Radiobiological considerations in combining doses from external beam radiotherapy and brachytherapy for cervical cancer

The recommended radio-therapeutic treatment for cervix cancer consists of a first phase of external beam radiotherapy (EBRT) plus a second phase of brachytherapy (BT), the combined treatment being delivered within 8 weeks.In order to assess a comprehensive dosimetry of the whole treatment, it is necessary to take into account that these two phases are characterized by different spatial and temporal dosimetric distributions, which complicates the task of the summation of the two contributions, EBRT and BT. Radiobiology allows to tackle this issue pragmatically by means of the LQ model and, in fact, this is the usual tool currently in use for this matter.In this work, we describe the rationale behind the summation of the dosimetric contributions of the two phases of the treatment, EBRT and BT, for cervix cancer, as carried out with the LQ model.Besides, we address, from a radiobiological point of view, several important considerations regarding the use of the LQ model for this task. One of them is the analysis of the effect of the overall treatment time in the result of the global treatment. Another important question considered is related to the fact that the capacity of LQ to predict the treatment outcomes is deteriorated when the dose per fraction of the radiotherapic scheme exceeds 6–10 Gy, which is a typical brachytherapy fractionation. Finally, we analyze the influence of the uncertainty and the variability of the main parameters utilized in the LQ model formulation in the assessment of the global dosimetry.     

Image-guided brachytherapy in cervical cancer: Experience in the Complejo Hospitalario de Navarra

PurposeTo evaluate dosimetric and clinical findings of MRI-guided HDR brachytherapy (HDR-B) for cervical carcinoma.Material and methodsAll patients had a CT, MRI and pelvic-paraaortic lymphadenectomy. Treatment: pelvic (+/−)para-aortic3D/IMRT radiotherapy (45 Gy), weekly cisplatin and HDR-B and pelvic node/parametrial boost 60 Gy until interstitial brachytherapy was done. Two implants: 2008–2011: 5 fractions of 6 Gy, 2011: 2016, 4 fractions of 7 Gy. MRI/TAC were done in each implant. The following were defined: GTV, CTH-HR, CTV-IR; OAR: rectum, bladder and sigmoid.ResultsFrom 2007 to 2016: 57 patients. Patients: T1b2-T2a: 4p, T2b 41p, T3a: 2p; T3B 8p T4a: 2p; N0: 32p, N1 21p, no lymphadenectomy: 4p. Median follow up: 74.6 m (16–122 m), recurrence: 5p local, 6p node, 9p metastasis and 37p without recurrence.Local control 5 years: 90.1%; Ib2-IIB: 94.8%, III-IVa: 72.2%. (p:0.01). RDFS 5y was 92.5%; IB2-IIB: 93%, III: 85% (p:0.024); for pN0: 100%; pN+ iliac-paraaortic: 71.4% (p: 0.007). MFS 5y was 84.1%. Overall survival (OS) at 5y: 66.6% and the cancer specific survival (CEOS) was 74%. Univariate analysis survival: stage Ib2-II 83% vs. III-IVa 41% (p = 0.001); histology: squamous 78%, adenocarcinoma 59.7% (p: ns); lymph node: N0 85% vs. PA+P− 72%, and PA+P+ 35% (p = 0.010). In relation with: HR-CTV dose > 85 Gy, CEOS: 82.5% vs. 77%, and volume CTV-HR < 30 cc: 81.8% and >30 cc: 67%; p: ns. Acute grade 2–3 toxicity: rectal 15.7%, intestinal 15.7% and vesical 15.5%.ConclusionUse of interstitial HDR-BQ guided by RM increased CTV-HR dose and local control, like EMBRACE results. Nodal boost improves RDFS and perhaps OS.     

Survival outcome after stereotactic body radiotherapy for locally advanced and borderline resectable pancreatic cancer: A systematic review and meta-analysis

BackgroundSome studies reported stereotactic body radiotherapy (SBRT) has demonstrated superior therapeutic results than conventional radiotherapy. Nevertheless, this statement is controversial and the trial attempting to prove this is underway. We conducted this systemic review and meta-analysis aiming to combine the latest and most complete information about the survival outcomes and toxicities following SBRT for locally advanced pancreatic cancer (LAPC) and borderline resectable pancreatic cancer (BRPC).MethodsItems involving SBRT and pancreatic cancer were searched in PubMed, EMBASE, Cochrane Library, SCOPUS and Web of Science. Median overall survival (OS), 1/2/3-year OS, median progression-free survival (PFS), 1/2/3-year PFS and incidence of grade 3–5 toxicities were the endpoints of interest in this meta-analysis. These endpoint proportions were pooled and analyzed using R.ResultsFor the LAPC series, the median OS was 14.1 months; pooled 1/2/3-year OS rates were 57%, 19% and 10%, respectively; the median PFS was 10 months; pooled 1/2/3-year PFS rates were 36%, 12% and 4%; pooled incidence rates of acute gastrointestinal (GI), acute hematologic and late GI toxicity (grade≥3) were 2%, 4% and 8%. For the BRPC series, the median OS was 17.5 months; pooled 1/2-year OS rates were 75% and 29%; the median PFS was 12.2 months; pooled 1/2-year PFS rates were 48% and 18%; the incidence rates of toxicity (grade ≥ 3) were all 0%.ConclusionsOur meta-analysis based on published results of OS, PFS and incidence rates of toxicity demonstrated that SBRT does not show desirable therapeutic result than the standard therapies for LAPC and BRPC.     

Review of strategies for MRI based reconstruction of endocavitary and interstitial applicators in brachytherapy of cervical cancer

Brachytherapy plays an essential role in the curative intent management of locally advanced cervical cancer. The introduction of the magnetic resonance (MR) as a preferred image modality and the development of new type of applicators with interstitial components have further improved its benefits.The aim of this work is to review the current status of one important aspect in the cervix cancer brachytherapy procedure, namely catheter reconstruction.MR compatible intracavitary and interstitial applicators are described. Considerations about the use of MR imaging (MRI) regarding appropriate strategies for applicator reconstruction, technical requirements, MR sequences, patient preparation and applicator commissioning are included.It is recommendable to perform the reconstruction process in the same image study employed by the physician for contouring, that is, T2 weighted (T2W) sequences. Nevertheless, a clear identification of the source path inside the catheters and the applicators is a challenge when using exclusively T2W sequences. For the intracavitary component of the implant, sometimes the catheters may be filled with some substance that produces a high intensity signal on MRI. However, this strategy is not feasible for plastic tubes or titanium needles, which, moreover, induce magnetic susceptibility artifacts. In these situations, the use of applicator libraries available in the treatment planning system (TPS) is useful, since they not only include accurate geometrical models of the intracavitary applicators, but also recent developments have made possible the implementation of the interstitial component. Another strategy to improve the reconstruction process is based on the incorporation of MR markers, such as small pellets, to be used as anchor points.Many institutions employ computed tomography (CT) as a supporting image modality. The registration of CT and MR image sets should be carefully performed, and its uncertainty previously assessed. Besides, an important research work is being carried out regarding the use of ultrasound and electromagnetic tracking technologies.     

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.     

The impact of respiratory gating on lung dosimetry in stereotactic body radiotherapy for lung cancer

The purpose of this study was to evaluate the impacts of respiratory gating and different gating windows (GWs) on lung dosimetry in stereotactic body radiotherapy (SBRT) for lung cancer.Gated SBRT plans were developed using the four-dimensional computed tomography data from 17 lung cancer patients treated with SBRT. Using amplitude-based end-exhalation gating, we established 2 fixed GWs with approximate duty cycles of 50% (50% GW) and 25% (25% GW), respectively, for this study.For highly mobile tumors (3D mobility > 10 mm), additional benefits in lung-dose reductions were achieved with the 25% GW, as a result of inadequate mobility and planning target volume reductions obtained with the 50% GW. In these tumors, the absolute differences compared to the non-gated and 50% gated plans, were 0.5 Gy and 0.33 Gy for the mean lung dose and 1.11% and 0.71% for the V20, respectively. Dosimetric benefits were achieved with the 50% GW, compared with the non-gated plan, for tumors with both low mobility and small volume (gross tumor volume ≤ 10 cc). Among the identified predictive factors of dosimetric benefits, the lateral distance from midspinal canal and the motion range in anterior–posterior direction might be stronger factors because of their correlations with many of the lung-dose parameters and greater predictive capacity.The results of the present study might facilitate the selection of appropriate patients and the optimal GW according to the tumor characteristics for gated lung SBRT.     

Intraoperative radiation therapy in uterine cervical cancer: A review

Locally advanced uterine cervical cancer continues to present a high number of pelvic relapses. Intraoperative radiation therapy (IORT) allows a precise therapeutic intensification in the surgical area in cases in which removal of the tumour recurrence is feasible. At the same time, IORT excludes the radiosensitive organs from the field of irradiation. While the first gynecological IORT took place in 1905, procedures have been limited over the years and the series are retrospective, including few patients. At the same, time recurrences are located at different pelvic areas. Both heterogeneity and the long recruiting time make it difficult to correctly interpret the published results. Despite this, we have reviewed the most relevant publications. Some institutions indicated IORT as a boost on the surgical bed of the excised tumor recurrence. In others, IORT permits an extra radiation dose after radical surgery of the primary tumor, usually in stage IIB. Most studies conclude that the addition of IORT increases the local control but probably with little impact on survival. On the other hand, there is a controversy in the indication of IORT in surgically resectable primary tumours. No clear advantage over the usual scheme of chemoradiation and brachytherapy has been detected. Randomized studies that allow a breakthrough in the conclusions are highly unlikely to be performed in this area.     

Dosimetric impact of hysteresis on lung cancer tomotherapy: A moving phantom study

PurposeTo investigate the dosimetric impact of hysteresis on lung cancer tomotherapy.MethodsMeasurements were acquired using MapCheck with an XY4D motion simulation table. Six hysteresis states (0, π/32, π/16, π/8, 3π/16, and π/4) were considered with sinusoidal motions in the superior–inferior and left–right orientations. The measured data were analyzed both globally (from all detectors) and structure-by-structure in the measurement plane. The dose difference (DD) analysis method with local normalization in the absolute dose mode with a DD threshold of 6 cGy was adopted to analyze each hysteresis vs. static state (H(1)S) and nonzero vs. zero hysteresis (H(1)0). The threshold was 10% for all analyses. Wilcoxon signed rank tests with significance level p = 0.05 were used for statistical analysis.ResultsThe DD analysis of each H(1)S mostly indicated that the passing rate differed between structures but was similar between hysteresis states. The DD analysis of H(1)0 showed that the passing rate decreased with increasing hysteresis. The differences between larger hysteresis (≥3π/16) and other states were significant for comparisons between global, left lung, chest wall, and target. Both analyses showed that the DD distribution changed with hysteresis.ConclusionsHysteresis difference causes the DD distribution to change. Structural difference had more impact than hysteresis state difference on hysteresis motion vs. static comparisons. Remarkable effects on nonzero vs. zero hysteresis comparisons were only seen for structures closely related to the target at large hysteresis. Small organs at risk that are close to the target need to be considered further.     

Dosimetric and physical comparison of IMRT and CyberKnife plans in the treatment of localized prostate cancer

Aim

The aim of our study was the dosimetric and physical evaluation of the CK and IMRT treatment plans for 16 patients with localized prostate cancer.

Background

Intensity modulated radiation therapy (IMRT) is one of the recent technical advances in radiotherapy. The prostate is a well suited site to be treated with IMRT. The challenge of accurately delivering the IMRT needs to be supported by new advances such as image-guidance and four-dimensional computed conformal radiation therapy (4DCRT) tomography. CyberKnife (CK) provides real time orthogonal X-ray imaging of the patient during treatment course to follow gold fiducials installed into the prostate and to achieve motion correlation between online acquired X-ray imaging and digital reconstructed radiographs (DRRs) which are obtained from planning computed tomography images by translating and rotating the treatment table in five directions.

Methods and materials

Sixteen IMRT and CK plans were performed to be compared in terms of conformity (CI), heterogeneity indices (HI), percentage doses of 100% (V100), 66% (V66), 50% (V50), 33% (V33) and 10% (V10) volumes of the bladder and rectum. Dose-volume histograms for target and critical organs, (CI) and indices (HI) and isodose lines were analyzed to evaluate the treatment plans.

Results

Statistically significant differences in the percentage rectal doses delivered to V10, V33, and V50 of the rectum were detected in favor of the CK plans (p values; <0.001, <0.001 and 0.019, respectively). The percentage doses for V66 and V100 of the rectum were larger in CK plans (13%, 2% in IMRT and 21%, 3% in CK plans, respectively). Percentage bladder doses for V10 and V33 were significantly lower in CK plans [96% in IMRT vs 48% in CK (p < 0.001) and 34% in IMRT vs 24% in CK (p = 0.047)]. Lower percentage doses were observed for V50, V66 of the bladder for the IMRT. They were 5.4% and 3.45% for IMRT and 13.4% and 8.05% for CK, respectively. Median CI of planning target volume (PTV) for IMRT and CK plans were 0.94 and 1.23, respectively (p < 0.001).

Conclusion

Both systems have a very good ability to create highly conformal volumetric dose distributions. Median HI of PTV for IMRT and CK plans were 1.08 and 1.33, respectively (p < 0.001).     

Dosimetric study of a hybrid plan technique for external beam radiotherapy in patients with cervical cancer

The aim of this study was to investigate the effect of a hybrid technique which results from combining intensity modulated radiotherapy (IMRT) and volumetric modulated arc therapy (VMAT) for the treatment of cervical cancer patients. Plans made with the hybrid technique and pure IMRT and VMAT were retrospectively compared in 20 patients with cervical cancer at different stages. All plans were made using the same contours based on the original computed tomography (CT) scans. Conformity (CI) and homogeneity (HI) indices of the planning target volumes (PTVs) were calculated for each technique in order to evaluate plan quality. All techniques were compared in terms of dose to organs at risk (OARs), number of monitor units (MUs) and treatment time. It turned out that plans made with the hybrid technique had improved dose conformity and homogeneity compared to plans made only with IMRT and VMAT (p < 0.001). Regarding the OARs, the maximum dose (D_max) delivered to the bladder, rectum and femoral heads was lower for the hybrid plans compared to the IMRT and VMAT plans (p < 0.001). The volumes irradiated to doses of 50 Gy (V_50Gy) for rectum, bladder and bowel were lower for the hybrid plans (p < 0.001, p = 0.002). Furthermore, the treatment time and MU values for the hybrid plans were found to be between of the values for the IMRT and VMAT plans. It is concluded that, as compared to IMRT and VMAT plans, the hybrid plan technique allowed a better conformity and homogeneity for the dose distribution in the PTV and a dose reduction to the OARs.

     

A comparison of a moderately hypofractionated IMRT planning technique used in a randomised UK external beam radiotherapy trial with an in-house technique for localised prostate cancer

AimTo compare the radiotherapy technique used in a randomised trial with VMAT and an in-house technique for prostate cancer.BackgroundTechniques are evolving with volumetric modulated arc therapy (VMAT) commonly used. The CHHiP trial used a 3 PTV forward planned IMRT technique (FP_CH). Our centre has adopted a simpler two PTV technique with locally calculated margins.Materials and methods25 patients treated with FP_CH to 60 Gy in 20 fractions were re-planned with VMAT (VMAT_CH) and a two PTV protocol (VMAT_60/52 and VMAT_60/48). Target coverage, conformity index (CI), homogeneity index (HI), monitor units (MU) and dose to the rectum, bladder, hips and penile bulb were compared.ResultsPTV coverage was high for all techniques. VMAT_CH plans had better CI than FP_CH (p ≤  0.05). VMAT_60/52/48 plans had better CI than VMAT_CH. FP_CH had better HI and fewer MU than VMAT (p ≤  0.05). More favourable rectum doses were found for VMAT _CH than FP_CH (V_48.6, V_52.8, V₅₇, p ≤  0.05) with less difference for bladder (p ≥  0.05). Comparing VMAT_CH to VMAT_60/52/48 showed little differences for the bladder and rectum but VMAT_CH had larger penile bulb doses (V_40.8, V_48.6, mean, D_2, p ≤  0.05). Femoral head doses (V_40.8) were similarly low for all techniques (p = ≥ 0.05).ConclusionVMAT produced more conformal plans with smaller rectum doses compared to FP_CH albeit worse HI and more MU. VMAT_60/52 and VMAT_60/48 plans had similar rectal and bladder doses to VMAT_CH but better CI and penile bulb doses which may reduce toxicity.     

Dosimetric and radiobiological comparison of TG-43 and Monte Carlo calculations in 192Ir breast brachytherapy applications

PurposeTo investigate the clinical significance of introducing model based dose calculation algorithms (MBDCAs) as an alternative to TG-43 in ¹⁹²Ir interstitial breast brachytherapy.Materials and methodsA 57 patient cohort was used in a retrospective comparison between TG-43 based dosimetry data exported from a treatment planning system and Monte Carlo (MC) dosimetry performed using MCNP v. 6.1 with plan and anatomy information in DICOM-RT format. Comparison was performed for the target, ipsilateral lung, heart, skin, breast and ribs, using dose distributions, dose-volume histograms (DVH) and plan quality indices clinically used for plan evaluation, as well as radiobiological parameters.ResultsTG-43 overestimation of target DVH parameters is statistically significant but small (less than 2% for the target coverage indices and 4% for homogeneity indices, on average). Significant dose differences (>5%) were observed close to the skin and at relatively large distances from the implant leading to a TG-43 dose overestimation for the organs at risk. These differences correspond to low dose regions (<50% of the prescribed dose), being less than 2% of the prescribed dose. Detected dosimetric differences did not induce clinically significant differences in calculated tumor control probabilities (mean absolute difference <0.2%) and normal tissue complication probabilities.ConclusionWhile TG-43 shows a statistically significant overestimation of most indices used for plan evaluation, differences are small and therefore not clinically significant. Improved MBDCA dosimetry could be important for re-irradiation, technique inter-comparison and/or the assessment of secondary cancer induction risk, where accurate dosimetry in the whole patient anatomy is of the essence.     

Dosimetric comparison between two MLC systems commonly used for stereotactic radiosurgery and radiotherapy: A Monte Carlo and experimental study

In this work dosimetric parameters of two multi-leaf collimator (MLC) systems, namely the beam modulator (BM), which is the MLC commercial name for Elekta “Synergy S” linear accelerator and Radionics micro-MLC (MMLC), are compared using measurements and Monte Carlo simulations. Dosimetric parameters, such as percentage depth doses (PDDs), in-plane and cross-plane dose profiles, and penumbras for different depths and field sizes of the 6 MV photon beams were measured using ionization chamber and a water tank. The collimator leakages were measured using radiographic films. MMLC and BM were modeled using the EGSnrc-based BEAMnrc Monte Carlo code and above dosimetric parameters were calculated. The energy fluence spectra for the two MLCs were also determined using the BEAMnrc and BEAMDP. Dosimetric parameters of the two MLCs were similar, except for penumbras. Leaf-side and leaf-end 80–20% dose penumbras at 10 cm depth for a 10 × 10 cm² field size were 4.8 and 5.1 mm for MMLC and 5.3 mm and 6.3 mm for BM, respectively. Both Radionics MMLC and Elekta BM can be used effectively based on their dosimetric characteristics for stereotactic radiosurgery and radiotherapy, although the former showed slightly sharper dose penumbra especially in the leaf-end direction.     

Palliative radiotherapy and quality of life in patients with locally advanced thoracic esophageal cancer: a single centre experience from Central India

BackgroundPatients with locally advanced esophageal squamous cell carcinoma (LAESCC ) have decreased quality of life (QoL) and, thus, require palliative external beam radiotherapy (EBRT). The present study was performed to evaluate the QoL in patients with LAESCC undergoing palliative EBRT.Materials and methodsThis was a prospective, observational study performed over a period of 18 months (from December 2018 to May 2020) in the Department of Radiation Oncology. Seventy patients with LAESCC received EBRT (30 Gy in 10 fractions, at 3 Gy per fraction over 2 weeks). Patients were followed-up at monthly intervals for 3 months. The dysphagia and odynophagia scores were calculated at baseline and follow-up visits. The QoL was assessed with 18-item EORTC QLQ-OES questionnaire at baseline and 3 months.ResultsOver the study period, significant decrease in mean dysphagia and odynophagia score was observed (p-value < 0.0001). On post-hoc analysis, significant decrease in both dysphagia and odynophagia score was observed between baseline and at the end of study and between various follow-up visits (p-value < 0.0001). Moreover, there was a significant increase in mean body weight (p-value < 0.0001). At 3 months, there was a significant decrease in dysphagia (p-value < 0.0001), eating (p-value < 0.0001), reflux (p-value = 0.005), pain (p-value < 0.0001), and saliva (p-value = 0.01) domains of EORTC QLQ-OES18 questionnaire.ConclusionIn patients with LAESCC, EBRT leads to significant decrease in dysphagia and odynophagia, and increase in body weight. These changes indirectly lead to improved QoL.