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Harry Bartelink

Publications and source records attributed to Harry Bartelink.

At least 37 records · Page 2Linked to original sources
PubMed2004

Low-dose-rate brachytherapy is superior to high-dose-rate brachytherapy for bladder cancer.

PURPOSE: To determine the efficacy and safety of a high-dose-rate (HDR) brachytherapy schedule in the treatment of bladder cancer and to investigate the impact of different values of repair half-times and alpha/beta ratios on the design of the HDR schedule. METHODS AND MATERIALS: Between 2000 and 2002, 40 patients with T1G3 and T2 bladder carcinoma were treated with 30 Gy external beam radiotherapy followed by interstitial HDR brachytherapy to a total dose of 32 Gy in 10 sessions of 3.2-Gy fractions in two fractions daily with a 6-h interfraction interval. The local control rate and toxicity were compared with a historical group of 108 patients treated with 30 Gy external beam radiotherapy followed by 40-Gy interstitial low-dose-rate (LDR) brachytherapy. The HDR schedule was designed to be biologically equivalent to the previously used LDR schedule with the linear-quadratic model, including incomplete mono-exponential repair. RESULTS: The local control rate at 2 years was 72% for HDR vs. 88% for LDR brachytherapy (p = 0.04). In the HDR group, 5 of 30 evaluable patients encountered serious late toxicity: 4 patients developed a contracted bladder with inadequate capacity (<100 mL), and 1 patient required cystectomy because of a painful ulcer at the implant site. In the LDR group, only 2 of 84 assessable patients developed serious late toxicity. One patient developed a persisting vesicocutaneous fistula and the other a urethral stricture due to fibrosis. The difference in observed late toxicity for HDR vs. LDR was statistically significant (p = 0.005). The increased late toxicity with the HDR schedule compared with the LDR schedule suggests a short repair half-time of 0.5-1 h for late-responding normal bladder tissue. CONCLUSION: Local control of HDR brachytherapy for bladder cancer was disappointing and late toxicity unexpectedly high. The increase in late toxicity suggested a short repair half-time of 0.5-1 h for late-responding normal bladder tissue, which would not support HDR brachytherapy in the treatment of bladder cancer. The analysis demonstrated that the calculation of equivalent HDR schedules on the basis of the LDR schedules used in clinical practice might be hazardous.

Aged↗
PubMed2004

Online ultrasound image guidance for radiotherapy of prostate cancer: impact of image acquisition on prostate displacement.

AIM: Numerous studies reported the use of ultrasound image-guidance system to assess and correct patient setup during radiotherapy for prostate cancer. We conducted a study to demonstrate and quantify prostate displacement resulting from pressure of the probe on the abdomen during transabdominal ultrasound image acquisition for prostate localization. MATERIAL AND METHODS: Ten healthy volunteers were asked to undergo one imaging procedure. The procedure was performed in a condition that simulates the localization of prostate during online ultrasound guidance. A 3D ultrasound machine was used. The procedure started with the placement of the probe on the abdomen above the pubis symphysis. The probe was tilted in a caudal and posterior direction until the prostate and seminal vesicle were visualized. The probe was then fixed with a rigid arm, which maintained the probe in a static position during image acquisition. The probe was then moved, in a short time, stepwise toward the prostate, acquiring images at each step. The prostate and seminal vesicles were identified and selected in all planes. The first 3D volume was used as reference 1, to which all other scans were matched using a gray value matching algorithm. RESULTS: Prostate motion was quantified as a 3D translation relative to the patient coordinate system. The resulting translations represented the amount of prostate movement as a function of probe displacement. Between 7 and 11 images were obtained per volunteer, with a maximal probe displacement ranging between 3 and 6 cm. Prostate displacement was measured in all volunteers for all the probe steps and in all directions. The largest displacements occurred in the posterior direction in all volunteers. The absolute prostate motion was less than 5 mm in 100% of the volunteers after 1 cm of probe displacement, in 80% after 1.5 cm, in 40% after 2 cm, in 10% after 2.5 cm, and 0% after 3 cm. To achieved a good-quality ultrasound images, the probe requires an average displacement of 1.2 cm, and this results in an average prostate displacement of 3.1 mm. No correlations were observed between prostate motion and prostate-probe distance or bladder size. CONCLUSION: Probe pressure during ultrasound image acquisition causes prostate displacement, which is correlated to the amount of probe displacement from initial contact. The induced uncertainty associated with this process needs to be carefully evaluated to determine a safe margin to be employed during online ultrasound image-guided radiotherapy of the prostate.

Adult↗
PubMed2004

Simplified intensity-modulated radiotherapy using pre-defined segments to reduce cardiac complications in left-sided breast cancer.

BACKGROUND AND PURPOSE: Left-sided breast cancer patients pose a difficult clinical challenge when significant heart and contralateral breast irradiation are present, particularly with tangential uniform beams. The aims of the study are: (1) to design and evaluate a simplified intensity-modulated radiotherapy (IMRT) (SI) solution using pre-defined segments, (2) to compare the SI technique with a conformal (CN) and a full fluence IMRT (FI) approach using two sets of beam orientations, clinical (-C) and optimal (-O), and (3) to quantify the benefits of treatment technique and beam orientation. PATIENTS AND METHODS: Nine left-sided breast cancer patients with a maximum heart distance of at least 2.0 cm were planned using three different techniques and two different beam orientations. All three techniques were planned using clinical orientations (i.e. CN-C, FI-C and SI-C). Two techniques were planned using more optimal orientations (i.e. FI-O and SI-O). Dose-volume histograms and radiobiologic modelling are used for plan evaluation. RESULTS: The average mean planning target volume (PTV) doses are 91.6+/-4.5, 98.4+/-6.3, 102.0+/-8.7, 100.0+/-5.9 and 103.9+/-8.3% for the CN-C, FI-C, SI-C, FI-O and SI-O plans, respectively. The average normal tissue complication probabilities for late excess cardiac mortality are 2.1+/-0.6, 0.2+/-0.1, 0.2+/-0.1, 0.1+/-0.0 and 0.1+/-0.0%, respectively. For a given beam orientation, FI plans are the best and CN plans are the worst. The dose distributions for the SI-C and FI-C plans are almost identical with significant heart sparing but at a cost of some target underdosage. The dose distributions are better conformed around the PTV with more optimal beam orientations, resulting in better sparing of adjacent organs at risk. FI-C plans are inferior to SI-O plans. CONCLUSIONS: For clinical uniform two-beam orientations, significant heart sparing is possible with the addition of intensity modulation but at the expense of worsening target coverage. Simplified IMRT can, for all intents, be substituted for full IMRT with clinical beam orientations. Applying more optimal non-uniform beam orientations improves PTV coverage while maintaining significant heart sparing but increases the PTV dose heterogeneity.

Breast↗
PubMed2004

The influence of the boost technique on local control in breast conserving treatment in the EORTC 'boost versus no boost' randomised trial.

BACKGROUND AND PURPOSE: The EORTC Trial 22881/10882 investigating the role of a boost dose in breast conserving therapy demonstrated a significantly better local control rate with the higher radiotherapy dose, especially in women younger than 50 years of age. This paper investigates the potential impact of the different boost techniques on local control and on fibrosis after breast conserving therapy. PATIENTS AND METHODS: From 1989 to 1996, 2661 patients were randomised to receive a boost dose of 16Gy to the primary tumour bed after microscopically complete tumorectomy and 50Gy whole breast irradiation. The choice of the boost technique was left to the treating investigator. Treatment data were prospectively recorded as well as the clinical outcome in terms of local control and fibrosis. Sixty-three percent of the patients received a boost dose with fast electrons, 28% with photon beams and 9% with interstitial brachytherapy. RESULTS: At 5 years, local recurrences were seen in 74 of the 1635 patients who received an electron boost (4.8%, CI 3.6-5.9%), in 28 of the 753 patients who received a photon boost (4.0%, CI 3.4-5.5%) and in 6 of the 225 patients after an interstitial boost (2.5%, CI 0.3-4.6%). The grade of fibrosis in the whole breast as well as at the primary tumour bed, as scored by the treating radiation oncologist, was similar in the three groups. CONCLUSIONS: Although the three groups are of a rather unequal size, the results of the interstitial boost seem similar in terms of fibrosis and at least as good in terms of local control, despite a lower treatment volume and a longer overall treatment time.

Adult↗
PubMed2004

Sophisticated radiotherapy with optimal surgery is the way forward.

PURPOSE OF REVIEW: Radiotherapy has been one of the cornerstones of treatment for breast cancer for more than a century and has contributed to conservation of the breast and improved locoregional control after mastectomy. This review assesses the most recent evidence generated by clinical scientists in the field of radiotherapy for breast cancer. RECENT FINDINGS: Results from mature trials investigating the role of radiotherapy in breast cancer treatment and the publication of meta-analyses of treatment effects have shown that in addition to improvements in local control, a survival benefit is obtained in several disease settings. These include breast-conserving therapy and postmastectomy radiotherapy. Further, improved diagnostic abilities and surgical techniques, together with advances in treatment delivery, will help to increase the therapeutic ratio of radiotherapy. SUMMARY: There is increasing evidence for long-term benefits of radiotherapy for breast cancer and a reduction in the risks of late side effects in recent decades. This can have a profound impact on clinical practice in the future, leading to a broadening and individualizing of the indications for radiotherapy and improvements in patient survival.

Breast Neoplasms↗
PubMed2004

Determining optimal two-beam axial orientations for heart sparing in left-sided breast cancer patients.

BACKGROUND AND PURPOSE: The optimal intensity fluence profile of a beam depends on the profiles of other beams but most optimizations assume fixed beam orientations, a priori. Breast cancer radiotherapy attempts to cover the target and to spare critical structures such as the heart and lungs. The study aims are (1) to determine and document the optimal two-beam orientation that best spares the heart for left-sided breast cancer patients and (2) to investigate the influence of the treatment technique (i.e., conformal versus intensity modulation) on the optimal objective cost function. MATERIAL AND METHODS: Ten left-sided breast cancer patients were planned using a conformal (3DCRT) and a simplified intensity modulated (sIMRT) technique using predefined segments and different two-beam orientations. Optimal segment weights were determined exhaustively for all axial two-beam combinations, in 5 degree increments, by minimizing a quadratic objective cost function. The resulting objective cost function was analyzed with respect to target geometry and treatment technique. RESULTS: The sIMRT plans are generally less sensitive to beam orientation compared to 3DCRT plans. Optimal two-beam orientations for 3DCRT and sIMRT plans exist and they correspond to a hinge angle of approximately 188 degrees and 160 degrees or 210 degrees (the latter is bimodal), respectively. CONCLUSIONS: The optimization software is a useful tool that can test many different beam combinations and estimate their associated objective cost values. Afterwards, the most promising beam orientations could be re-optimized under the TPS to fine-tune and verify the dose distributions. Optimal uniform two-beam orientations for the breast consist of opposing tangential medial and lateral beams. Optimal nonuniform two-beam orientations for left-sided breast cancers are bimodal, containing hinge angles around 160 degrees and 210 degrees. Nonuniform beam techniques are less sensitive to beam orientation compared to uniform beam techniques and result in significantly improved heart sparing but at a cost of slightly compromised planning target volume coverage.

Breast↗
PubMed2003

Long-term cause-specific mortality of patients treated for Hodgkin's disease.

PURPOSE: To assess long-term cause-specific mortality of young Hodgkin's disease (HD) patients. PATIENTS AND METHODS: The study population consisted of 1,261 patients treated for HD before age 41 between 1965 and 1987. Follow-up was complete until October 2000. For 95% of deaths, the cause was known. Long-term cause-specific mortality was compared with general population rates to assess relative risk (RR) and absolute excess risk (AER) of death. RESULTS: After a median follow-up of 17.8 years, 534 patients had died (55% of HD). The RR of death from all causes other than HD was 6.8 times that of the general population, and still amounted to 5.1 after more than 30 years. RRs of death resulting from solid tumors (STs) and cardiovascular disease (CVD) were increased overall (RR = 6.6 and 6.3, respectively), but especially in patients treated before age 21 (RR = 14.8 and 13.6, respectively). When these patients grew older, this elevated mortality decreased. The overall AER of death from causes other than HD increased throughout follow-up. Patients receiving salvage chemotherapy had a significantly increased RR of death from STs, compared to patients receiving initial therapy only. CONCLUSION: The main cause of death among HD patients was lymphoma, but after 20 years, HD mortality was negligible. The RRs and AERs of death from second primary cancers (SCs) and CVDs continued to increase after 10 years. Even more than 30 years after diagnosis, HD patients experienced elevated risk of death from all causes other than HD. Increased risk of death from SCs and CVDs was found especially in patients treated before age 21, but these risks seemed to abate with age.

Adult↗
PubMed2003

Thallium-201-chloride scintigraphy in staging and monitoring radiotherapy response in follicular lymphoma patients.

PURPOSE: To study thallium-201-chloride scintigraphy (201Tl-S) in staging and monitoring response after radiotherapy in follicular lymphoma (FL) patients. PATIENTS AND METHODS: Forty-one consecutive and unselected FL patients were examined by 'Conventional Standard Staging' (CSS) procedures (history and physical examination, ultrasound, CT scans, biopsies and fine needle aspiration cytology) prior to irradiation. Eight standardized potentially affected lymphoma localizations (neck, axilla, mediastinum, spleen, paraaortic, parailiac, femoral and extranodal) per patient were separately studied, resulting in the investigation of 328 localizations. Thirty minutes after the intravenous administration of a tracer dose of 150 MBq thallium-201-chloride total body images were made, immediately followed by single photon emission computed tomography acquisition. All lymphoma localizations were subsequently irradiated. Patients were re-examined after a median of 4 weeks (range 3-6 weeks) by all CSS modalities and 201Tl-S. Diagnostic performance was evaluated both per site and per patient, both in the diagnostic phase of the study as well as in the post-treatment re-evaluation phase. RESULTS: In staging, 201Tl-S was positive in 82 of the 129 initial positive regions by CSS (64%). This percentage increased to 70% when eliminating upper abdominal lymph nodes from the analysis. In 24 patients all lesions were visualized by 201Tl-S, in 11 patients some but not all lesions were detected. In six patients none of the lesions were detected by 201Tl-S. In four patients, four additional lesions were initially found by 201Tl-S only. After irradiation, 83 of the total 86 positive regions reached a complete or partial remission by CSS. Eighty-one of these were also diagnosed as remission by 201Tl-S and two as stable disease. In 31 out of 35 patients (89%; 95% CI: 73-97%) the overall response in all irradiated sites was identical by 201Tl-S and CSS. Only two patients, in remission on CSS modalities, showed stable disease on 201Tl-S, while two others were diagnosed as CR by CSS and PR by 201Tl-S. CONCLUSIONS: 201Tl-S has limited additional value in staging FL patients, since only two-thirds of all localizations are detected. However, 201Tl-S is accurate in monitoring radiation treatment response in FL patients. If an FL patient with a positive 201Tl-S at diagnosis is treated by irradiation, the treatment response can be reliably ascertained by only performing a 201Tl-S.

Adult↗
PubMed2003

Radiotherapy to the conserved breast, chest wall, and regional nodes: is there a standard?

BACKGROUND: The role of radiotherapy in the treatment of breast cancer has changed considerable during the last two decades. It has now become the standard part of the breast-conserving procedure, as well as in patients who underwent mastectomy with T3+tumor and/or 4 or more positive lymphnodes in axilla. METHODS: Improvements are seen in the postmastectomy radiotherapy area by delivering better treatment techniques herewith avoiding treatment of the heart and lungs in order to optimize the improvement of local control and the significant improvement in survival. Indications exist that the largest impact of postmastectomy radiotherapy on survival is mostly seen in patients with minimal tumorload, i.e. small tumors and/or 1 or 2 positive lymphnodes. RESULTS: In several clinical trials, it was shown that the relapse rate in the ipsilateral breast is reduced with a HR of 4 if whole breast irradiation is given after tumorectomy. The update of the Oxford meta-analysis demonstrated that this improvement in local control has also led to an improved survival in these patients. More information is recently gained on the required radiation dose in breast-conserving therapy. Especially patients less than 50 years of age have to be treated with a high radiation dose, 50 + 16 Gy boost, while a dose of 50 Gy in 5 weeks seems sufficient for patients older than 50 years, who have a microscopically complete excision. Further optimization of the radiotherapy technique is found in imaged guided approaches and intensity modulated radiotherapy. Combining these efforts allows for a more precise delivery of the radiation dose to a limited volume, so that the side effects like fibrosis will be reduced. CONCLUSIONS: Partial breast irradiation, instead of whole breast irradiation, is now being tested in a few randomized trials. Although this approach may be useful in certain patients groups, it still cannot be accepted as standard treatment, as no proper selection criteria exist and no long-term follow-up data have been presented.

Breast Neoplasms↗
PubMed2003

Anti-cancer alkyl-lysophospholipids inhibit the phosphatidylinositol 3-kinase-Akt/PKB survival pathway.

Synthetic alkyl-lysophospholipids (ALPs) represent a new class of anti-tumor agents that target cell membranes and induce apoptosis. However, the exact mechanisms by which ALPs exert these effects remain unclear. Here, we investigated in the epithelial carcinoma cell lines A431 and HeLa the effect of three clinically relevant ALPs [Et-18-OCH3 (Edelfosine), HePC (Miltefosine) and D-21266 (Perifosine)] on the phosphatidylinositol 3-kinase (PI3K)-Akt/PKB survival pathway. We found that growth factor-induced Akt/PKB activation in these cells is dependent on PI3K and that all three ALPs inhibited this pathway in a dose-dependent manner. We further showed that inhibition of the PI3K-Akt/PKB pathway by wortmannin or ALPs is associated with activation of the pro-apoptotic SAPK/JNK pathway. Inhibition of the PI3K-Akt/PKB survival pathway represents a novel mode of action of ALPs that may significantly contribute to the induction of apoptosis.

Antineoplastic Agents↗
PubMed2003

Reproducibility of the assessment of tumor extent in the breast using multiple image modalities.

The accuracy of breast-conserving therapy (BCT) is limited by uncertainties in the assessment of tumor extent. These uncertainties may result in too wide treatment volumes leading to undesirable cosmetic results, or too narrow treatment volumes leading to higher probabilities of local recurrence. The aim of this study is to quantify the reproducibility of the assessment of tumor extent in the breast at preoperative diagnostic imaging with multiple imaging modalities and at pathology, applied to (1) determining minimum surgical safety margins to reduce the probability of underestimating the tumor extent due to uncertainty in the radiological assessment, and (2) defining the minimum difference between two measurements of tumor size that indicates a significant reduction of tumor extent in response to neoadjuvant chemotherapy or hormonal therapy. Measurements of the largest tumor diameter in mammography, ultrasonography, contrast-enhanced magnetic resonance imaging, and at pathology were retrieved, retrospectively, for 105 patients eligible for BCT. An analysis of variance technique is employed to separate uncertainty at preoperative diagnostic imaging from uncertainty at pathology. The random variations are thus calculated independently of the systematic deviations, avoiding the necessity to choose a gold standard. Moreover, the technique does not require repeat measurements of tumor extent, thus allowing the use of data that is obtained in daily clinical practice, while avoiding bias due to recollection. The magnitude of the random variations is used to determine minimum surgical safety margins and to define the minimum significant difference between two measurements of tumor size. The overall random variations in the assessment of tumor extent are on the order of 3 mm (1 s.d.) with only little differences of about 0.3 mm between the four techniques. The dependence of the random variations on tumor size was found significant (p < 0.05) for mammography (2.7 mm vs 4.2 mm, 1 s.d.) and ultrasonography (2.5 mm vs 3.8 mm, 1 s.d.) for tumors up to 17 mm compared to those that are larger. A minimum surgical safety margin on the order of 5 mm for tumors up to 17 mm and 7 mm for larger tumors takes the uncertainty in radiological assessment of the tumor extent into account effectively in 95% of the performed surgical procedures. A minimum difference in largest tumor diameter of 7 mm for tumors up to 17 mm and 9 mm for those that are larger indicates a significant (p < 0.05) reduction of tumor extent in response to neoadjuvant chemotherapy or hormonal therapy. The reproducibility of the assessment of tumor extent at preoperative diagnostic imaging is of comparable magnitude to the reproducibility at pathology. The uncertainty in the preoperative assessment of tumor extent constitutes a large portion (5-7 mm) of the current safety margin in breast-conserving surgery (10 mm). In monitoring response to neoadjuvant chemotherapy or hormonal therapy using repeat imaging before and after treatment, the current clinical guidelines may produce approximately 10% false-positive responses for tumors between 20 and 30 mm.

Adult↗
PubMed2002

A gene-expression signature as a predictor of survival in breast cancer.

BACKGROUND: A more accurate means of prognostication in breast cancer will improve the selection of patients for adjuvant systemic therapy. METHODS: Using microarray analysis to evaluate our previously established 70-gene prognosis profile, we classified a series of 295 consecutive patients with primary breast carcinomas as having a gene-expression signature associated with either a poor prognosis or a good prognosis. All patients had stage I or II breast cancer and were younger than 53 years old; 151 had lymph-node-negative disease, and 144 had lymph-node-positive disease. We evaluated the predictive power of the prognosis profile using univariable and multivariable statistical analyses. RESULTS: Among the 295 patients, 180 had a poor-prognosis signature and 115 had a good-prognosis signature, and the mean (+/-SE) overall 10-year survival rates were 54.6+/-4.4 percent and 94.5+/-2.6 percent, respectively. At 10 years, the probability of remaining free of distant metastases was 50.6+/-4.5 percent in the group with a poor-prognosis signature and 85.2+/-4.3 percent in the group with a good-prognosis signature. The estimated hazard ratio for distant metastases in the group with a poor-prognosis signature, as compared with the group with the good-prognosis signature, was 5.1 (95 percent confidence interval, 2.9 to 9.0; P<0.001). This ratio remained significant when the groups were analyzed according to lymph-node status. Multivariable Cox regression analysis showed that the prognosis profile was a strong independent factor in predicting disease outcome. CONCLUSIONS: The gene-expression profile we studied is a more powerful predictor of the outcome of disease in young patients with breast cancer than standard systems based on clinical and histologic criteria.

Adult↗
PubMed2002

The role of DNA polymerase beta in determining sensitivity to ionizing radiation in human tumor cells.

Lethal lesions after ionizing radiation are thought to be mainly unrepaired or misrepaired DNA double-strand breaks, ultimately leading to lethal chromosome aberrations. However, studies with radioprotectors and repair inhibitors indicate that single-strand breaks, damaged nucleotides or abasic sites can also influence cell survival. This paper reports on studies to further define the role of base damage and base excision repair on the radiosensitivity of human cells. We retrovirally transduced human tumor cells with a dominant negative form of DNA polymerase beta, comprising the 14 kDa DNA-binding domain of DNA polymerase beta but lacking polymerase function. Radiosensitization of two human carcinoma cell lines, A549 and SQD9, was observed, achieving dose enhancement factors of 1.5-1.7. Sensitization was dependent on expression level of the dominant negative and was seen in both single cell clones and in unselected virally transduced populations. Sensitization was not due to changes in cell cycle distribution. Little or no sensitization was seen in G(1)-enriched populations, indicating cell cycle specificity for the observed sensitization. These results contrast with the lack of effect seen in DNA polymerase beta knockout cells, suggesting that polDN also inhibits the long patch, DNA polymerase beta-independent repair pathway. These data demonstrate an important role for BER in determining sensitivity to ionizing radiation and might help identify targets for radiosensitizing tumor cells.

Cell Cycle↗
PubMed2002

Increased risk of ischemic stroke after radiotherapy on the neck in patients younger than 60 years.

PURPOSE: To estimate the risk of ischemic stroke in patients irradiated for head and neck tumors. PATIENTS AND METHODS: The incidence of ischemic stroke was determined in 367 patients with head and neck tumors (162 larynx carcinomas, 114 pleomorphic adenomas, and 91 parotid carcinomas) who had been treated with local radiotherapy (RT) at an age younger than 60 years. Relative risk (RR) of ischemic stroke was determined by comparison with population rates from a stroke-incidence register, adjusted for sex and age. Other risk factors for stroke (hypertension, smoking, hypercholesterolemia, diabetes mellitus [DM]) were registered. The median follow-up time after RT was 7.7 years (3,011 person-years of follow-up). RESULTS: Fourteen cases of stroke occurred (expected, 2.5; RR, 5.6; 95% confidence interval [CI], 3.1 to 9.4): eight in patients with laryngeal carcinoma (expected,1.56; RR, 5.1; 95% CI, 2.2 to 10.1), four in pleomorphic adenoma patients (expected, 0.71; RR, 5.7; 95% CI, 1.5 to 14.5), and two in parotid carcinoma patients (expected, 0.24; RR, 8.5, 95% CI, 1.0 to 30.6). Five of six strokes in patients irradiated for a parotid tumor occurred at the ipsilateral side. Analysis of other risk factors for cerebrovascular disease showed hypertension and DM to cause an increase of the RR after RT. After more than 10 years' follow-up, the RR was 10.1 (95% CI, 4.4 to 20.0). The 15-year cumulative risk of stroke after RT on the neck was 12.0% (95% CI, 6.5% to 21.4%). CONCLUSION: This is the first study to demonstrate an increased risk of stroke after RT on the neck. During medical follow-up, preventive measures should be taken to reduce the impact of the risk factors for cerebrovascular disease, to decrease stroke in these patients.

Actuarial Analysis↗
PubMed2002

The effect of set-up uncertainties, contour changes, and tissue inhomogeneities on target dose-volume histograms.

Understanding set-up uncertainty effects on dose distributions is an important clinical problem but difficult to model accurately due to their dependence on tissue inhomogeneities and changes in the surface contour (i.e., variant effects). The aims are: (1) to evaluate and quantify the invariant and variant effects of set-up uncertainties, contour changes and tissue inhomogeneities on target dose-volume histograms (DVHs); (2) to propose a method to interpolate (variant) DVHs. We present a lung cancer patient to estimate the significance of set-up uncertainties, contour changes and tissue inhomogeneities in target DVHs. Differential DVHs are calculated for 15 displacement errors (with respect to the isocenter) using (1) an invariant shift of the dose distribution at the isocenter, (2) a full variant calculation, and (3) a B-spline interpolation applied to sparsely sampled variant DVHs. The collapsed cone algorithm was used for all dose calculations. Dosimetric differences are quantified with the root mean square (RMS) deviation and the equivalent uniform dose (EUD). To determine set-up uncertainty effects, weighted mean EUDs, assuming normally distributed displacement errors, are used. The maximum absolute difference and RMS deviation in the integral DVHs' relative dose between (1) the invariant and calculated curves are 65.2% and 5.8% and (2) the interpolated and calculated curves are 16.9% and 2.5%. Similarly, the maximum absolute difference and RMS deviation in mean EUD as a function of the set-up uncertainty's standard deviation between (1) the invariant and calculated curves are 0.02 and 0.01 Gy; and (2) the interpolated and calculated curves are 0.01 and 0.006 Gy. Since a "worst-case" example is selected, we conclude that, in the majority of clinical cases, the variant effects of contour changes, tissue inhomogeneities and set-up uncertainties on EUD are negligible. Interpolation is a valid, efficient method to approximate DVHs.

Algorithms↗