Mallinckrodt Institute Of Radiology Research Articles

Comparison of Clinical Outcome in Black and White Women Treated With Radiotherapy for Cervical Carcinoma

Abstract Background. The purpose of this investigation was to evaluate the significance of race on the cancer-specific survival outcome of women treated with radiotherapy for advanced-stage cancer of the uterine cervix. Methods. Data from 922 women with cancer of the uterine cervix treated with radiotherapy were reviewed. Patients were treated at the Mallinckrodt Institute of Radiology from 1959 through 1993. There were 576 women with clinical Stage II cancer and 346 women with clinical Stage III cancer. All women were treated following standard medical care treatment policies according to the stage of their disease. Data were analyzed by race and known treatment-related prognostic factors. Overall and cancer-specific survivals were evaluated. Results. The 5-year cancer-specific survivals for clinical Stage II were 66 and 61% ( P = 0.56) for white and black women, respectively. The corresponding 5-year overall survivals were 60 and 51% ( P = 0.02). The 5-year cancer-specific survivals for clinical Stage III were 38 and 47% ( P = 0.34) for white and black women, respectively. The associated 5-year overall survivals were 32 and 40% ( P = 0.37). No differences in treatment-related factors were identified. Conclusions. In a cancer treatment system where black and white women with clinical Stage II and III cancer of the uterine cervix are all treated with radiotherapy alone, following standard treatment policies, no significant difference in cancer-specific survival outcome is shown. Multivariate analysis revealed that clinical stage and overall treatment time are significant variables affecting the control of tumor by radiotherapy. Overall survivals for the two racial groups are different and may be related to other non-cancer-related factors.

Gould Is AAPM President-Elect

Robert G. Gould, a professor of radiology and bioengineering at the University of California, San Francisco (UCSF), took office as president-elect of the American Association of Physicists in Medicine on 1 January. He will become president in 2002 and then chairman of the board in 2003, succeeding Charles W. Coffrey II, chief clinical physician at Vanderbilt University.“We should recognize that changes in health-care funding will continue and the AAPM must advocate vigilantly for the professional interests of its members,” says Gould.After earning a BA in chemistry from the College of Wooster and an MS in biomedical engineering from the University of Pennsylvania, Gould received an ScD in medical physics from Harvard University in 1977. In 1978, he joined UCSF’s radiology department, where he currently works on digital imaging, advances in three-dimensional imaging, and a picture-archiving and communications system that allows medical images to be stored and accessed via the Internet. Others who took office on 1 January for three-year terms on AAPM’s board of directors were Gary Ezzell, a senior physicist at the Mayo Clinic in Scottsdale, Arizona; John D. Hazle, a physicist at the M.D. Anderson Cancer Center at the University of Texas in Houston; Eric E. Klein, an assistant professor of physics at the Mallinckrodt Institute of Radiology in St. Louis, Missouri; and Robert J. Pizzutiello Jr, president of Upstate Medical Physics in Victor, New York. Gould PPT|High resolution© 2001 American Institute of Physics.

Cervical tumor control evaluated with ICRU 38 reference volumes and integrated reference air kerma

Purpose: The purpose of this investigation was to evaluate the relationship of ICRU 38 reference volumes and integrated reference air kerma to primary cervical tumor control. Materials and methods: This retrospective study includes 1253 women with carcinoma of the uterine cervix treated with radiotherapy. Patients were treated from 1959 to 1993 at the Mallinckrodt Institute of Radiology. There were 39 women with stage Ia disease, 211 with stage Ib1, 88 with stage Ib2, 580 with stage 2, and 335 with stage 3 disease. Most patients with stage Ia disease were treated with low dose rate brachytherapy alone. All other patients were treated with external irradiation and low dose rate brachytherapy. External irradiation doses ranged from 8.2–63.8 Gy to the whole pelvis and an additional parametrial boost to deliver a total of 65–75 Gy to Point P depending on tumor stage. Low dose rate brachytherapy was delivered to the primary tumor with doses ranging from 40×10 4–60×10 4 Gy cm 2 (integrated reference air kerma; IRAK). Isodose reference volumes (60–160 Gy) and point A doses were determined for all patients. Tumor control was defined as control of the primary cervical cancer with or without failure at other pelvic or distant sites. Results: The mean 60 Gy volume was calculated to be 139.5 cm 3 for stage Ia, 200.4 cm 3 for stage Ib1, 270.9 cm 3 for stage Ib2, 235 cm 3 for stage 2, and 293.4 cm 3 for stage 3. No patient with stage Ia disease had a failure in the cervix. For stage Ib1 tumors the mean 60 Gy volume was 219.1 cm 3 for those who failed in the cervix and 199.9 cm 3 for those who did not fail ( P=0.73). For stage Ib2 tumors the mean 60 Gy volume was 354.4 cm 3 for those who failed and 260.2 cm 3 for those who did not fail ( P=0.004). The mean 60 Gy volume was 249.3 cm 3 for those with stage 2 disease who failed and 233.8 cm 3 for those who did not fail ( P=0.02). For patients with stage 3 cancer the mean 60 Gy volume was 321.6 cm 3 for those who failed and 287.3 cm 3 for those who did not fail ( P=0.20). Reference volumes from 70–160 Gy were not statistically different within each stage for those who failed in the cervix compared to those who did not fail. Cervical recurrences by clinical stage did not have statistically significant differences for mean IRAK except for stage II disease ( P=0.001). Conclusion: Analysis of the 60–160 Gy reference volumes and IRAK failed to demonstrate a consistent positive increasing correlation of these values to primary cervical tumor control.

Comparison of Clinical Outcome in Black and White Women Treated with Radiotherapy for Cervical Carcinoma

Background. The purpose of this investigation was to evaluate the significance of race on the cancer-specific survival outcome of women treated with radiotherapy for advanced-stage cancer of the uterine cervix.Methods. Data from 922 women with cancer of the uterine cervix treated with radiotherapy were reviewed. Patients were treated at the Mallinckrodt Institute of Radiology from 1959 through 1993. There were 576 women with clinical Stage II cancer and 346 women with clinical Stage III cancer. All women were treated following standard medical care treatment policies according to the stage of their disease. Data were analyzed by race and known treatment-related prognostic factors. Overall and cancer-specific survivals were evaluated.Results. The 5-year cancer-specific survivals for clinical Stage II were 66 and 61% (P = 0.56) for white and black women, respectively. The corresponding 5-year overall survivals were 60 and 51% (P = 0.02). The 5-year cancer-specific survivals for clinical Stage III were 38 and 47% (P = 0.34) for white and black women, respectively. The associated 5-year overall survivals were 32 and 40% (P = 0.37). No differences in treatment-related factors were identified.Conclusions. In a cancer treatment system where black and white women with clinical Stage II and III cancer of the uterine cervix are all treated with radiotherapy alone, following standard treatment policies, no significant difference in cancer-specific survival outcome is shown. Multivariate analysis revealed that clinical stage and overall treatment time are significant variables affecting the control of tumor by radiotherapy. Overall survivals for the two racial groups are different and may be related to other non-cancer-related factors.

Intensity-modulated radiation therapy in head and neck cancers: The Mallinckrodt experience.

The purpose of the study was to investigate the feasibility and the optimization of tomotherapy-based intensity-modulated radiation therapy (IMRT) in patients with head and neck cancer. From February 1997 to November 1997, 17 patients with squamous cell carcinoma of the head and neck were treated with IMRT. Patients were immobilized with a noninvasive mask and treated using a serial tomotherapy device on a 6 MV linear accelerator. Treatment planning was performed on a Peacock inverse planning system and prescription optimization was used to achieve the best plan for target coverage and parotid sparing. The treatment planning system process has a dosimetric characteristic of delivering different doses to different target structures simultaneously in each daily treatment; therefore, the biological equivalent dose was implemented using the linear-quadratic model to adjust the total dose to the target volume receiving a daily dose of less than 1.9 Gy. All eight patients with gross disease (six in the nasopharynx, two in the tonsil) and one patient with recurrent nasopharyngeal carcinoma received concurrent cisplatin chemotherapy. Six postoperative patients were treated with irradiation alone. Median follow-up was 2.2 years (range 2.6-1.8 years). All patients completed the prescribed treatment without unexpected interruption. Acute side effects were comparable to those of patients treated with conventional beam arrangements during the same period. No patient required gastrostomy during irradiation. The preliminary experience showed that the noninvasive immobilization mask yielded high positioning reproducibility for our patients. To spare the parotid gland, which is in the proximity of the target, a fraction of the target volume may not receive the prescribed dose. In the best-achievable plan of our studied cohort, only 27% +/- 8% of parotid gland volumes were treated to more than 30 Gy, while an average of 3.3% +/- 0.6% of the target volume received less than 95% of the prescribed dose. This is mainly related to the steep dose gradient in the region where the target abuts the parotid gland. The inverse planning system allowed us the freedom of weighting normal tissue-sparing and target coverage to select the best-achievable plan. Local control was achieved in eight patients with gross tumor; six were treated postoperatively. Of three reirradiated patients, two had symptomatic improvement but persistent disease, and one is without evidence of disease. In summary, a system for patient immobilization, setup verification, and dose optimization for head and neck cancer with parotid sparing without significantly compromising target coverage is being implemented for a tomotherapy-based IMRT plan at the Mallinckrodt Institute of Radiology. The initial clinical experience in tumor control is promising, and no severe adverse acute side effects have been observed. Further refining of delivery technology and the inverse planning system, gaining clinical experience to address target definition and dose inhomogeneity within the targets, and understanding the partial volume effect on normal tissue tolerance are needed for IMRT to excel in the treatment of head and neck cancer. Int. J. Cancer (Radiat. Oncol. Invest.) 90, 92-103, (2000).

Thioredoxin nuclear localization and interaction with ref-1 induces AP-1 DNA-binding following IR: [formula omitted] Jack Wei, Ana Botero, and Douglas R. Spitz. Radiation Oncology, Mallinckrodt Institute of Radiology, Washington University School of Medicine, St. Louis, MO

The effects of replacing fishmeal by increasing levels of hydrolyzed feather meal (HF) on the nutrient utilization, growth performance and muscle fatty acid composition of European seabass (Dicentrarchus labrax) juveniles were evaluated. The humoral non-specific immune parameters were also evaluated in plasma. A growth trial was conducted for 18 weeks, using a practical feed formulation with 32% fishmeal and no HF added, as control (FM). Three experimental diets were formulated with the inclusion of 5 (HF5), 7.5 (HF7.5) and 12.5% HF (HF12.5), leading to a replacement of about 28, 55 and 76% fishmeal compared to the FM diet.The protein apparent digestibility coefficient (ADC) was lowest in the HF12.5 diet and was associated with higher nitrogen fecal losses, but N gain was similar among diets. Phosphorus ADC was significantly improved with the dietary incorporation of HF, decreasing fecal P losses into the environment. Fish fed the diets containing HF grew as well as those fed the FM diet. The feed intake, feed conversion ratio and protein efficiency ratio were statistically similar among dietary treatments. The protein and lipid whole body composition, as well as the muscle long-chain omega-3 fatty acid profile, remained unaffected by the fishmeal replacement. The immunological parameters assessed (lysozyme, peroxidase and ACH50) were not affected by the HF inclusion.The present study shows that an inclusion of up to 12.5% HF (76% fishmeal replacement) is possible in European seabass without impairing feed intake, growth, immune response or EPA and DHA levels in the muscle. Although energy and protein apparent digestibility coefficients (ADC) were lowest in the HF12.5 diet, energy and nutrient gain remained similar among dietary treatments. Altogether results suggest that HF is an interesting ingredient to be used in practical feed formulations for this species.

Use of the internet for teaching in nuclear medicine

The Internet provides several new capabilities for education in nuclear medicine, including learning at a distance, facilitation of collaboration, increased availability of training resources, and ability to develop interactive teaching materials. Dedicated case-authoring software aided development of digital teaching files at the Mallinckrodt Institute of Radiology and the Joint Program in Nuclear Medicine. Accesses to these two teaching files from sites around the world have grown rapidly. Improvements in the speed of the Internet will allow inclusion of more images at higher resolution and more extensive use of cine. Development of server-based software will allow simulation of the actual image-reading environment. A better understanding of how to use this new media will spur continued expansion in use of the Internet for nuclear medical education.

The Clinical Implications of Hydronephrosis and the Level of Ureteral Obstruction in Stage IIIB Cervical Cancer

Purpose: There are two criteria for the diagnosis of Stage IIIB cervical cancer in the FIGO staging system: tumor fixation to the pelvic side wall and/or the presence of hydronephrosis due to tumor. However, we often encounter hydronephrosis without tumor fixed to the pelvic side wall or the level of ureteral obstruction not corresponding to the main tumor mass in the pelvis. The clinical implication of these phenomena remains unclear. We investigated the Stage IIIB population treated at the Mallinckrodt Institute of Radiology and hypothesized that, if hydronephrosis presents without tumor fixation to the pelvic side wall or if the level of ureteral obstruction is above the main pelvic tumor mass, it most likely resulted from external compression of ureter(s) by enlarged lymph nodes and, consequently, a worse outcome is expected. Methods and Materials: From 1959 to 1989, there were 297 patients with Stage IIIB cervical cancer who received definitive radiation therapy at the Mallinckrodt Institute of Radiology and were assessable for the presence of hydronephrosis and the level of ureteral obstruction. There were 281 patients who presented with tumor fixed to the pelvic side wall, and 62 of them were associated with concurrent hydronephrosis. An additional 16 patients presented with hydronephrosis without tumor fixation to the pelvic side wall. Among these 78 documented cases of hydronephrosis, the level of ureteral obstruction was above the true pelvis in 39 patients, and below the true pelvis in the other 39. Radiation therapy was individualized according to tumor extension and configuration; para-aortic lymph nodes were not routinely treated except in patients with clinical evidence of nodal metastasis. Results: The progression-free survival (PFS) at 5 years was 35% in 62 patients with hydronephrosis and tumor fixed to the pelvic side wall vs. 43% in 213 patients with tumor fixed to the pelvic side wall only ( p = 0.12). However, PFS at 5 years decreased to 23% in 16 patients who presented with hydronephrosis without tumor fixation to the pelvic side wall ( p < 0.001). When the level of ureteral obstruction was investigated, 5-year PFS was 39% vs. 22%, respectively, for the obstruction below vs. above the true pelvis ( p = 0.02). The majority of patients with ureteral obstruction above the true pelvis died of distant metastasis. Conclusions: The additional presence of hydronephrosis did not significantly worsen the PFS among Stage IIIB patients with tumor fixation to the pelvic side wall. However, hydronephrosis without tumor extending to the pelvic side wall or the level of ureteral obstruction above the true pelvis was associated with poor outcome due to a significant increase in distant failure. We propose that this population be separated from current Stage IIIB classification.

Uterosacral space involvement in locally advanced carcinoma of the uterine cervix

Radiation therapy is the standard management for locally advanced cervical cancer, but it has not yielded fully satisfactory results; a relatively high incidence of local failure remains. Standard radiation therapy techniques combine external beam radiation and brachytherapy generating a homogeneously composite dose distribution covering the lateral parametria but may not be adequate in the uterosacral and perirectal areas due to the spatial arrangement of intracavitary system and the constraints of rectal tolerance. We hypothesize that these dosimetric characteristics might lead to a higher incidence of central/marginal failures when the uterosacral space is involved by locally advanced carcinoma of uterine cervix. Between January 1970 and December 1989, 343 patients with clinical Stage IIIB cervical cancer were treated at the Mallinckrodt Institute of Radiology with radiation therapy alone. We identified 83 patients with clinical evidence of tumor in the uterosacral region; the remaining 260 patients either did not have uterosacral involvement or were unspecified. The dose of external beam irradiation ranged from 18.02 to 33.20 Gy to the central pelvis and 48.22 to 59.40 Gy to the lateral parametrium. The average total dose, including brachytherapy contribution, to point A and the lateral pelvis was 80.30 to 86.46 Gy and 60.50 to 73.40 Gy, respectively. External beam dose to the lateral parametria was, on average, 10 Gy higher in patients with uterosacral involvement. We categorized the patterns of pelvic failure into central/marginal (including medial parametrium) and lateral parametria. The cumulative incidence of central/marginal failure at 5 years was significantly higher in the group of patients with uterosacral involvement (36% compared with 21% for patients without uterosacral involvement or unspecified) (p = 0.002). Lateral parametrial failure was similar for patients with and without uterosacral involvement (39% and 38% at 5 years, respectively) (p = 0.42). The actuarial incidence of distant metastasis was identical in the two groups: 46% at 5 years. Multivariate analysis confirmed that uterosacral space involvement increased the risk of pelvic recurrence (p = 0.044) and was the most significant factor that influenced the central/marginal pelvic failure (p = 0.002). Uterosacral involvement by locally advanced carcinoma of the uterine cervix significantly increased overall pelvic failure and was the most significant prognosticator of central/marginal pelvic failure. This is the result of the spatial constraints of the standard intracavitary geometry that deliver inadequate dose posteriorly to encompass the uterosacral space. Plausible ways to compensate the underdose in the uterosacral space include increasing whole pelvis dose without compromising the intracavitary brachytherapy dose, using a supplemental interstitial implant or adding a posterior oblique external beam boost.

Heat shock inhibits radiation-induced activation of DNA-binding and nuclear localization of NF-KB: [formula omitted], R.A. Clemens, D. R. Spitz, A. Botero, S. Lofrem, and D. Gius. Radiation Oncology Center, Mallinckrodt Institute of Radiology

Heat shock inhibits radiation-induced activation of DNA-binding and nuclear localization of NF-KB: [formula omitted], R.A. Clemens, D. R. Spitz, A. Botero, S. Lofrem, and D. Gius. Radiation Oncology Center, Mallinckrodt Institute of Radiology

The incidence of breast cancer following mantle field radiation therapy as a function of dose and technique

There is an increased incidence of breast cancer following mantle field radiation therapy for Hodgkin's disease (HD). We reviewed the experience at the Mallinckrodt Institute of Radiology (MIR) for radiation factors related to the development of breast cancer after mantle field radiation therapy for HD. The radiation therapy records of 152 women treated with mantle field irradiation for HD at MIR between 1966-1985 were reviewed for the development of breast cancer and treatment-related factors. All patients had a minimum of 5 years of follow-up. The treatment era (1966-1974 vs. 1975-1985), stage of HD, mediastinal dose, axillary dose, maximum dose from the anterior field (anterior d(max) dose), the anterior-posterior:posterior-anterior (AP:PA) ratio, age at the time of treatment, length of follow-up, and history of splenectomy were analyzed as possible contributing factors for the development of breast cancer. The observed number of breast cancers was compared to the expected number based on age-adjusted incidences from the Connecticut Tumor Registry. Ten breast cancers occurred in the population. Eight involved an upper outer quadrant. In a multivariate analysis, the development of breast cancer was significantly associated with axillary dose. Patients in the early treatment era were at an increased risk for the development of breast cancer due to high anterior d(max) and breast doses from weighting the fields anteriorly on a low energy linear accelerator. The use of current radiation therapy techniques was not related to an increased risk of breast cancer with a median follow-up of 13 years. A high dose to the axilla and the anterior d(max) point is significantly associated with the development of breast cancer after mantle field irradiation for HD. Efforts to protect the breast from high doses will likely lessen the increased risk of breast cancer in women treated with radiation therapy for HD.

Radiation therapy for intrathoracic recurrence of non-small cell lung cancer.

Fifty-two of 2,315 patients (2.4%) with non-small cell lung cancer (NSLC) treated with radiation therapy at the Mallinckrodt Institute of Radiology and St. Luke's Hospital between 1975 and 1988 presented with local recurrence after definitive surgery. No patient received radiation therapy after surgery as part of initial treatment and none had evidence of distant metastases at the time of local recurrence. The median time to first recurrence was 14 months. At recurrence, patients presented with disease in the bronchial stump (eight patients), ipsilateral lung parenchyma (10), chest wall (six), regional lymph nodes (five), or some combination thereof (23). Sixty-five percent of patients had histologic evidence of recurrence. Radiation therapy consisted of > 5,000 cGy in conventional fractionation to areas of gross disease in 35 of 52 patients. Of 15 patients receiving > 6,000 cGy, 13 had a favorable--complete (CR) or partial (PR) response--tumor response to radiation therapy. Among these patients, local control was achieved in 70% of patients with marginal recurrences (i.e., stump, parenchyma, or chest wall) and in 50% with nodal recurrences. The median survival after radiation therapy for all patients was 8.5 months. The best indicators for long-term survival were the interval from initial surgery to first recurrence and tumor response to radiation therapy.

Aunt Minnie's corner. Ovarian teratoma.

Address correspondence and reprint requests to Dr. K. L. Ford III at Mallinckrodt Institute of Radiology, 510 South Kingshighway Blvd., St. Louis, MO 63110, U.S.A. Dr. Ford is editor of a collection of similar cases that can be found in a forthcoming Williams & Wilkins publication entitled Aunt Minnie's Atlas and Imaging Specific Diagnosis, available December 1996.

Preliminary results of a prospective trial using three dimensional radiotherapy for lung cancer

To evaluate the preliminary results of a prospective trial using three-dimensional (3D) treatment for lung cancer. Seventy patients with inoperable Stage I through IIIB lung cancer were treated with three-dimensional thoracic irradiation with or without chemotherapy (35% received chemotherapy). Total prescribed dose to the tumor ranged from 60-74 Gy (uncorrected for lung density). All patients were evaluated for local control, survival, and development of pneumonitis. These parameters were evaluated in respect to and compared with three-dimensional parameters used in their treatment planning. With a minimum follow-up of 6 to 30 months, the 2-year cause-specific survival rate for Stages I and II was 90% and 53% for Stage III (no difference between Stages IIIA and IIIB). Patients with local tumor control had a better 2-year overall survival rate (47%) than those with local failure (31%). Volumetrically heterogeneously calculated doses were important to the accurate delineation of dose-volume coverage as there was a wide range of discrepancies between a homogeneously prescribed point dose calculation and the heterogeneously calculated volume coverage of that prescription. High-grade pneumonitis was correlated with the location of the tumor with lower lobe tumors having a much higher risk than those with upper lobe tumors. A critical volume effect and threshold dose were apparent in the development of high-grade pneumonitis. Three-dimensional therapy for lung cancer has been practically implemented at the Mallinckrodt Institute of Radiology and shows promising results in our preliminary analysis. The incidence of high-grade pneumonitis, however, warrants careful selection of patients for future dose escalation. Future dose escalation trials in lung cancer should be directed to volumes that limit the amount of elective nodal irradiation. However, the volume of necessary elective nodal irradiation remains unknown and should be studied prospectively. Dose escalation trials are indicated and may be facilitated by smaller target volumes.

Secondary malignancy among seminoma patients treated with adjuvant radiation therapy

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. 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. 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. 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.

Rates of growth of human solid neoplasms: Part I.

The purpose of this article is to consolidate data collected from a variety of sources that have permitted calculations of the rates of growth of human neoplasms. These sources include Fischel State Cancer Hospital (Columbia, MO); Mallinckrodt Institute of Radiology, (St. Louis, MO); Roentgen Diagnostic Institute, Allmanna Sjukhuset (Malmo, Sweden); University of Louisville (Louisville, Kentucky); University of Heidelberg (Heidelberg, Germany); and St. Luke's Hospital (St. Louis, MO). Included in the data are laboratory measurements of cell replication rates. All gross measurements were made either on imaging studies or with a centimeter scale for surface or palpable neoplasms. Data have been reported for breast and pulmonary cancers and metastases of many types, melanomas, skeletal sarcomas, benign and malignant colonic neoplasms, and isolated cases of less frequent neoplasms. Related cytokinetic measurements by tritriated thymidine labelling, bromodeoxyuridine labelling, S-phase fraction from DNA flow cytometric analysis, and mitotic indices are discussed. The various mathematical formulae applicable to the analysis of the collected data and the determination of rates and patterns of growth are included. Also considered are the clinical implications of these data and the importance of ever better knowledge on the cytokinetics of human cancer. Prior studies on the evolution of insight into this field are cited and discussed. The authors conclude that a more accurate quantification of the growth rates of human cancer is essential for understanding the biological variance of human cancers seen clinically.

A convolution-adapted ratio-TAR algorithm for 3D photon beam treatment planning.

A convolution-adapted ratio of tissue-air ratios (CARTAR) method of dose calculation has been developed at the Mallinckrodt Institute of Radiology. This photon pencil-beam algorithm has been developed and implemented specifically for three-dimensional treatment planning. In a standard ratio of tissue-air ratios (RTAR) algorithm, doses to points in irregular field geometries are not adequately modeled. This is inconsistent with the advent of conformal therapy, the goal of which is to conform the dose distribution to the target volume while sparing neighboring sensitive normal critical structures. This motivated us to develop an algorithm that can model the beam penumbra near irregular field edges, while retaining much of the speed for the original RTAR algorithm. The dose calculation algorithm uses two-dimensional (2D) convolutions, computed by 2D fast Fourier transform, of pencil-beam kernels with a beam transmission array to calculate 2D off-axis profiles at a series of depths. These profiles are used to replace the product of the transmission function and measured square-field boundary factors used in the standard RTAR calculation. The 2D pencil-beam kernels were derived from measured data for each modality using commonly available dosimetry equipment. The CARTAR algorithm is capable of modeling the penumbra near block edges as well as the loss of primary and scattered beam in partially blocked regions. This paper describes the dose calculation algorithm, implementation, and verification.

Reirradiation of recurrent skin cancer of the face. A successful salvage modality.

The aim of this study was to assess the effectiveness of full doses of reirradiation to salvage previously irradiated recurrent skin cancer of the face. As of December 1990, 17 patients at the Mallinckrodt Institute of Radiology were reirradiated for recurrent skin cancer in previously irradiated areas of the face. There were eight basal cell and nine squamous cell carcinomas. The interval between the two treatments ranged from 6 months to 15 years (median, 4 years). The dosimetry was reviewed, and the radiation doses were recomputed by the biologic effective dose (BED) formula. The accumulated BED from the two irradiation regimens ranged from 48.78 to 143.5 Gy on the skin surface (median, 103 Gy) and 80.93 to 160.68 Gy at 5 mm depth (median, 108 Gy). Local control was achieved in ten patients; two of them had skin defects that required reconstruction. Six of seven patients with persistent tumors had squamous cell carcinoma. Those patients with BED of previous treatment at 5 mm depth less than 55 Gy, and accumulated BED on skin surface of no more than 110 Gy had the best outcome. The residual damage of skin from previous treatment is a function of fraction size and total dose. Reirradiation is a feasible treatment alternative for recurrent skin cancer of the face when cosmesis is a concern.

Femoral neck fracture following groin irradiation

Purpose : The incidence and risk factors are evaluated for femoral rneck fracture following groin irradiation for gynecologic malignancies. Methods and Materials : The radiation therapy records of 1313 patients with advanced and recurrent cancer of the vagina, vulva, cervix, and endometrium, treated at the mallinckrodt Institute of Radiology from 1954 to 1992, were reviewed. Median follow-up was 12.7 years. From this group, 207 patients were identified who received irradiation to the pelvis and groins with anterposterior-posterior anterior (AP-PA), 18 MV photons. Data were reviewed regarding irradiation dose to the fermoral neck and other presumed risk factors including age, primary site, stage, groin node status, menopausal status, estrogen use, cigarette use, alcohol consumption, adn osteoporosis. Results : The per-patient incidence of fermoral neck fracture was 4.8% (10 out of 207). Four patients developed bilateral fractures. However, the cumulative actuarial incidence of fracture was 11% at 5 years and 15% at 10 years. Cox multivariate analysis of age, weight, and irradiation dose showed that only irradiation dose may be important to developing fracture. Step-wise logistic regression of presumed prognostic factors revealed that only cigarette use and x-ray evidence of osteoporosis prior to irradiation treatment were predictive of fracture. Conclusion : Femoral head fracture is a common complication of groin irradiation for gynecologic malignancies. Fractrue in our database appears to be related to irradiation dose, cigarette use, and x-ray evidence of osteoporosis. Special should be given in treatment planning (i.e., shielding of femoral head/neck and use of appropriate electron beam energies for a portion of treatment) to the incidence of this complication.

Minimization of target positioning error in accelerator-based radiosurgery.

The stereotactic radiosurgery system used at the Mallinckrodt Institute of Radiology is patterned after that developed at the Joint Center for Radiation Therapy (Brigham & Women's Hospital, Boston, MA) and uses the Brown-Roberts-Wells computed tomography (CT) stereotactic system. The patient's head is attached to a stand that rotates with the treatment couch. The irradiation is conducted using a set of converging arcs of irradiation. Because of mechanical limitations, no accelerator or treatment couch is capable of placing the center of the radiation beam at precisely the same point for all gantry and couch angles and a compromise must be made when locating the nominal isocenter. The stand settings are checked by placing a radiopaque QA sphere at the desired target location. The QA sphere is imaged using a series of eight films exposed at a set of couch and gantry angles that encompass the treatment angles. The distances between the QA sphere image and the center of the radiation field indicate if the correct coordinates were set on the stand and if the radiation beam converges to a sufficiently small region (< 0.1-cm diameter) for treatment. A mathematical procedure has been developed to use the film-measured position errors to determine a stand offset that will minimize the distance between the accelerator isocenter and the target. The technique is capable of reducing the average placement error, as measured by imaging the QA sphere, to 0.035 cm with a maximum deviation of 0.07 cm.