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Biomedical subjects

Jean-Philippe Pignol

Publications and source records attributed to Jean-Philippe Pignol.

14 recordsLinked to original sources

The management of ductal carcinoma in situ of the breast: a screened population-based analysis.

BACKGROUND: A recent SEER study identified significant variations in the care of women with DCIS, yet several potential confounding variables were not included. We report a patterns of care study of women with DCIS to better understand the gap between evidence-based knowledge and the management of DCIS. METHODS: We studied all cases of DCIS diagnosed through the Ontario Breast Screening Program from 1991 to 2000. Data was obtained by database linkage and chart abstraction. A logistic regression model using generalized estimating equations to adjust for clustering was used. RESULTS: About 320,236 women were screened and 727 individuals were diagnosed with DCIS. The rate of mastectomy was 30% and was associated with multifocality (OR: 3.5 [1.7, 7.1], P = 0.0005), tumor size (OR: >2 cm vs. 1 cm (OR: 2.4 [1.3, 4.4], P = 0.006). Half of cases with margins <1 cm did not receive XRT. CONCLUSIONS: Our study corroborates previous reports on the persistent rates of mastectomy and axillary nodal dissection and the limited use of XRT in the treatment of DCIS.

Age Distribution↗

Improvement of radiological penumbra using intermediate energy photons (IEP) for stereotactic radiosurgery.

Using efficient immobilization and dedicated beam collimation devices, stereotactic radiosurgery ensures highly conformal treatment of small tumours with limited microscopic extension. One contribution to normal tissue irradiation remains the radiological penumbra. This work aims at demonstrating that intermediate energy photons (IEP), above orthovoltage but below megavoltage, improve dose distribution for stereotactic radiosurgery for small irradiation field sizes due to a dramatic reduction of radiological penumbra. Two different simulation systems were used: (i) Monte Carlo simulation to investigate the dose distribution of monoenergetic IEP between 100 keV and 1 MeV in water phantom; (ii) the Pinnacle3 TPS including a virtual IEP unit to investigate the dosimetry benefit of treating with 11 non-coplanar beams a 2 cm tumour in the middle of a brain adjacent to a 1 mm critical structure. Radiological penumbrae below 300 microm are generated for field size below 2 x 2 cm2 using monoenergetic IEP beams between 200 and 400 keV. An 800 kV beam generated in a 0.5 mm tungsten target maximizes the photon intensity in this range. Pinnacle3 confirms the dramatic reduction in penumbra size. DVHs show for a constant dose distribution conformality, improved dose distribution homogeneity and better sparing of critical structures using a 800 kV beam compared to a 6 MV beam.

Body Burden↗

Prediction of lung tumour position based on spirometry and on abdominal displacement: accuracy and reproducibility.

BACKGROUND AND PURPOSE: A simulation investigating the accuracy and reproducibility of a tumour motion prediction model over clinical time frames is presented. The model is formed from surrogate and tumour motion measurements, and used to predict the future position of the tumour from surrogate measurements alone. PATIENTS AND METHODS: Data were acquired from five non-small cell lung cancer patients, on 3 days. Measurements of respiratory volume by spirometry and abdominal displacement by a real-time position tracking system were acquired simultaneously with X-ray fluoroscopy measurements of superior-inferior tumour displacement. A model of tumour motion was established and used to predict future tumour position, based on surrogate input data. The calculated position was compared against true tumour motion as seen on fluoroscopy. Three different imaging strategies, pre-treatment, pre-fraction and intrafractional imaging, were employed in establishing the fitting parameters of the prediction model. The impact of each imaging strategy upon accuracy and reproducibility was quantified. RESULTS: When establishing the predictive model using pre-treatment imaging, four of five patients exhibited poor interfractional reproducibility for either surrogate in subsequent sessions. Simulating the formulation of the predictive model prior to each fraction resulted in improved interfractional reproducibility. The accuracy of the prediction model was only improved in one of five patients when intrafractional imaging was used. CONCLUSIONS: Employing a prediction model established from measurements acquired at planning resulted in localization errors. Pre-fractional imaging improved the accuracy and reproducibility of the prediction model. Intrafractional imaging was of less value, suggesting that the accuracy limit of a surrogate-based prediction model is reached with once-daily imaging.

Abdomen↗

Body radiation exposure in breast cancer radiotherapy: impact of breast IMRT and virtual wedge compensation techniques.

PURPOSE: Recent reports demonstrate a dramatically increased rate of secondary leukemia for breast cancer patients receiving adjuvant high-dose anthracycline and radiotherapy, and that radiation is an independent factor for the development of leukemia. This study aimed to evaluate the radiation body exposure during breast radiotherapy and to characterize the factors associated with an increased exposure. PATIENTS AND METHODS: In a prospective cohort of 120 women, radiation measurements were taken from four sites on the body at the time of adjuvant breast radiotherapy. Multiple regression analysis was performed to analyze patient and treatment factors associated with the amount of scattered radiation. RESULTS: For standard 50 Gy breast radiotherapy, the minimal dose received by abdominal organs is on average 0.45 Gy, ranging from 0.06 to 1.55 Gy. The use of physical wedges as a compensation technique was the most significant factor associated with increased scattered dose (p < 0.001), resulting in approximately three times more exposure compared with breast intensity-modulated radiation therapy (IMRT) and dynamic wedge. CONCLUSIONS: The amount of radiation that is scattered to a patient's body is consistent with exposure reported to be associated with excess of leukemia. In accordance with the As Low As Reasonably Achievable (ALARA) principle, we recommend using breast IMRT or virtual wedging for the radiotherapy of breast cancer receiving high-dose anthracycline chemotherapy.

Body Height↗

First report of a permanent breast 103Pd seed implant as adjuvant radiation treatment for early-stage breast cancer.

PURPOSE: A new technique of adjuvant partial breast irradiation using 103Pd permanent breast seed implants (PBSI) is presented. The procedure is performed in a single 1-hour session under local anesthesia. METHODS AND MATERIALS: Patients referred to a single institution for adjuvant radiotherapy after lumpectomy for an infiltrating ductal carcinoma < or = 3 cm in diameter, surgical margin > or = 2 mm, no extensive in situ carcinoma, no lymphovascular invasion, and minimal or negative lymph node involvement were offered a PBSI. RESULTS: Between May and December 2004, 31 eligible patients underwent CT scan and ultrasound simulations assessing PBSI feasibility. Fifteen were excluded because of feasibility issues, and 16 received PBSI. A minimal peripheral dose of 90 Gy was prescribed to the planning target volume corresponding to the clinical target volume identified on the CT scan plus a margin of 1 cm. The procedure was well tolerated; 56% of the patients reported no pain during the procedure, and 46% of the patients developed National Cancer Institute Common Toxicity Criteria Grade 1 acute reaction. None experienced toxicity Grade 2 or 3. CONCLUSIONS: Permanent breast seed implantation seems feasible and well tolerated on these preliminary clinical data and represents an ultimate step in the reduction of treatment fraction for partial breast irradiation.

Brachytherapy↗

Individualized planning target volumes for intrafraction motion during hypofractionated intensity-modulated radiotherapy boost for prostate cancer.

PURPOSE: The objective of the study was to access toxicities of delivering a hypofractionated intensity-modulated radiotherapy (IMRT) boost with individualized intrafraction planning target volume (PTV) margins and daily online correction for prostate position. METHODS AND MATERIALS: Phase I involved delivering 42 Gy in 21 fractions using three-dimensional conformal radiotherapy, followed by a Phase II IMRT boost of 30 Gy in 10 fractions. Digital fluoroscopy was used to measure respiratory-induced motion of implanted fiducial markers within the prostate. Electronic portal images were taken of fiducial marker positions before and after each fraction of radiotherapy during the first 9 days of treatment to calculate intrafraction motion. A uniform 10-mm PTV margin was used for the first phase of treatment. PTV margins for Phase II were patient-specific and were calculated from the respiratory and intrafraction motion data obtained from Phase I. The IMRT boost was delivered with daily online correction of fiducial marker position. Acute toxicity was measured using National Cancer Institute Common Toxicity Criteria, version 2.0. RESULTS: In 33 patients who had completed treatment, the average PTV margin used during the hypofractionated IMRT boost was 3 mm in the lateral direction, 3 mm in the superior-inferior direction, and 4 mm in the anteroposterior direction. No patients developed acute Grade 3 rectal toxicity. Three patients developed acute Grade 3 urinary frequency and urgency. CONCLUSIONS: PTV margins can be reduced significantly with daily online correction of prostate position. Delivering a hypofractionated boost with this high-precision IMRT technique resulted in acceptable acute toxicity.

Aged↗

A permanent breast seed implant as partial breast radiation therapy for early-stage patients: a comparison of palladium-103 and iodine-125 isotopes based on radiation safety considerations.

PURPOSE: A permanent breast seed implant (PBSI) technique has been developed as a new form of partial adjuvant radiation therapy for early-stage breast cancer. This study compares iodine-125 ((125)I) and palladium-103 ((103)Pd) isotopes by examining the exposure and effective dose (ED) to a patient's partner. METHODS AND MATERIALS: A low-energy survey meter was used to measure exposure rates as a function of bolus thickness placed over (103)Pd or (125)I seeds. A general mathematical expression for the initial exposure rate at 1 m (x(o,1m)) from the skin surface as a function of the implant size, R, and the distance between the skin surface and the implant, d, was derived. Also, a second general equation is proposed to calculate the ED to the patient's partner. RESULTS: The initial exposure rate at 1 meter and the ED are calculated as follows: x(o,1m) = 3alpha2R(3) ; ;beta(3) [e(-beta(2R+d))(betaR + 1) + e(-betad)(betaR - 1)], and ED = aR(b) [e(-c(2R+d)) (cR + 1) + e(-cd) (cR - 1)]. For (125)I, the parameters are: alpha = 0.154409, beta = 0.388460, a = 197, b = -0.95, and c = 0.38846. For (103)Pd, they are: alpha = 0.06877, beta = 0.421098, a = 18.6, b = -0.78, and c = 0.421098. For implant diameters varying from 2 to 6 cm and skin-to-implant distances varying from 0.7 to 4 cm, the ED is consistently below 2.6 mSv using the (103)Pd isotope, but more than 5 mSv in many instances and possibly up to 20 mSv using (125)I. CONCLUSIONS: PBSI using (103)Pd seeds appears safe because the patient's partner ED is consistently below 5 mSv. The(125)I isotope is not recommended for PBSI.

Algorithms↗

Complementary and alternative medicine use is associated with an increased perception of breast cancer risk and death.

PURPOSE: Complementary and alternative medicines (CAMS) are frequently used by patients with breast cancer and their use may be related to the presence of psychosocial distress. The objective of this study is to assess the presence of anxiety and depression in breast cancer patients who use CAM and assess how they perceive their risks of recurrence and dying from breast cancer compared to non-users. METHODS: Breast cancer patients attending ambulatory clinics at a single cancer center were approached by their oncologist. Participants completed a self-administered survey regarding CAM usage, beliefs associated with CAM, views of their risks of developing recurrent cancer, and of dying of breast cancer. The presence of anxiety and depression was scored using the Hospital Anxiety and Depression Scale (HADS). Responses were scored and compared between CAM users and non-users. RESULTS: A total of 251 patients completed the survey. CAM usage was reported by 43% of patients. Individuals who used CAM were younger [53.1 versus 63.0 year (p < 0.001)], had higher education (p < 0.001), were more likely to have full time employment [25.7 versus 16.3% (p < 0.001)] and have private insurance for medications (76 versus 60%, p = 0.007) compared to non-users. CAM users perceived their risk of recurrence (p = 0.011) and death from breast cancer (p = 0.0001) as being significantly greater than non-users. There were no significant differences in anxiety or depression scores between CAM and non-users. CONCLUSION: CAM use is associated with an increased perception of breast cancer recurrence and of breast cancer-related death. There was no association between the presence of anxiety or depression and CAM use. Improved patient understanding of actual risks of recurrence and death are required such that women will be able to make more informed decisions about using CAMs.

Adult↗

Inverse vs. forward breast IMRT planning.

Breast intensity-modulated radiation therapy (IMRT) improves dose distribution homogeneity within the whole breast. Previous publications report the use of inverse or forward dose optimization algorithms. Because the inverse technique is not widely available in commercial treatment planning systems, it is important to compare the 2 algorithms. The goal of this work is to compare them on a prospective cohort of 30 patients. Dose distributions were evaluated on differential dose-volume histograms using the volumes receiving more than 105% (V(105)) and 110% (V(110)) of the prescribed dose, and on the maximum dose (D(max)) or hot spot and the sagittal dose gradient (SDG) being the gradient between the dose on inframammary crease and the dose prescribed. The data were analyzed using Wilcoxon signed rank test. The inverse planning significantly improves the V(105) (mean value 9.7% vs. 14.5%, p=0.002), and the V(110) (mean value 1.4% vs. 3.2%, p=0.006). However, the SDG is not statistically significantly different for either algorithm. Looking at the potential impact on skin acute reaction, although there is a significant reduction of V(110) using an inverse algorithm, it is unlikely this 1.6% volume reduction will present a significant clinical advantage over a forward algorithm. Both algorithms are equivalent in removing the hot spots on the inframammary fold, where acute skin reactions occur more frequently using a conventional wedge technique. Based on these results, we recommend that both forward and inverse algorithms should be considered for breast IMRT planning.

Algorithms↗

Correlation of lung tumor motion with external surrogate indicators of respiration.

PURPOSE: To assess the correlation of respiratory volume and abdominal displacement with tumor motion as seen with X-ray fluoroscopy. Measurements throughout the patient's treatment course allowed an assessment of the interfractional reproducibility of this correlation. METHODS AND MATERIALS: Data were acquired from 11 patients; 5 were studied over multiple days. Measurements of respiratory volume by spirometry and abdominal displacement by a real-time position tracking system were correlated to simultaneously acquired X-ray fluoroscopy measurements of superior-inferior tumor displacement. The linear correlation coefficient was computed for each data acquisition. The phase relationship between the surrogate and tumor signals was estimated through cross-correlation delay analysis. RESULTS: Correlation coefficients ranged from very high to very low (0.99-0.39, p < 0.0001). The correlation between tumor displacement and respiratory volume was higher and more reproducible from day to day than between tumor displacement and abdominal displacement. A nonzero phase relationship was observed in nearly all patients (-0.65 to +0.50 s). This relationship was observed to vary over inter- and intrafractional time scales. Only 1 of 5 patients studied over multiple days had a consistent relationship between tumor motion and either surrogate. CONCLUSIONS: Respiratory volume has a more reproducible correlation with tumor motion than does abdominal displacement. If forming a tumor-surrogate prediction model from a limited series of observations, the use of surrogates to guide treatment might result in geographic miss.

Aged↗

Comparison of the efficacy and acute toxicity of weekly versus daily chemoradiotherapy for non-small-cell lung cancer: a meta-analysis.

PURPOSE: Recent studies have reported improved survival with concurrent chemoradiotherapy (ChRT) for inoperable non-small-cell lung cancer (NSCLC). ChRT includes the delivery of low-dose chemotherapy given daily during radiotherapy (RT) or higher doses administered weekly. It remains unknown whether a difference in efficacy or toxicity exists between these approaches. A systematic review was performed to compare the efficacy and toxicity of weekly vs. daily ChRT. METHODS AND MATERIALS: The results from randomized studies comparing ChRT to RT for NSCLC were pooled using meta-analyses. The relative risk (RR) of death at 1, 2, and 3 years and of acute esophagitis, pneumonitis, or neutropenia (World Health Organization Grade 3 or greater) were determined. RESULTS: Ten studies involving 1802 patients were included. No significant difference in mortality or toxicity was observed between the weekly and daily regimens: RR of death at 2 years-weekly 0.93, 95% confidence interval [CI] 0.87-0.99; daily 0.92, 95% CI 0.85-1.00; RR of death at 3 years-weekly 0.93, 95% CI 0.89-0.98; daily 0.90, 95% CI 0.81-1.01; RR of esophagitis-weekly 2.07, 95% CI 0.96-4.46; daily 1.70, 95% CI 1.17-2.48; RR of pneumonitis-weekly 1.52, 95% CI 0.93-2.48; daily 1.17, 95% CI 0.65-2.09; and RR of neutropenia-weekly 8.57, 95% CI 3.75-19.58; daily 11.93, 95% CI 1.55-92.12. CONCLUSION: No statistically significant difference in efficacy or acute toxicity was observed to suggest the superiority of daily vs. weekly ChRT regimens for NSCLC.

Antineoplastic Agents↗

Is expert breast pathology assessment necessary for the management of ductal carcinoma in situ ?

BACKGROUND: Current guidelines include a recommendation that a pathologist with expertise in breast disease review all ductal carcinoma in situ (DCIS) specimens due to the presence of significant variability in pathologic reporting of DCIS. The objective of this study was to evaluate the completeness and accuracy of pathologic reporting of DCIS over the past decade and to determine the current impact of expert breast pathology assessment on the management of DCIS. METHODS: All patients with a diagnosis of DCIS referred to a single regional cancer centre between 1982 and 2000 have been reviewed. Inter-observer variability between initial and secondary reports has been evaluated using kappa statistics. For each case, the Van Nuys Prognostic Index (VNPI) using pathologic data obtained from the initial and reviewed pathology reports were compared. The impact of expert breast pathology on risk assessment and treatment was determined. RESULTS: 481 individuals with DCIS were referred and pathology review was performed on 350 patients (73%). Inter-observer agreement was high for the main pathologic features of DCIS. From 1996 to 2000, secondary pathology assessments lead to a change in the assessment of local recurrence risk in 100 cases (29%) and contributed to a change in treatment recommendation in 93 (43%) cases. CONCLUSION: Expert breast pathology assessments continue to be necessary in the management of DCIS.

Adult↗

Clinical significance of atomic inner shell ionization (ISI) and Auger cascade for radiosensitization using IUdR, BUdR, platinum salts, or gadolinium porphyrin compounds.

PURPOSE: Halogenated pyrimidines (iododeoxyuridine [IUdR] and bromodeoxyuridine [BUdR]), platinum salts, and gadolinium porphyrins are heavy atom compounds used as radiosensitizers. For IUdR, it has been hypothesized that iodine inner shell ionizations (ISI) and Auger cascades could be one of the primary radiosensitization mechanisms. The purpose of this paper is to estimate the number of ISI produced per tumor cell and per 2 Gy irradiation in clinically relevant modelings. MATERIALS AND METHODS: ISI were evaluated using a two-step method. Photon-induced ISI were calculated using the MCNP-4C Monte Carlo code, heavy atom concentrations from clinical data published in the literature, and at various depths in a water phantom irradiated with 6-MV, (60)Co, (137)Cs, or (192)Ir sources. Electron knock-on induced ISI on K, L, and M atomic shells were evaluated with an hybrid method, using simulated electron spectra and cross-sections derived from the Møller formalism. Using a biological dose equivalence of 0.05 Gy per cell ISI, relative biological effectiveness (RBE) values were calculated for each situation. RESULTS: For platinum and gadolinium, ISI occurs in far less than 0.1% of the cell, whichever is the configuration. For IUdR and BUdR, ISI occurs in between 45% to 483% of the cell. Due to spectrum degradation, about 3 times more photoelectric ISI are generated at greater than shallower depths, and 10 times more for (192)Ir compared with (60)Co or 6-MV X-rays. Photoelectric ISI are about 3 times more frequent for iodine than bromine, but electron knock-on ISI are more frequent on bromine, and at the end about the same number of ISI are generated for both elements. RBEs were found to be between 1.01 and 1.12 for clinically relevant irradiation settings. CONCLUSIONS: The mechanisms of radiosensitization for platinum and gadolinium are clearly not related to an Auger cascade. For halogenated pyrimidines, however, clinically relevant numbers of ISI are generated within each cell. For IUdR, ISI appears to be strongly tied to the photon spectra. Halogenated pyrimidines should be evaluated again clinically, but using lower energy photons like a (192)Ir implant.

Bromodeoxyuridine↗

A comparison of risk perception and psychological morbidity in women with ductal carcinoma in situ and early invasive breast cancer.

PURPOSE: To assess how women with ductal carcinoma in situ (DCIS) perceive their risks of recurrence, dying from breast cancer, and psychological distress compared to women with early stage invasive breast cancer (EIBC). PATIENTS AND METHODS: Eligible patients included those with DCIS or EIBC (T1 or T2, N0) referred to one cancer center between November 1998 and June 1999. Participants completed a self-administered survey regarding their views of their risks of developing recurrent cancer, of dying of breast cancer and the presence of psychological symptoms of distress. Responses were scored and compared between the two groups. RESULTS: In total, 495 patients were screened, 240 found ineligible, 228 patients who agreed to participate. No significant difference between the two groups was observed in perceptions of risk related to the likelihood of developing local recurrence (DCIS: 53%, EIBC 45%, P = 0.14), distant recurrence (DCIS: 36%; EIBC: 39%, P = 0.35) or dying of breast cancer (DCIS: 27%, EIBC 27%, P = 0.5). Both groups expressed similar levels of psychological distress (anxiety, DCIS: 56%, EIBC 54%, P = 0.38; depression, DCIS: 41%, EIBC, 48%, P = 0.17). CONCLUSIONS: Despite the excellent prognosis, women with DCIS express serious concerns and report similar psychological morbidity as women with invasive cancer.

Adult↗