Does the evidence support the enthusiasm over 3D conformal radiation therapy and dose escalation in the treatment of prostate cancer?
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Attitude of Health Personnel↗
Biomedical subjects
J M Michalski
Publications and source records attributed to J M Michalski.
Chemical disease-free survival in localized carcinoma of prostate treated with external beam irradiation: comparison of American Society of Therapeutic Radiology and Oncology Consensus or 1 ng/mL as endpoint.
PURPOSE: To compare postirradiation biochemical disease-free survival using the American Society of Therapeutic Radiology and Oncology (ASTRO) Consensus or elevation of postirradiation prostate-specific antigen (PSA) level beyond 1 ng/mL as an endpoint and correlate chemical failure with subsequent appearance of clinically detected local recurrence or distant metastasis. METHODS AND MATERIALS: Records of 466 patients with histologically confirmed adenocarcinoma of the prostate treated with irradiation alone between January 1987 and December 1995 were analyzed; 339 patients were treated with bilateral 120 degrees arc rotation and, starting in 1992, 117 with three-dimensional conformal irradiation. Doses were 68--77 Gy in 1.8 to 2 Gy daily fractions. Minimum follow-up is 4 years (mean, 5.5 years; maximum, 9.6 years). A chemical failure was recorded using the ASTRO Consensus or when postirradiation PSA level exceeded 1 ng/mL at any time. Clinical failures were determined by rectal examination, radiographic studies, and, when clinically indicated, biopsy. RESULTS: Six-year chemical disease-free survival rates using the ASTRO Consensus according to pretreatment PSA level for T1 tumors were: < or = 4 ng/mL, 100%; 4.1--20 ng/mL, 80%; and > 20 ng/mL, 50%. For T2 tumors the rates were: < or = 4 ng/mL, 91%; 4.1--10 ng/mL, 81%; 10.1--20 ng/mL, 55%; 20.1--40 ng/mL, 63%; and > 40 ng/mL, 46%. When postirradiation PSA levels higher than 1 ng/mL were used, the corresponding 6-year chemical disease-free survival rates for T1 tumors were 92% for pretreatment PSA levels of < or = 4 ng/mL, 58--60% for levels of 4.1--20 ng/mL, and 30% for levels > 20 ng/mL. For T2 tumors, the 6-year chemical disease-free survival rates were 78% in patients with pretreatment PSA levels of 4--10 ng/mL, 45% for 10.1--40 ng/mL, and 25% for > 40 ng/mL. Of 167 patients with T1 tumors, 30 (18%) developed a chemical failure, 97% within 5 years from completion of radiation therapy; no patient has developed a local recurrence or distant metastasis. In patients with T2 tumors, overall 45 of 236 (19%) had chemical failure, 94% within 5 years of completion of radiation therapy; 4% have developed a local recurrence, and 10%, distant metastasis. In patients with T3 tumors, overall, 24 of 65 (37%) developed a chemical failure, 100% within 3.5 years from completion of radiation therapy; 4% of these patients developed a local recurrence within 2 years, and 12% developed distant metastasis within 4 years of completion of irradiation. The average time to clinical appearance of local recurrence or distant metastasis after a chemical failure was detected was 5 years and 3 years, respectively. CONCLUSION: There was a close correlation between the postirradiation nadir PSA and subsequent development of a chemical failure. Except for patients with T1 tumors and pretreatment PSA of 4.1--20 ng/mL, there is good agreement in 6-year chemical disease-free survival using the ASTRO Consensus or PSA elevations above 1 ng/mL as an endpoint. Although the ASTRO Consensus tends to give a higher percentage of chemical disease-free survival in most groups, the differences with longer follow-up are not statistically significant (p > 0.05). It is important to follow these patients for at least 10 years to better assess the significance of and the relationship between chemical and clinical failures.
Disease-Free Survival↗
In regard to Beyer, Nath, and Butler et al. IJROBP 2000;47:273-275.
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Brachytherapy↗
Importance of the mini-mental status examination in the treatment of patients with brain metastases: a report from the Radiation Therapy Oncology Group protocol 91-04.
PURPOSE: Little information is available on the importance of pretreatment Mini-Mental Status Exam (MMSE) on long-term survival and neurologic function following treatment for unresectable brain metastases. This study examines the importance of the MMSE in predicting outcome in a group of patients treated with an accelerated fractionation regimen of 30 Gy in 10 daily fractions in 2 weeks. MATERIALS AND METHODS: The Radiation Therapy Oncology Group (RTOG) accrued 445 patients to a Phase III comparison of accelerated hyperfractionated (AH) radiotherapy (1.6 Gy b.i.d.) to a total dose of 54.4 Gy vs. an accelerated fractionation (AF) of 30 Gy in 10 daily fractions from 1991 through 1995. All patients had histologic proof of malignancy at the primary site. Brain metastases were measurable by CT or MRI scan and all patients had a Karnofsky performance score (KPS) of at least 70 and a neurologic function classification of 1 or 2. Two hundred twenty-four patients were entered on the accelerated fractionated arm, and 182 were eligible for analysis (7 patients were judged ineligible, no MMSE information in 29, no survival data in 1, no forms submitted in 1). RESULTS: Average age was 60 years; 58% were male and 25% had a single intracranial lesion on their pretherapy evaluation. KPS was 70 in 32%, 80 in 31%, 90 in 29%, and 100 in 14%. The average MMSE was 26.5, which is the lower quartile for normal in the U.S. population. The range of the MMSE scores was 11-30 with 30 being the maximum. A score of less than 23 indicates possible dementia, which occurred in 16% of the patients prior to treatment. The median time from diagnosis to treatment was 5 days (range, 0-158 days). The median survival was 4.2 months with a 95% confidence interval of 3.7-5.1 months. Thirty-seven percent of the patients were alive at 6 months, and 17% were alive at 1 year. The following variables were examined in a Cox proportional-hazards model to determine their prognostic value for overall survival: age, gender, KPS, baseline MMSE, time until MMSE below 23, time since diagnosis, number of brain metastases, and radiosurgery eligibility. In all Cox model analyses, age, KPS, baseline MMSE, time until MMSE below 23, and time since diagnosis were treated as continuous variables. Statistically significant factors for survival were pretreatment MMSE (p = 0.0002), and KPS (p = 0.02). Age was of borderline significance (p = 0.065) as well as gender (p = 0.074). A poorer outcome is associated with an increasing age, male gender, lower MMSE, and shorter time until MMSE below 23. Improvement in MMSE over time was assessed; 62 patients died prior to obtaining follow-up MMSE, and 30 patients had a baseline MMSE of 30 (the maximum), and, therefore, no improvement could be expected. Of the remaining 88, 48 (54.5%) demonstrated an improvement in their MMSE at any follow-up visit. Lack of decline of MMSE below 23 was seen in long-term survivors, with 81% at 6 months and 66% at 1 year of patients maintaining a MMSE above 23. Analysis of time until death from brain metastases demonstrated that decreasing baseline MMSE (p = 0.003) and primary site (breast vs. lung vs. other p = 0.032) were highly associated with a terminal event. CONCLUSION: While gender and perhaps age remain significant predictors for survival, MMSE is also an important way of assessing a patient's outcome. Accelerated fractionation used in the treatment of brain metastases (30 Gy in 10 fractions) appears to also be associated with an improvement in MMSE and a lack of decline of MMSE below 23 in long-term survivors.
Adult↗
Three-dimensional conformal therapy or standard irradiation in localized carcinoma of prostate: preliminary results of a nonrandomized comparison.
PURPOSE: We present preliminary results of a nonrandomized comparison of three-dimensional conformal radiation therapy (3D CRT) and standard radiation therapy (SRT) in localized carcinoma of the prostate in two groups of patients with comparable prognostic factors treated during the same period. METHODS AND MATERIALS: Between January 1992 and December 1997, 146 patients were treated with 3D CRT and 131 with SRT alone for clinical stage T1c or T2 histologically confirmed carcinoma of the prostate. None of these patients received hormonal therapy. Mean follow-up for all patients is 3 years (range, 1-6 years). For 3D CRT, 7 intersecting fields were used (Cerrobend blocking or multileaf collimation) to deliver 68-73.8 Gy to the prostate; 3D dose distributions and dose-volume histograms (DVHs) of the planning target volume, bladder, and rectum were obtained. SRT consisted of bilateral 120 degrees rotational arcs, with portals with 2-cm margins around the prostate to deliver 68-70 Gy to the prostate. The criterion for chemical disease-free survival was a postirradiation prostate-specific antigen (PSA) (Tandem-R, Hybritech) value following the American Society for Therapeutic Radiology and Oncology guidelines. Symptoms during treatment were quantitated weekly, and late effects were assessed every 4-6 months. RESULTS: DVHs showed a two-thirds reduction in normal bladder or rectum receiving 70 Gy or more with 3D CRT. Higher 5-year chemical disease-free survival was observed with 3D CRT (91% for T1c and 96% for T2 tumors) compared with SRT (53% and 58%, respectively). There was no statistically significant difference in chemical disease-free survival in patients with Gleason score of 4 or less (p = 0.83), but with Gleason score of 5-7, the 5-year survival rates were 96% with 3D CRT and 53% with SRT (p < or = 0.01). In 111 patients with pretreatment PSA of 10 ng/mL or less, treated with 3D CRT, the chemical disease-free rate was 96% vs. 65% in 94 patients treated with SRT (p < or = 0.01). In patients with PSA of 10. 1-20 ng/mL, the chemical disease-free survival rate for 26 patients treated with 3D CRT was 88% compared with 40% for 20 patients treated with SRT (p = 0.05). The corresponding values were 71% and 26%, respectively, for patients with PSA levels of greater than 20 ng/mL (p = 0.30). On multivariate analysis, the most important prognostic factors for chemical failure were pretreatment PSA (p = 0. 023), nadir PSA (p = 0.001), and 3D CRT technique (p = 0.033). Moderate dysuria and difficulty in urinating were reported by 2-5% of patients treated with 3D CRT in contrast to 6-9% of patients treated with SRT; moderate urinary frequency and nocturia were reported by 18-24% treated with 3D CRT and 18-27% of patients in the SRT group. The incidence of moderate loose stools/diarrhea, usually after the 4th week of treatment, was 3-5% in the 3D CRT patients and 8-19% in the SRT group. Late intestinal morbidity (proctitis, rectal bleeding) was very low (1.7%) in the 3D CRT group in contrast to the SRT patients (8%). CONCLUSION: Three-dimensional CRT spares more normal tissues, yields higher chemical disease-free survival, and results in less treatment morbidity than SRT in treatment of Stage T1-T2 prostate cancer. Longer follow-up is needed to confirm these preliminary observations.
Disease-Free Survival↗
Preliminary report of toxicity following 3D radiation therapy for prostate cancer on 3DOG/RTOG 9406.
PURPOSE: A prospective Phase I dose escalation study was conducted to determine the maximally-tolerated radiation dose in men treated with three-dimensional conformal radiation therapy (3D CRT) for localized prostate cancer. This is a preliminary report of toxicity encountered on the 3DOG/RTOG 9406 study. METHODS AND MATERIALS: Each participating institution was required to implement data exchange with the RTOG 3D quality assurance (QA) center at Washington University in St. Louis. 3D CRT capabilities were strictly defined within the study protocol. Patients were registered according to three stratification groups: Group 1 patients had clinically organ-confined disease (T1,2) with a calculated risk of seminal vesicle invasion of < 15%. Group 2 patients had clinical T1,2 disease with risk of SV invasion > or = 15%. Group 3 (G3) patients had clinical local extension of tumor beyond the prostate capsule (T3). All patients were treated with 3D techniques with minimum doses prescribed to the planning target volume (PTV). The PTV margins were 5-10 mm around the prostate for patients in Group 1 and 5-10 mm around the prostate and SV for Group 2. After 55.8 Gy, the PTV was reduced in Group 2 patients to 5-10 mm around the prostate only. Minimum prescription dose began at 68.4 Gy (level I) and was escalated to 73.8 Gy (level II) and subsequently to 79.2 Gy (level III). This report describes the acute and late toxicity encountered in Group 1 and 2 patients treated to the first two study dose levels. Data from RTOG 7506 and 7706 allowed calculation of the expected probability of observing a > or = grade 3 late effect more than 120 days after the start of treatment. RTOG toxicity scores were used. RESULTS: Between August 23, 1994 and July 2, 1997, 304 Group 1 and 2 cases were registered; 288 cases were analyzable for toxicity. Acute toxicity was low, with 53-54% of Group 1 patients having either no or grade 1 toxicity at dose levels I and II, respectively. Sixty-two percent of Group 2 patients had either none or grade 1 toxicity at either dose level. Few patients (0-3%) experienced a grade 3 acute bowel or bladder toxicity, and there were no grade 4 or 5 toxicities. Late toxicity was very low in all patient groups. The majority (81-85%) had either no or mild grade 1 late toxicity at dose level I and II, respectively. A single late grade 3 bladder toxicity in a Group 2 patient treated to dose level II was recorded. There were no grade 4 or 5 late effects in any patient. Compared to historical RTOG controls (studies 7506, 7706) at dose level I, no grade 3 or greater late effects were observed in Group 1 and Group 2 patients when 9.1 and 4.8 events were expected (p = 0.003 and p = 0.028), respectively. At dose level II, there were no grade 3 or greater toxicities in Group 1 patients and a single grade 3 toxicity in a Group 2 patient when 12.1 and 13.0 were expected (p = 0.0005 and p = 0.0003), respectively. Multivariate analysis demonstrated that the relative risk of developing acute bladder toxicity was 2.13 if the percentage of the bladder receiving > or = 65 Gy was more than 30% (p = 0.013) and 2.01 if patients received neoadjuvant hormonal therapy (p = 0.018). The relative risk of developing late bladder complications also increased as the percentage of the bladder receiving > or = 65 Gy increased (p = 0.026). Unexpectedly, there was a lower risk of late bladder complications as the mean dose to the bladder and prescription dose level increased. This probably reflects improvement in conformal techniques as the study matured. There was a 2.1 relative risk of developing a late bowel complication if the total rectal volume on the planning CT scan exceeded 100 cc (p = 0.019). CONCLUSION: Tolerance to high-dose 3D CRT has been better than expected in this dose escalation trial for Stage T1,2 prostate cancer compared to low-dose RTOG historical experience. With strict quality assurance standards and review, 3D CRT can be safely studied in a co
Adult↗
Health-related quality of life and morbidity in patients receiving brachytherapy for clinically localized prostate cancer.
Health-related quality of life must be a factor when treatment options are discussed with a patient. Quality of life is measured by validated questionnaires that include generic and disease-targeted measures. Urinary and rectal symptoms and sexual function are evaluated after treatment for prostate cancer. Quality of life is adversely affected in the early post-brachytherapy period primarily by the urinary morbidity. Urinary symptoms peak 2 months after treatment and decline thereafter, although severe long-term urinary toxicity occurs in 3% to 12% of patients. Urinary symptoms are generally treated with alpha-blocker and anticholinergic drugs, but 2% to 5% of patients require transurethral resection of the prostate to relieve persistent obstruction. However, 6 months after treatment, overall satisfaction is excellent, and the majority of patients would recommend the procedure to a friend.
Brachytherapy↗
A critical evaluation of the planning target volume for 3-D conformal radiotherapy of prostate cancer.
PURPOSE: To determine an adequate planning target volume (PTV) margin for three-dimensional conformal radiotherapy (3D CRT) of prostate cancer, the uncertainties in the internal positions of the prostate and seminal vesicles (SV) and in the treatment setups were measured. METHODS AND MATERIALS: Weekly computed tomography (CT) scans of the pelvis (n=51) and daily electronic portal images (n=1630) were reviewed for eight patients who received seven-field 3D CRT for prostate cancer. The CT scans were registered in three dimensions to the original planning CT scan using commercially available software to measure the center-of volume (COV) motion of the prostate and SV. The daily portal images were registered to the corresponding simulation films to measure the setup displacements. The standard deviation (SD) of the internal organ motions was added to the SD of the setups in quadrature to determine the total uncertainty. Positive directions were left, anterior, and superior. Rotations necessary to register the CT scans and portal images were minimal and not further analyzed. RESULTS: The mean motion for the COV of the prostate+/-the SD was 0+/-0.9 mm in the left-right (LR), 0.5+/-2.6 mm in the anterior-posterior (AP), and 1.5+/-3.9 mm in the superior-inferior (SI) directions. The mean motion for the COV of the SV+/-the SD was 0.3+/-1.7 mm in the LR, 0.7+/-3.8 mm in the AP, and 0.9+/-3.5 mm in the SI directions. For all patients the mean isocenter displacement+/-the SD was 0+/-3.1 mm in the LR, 1.4+/-3.0 mm in the AP, and -0.4+/-2.1 mm in the SI directions. The total uncertainty for the prostate was 3.2 mm, 4.0 mm, and 4.4 mm in the LR, AP, and SI directions, respectively. For the SV, the total uncertainty was 3.5, 4.8, and 4.1 mm in the LR, AP, and SI directions, respectively. CONCLUSIONS: PTV margins of 10 to 16 mm are required to encompass all (99%) possible positions of the prostate or SV during 3D CRT. PTV margins of 7 to 11 mm will encompass the measured uncertainties with a 95% probability. PTV margins of 5 mm may not adequately cover the intended volume.
Humans↗
Efficacy of total lymphoid irradiation for chronic allograft rejection following bilateral lung transplantation.
PURPOSE: To assess the safety and efficacy of total lymphoid irradiation (TLI) in patients experiencing chronic rejection following bilateral lung transplantation (BLT). PATIENTS AND MATERIALS: Eleven patients received TLI for chronic allograft rejection (bronchiolitis obliterans syndrome) refractory to conventional treatment modalities. Radiation therapy (RT) was prescribed as 8 Gy delivered in 10 0.8-Gy fractions, 2 fractions/week, via mantle, paraaortic, and inverted-Y fields. Serial pre- and post-RT pulmonary function values, complete blood counts, and immunosuppressive augmentation requirements [use of methylprednisolone, murine anti-human mature T-cell monoclonal antibody (OKT3), polyclonal antithymocyte globulin (ATG), and tacrolimus] were monitored. RESULTS: In the 3 months preceding TLI, the average decrease in forced expiratory volume in 1 s (FEV1) was 34% (range 0-75%) and the median number of immunosuppression augmentations was 3 (range 0-5). Only 4 of 11 patients completed all 10 TLI treatment fractions. Reasons for discontinuation included progressive pulmonary decline (four patients), worsening pulmonary infection (two patients), and persistent thrombocytopenia (one patient). Seven of the 11 patients failed within 8 weeks of treatment cessation. One patient had unabated rejection and received bilateral living related-donor transplants; he is alive and well. Six patients died. Two of these deaths were due to pulmonary infection from organisms isolated prior to the start of RT; the other four deaths were from progressive pulmonary decline. The four remaining patients had durable positive responses to TLI (mean follow-up of 47 weeks; range 24-72). Comparing the 3 months preceding RT to the 3 months following treatment, these four patients had improvements in average FEV1 (40% decline vs. 1% improvement) and fewer median number of immunosuppressive augmentations (3.5 vs. 0). None of these patients has developed lymphoproliferative disease or has died. Features suggestive of a positive response to TLI included longer interval from transplant to RT, higher FEV1 at initiation of RT, and absence of preexisting pulmonary infection. CONCLUSION: Total lymphoid irradiation for chronic allograft rejection refractory to conventional medical management following BLT was tolerable. A subset of patients experienced durable preservation of pulmonary function and decreased immunosuppressive requirements. Patients with rapidly progressive allograft rejection, low FEV1, or preexisting infection were least likely to benefit from irradiation. Early initiation of TLI for patients experiencing chronic allograft rejection following BLT may be warranted.
Adolescent↗
Physician resource utilization in radiation oncology: a model based on management of carcinoma of the prostate.
PURPOSE: To develop a methodology to estimate the comparative cost of physician time in treating patients with localized prostate cancer, using as an example two-dimensional (2D) vs. three-dimensional (3D) conformal irradiation techniques, and to illustrate how current cost-accounting techniques can be used to quantify the cost of physician time and effort of any treatment. METHODS AND MATERIALS: Activity-based costing, a recent innovation in accounting, widely recommended for estimating and managing the costs of specific activities, was used to derive physician resource utilization costs (actual cost of the physician services and related support services consumed). RESULTS: Patients treated with 3D conformal irradiation consume about 50% more physician time than patients receiving 2D conventional radiation therapy. The average professional reimbursement for the 3D conformal irradiation is only about 26% more than for the 2D treatment. Substantial variations in cost are found depending on the total available physician working hours. In an academic institution, a physician working 40 hours a week would have to spend an average of about 60% of available time on clinical services to break even on a 2D treatment process and over 74% of available time on clinical work to break even on a 3D treatment process. The same physician working 50 hours a week would have to spend an average of about 48% of available time on 2D clinical services and about 60% of available time on 3D clinical work to break even. Current Medicare reimbursement for 3D treatment falls short of actual costs, even if physicians work 100% of a 50-hour week. Medicare reimbursement for 2D barely allows the department to break even for 2D treatments. CONCLUSIONS: Costs based on estimates of resource use can be substantially under- or overestimated. A consistent language (method) is needed to obtain and describe the costs of radiation therapy. The methodology described here can help practitioners and researchers more accurately interpret actual cost information. Future use of such cost-estimation methodologies could provide consistent and comparable costs for negotiations with health care providers and help assess different treatment strategies.
Aged↗
Cloning, characterization, and chromosomal mapping of a phospholipase (lecithinase) produced by Vibrio cholerae.
Phospholipases are associated with virulence in bacterial diseases. Vibrio cholerae produces a phospholipase (lecithinase), with enzyme production visualized as a zone of clearing around colonies plated on egg yolk agar. The role of phospholipase in gut colonization or disease pathogenesis is unknown. We used the egg yolk agar assay to clone and characterize a gene encoding a phospholipase from V. cholerae El Tor strain E7946. Sequence analysis revealed a 1,254-bp open reading frame (lec) encoding a 418-amino-acid protein with a predicted molecular weight of 47,600. The predicted sequence exhibits DNA homology to other Vibrionaceae phospholipases. A potential signal sequence exists in the predicted amino acid sequence, as does a lipid binding motif found in prokaryotic and eukaryotic phospholipases and lipases. Polyacrylamide gel electrophoresis combined with an egg yolk agarose overlay demonstrated phospholipase activity migrating at a relative molecular weight of 45,000 in preparations of V. cholerae and the Escherichia coli clone. Restriction mapping and Southern blot analysis revealed that lec, hlyA (hemolysin), and hlyC (lipase) are adjacent on the V. cholerae chromosome, and chromosomal digests of several El Tor, classical, and O139 (Bengal) strains demonstrated conservation of this gene arrangement. An in-frame internal deletion of the lec gene was constructed and recombined into the chromosome of attenuated V. cholerae El Tor strain CVD 110. The resulting mutant lacked lecithinase activity on egg yolk agar but had undiminished reactivity in rabbit ligated ileal loop assays.
Amino Acid Sequence↗
Prospective clinical evaluation of an electronic portal imaging device.
PURPOSE: To determine whether the clinical implementation of an electronic portal imaging device can improve the precision of daily external beam radiotherapy. METHODS AND MATERIALS: In 1991, an electronic portal imaging device was installed on a dual energy linear accelerator in our clinic. After training the radiotherapy technologists in the acquisition and evaluation of portal images, we performed a randomized study to determine whether online observation, interruption, and intervention would result in more precise daily setup. The patients were randomized to one of two groups: those whose treatments were actively monitored by the radiotherapy technologists and those that were imaged but not monitored. The treating technologists were instructed to correct the following treatment errors: (a) field placement error (FPE) > 1 cm; (b) incorrect block; (c) incorrect collimator setting; (d) absent customized block. Time of treatment delivery was recorded by our patient tracking and billing computers and compared to a matched set of patients not participating in the study. After the patients radiation therapy course was completed, an offline analysis of the patient setup error was planned. RESULTS: Thirty-two patients were treated to 34 anatomical sites in this study. In 893 treatment sessions, 1,873 fields were treated (1,089 fields monitored and 794 fields unmonitored). Ninety percent of the treated fields had at least one image stored for offline analysis. Eighty-seven percent of these images were analyzed offline. Of the 1,011 fields imaged in the monitored arm, only 14 (1.4%) had an intervention recorded by the technologist. Despite infrequent online intervention, offline analysis demonstrated that the incidence of FPE > 10 mm in the monitored and unmonitored groups was 56 out of 881 (6.1%) and 95 out of 595 (11.2%), respectively; p < 0.01. A significant reduction in the incidence of FPE > 10 mm was confined to the pelvic fields. The time to treat patients in this study was 10.78 min (monitored) and 10.10 min (unmonitored). Features that were identified that prevented the technologists from recognizing more errors online include poor image quality inherent to the portal imaging device used in this study, artifacts on the portal images related to table supports, and small field size lacking sufficient anatomical detail to detect FPEs. Furthermore, tools to objectively evaluate a portal image for the presence of field placement error were lacking. These include magnification factor corrections between the simulation of portal image, online measurement tools, image enhancement tools, and image registration algorithms. CONCLUSION: The use of an electronic portal imaging device in our clinic has been implemented without a significant increase in patient treatment time. Online intervention and correction of patient positioning occurred rarely, despite FPEs of > 10 mm being present in more than 10% of the treated fields. A significant reduction in FPEs exceeding 10 mm was made in the group of patients receiving pelvic radiotherapy. It is likely that this improvement was made secondarily to a decrease in systematic error and not because of online interventions. More significant improvements in portal image quality and the availability of online image registration tools are required before substantial improvements can be made in patient positioning with online portal imaging.
Brain Neoplasms↗
An analysis of intratreatment and intertreatment displacements in pelvic radiotherapy using electronic portal imaging.
PURPOSE: To evaluate the relative frequency and magnitude of intratreatment and intertreatment displacements in the patient positioning for pelvic radiotherapy using electronic portal imaging. METHODS AND MATERIALS: Five hundred ninety-four electronic portal images of seven patients treated with a four-field pelvic technique were evaluated. All patients were treated prone without an immobilization device. Two fields were treated per day, from which an average of two electronic portal images were obtained for each field. No treatment was interrupted or adjusted on the basis of these images. Each image was aligned to the corresponding simulation film to measure the displacements in the mediolateral, craniocaudal, and anteroposterior directions relative to the simulated center. The intertreatment displacement was the displacement measured from the initial image for each daily treated field. For each daily treated field the intratreatment displacement was calculated by subtracting the displacement measured on the initial image from the displacement measured on the final image. RESULTS: The frequency of the intertreatment displacements exceeding 10 mm was 3%, 16%, and 23% for the mediolateral, craniocaudal, and anteroposterior translations, respectively. There were no intratreatment displacements exceeding 10mm (p < 0.001). The frequency of intertreatment displacements exceeded 5 mm was 40, 52, and 51% for the mediolateral, craniocaudal, and anteroposterior translations, respectively; whereas, the frequency of intratreatment displacements exceeding 5 mm was 1, 5, and 7% for the same translations, respectively (p < 0.001). The standard deviation of the intertreatment displacements was at least three times as great as the standard deviation of the intratreatment displacements for all translations. These deviations were greater than the precision limit of the measurement technique, which is approximately 1mm. Each patient had one direction where systematic error predominated in intertreatment positioning. Random error predominated for intratreatment positioning and for the other two directions in intertreatment positioning. CONCLUSIONS: During a course of pelvic radiotherapy, the frequency of intertreatment displacements exceeding 5 and 10 mm is significantly greater than the frequency of intratreatment displacements of these magnitudes. Errors in intertreatment positioning are predominantly systematic in one direction for each patient, whereas intratreatment error is predominantly random. Because patients do not move considerably during the daily treatment of a pelvic field, a single electronic portal image per daily field may be considered representative of the treated position.
Adenocarcinoma↗
Cloning and sequence of a region encoding a surface polysaccharide of Vibrio cholerae O139 and characterization of the insertion site in the chromosome of Vibrio cholerae O1.
Vibrio cholerae serogroup O139 Bengal is the first documented serogroup other than O1 to cause epidemic cholera. The O139 Bengal strains are very similar to V. cholerae serogroup O1 biotype El Tor strains. The major differences between the two serogroups are that O139 Bengal contains a distinct O antigen and produces a polysaccharide capsule. We previously described three TnphoA mutants of O139 strain AI1837 which abolish both O antigen and capsule production. These TnphoA insertions were mapped to a 21.5 kb EcoRI fragment of the O139 chromosome. We describe here the cloning and mapping of this 21.5 kb EcoRI fragment and it was shown to complement each of the mutants in trans to produce O antigen and capsule. The EcoRI fragment contains 13 kb of DNA that is specific to O139 and 8.5 kb of DNA that is common to O1 and O139. Sequence analysis of the 13 kb of O139-specific DNA revealed that it contains 11 open reading frames all of which are transcribed in the same direction. Eight of the 11 open reading frames are homologous to sugar biosynthesis genes from other organisms. Using extended polymerase chain reactions, we show that the extent of the DNA region in O139 that is not present in O1 is approximately 35 kb. The site of insertion of this O139-specific DNA in the O1 chromosome was mapped to the rfbO1 region. We also demonstrate that O139 Bengal strain AI1837 contains a deletion of 22 kb that in serogroup O1 strains contains the rfb region. Therefore, O139 Bengal probably arose from an O1 strain that had undergone genetic rearrangements including deletion of the O1 rfb region and acquisition of a 35 kb region of DNA which encodes O139 surface polysaccharide.
Bacterial Capsules↗
The CT-simulation 3-D treatment planning process.
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Computer Simulation↗
Radiation Oncology Picture Archiving and Communications System: the electronic viewbox.
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Data Display↗
Three dimensional conformal radiation therapy in pediatric parameningeal rhabdomyosarcomas.
PURPOSE: We evaluated the utility of three dimensional (3D) treatment planning in the management of children with parameningeal head and neck rhabdomyosarcomas. METHODS AND MATERIALS: Five children with parameningeal rhabdomyosarcoma were referred for treatment at our radiation oncology center from May 1990 through January 1993. Each patient was evaluated, staged, and treated according to the Intergroup Rhabdomyosarcoma Study. Patients were immobilized and underwent a computed tomography scan with contrast in the treatment position. Tumor and normal tissues were identified with assistance from a diagnostic radiologist and defined in each slice. The patients were then planned and treated with the assistance of a 3D treatment planning system. A second plan was then devised by another physician without the benefit of the 3D volumetric display. The target volumes designed with the 3D system and the two-dimensional (2D) method were then compared. The dosimetric coverage to tumor, tumor plus margin, and normal tissues was also compared with the two methods of treatment planning. RESULTS: The apparent size of the gross tumor volume was underestimated with the conventional 2D planning method relative to the 3D method. When margin was added around the gross tumor to account for microscopic extension of disease in the 2D method, the expected area of coverage improved relative to the 3D method. In each circumstance, the minimum dose that covered the gross tumor was substantially less with the 2D method than with the 3D method. The inadequate dosimetric coverage was especially pronounced when the necessary margin to account for subclinical disease was added. In each case, the 2D plans would have delivered substantial dose to adjacent normal tissues and organs, resulting in a higher incidence of significant complications. CONCLUSIONS: 3D conformal radiation therapy has a demonstrated advantage in the treatment of sarcomas of the head and neck. The improved dosimetric coverage of the tumor and its margin for subclinical extensions may result in improvement in local control of these tumors. In addition, lowering of radiation dose to adjacent critical structures may help lower the incidence of adverse late effects in children.
Child↗
Secondary malignancy among seminoma patients treated with adjuvant radiation therapy.
PURPOSE: Early-stage testicular seminoma is among the most radiosensitive tumors, with an overall cure rate of over 90%. Among those cured of the disease by orchiectomy and postoperative irradiation, there is a risk of having a second malignancy. We conducted a study to determine the relative risk of the occurrence of secondary malignancy. METHODS AND MATERIALS: From 1964 through 1988, 128 patients with histologically confirmed early-stage seminoma of the testis underwent orchiectomy and postoperative irradiation at the Radiation Oncology Center, Mallinckrodt Institute of Radiology, and affiliate hospitals. The follow-up periods ranged from 5 to 29 years, with a median of 11.7 years. The expected rate of developing a second cancer was computed by the standardized incidence ratio using the Connecticut Tumor Registry Database. The rate is based on the number of person-years at risk, taking into account age, gender, and race. RESULTS: Nine second nontesticular malignancies were found; the time of appearance in years is indicated in brackets: two squamous cell carcinomas of the lung [3, 11], one adenocarcinoma of the rectum [15], one chronic lymphocytic leukemia [2], one adenocarcinoma of the pancreas [14], one diffuse histiocytic lymphoma of the adrenal gland [7], one sarcoma of the pelvis [5], and two transitional cell carcinomas of the renal pelvis and ureter [14, 17]. One patient who developed a contralateral testicular tumor was excluded from risk assessment. The actuarial risk of second nontesticular cancer is 3%, 5%, and 20%, respectively, at 5, 10, and 15 years of follow-up. When compared with the general population, the overall risk of second nontesticular cancer in the study group did not reach the 0.05 significance level, with an observed/expected (O/E) ratio of 2.09 (95% confidence interval, 0.39-3.35). When analyzed by the latency period after radiation treatment, during the period of 11 to 15 years, the risk was higher (O/E ratio of 4.45, 95% confidence interval, 1.22-11.63) than expected. The median duration for developing a second cancer was 11 years for tumors arising from tissues outside the irradiated field and 14 years for those within or near the irradiated area. CONCLUSIONS: The overall observed incidence of second nontesticular malignancy among patients with early-stage testicular seminoma treated with adjuvant radiation therapy was not significantly increased in comparison with the expected incidence. Clinical implications are discussed.
Adolescent↗