Should we affraid of induced cancer in group of patients after radical radiotherapy of prostate cancer?

Radiotherapy is one of the basic methods of radical treatment of prostate cancer. Because of that getting to know all factors of post-radiation complications, and in consequence the possibility to limit them, is one of the challenges of contemporary radiotherapy.One of the potential complications associated with radiation treatment is radiation-induced cancer. Despite a whole range of epidemiological analyses there is still lacking a fully credible model that would allow one to estimate the magnitude of risk of inducing such cancers. The last decades have seen the entry into clinical practice of technologically advanced methods of radiation therapy, such as the 3DCRT and IMRT. As the previous epidemiological analyses refer mainly to older radiation techniques, there is still a lack of credible data estimating the risk of inducing secondary cancers for new techniques, and in particular IMRT. It should be emphasized that IMRT allows one to escalate the dose, which may contribute to the improvement of radiotherapy effectiveness. From this there follows a new problem to be solved in future, i.e. how the escalation of the dose may influence the magnitude of risk of radiation carcinogenesis.The problem of carcinogenesis may concern the group of younger patients for whom long survival is very likely, and the competitive edge of RT relative to surgery, in particular in the aspect of late complications, has to be thoroughly justified.     

Problems and solutions in IGRT for cervical cancer

The contribution of Image-guided Radiotherapy (IGRT) to modern radiotherapy is undeniable, being the way to bring into daily practice the dosimetric benefits of Intensity-Modulated Radiotherapy (IMRT). Organ and target motion is constant and unpredictable at the pelvis, thus posing a challenge to the safe execution of IMRT. There are potential benefits of IMRT in the radical treatment of cervical cancer patients, both in terms of dose escalation and decrease of toxicity. But it is essential to find IGRT solutions to control the aspects that can lead to geographic miss targeting or organs at risk (OAR) overdose. This review seeks to describe the problems and possible solutions in the clinical implementation of IMRT/IGRT protocols to treat intact cervical cancer patients.     

Prostate cancer radiation therapy: A physician’s perspective

Prostate cancer is the second most common cancer in men and a major cause of cancer deaths worldwide. Ionizing radiation has played a substantial role in the curative treatment of this disease. The historical evolution of radiotherapy techniques through 3D-conformal radiotherapy (3D-CRT), intensity-modulated radiotherapy (IMRT), and image-guided radiotherapy (IGRT) has allowed more accurate and precise treatments toward significant improvements in the therapeutic ratio. The addition of androgen deprivation therapy has significantly improved overall survival becoming the standard therapy for intermediate- and high-risk disease. Many randomized controlled trials have shown improved local control with dose escalation, and hypofractionated RT has been consolidated with proven efficacy and safe clinical results. However, several questions remain open in the radiotherapeutic management of prostate cancer patients and hopefully ongoing studies will shed light on these uncertainties. More individualized approaches are essential through better prognostic and novel predictive biomarkers of prostate radiotherapy response. Clinicians should critically interpret the evolving technologies in prostate cancer radiotherapy with important optimism but balancing the costs and the actual magnitude of clinical benefit. This article provides an overview of the basic aspects of radiotherapy treatment in localized prostate cancer from a physician’s perspective.     

调强适形放疗联合化疗治疗局部晚期食管癌的疗效观察

目的:观察调强适形放疗(intensity modulated radiation therapy,IMRT)联合多西他赛、奈达铂方案化疗同步治疗局部晚期食管癌的疗效及安全性。方法:选择66例局部晚期食管癌患者为研究对象,将其随机分为2组,其中常规放疗组(A组)共30例,采用常规照射方法,6/8 MV高能X线,2.0 Gy/次,5次/周;40 Gy/20次后再次定位剂量达60~66 Gy,强调放疗组(B组)共36例,采用强调适应性放疗,6/8MV-X射线照射,以95%等剂量线包绕PTV(计划靶区),处方剂量GTV(肿瘤区)66 Gy/30次,CTV(临床靶区)60 Gy/30次,PTV 60 Gy/30次,每天1次,每周5次。强调放疗组同期接受IMRT和多西他赛、柰达伯化疗,21天1个周期,连续2个周期。治疗结束后根据实体瘤疗效评价标准(RECIST)评定临床疗效;参照WHO毒性反应分度标准评价毒副反应。结果:常规放疗组和强调放疗组的总有效率分别为46.66%和91.67%(x2=17.26,P0.05);常规放疗组的毒副反应发生率显著高于强调放疗组,包括骨髓抑制、放射性食管炎和消化道反应的发生率存在显著差异(P0.05)。结论:调强适形放疗联合多西他赛、奈达铂化疗同步治疗局部晚期食管癌疗效较好,毒副反应可耐受,具有潜在的推广应用价值,值得临床进一步研究。     

Cardiac toxicity of lung cancer radiotherapy

Radical radiotherapy of lung cancer with dose escalation has been associated with increased tumor control. However, these attempts to continually improve local control through dose escalation, have met mixed results culminating in the findings of the RTOG trial 0617, where the heart dose was associated with a worse overall survival, indicating a significant contribution to radiation-induced cardiac morbidity. It is, therefore, very likely that poorly understood cardiac toxicity may have offset any potential improvement in overall survival derived from dose escalation and may be an obstacle that limits disease control and survival of patients. The manifestations of cardiac toxicity are relatively common after high dose radiotherapy of advanced lung cancers and are independently associated with both heart dose and baseline cardiac risk. Toxicity following the treatment may occur earlier than previously thought and, therefore, heart doses should be minimized. In patients with lung cancer, who not only receive substantial heart dose, but are also older with more comorbidities, all cardiac events have the potential to be clinically significant and life-threatening.Sophisticated radiation treatment planning techniques, charged particle therapy, and modern imaging methods in radiotherapy planning, may lead to reduction of the heart dose, which could potentially improve the clinical outcomes in patients with lung cancer. Efforts should be made to minimize heart radiation exposure whenever possible even at doses lower than those generally recommended. Heart doses should be limited as much as possible.A heart dosimetry as a whole is important for patient outcomes, rather than emphasizing just one parameter.     

三维适形放疗与调强放疗对晚期非小细胞肺癌患者血清肿瘤标志物及剂量学参数比较研究

目的:对比晚期非小细胞肺癌患者经三维适形放疗(3D-CRT)与调强放疗(IMRT)后,其血清肿瘤标志物及剂量学参数的变化。方法:选择2015年1月-2016年12月期间我院收治的非小细胞肺癌患者120例,根据放疗方案将其分为IMRT组60例与3D-CRT组60例。比较两组临床疗效、药物毒副反应、1年内的生存率、放射剂量参数,以及治疗前与治疗后血清肿瘤标志物的变化。结果:IMRT组治疗的总有效率与3D-CRT组对比差异无统计学意义(P0.05)。IMRT组血小板减少、Ⅲ度放射性食管炎、Ⅲ度消化道反应、Ⅲ度放射性肺炎、Ⅲ度白细胞减少的发生率均低于3D-CRT组(P0.05)。IMRT组1年内的生存率90.00%,高于3D-CRT组的75.00%(P0.05)。IMRT组CI值与HI值均高于3D-CRT组(P0.05),IMRT组与3D-CRT组平均剂量对比差异无统计学意义(P0.05)。治疗后两组鳞状细胞癌抗原(SCC)、细胞角蛋白19片段抗原21-1(CYFRA21-1)与肿瘤特异性生长因子(TSGF)水平均显著降低,且IMRT组低于3D-CRT组(P0.05)。结论:IMRT与3D-CRT对于晚期非小细胞肺癌患者的临床疗效相当,但IMRT药物毒副反应少、放射剂量低,可能通过控制肿瘤来降低肿瘤标志物水平。     

Comparison of patient-specific intensity modulated radiation therapy quality assurance for the prostate across multiple institutions

AimTo evaluate the success of a patient-specific intensity modulated radiation therapy (IMRT) quality assurance (QA) practice for prostate cancer patients across multiple institutions using a questionnaire survey.BackgroundThe IMRT QA practice involves different methods of dose distribution verification and analysis at different institutions.Materials and MethodsTwo full-arc volumetric modulated arc therapy (VMAT) plan and 7 fixed-gantry IMRT plan with DMLC were used for patient specific QA across 22 institutions. The same computed tomography image and structure set were used for all plans. Each institution recalculated the dose distribution with fixed monitor units and without any modification. Single-point dose measurement with a cylindrical ionization chamber and dose distribution verification with a multi-detector or radiochromic film were performed, according to the QA process at each institution.ResultsTwenty-two institutions performed the patient-specific IMRT QA verifications. With a single-point dose measurement at the isocenter, the average difference between the calculated and measured doses was 0.5 ± 1.9%. For the comparison of dose distributions, 18 institutions used a two or three-dimensional array detector, while the others used Gafchromic film. In the γ test with dose difference/distance-to-agreement criteria of 3%?3 mm and 2%?2 mm with a 30% dose threshold, the median gamma pass rates were 99.3% (range: 41.7%–100.0%) and 96.4% (range: 29.4%–100.0%), respectively.ConclusionThis survey was an informative trial to understand the verification status of patient-specific IMRT QA measurements for prostate cancer. In most institutions, the point dose measurement and dose distribution differences met the desired criteria.     

A novel dynamic field-matching technique for treatment of patients with para-aortic node-positive cervical cancer: Clinical experience

Aim

To report outcomes for patients with para-aortic lymph node positive cervical cancer treated with a dynamic field-matching technique.

Background

PET staging of cervical cancer has increased identification of patients with para-aortic lymph node metastasis. IMRT enables dose escalation in this area, but matching IMRT fields with traditional whole pelvis fields presents a challenge.

Materials and methods

From 2003 to 2012, 20 patients with cervical cancer and para-aortic lymph node metastasis were treated utilizing the dynamic field-matching technique. As opposed to single-isocenter half-beam junction techniques, this technique employs wedge-shaped dose junctions for the abutment of fields. We reviewed the records of all patients who completed treatment with the technique and abstracted treatment, toxicity, and disease-related outcome data for analysis.

Results

Median prescribed dose to the whole pelvis field was 45 Gy and para-aortic IMRT field 50.4 Gy. All but 3 patients underwent HDR (13 pts) or LDR (4 pts) brachytherapy. All patients developed lower GI toxicity; 10 grade 1, 9 grade 2, and 1 grade 4 (enterovaginal fistula). Median DFS was 12.4 months with 1 and 2-year DFS 60.0% and 38.1%. One-year OS was 83.7% and 2-year OS, 64.4%. A total of 10 patients developed recurrence; none occurred at the matched junction.

Conclusions

The dynamic field-matching technique provides a means for joining conventional whole pelvis fields and para-aortic IMRT fields that substantially reduces dose deviations at the junction due to field mismatch. Treatment with the dynamic matching technique is simple, effective, and tolerated with no apparent increase in toxicity.     

Three-dimensional quality assurance of IMRT prostate plans using gel dosimetry

Intensity modulated radiotherapy (IMRT) is one of the most modern radiation therapy treatment techniques. Although IMRT can deliver high and complex conformational doses to the tumor volume, its implementation requires rigorous quality assurance (QA) procedures that include a dosimetric pre-treatment verification of individual patient planning. This verification usually involves measuring a small volume of absolute dose with an ionization chamber and checking bi-dimensional fluency with an array of detectors. The planning technique has tri-dimensional characteristics, but no tridimensional dosimetry has been established in the clinical routine. One strategy to perform three-dimensional dosimetry is to use polymeric gels associated with magnetic resonance imaging to evaluate dose distribution. Here, we have compared the results of conventional QA procedures involving one- and two-dimensional dosimetry to the results of three-dimensional dosimetry conducted with MAGIC-f gel in 10 cases of prostate cancer IMRT planning. More specifically, we used the gamma index (3%/3 mm) to compare the results of three-dimensional dosimetry to the expected dose distributions obtained with the treatment planning system. Except for one IMRT treatment plan, the gel dosimetry results agreed with the conventional quality control and provided an overview of dose distribution in the target volume.     

Intelligence-guided beam angle optimization in treatment planning of intensity-modulated radiation therapy

An intelligence guided approach based on fuzzy inference system (FIS) was proposed to automate beam angle optimization in treatment planning of intensity-modulated radiation therapy (IMRT). The model of FIS is built on inference rules in describing the relationship between dose quality of IMRT plan and irradiated region of anatomical structure. Dose quality of IMRT plan is quantified by the difference between calculated and constraint doses of the anatomical structures in an IMRT plan. Irradiated region of anatomical structure is characterized by the metric, covered region of interest, which is the region of an anatomical structure under radiation field while beam’s eye-view is conform to target volume. Initially, an IMRT plan is created with a single beam. The dose difference is calculated for the input of FIS and the output of FIS is obtained with processing of fuzzy inference. Later, a set of candidate beams is generated for replacing the current beam. This process continues until no candidate beams is found. Then the next beam is added to the IMRT plan and optimized in the same way as the previous beam. The new beam keeps adding to the IMRT plan until the allowed beam number is reached. Two spinal cases were investigated in this study. The preliminary results show that dose quality of IMRT plans achieved by this approach is better than those achieved by the default approach with equally spaced beam setting. It is effective to find the optimal beam combination of IMRT plan with the intelligence-guided approach.     

Comparative analysis of several detectors for the measurement of radiation transmission and leakage from a multileaf collimator

The multileaf collimator (MLC) is the standard device used to shape radiation beams for 3-d conformal and intensity-modulated radiation therapy (IMRT). Due to the inherent properties of MLC, there is a small amount of radiation transmitted through the leaves, called radiation transmission (RT). Accurate measurements of this radiation are required to commission and validate IMRT-capable treatment planning systems because this radiation may impact the dosimetry of IMRT-calculated dose distributions. This work compares several detectors in the measurement of RT for a micro-multileaf collimation system. The results show that there are statistically significant differences in the measured RT values between detectors from 3.5 to 12.5% for the same MLC model and less than 0.2% relative to the isocentre dose for an open reference field. However, although small in magnitude, these differences may impact the dosimetry of IMRT treatment planning by up to 1.78 Gy to the healthy tissue surrounding the target for a treatment of 60 Gy in 30 fractions. By the later, these differences must be included as a source of uncertainty in IMRT dose delivery. Also, it must be established which detector offers the most reliable results in the measurement of the RT by using Monte Carlo simulation methods.     

Significant impact on the oncologic outcomes with intensity modulated radiotherapy and conformational radiotherapy over conventional radiotherapy in cervix cancer patients treated with radiotherapy

ObjectiveWe designed a retrospective cohort of women with cervix cancer treated by radiation therapy with an extended follow-up to evaluate if the incorporation of modern radiation techniques was a prognostic factor.Material and methodsWe studied a cohort of patients with cervix cancer FIGO stage I-IVa treated in the last fifteen years. Patients were treated with radiotherapy alone (RT) or chemoradiation alone (CRT) using conventional radiotherapy (2DRT), conformational radiotherapy (3DRT), or intensity-modulated radiotherapy (IMRT) followed by high dose rate brachytherapy. Univariate and multivariate analysis was conducted to identify significant prognostic factors (p < 0.05).Results228 patients with cervix cancer were included. The treatment groups were CRT (64.8%), and RT (34.2%), with 31.6% submitted to 2DRT and 68.4% to IMRT/3DRT. The median follow-up was 6.3 years, the OS in 5 years according to the treatment groups was 48% for CRT, and 27.8% for RT (p < 0.001). The early-stage I-IIa (p = 0.001), CRT, and IMRT/3DRT were significant factors for better overall survival (OS) in the multivariate analysis. For the cancer-specific survival (CSS), chemoradiation, age <60 years, and IMRT/3DRT were significant. Treatment with IMRT/3DRT was the only prognostic factor associated with event-free survival (EFS).ConclusionIn a long-term follow-up, chemoradiation, early-clinical stage, and age <60 years were significant factors associated with better OS and CSS at 5 and 8 years. The incorporation of new radiation techniques, such as IMRT/3DRT, over time has a significant impact on all endpoints (EFS, OS, and CSS) of this cohort. These outcomes are useful to decide about the radiation technique to achieve satisfactory oncological results outside a clinical trial.     

A calibration method for patient specific IMRT QA using a single therapy verification film

Aim

The aim of the present study is to develop and verify the single film calibration procedure used in intensity-modulated radiation therapy (IMRT) quality assurance.

Background

Radiographic films have been regularly used in routine commissioning of treatment modalities and verification of treatment planning system (TPS). The radiation dosimetery based on radiographic films has ability to give absolute two-dimension dose distribution and prefer for the IMRT quality assurance. However, the single therapy verification film gives a quick and significant reliable method for IMRT verification.

Materials and methods

A single extended dose rate (EDR 2) film was used to generate the sensitometric curve of film optical density and radiation dose. EDR 2 film was exposed with nine 6 cm × 6 cm fields of 6 MV photon beam obtained from a medical linear accelerator at 5-cm depth in solid water phantom. The nine regions of single film were exposed with radiation doses raging from 10 to 362 cGy. The actual dose measurements inside the field regions were performed using 0.6 cm³ ionization chamber. The exposed film was processed after irradiation using a VIDAR film scanner and the value of optical density was noted for each region. Ten IMRT plans of head and neck carcinoma were used for verification using a dynamic IMRT technique, and evaluated using the gamma index method with TPS calculated dose distribution.

Results

Sensitometric curve has been generated using a single film exposed at nine field region to check quantitative dose verifications of IMRT treatments. The radiation scattered factor was observed to decrease exponentially with the increase in the distance from the centre of each field region. The IMRT plans based on calibration curve were verified using the gamma index method and found to be within acceptable criteria.

Conclusion

The single film method proved to be superior to the traditional calibration method and produce fast daily film calibration for highly accurate IMRT verification.     

Implementation of intensity modulated radiotherapy for prostate cancer in a private radiotherapy service in Mexico

Intensity modulated radiation therapy (IMRT) allows physicians to deliver higher conformal doses to the tumour, while avoiding adjacent structures. As a result the probability of tumour control is higher and toxicity may be reduced. However, implementation of IMRT is highly complex and requires a rigorous quality assurance (QA) program both before and during treatment. The present article describes the process of implementing IMRT for localized prostate cancer in a radiation therapy department. In our experience, IMRT implementation requires careful planning due to the need to simultaneously implement specialized software, multifaceted QA programs, and training of the multidisciplinary team. Establishing standardized protocols and ensuring close collaboration between a multidisciplinary team is challenging but essential.     

Potential interest of developing an integrated boost dose escalation for stereotactic irradiation of primary prostate cancer

IntroductionThe stereotactic irradiation is a new approach for low-risk prostate cancer. The aim of the present study was to evaluate a schema of stereotactic irradiation of the prostate with an integrated-boost into the tumor.Material and methodsThe prostate and the tumor were delineated by a radiologist on CT/MRI fusion. A 9-coplanar fields IMRT plan was optimized with three different dose levels: 1) 5 × 6.5 Gy to the PTV1 (plan 1), 2) 5 × 8 Gy to the PTV1 (plan 2) and 3) 5 × 6.5 Gy on the PTV1 with 5 × 8 Gy on the PTV2 (plan 3). The maximum dose (MaxD), mean dose (MD) and doses received by 2% (D2), 5% (D5), 10% (D10) and 25% (D25) of the rectum and bladder walls were used to compare the 3 IMRT plans.ResultsA dose escalation to entire prostate from 6.5 Gy to 8 Gy increased the rectum MD, MaxD, D2, D5, D10 and D25 by 3.75 Gy, 8.42 Gy, 7.88 Gy, 7.36 Gy, 6.67 Gy and 5.54 Gy. Similar results were observed for the bladder with 1.72 Gy, 8.28 Gy, 7.01 Gy, 5.69 Gy, 4.36 Gy and 2.42 Gy for the same dosimetric parameters. An integrated SBRT boost only to PTV2 reduced by about 50% the dose difference for rectum and bladder compared to a homogenous prostate dose escalation. Thereby, the MD, D2, D5, D10 and D25 for rectum were increased by 1.51 Gy, 4.24 Gy, 3.08 Gy, 2.84 Gy and 2.37 Gy in plan 3 compared to plan 1.ConclusionsThe present planning study of an integrated SBRT boost limits the doses received by the rectum and bladder if compared to a whole prostate dose escalation for SBRT approach.     

Estimation of radiation-induced second cancer risk associated with the institutional field matching craniospinal irradiation technique: A comparative treatment planning study

AimTo estimate and compare the lifetime attributable risk (LAR) of radiation-induced second cancer (SC) in pediatric medulloblastoma patients planned with institutional 3D conformal field matching method, gap junction method and Intensity Modulated Radiotherapy (IMRT).BackgroundThe epidemiological studies on childhood cancer survivors reported that long-term cancer survivors who received radiotherapy are at a significantly increased risk for the development of SC. Hence, the increased concern to predict the SC risk for long-term survivors.Materials and methodsIn addition to institutional field matching planning method, IMRT and gap junction methods were created for ten pediatric medulloblastoma patients. The risk estimates were made based on the site-specific cancer risk coefficient provided by the BEIR VII committee according to the organ equivalent dose for various critical organs. Also, plans were compared for target volume dose distribution and dose received by critical organs.ResultsWhen compared to the gap junction method, the IMRT and institutional field matching method were superior in normal tissue sparing and dose conformity. However, highly significant volume of low dose associated with IMRT was the main concern for the SC risk. The accumulated LAR for all the critical organs with 3D conformal gap junction and IMRT method was 23–25% while for the 3D conformal field matching method it was 21%.ConclusionThe LAR associated with the institutional field matching technique was substantially lower. As this method is highly robust and easy to set up, it can be a better choice of a craniospinal irradiation technique where 3DCRT is the only choice of treatment.     

A tolerability and pharmacokinetic study of adjuvant erlotinib and capecitabine with concurrent radiation in resected pancreatic cancer

BACKGROUND: Erlotinib is approved for the treatment of advanced pancreas cancer. We conducted a prospective trial to determine the safety profile and recommended phase 2 dose of erlotinib and capecitabine given concurrently with intensity-modulated radiation therapy (IMRT) in resected pancreatic cancer patients. The pharmacokinetic profile of this combination was also evaluated. METHODS: Patients with resected pancreatic adenocarcinoma received erlotinib and capecitabine concurrently with IMRT delivered at 1.8 Gy daily in 28 fractions (total = 50.4 Gy). The starting dose level (DL 1) was erlotinib 150mgdaily and capecitabine 800 mg/m² twice daily without interruption. The next lower dose level (DL -1) was erlotinib 100 mg daily and capecitabine 800 mg/m² twice daily (Monday to Friday). Plasma samples were obtained for pharmacokinetic analysis. RESULTS: Thirteen patients were enrolled in total. At DL 1, six of the seven treated patients were evaluable for toxicities. Four completed planned treatment, but all required treatment interruption or dose reduction. The dose-limiting toxicities were neutropenia, diarrhea, and rash. Six patients were subsequently enrolled to and completed planned treatment in DL-1. Themost common toxicities were fatigue, elevated liver enzymes, and anorexia. The pharmacokinetic parameters of erlotinib and OSI-420 were not significantly different in the presence or absence of capecitabine and were consistent with historical controls. CONCLUSIONS: When administered concurrently with IMRT, erlotinib 100 mg daily and capecitabine 800 mg/m² twice daily (Monday to Friday) can be administered safely in resected pancreas cancer patients, and is the recommended regimen for efficacy studies using this regimen.