adverse events in the combined group was similar compared with the simple chemotherapy group.ConclusionsPembrolizumab combined with chemotherapy showed promising activity with a manageable safety profile. And it could offer a potential new neoadjuvant treatment approach for patients with ESCC.