Abstract Purpose To report the prognostic factors for local control in patients treated for locally advanced cervical cancer with image guided pulsed-dose rate brachytherapy. Materials/methods ...Patients treated with curative intent by a combination of external beam radiotherapy and pulsed-dose rate brachytherapy were selected. Local failure was defined as any relapse in the cervix, vagina, parametria, or uterus during follow-up. Prognostic factors were selected based on log rank tests and then analyzed with a Cox model. Dose/effect correlations were performed using the probit model. Results Two hundred and twenty-five patients treated from 2006 to 2011 were included. According to the FIGO classification, 29% were stage IB, 58% stage II, 10% stage III, and 3% stage IVA; 95% received concomitant chemotherapy. Thirty patients were considered having incomplete response or local failure. Among the selected parameters, D90 for HR-CTV, D90 for IR-CTV, the overall treatment time, the TRAK, and the HR-CTV volume appeared significantly correlated with local control in univariate analysis. In multivariate analysis, overall treatment time >55 days and HR-CTV volume >30 cm3 appeared as independent. The probit analysis showed significant correlations between the D90 for both CTVs, and the probability of achieving local control ( p = 0.008 and 0.024). The thresholds to reach to warrant a probability of 90% of local control were 85 Gy to the D90 of the HR-CTV and 75 Gy to 90% of the IR-CTV (in 2 Gy equivalent, α / β = 10). To warrant the same local control rate, the D90 HR-CTV should be significantly increased in stage III–IV tumors, in case of HR-CTV >30 cm3 , excessive treatment time, or tumor width at diagnosis >5 cm (97, 92, 105, and 92 Gy respectively). Conclusions Overall treatment time and HR-CTV volume were independent prognostic factors for local control. The D90 for HR and IR CTV were significantly correlated with local control, and D90 HR-CTV should be adapted to clinical criteria.
The purpose of this study was to assess the role of treatment in long-term overall and cardiovascular mortality after childhood cancer.
We studied 4,122 5-year survivors of a childhood cancer ...diagnosed before 1986 in France and the United Kingdom. Information on chemotherapy was collected, and the radiation dose delivered to the heart was estimated for 2,870 patients who had received radiotherapy.
After 86,453 person-years of follow-up (average, 27 years), 603 deaths had occurred. The overall standardized mortality ratio (SMR) was 8.3-fold higher (95% CI, 7.6-fold to 9.0-fold higher) in relation to the general populations in France and the United Kingdom. Thirty-two patients had died as a result of cardiovascular diseases (ie, 5.0-fold 95% CI, 3.3-fold to 6.7-fold more than expected). The risk of dying as a result of cardiac diseases (n = 21) was significantly higher in individuals who had received a cumulative anthracycline dose greater than 360 mg/m(2) (relative risk RR, 4.4; 95% CI, 1.3 to 15.3) and in individuals who received an average radiation dose that exceeded 5 Gy (RR, 12.5 and 25.1 for 5 to 14.9 Gy and > 15 Gy, respectively) to the heart. A linear relationship was found between the average dose of radiation to the heart and the risk of cardiac mortality (estimated excess corrected RR at 1 Gy, 60%).
This study is the first, to our knowledge, to establish a relationship between the radiation dose received by the heart during radiotherapy for a childhood cancer and long-term cardiac mortality. This study also confirms a significant excess risk of cardiac mortality associated with a high cumulative dose of anthracyclines.
Abstract Objective To report the outcomes and late toxicities of patients with locally advanced cervical cancer treated with concomitant chemoradiation (CRT) followed by intracavitary image-guided ...adaptive brachytherapy (IGABT). Methods Data from consecutive patients with histologically proven stage IB-IVA cervical cancer treated with curative intent in a single institution were analyzed. After pelvic +/− para-aortic external-beam radiation therapy, they received pulsed-dose rate IGABT following GEC-ESTRO recommendations. Results Two hundred and twenty-five patients were enrolled. Sixty-five percent were stage ≥ IIB according to FIGO classification. Ninety-five percent received CRT. Mean D90 to HR and IR-CTV were 80.4 +/− 10.3 Gy and 67.7 +/− 6.1 Gy. After a median follow-up of 38.8 months, 3-year local control and overall survival rates were 86.4% and 76.1%, respectively. A trend for a detrimental effect of tumor stage on local control rates was observed with 3-year local control rates of 100% for stages IB1 and IIA, 90.5 for IB2, 85.8% for IIB, 50% for IIIA, 77.1 for IIIB, and 66.7% for IVA tumors (p = 0.06). Local control rates at 3 years were 95.6% in the group of patients with D90 of HR-CTV ≥ 85 Gy, 88.8% in those with D90 between 80 and 85 Gy, and 80% when D90 < 80 Gy (p = 0.018). Eighteen severe late gastrointestinal and urinary effects affecting 14 patients were reported corresponding with a crude incidence of 6.6%. Conclusions CRT followed by IGABT provides high local control rates with limited toxicity. Reaching high doses is mandatory to achieve local control and interstitial brachytherapy is necessary in advanced diseases.
To provide better estimates of the frequency distribution of second malignant neoplasm (SMN) sites in relation to previous irradiated volumes, and better estimates of the doses delivered to these ...sites during radiotherapy (RT) of the first malignant neoplasm (FMN).
The study focused on 115 patients who developed a solid SMN among a cohort of 4581 individuals. The homemade software package Dos_EG was used to estimate the radiation doses delivered to SMN sites during RT of the FMN. Three-dimensional geometry was used to evaluate the distances between the irradiated volume, for RT delivered to each FMN, and the site of the subsequent SMN.
The spatial distribution of SMN relative to the irradiated volumes in our cohort was as follows: 12% in the central area of the irradiated volume, which corresponds to the planning target volume (PTV), 66% in the beam-bordering region (i.e., the area surrounding the PTV), and 22% in regions located more than 5 cm from the irradiated volume. At the SMN site, all dose levels ranging from almost zero to >75 Gy were represented. A peak SMN frequency of approximately 31% was identified in volumes that received <2.5 Gy.
A greater volume of tissues receives low or intermediate doses in regions bordering the irradiated volume with modern multiple-beam RT arrangements. These results should be considered for risk-benefit evaluations of RT.
To assess the additional benefits of using the deep-inspiration breath-hold (DIBH) technique with intensity-modulated radiotherapy (IMRT) in terms of the protection of organs at risk for patients ...with mediastinal Hodgkin's disease.
Patients with early-stage Hodgkin's lymphoma with mediastinal involvement were entered into the study. Two simulation computed tomography scans were performed for each patient: one using the free-breathing (FB) technique and the other using the DIBH technique with a dedicated spirometer. The clinical target volume, planning target volume (PTV), and organs at risk were determined on both computed tomography scans according to the guidelines of the European Organization for Research and Treatment of Cancer. In both cases, 30 Gy in 15 fractions was prescribed. The dosimetric parameters retrieved for the statistical analysis were PTV coverage, mean heart dose, mean coronary artery dose, mean lung dose, and lung V20.
There were no significant differences in PTV coverage between the two techniques (FB vs. DIBH). The mean doses delivered to the coronary arteries, heart, and lungs were significantly reduced by 15% to 20% using DIBH compared with FB, and the lung V20 was reduced by almost one third. The dose reduction to organs at risk was greater for masses in the upper part of the mediastinum. IMRT with DIBH was partially implemented in 1 patient. This combination will be extended to other patients in the near future.
Radiation exposure of the coronary arteries, heart, and lungs in patients with mediastinal Hodgkin's lymphoma was greatly reduced using DIBH with IMRT. The greatest benefit was obtained for tumors in the upper part of the mediastinum. The possibility of a wider use in clinical practice is currently under investigation in our department.
To describe a novel method to explore radiation dose-volume effects. Functional data analysis is used to investigate the information contained in differential dose-volume histograms. The method is ...applied to the normal tissue complication probability modeling of rectal bleeding (RB) for patients irradiated in the prostatic bed by 3-dimensional conformal radiation therapy.
Kernel density estimation was used to estimate the individual probability density functions from each of the 141 rectum differential dose-volume histograms. Functional principal component analysis was performed on the estimated probability density functions to explore the variation modes in the dose distribution. The functional principal components were then tested for association with RB using logistic regression adapted to functional covariates (FLR). For comparison, 3 other normal tissue complication probability models were considered: the Lyman-Kutcher-Burman model, logistic model based on standard dosimetric parameters (LM), and logistic model based on multivariate principal component analysis (PCA).
The incidence rate of grade ≥2 RB was 14%. V65Gy was the most predictive factor for the LM (P=.058). The best fit for the Lyman-Kutcher-Burman model was obtained with n=0.12, m = 0.17, and TD50 = 72.6 Gy. In PCA and FLR, the components that describe the interdependence between the relative volumes exposed at intermediate and high doses were the most correlated to the complication. The FLR parameter function leads to a better understanding of the volume effect by including the treatment specificity in the delivered mechanistic information. For RB grade ≥2, patients with advanced age are significantly at risk (odds ratio, 1.123; 95% confidence interval, 1.03-1.22), and the fits of the LM, PCA, and functional principal component analysis models are significantly improved by including this clinical factor.
Functional data analysis provides an attractive method for flexibly estimating the dose-volume effect for normal tissues in external radiation therapy.
To assess the clinical outcome of the involved-node radiotherapy (INRT) concept using modern radiation treatments (intensity-modulated radiotherapy IMRT or deep-inspiration breath-hold radiotherapy ...DIBH) in patients with localized supradiaphragmatic Hodgkin lymphoma.
All but 2 patients had early-stage Hodgkin lymphoma, and they were treated with chemotherapy prior to irradiation. Radiation treatments were delivered using the INRT concept according to European Organization for Research and Treatment of Cancer guidelines. IMRT was performed with the patient free-breathing. For the adapted breath-hold technique, a spirometer dedicated to DIBH radiotherapy was used. Three-dimensional conformal radiotherapy was performed with those patients.
Fifty patients with Hodgkin lymphoma (48 patients with primary Hodgkin lymphoma, 1 patient with recurrent disease, and 1 patient with refractory disease) entered the study from January 2003 to August 2008. Thirty-two patients were treated with IMRT, and 18 patients were treated with the DIBH technique. The median age was 28 years (range, 17-62 years). Thirty-four (68%) patients had stage I - (I-IIA) IIA disease, and 16 (32%) patients had stage I - (I-IIB) IIB disease. All but 3 patients received three to six cycles of adriamycin, bleomycin, vinblastine, and dacarbazine (ABVD). The median radiation doses to patients treated with IMRT and DIBH were, respectively, 40 Gy (range, 21.6-40 Gy) and 30.6 Gy (range, 19.8-40 Gy). Protection of various organs at risk was satisfactory. Median follow-up was 53.4 months (range, 19.1-93 months). The 5-year progression-free and overall survival rates for the whole population were 92% (95% confidence interval CI, 80%-97%) and 94% (95% CI, 75%-98%), respectively. Recurrences occurred in 4 patients: 2 patients had in-field relapses, and 2 patients had visceral recurrences. Grade 3 acute lung toxicity (transient pneumonitis) occurred in 1 case.
Our results suggest that patients with localized Hodgkin lymphoma can be safely and efficiently treated using the INRT concept and modern radiation treatment techniques such as IMRT and DIBH.
Abstract Background and purpose Conformal radiation therapy techniques require the delineation of volumes of interest, a time-consuming and operator-dependent task. In this work, we aimed to evaluate ...the potential interest of an atlas-based automatic segmentation software (ABAS) of brain organs at risk (OAR), when used under our clinical conditions. Materials and methods Automatic and manual segmentations of the eyes, optic nerves, optic chiasm, pituitary gland, brain stem and cerebellum of 11 patients on T1-weighted magnetic resonance, 3-mm thick slice images were compared using the Dice similarity coefficient (DSC). The sensitivity and specificity of the ABAS were also computed and analysed from a radiotherapy point of view by splitting the ROC (Receiver Operating Characteristic) space into four sub-regions. Results Automatic segmentation of OAR was achieved in 7–8 min. Excellent agreement was obtained between automatic and manual delineations for organs exceeding 7 cm3 : the DSC was greater than 0.8. For smaller structures, the DSC was lower than 0.41. Conclusions These tests demonstrated that this ABAS is a robust and reliable tool for automatic delineation of large structures under clinical conditions in our daily practice, even though the small structures must continue to be delineated manually by an expert.
Context:
Thyroid carcinoma is a frequent complication of childhood cancer radiotherapy. The dose response to thyroid radiation dose is now well established, but the potential modifier effect of other ...factors requires additional investigation.
Objective:
This study aimed to investigate the role of potential modifiers of the dose response.
Design:
We followed a cohort of 4338 5-year survivors of solid childhood cancer treated before 1986 over an average of 27 years. The dose received by the thyroid gland and some other anatomical sites during radiotherapy was estimated after reconstruction of the actual conditions in which irradiation was delivered.
Results:
Fifty-five patients developed thyroid carcinoma. The risk of thyroid carcinoma increased with a radiation dose to the thyroid of up to two tenths of Gy, then leveled off for higher doses. When taking into account the thyroid radiation dose, a surgical or radiological splenectomy (>20 Gy to the spleen) increased thyroid cancer risk (relative risk RR = 2.3; 95% confidence interval CI, 1.3–4.0), high radiation doses (>5 Gy) to pituitary gland lowered this risk (RR = 0.2; 95% CI, 0.1–0.6). Patients who received nitrosourea chemotherapy had a 6.6-fold (95% CI, 2.5–15.7) higher risk than those who did not. The excess RR per Gy of radiation to the thyroid was 4.7 (95% CI, 1.7–22.6). It was 7.6 (95% CI, 1.6–33.3) if body mass index at time of interview was equal or higher than 25 kg/m2, and 4.1 (95% CI, 0.9–17.7) if not (P for interaction = .1).
Conclusion:
Predicting thyroid cancer risk following childhood cancer radiation therapy probably requires the assessment of more than just the radiation dose to the thyroid. Chemotherapy, splenectomy, radiation dose to pituitary gland, and obesity also play a role.
The purpose of this study was to evaluate the inverse planning simulated annealing (IPSA) software for the optimization of dose distribution in patients with cervix carcinoma treated with MRI-based ...pulsed-dose rate intracavitary brachytherapy.
Thirty patients treated with a technique using a customized vaginal mold were selected. Dose-volume parameters obtained using the IPSA method were compared with the classic manual optimization method (MOM). Target volumes and organs at risk were delineated according to the Gynecological Brachytherapy Group/European Society for Therapeutic Radiology and Oncology recommendations. Because the pulsed dose rate program was based on clinical experience with low dose rate, dwell time values were required to be as homogeneous as possible. To achieve this goal, different modifications of the IPSA program were applied.
The first dose distribution calculated by the IPSA algorithm proposed a heterogeneous distribution of dwell time positions. The mean D90, D100, and V100 calculated with both methods did not differ significantly when the constraints were applied. For the bladder, doses calculated at the ICRU reference point derived from the MOM differed significantly from the doses calculated by the IPSA method (mean, 58.4 vs. 55 Gy respectively; p = 0.0001). For the rectum, the doses calculated at the ICRU reference point were also significantly lower with the IPSA method.
The inverse planning method provided fast and automatic solutions for the optimization of dose distribution. However, the straightforward use of IPSA generated significant heterogeneity in dwell time values. Caution is therefore recommended in the use of inverse optimization tools with clinical relevance study of new dosimetric rules.
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