Lani Ignacio

Changing face and different countenances of prostate cancer: Racial and geographic differences in prostate-specific antigen (PSA), stage, and grade trends in the PSA era

The purpose of this investigation was to examine changes in pretreatment prostate‐specific antigen (PSA), stage, and grade over the past decade as a function of race and geographic region. A multiinstitutional database representing 6,790 patients (1,417 African‐American, 5,373 white) diagnosed with nonmetastatic prostate cancer between 1988 and 1997 was constructed. PSA, stage, and grade data were tabulated by calendar year and region, and time trend analyses based on race and region were performed. There was an overall decline of PSA of 0.8%/year, which was significant (P = 0.0001), with a faster rate of decline in African‐Americans (1.9%/year) than for whites (0.6%/year). The odds ratio (OR) for a stage shift was 1.09, which was significant (P < 0.0001), and this shift was greater in whites. The OR for an overall grade shift was 1.15, which was significant (P < 0.0001). Although grade and PSA trends were similar for the different regions, there were significant regional differences in stage trends. The implications are that the face of prostate cancer has changed over the past decade; i.e., the distributions of stage, grade, and PSA (the most important prognosticators) have changed. In addition, the countenances of that face are different for whites and African‐Americans. For African‐Americans, this is good news: the stage, grade, and PSA distributions are more favorable now than before. For whites, the trends are more complex and more dependent on region. These findings should be used for future clinical and health‐policy decisions in the screening and treatment of prostate cancer.

Caution in interpreting biochemical control rates after treatment for prostate cancer: length of follow-up influences results

OBJECTIVES Prostate-specific antigen (PSA) based end points are commonly used to report outcomes after treatment for prostate cancer. This study examines the influence of follow-up length on biochemical control (bNED) rates. METHODS We reviewed 437 patients with clinically localized prostate cancer treated with conformal radiotherapy without neoadjuvant androgen deprivation. Biochemical failure was defined as three consecutive PSA increases or an increase large enough to prompt androgen deprivation therapy. The failure date was projected back to the midpoint between the PSA nadir and the first PSA increase (or between the nadir and the initiation of androgen deprivation therapy). The analysis was performed by censoring patients with longer follow-up in a stepwise fashion, thus creating smaller subgroups with shorter follow-up intervals. Subgroup 1 (n = 191) and subgroup 2 (n = 273) were defined to include those patients monitored for up to 2 years and up to 3 years, respectively. RESULTS The median follow-up intervals for subgroup 1, subgroup 2, and the original study population were 1.1, 1.5, and 2.5 years. No significant differences were seen in pretreatment prognostic factors among the three groups. The 2-year bNED of subgroup 1, subgroup 2, and the original population was 86%, 77%, and 73%, respectively. Although subgroup 1 had a superior bNED compared with the original population (P = 0.04), no differences in clinical recurrence rates were seen among any of the three groups. CONCLUSIONS Because of projecting the biochemical failure dates back according to commonly used bNED definitions, control rates are highly dependent on the length of follow-up.

Self-assessed health-related quality of life in men being treated for prostate cancer with radiotherapy: instrument validation and its relation to patient-assessed bother of symptoms

OBJECTIVES To develop a psychometrically valid and clinically useful questionnaire to assess health-related quality of life (HRQOL) in patients with prostate cancer (PCa) undergoing external beam radiotherapy. The most important factors in three dimensions (bowel function [BF], urinary function [UF], and sexual function [SF]) were identified by patient survey. METHODS Three HRQOL dimensions were assessed using Likert-type questions. Responses were analyzed by factor analysis to create HRQOL scales. Reliability and validity of the scales were assessed. Because patients can suffer symptoms yet not report their lives to be affected, the scales were compared with patient-reported bother. RESULTS Two scales were identified within each dimension: BF, urgency and daily living; UF, urgency and weakness of stream; and SF, interest/satisfaction and impotence. Cronbachs alpha for the scales ranged from 0.63 to 0.94, and item-scale correlations and item-scale divergence correlations supported scale validity. Rising median scores correlated with rising levels of perceived bother. CONCLUSIONS The questionnaire is a suitable tool for assessing HRQOL in three distinct dimensions for patients undergoing radiotherapy for PCa. Six dimensions of HRQOL were found to be related to bother, suggesting important relationships to be monitored for patients. Urgency of bowel movements, urgency of urination, and level of interest/satisfaction in sex correlated most strongly with bother.

Analysis of weekly complete blood counts in patients receiving standard fractionated partial body radiation therapy

PURPOSE Hematopoiesis is among the most sensitive systems in the body to radiation. Routine complete blood counts (CBCs) are common in clinical radiotherapy practice. Only a few studies have attempted to characterize the behavior of peripheral blood levels during partial body radiation therapy with field sizes smaller than those used in hemibody or total nodal irradiation. Such information is needed to identify which patients are at risk for cytopenia and require close monitoring. METHODS AND MATERIALS In 1993, 412 new patients were seen at Michael Reese Hospital for radiotherapy. A total of 972 weekly CBCs were identified for 155 patients receiving a minimum of 5 weeks of treatment for breast, prostate, lung, gynecological, or head and neck malignancies. Linear regression models were fitted to the weekly CBC values for those patients who had pretreatment CBC values recorded. Factors affecting starting levels, rates of decline, and nadirs during treatment were determined for leukocytes, platelets, and hemoglobin. RESULTS Leukocytes declined most dramatically during the first week of treatment (16% from pretreatment to Week 1 levels) and then at a rate of 3.3% per week from Week 1 to Week 7 (p < 0.001). Total mean leukocyte decrease over 7 weeks of therapy was 30%. Platelets declined 9% on average during the first week of therapy and then at a mean rate of 1.4% per week (p < 0.02). A statistically significant decrease in hemoglobin levels could not be detected. No difference in the rate of decrease could be found for different disease sites, age groups, or amount of marrow irradiated. The effects of chemotherapy were variable, depending on blood element and whether therapy was sequential or concomitant. The odds of a nadir < 2000 counts/mm3 for white blood count (WBC), < 50,000 counts/mm3 for platelets, and < 8.0 g/dl for hemoglobin were all well below 5%. A strong correlation existed between starting CBC values and nadirs; patients with lower Week 1 CBC levels were most likely to have the lowest nadirs. CONCLUSIONS Low CBC levels during radiation therapy are likely to be the result of other medical problems that cancer patients face. Regional irradiation with small field sizes (< 40% of total body marrow) typically used in clinical radiotherapy is unlikely to be the cause of marrow depression significant enough to warrant medical intervention. Blood levels taken during the first week of treatment (Week 1) can be used to determine risks of developing critical nadirs. Localized breast and prostate cancer patients are unlikely to require routine CBCs if initial levels are normal. Routine CBC levels on all radiation oncology patients without other reasons for hematopoietic depression requires reevaluation, as millions of dollars are spent on unnecessary testing. If weekly CBC blood levels are avoided in localized breast and prostate cancer patients, this alone could potentially result in a savings of as much as

Equivalent racial outcome after conformal radiotherapy for prostate cancer: a single departmental experience.

40 million a year nationally.

Results of a phase II concurrent chemoradiotherapy study using three‐dimensional conformal radiotherapy with cisplatin and oral etoposide in stage III nonsmall‐cell lung cancer

PURPOSE African-American (AA) men with prostate cancer present with advanced disease, relative to white (W) men. This report summarizes our clinical and biochemical control (bNED) rates after conformal radiotherapy (RT). In particular, we aim to characterize any race-based outcome differences seen after comparable treatment. PATIENTS AND METHODS We reviewed 893 patients (418 AA and 475 W) with clinically localized prostate cancer treated between 1988 and 1997. Neoadjuvant hormonal blockade was used in 22.5% of cases, and all patients received conformal RT to a median dose of 68 Gy (range, 60 to 74.8 Gy). Biochemical failure was defined according to the American Society of Therapeutic Radiology and Oncology consensus definition. Median follow-up was 24 months (range, 1 to 114 months). RESULTS The 5-year actuarial survival, disease-free survival, and bNED rates for the entire population were 80.5%, 70.0%, and 57.6%, respectively. When classified by prognostic risk category, the 5-year actuarial bNED rates were 78.7% for favorable, 57.7% for intermediate, and 39.8% for unfavorable category patients. AA men presented at younger ages and with more advanced disease. Controlled for prognostic risk category, AA and W men had similar 5-year actuarial bNED rates in favorable (78% v 79%, P: = .91), intermediate (52% v 62%, P: =.44), and unfavorable categories (36% v 45%, P: = .09). Race was not an independent prognostic factor (P: = .36). CONCLUSION Conformal RT is equally effective for AA and W patients. More research is needed in order to understand and correct the advanced presentations in AA men. These data suggest a need for early screening in AA populations.

Self-assessed health-related quality of life in men who have completed radiotherapy for prostate cancer : Instrument validation and its relation to patient-assessed bother of symptoms

This phase II study was designed to utilize conformal radiation therapy with cisplatin and oral etoposide in patients with stage III or locally recurrent non-small-cell lung cancer to determine tolerance and toxicity of therapy. From April 1992-February 1996, 18 patients with pathologically confirmed stage IIIA, IIIB, or locally recurrent non-small-cell lung cancer (NSCLC) were entered on study. Metastatic workup included a CT scan of the thorax and upper abdomen as well as a bone scan. Chemotherapy consisted of IV cisplatin (100 mg/m2) with IV etoposide (25 mg/m2) on day 1; oral etoposide was given (50 mg/m2) days 2-14. Using three-dimensional planning, 40-45 Gy were delivered to the clinical target volume, followed by a boost to the gross tumor volume for a total of 70 Gy. Patients with recurrent disease received 40-50 Gy in total. Eighteen patients were enrolled: 16 patients were treated with curative intent and were evaluable for outcome. Two patients were treated for locally recurrent NSCLC and were not included in the outcome analysis. Stages included IIIA (44%) and stage IIIB (54%). Forty-four percent had T3/4 tumors, and 69% had N2/3 disease. Overall survival at 1 year was 64%, while 2-year overall survival was 50%. Distant metastasis-free survival at 1 year was 67%, and at 2 years 60%. The 1-year chest progression-free survival was 57%, and at 2 years 50%. Sixty-three percent required hospitalization for dehydration or neutropenia. Fifty-six percent developed leukopenia (<1,000 cells/microl) sometime during the therapy. We conclude that concurrent cisplatin and oral etoposide with conformal radiation therapy provide encouraging results in stage III lung cancer. The major toxicities of this therapy included leukopenia, thrombocytopenia, and mucosal esophagitis. Local progression of disease continues to be a problem with the current doses given. Future studies should evaluate dose escalation of radiation therapy with limited volumes, utilizing conformal radiation and chemotherapy to improve local control and potentially impact upon distant metastases.

Evolution of toxicity after conformal radiotherapy for prostate cancer

The purpose of this study was to develop a psychometrically reliable and valid questionnaire to assess the disease‐specific dimensions of health‐related quality of life (HRQOL) in the urinary function (UF), bowel function (BF), and sexual function (SF) domains of prostate cancer (PCa) patients treated with radiation therapy. Patients were given a six‐page questionnaire using Likert‐type questions assessing three HRQOL dimensions during their follow‐up visits after completing radiotherapy. Scales created from an earlier study were utilized and tested for reliability and validity. In addition, we assessed the relationship between these dimensions and the degree to which a decreased HRQOL increases the degree to which patients feel bothered about their symptoms. There are two scales within each dimension: BF, Urgency and Daily Living; UF, Urgency and Weakness of Stream; SF, Interest/Satisfaction and Impotence. Internal‐consistency reliability coefficients (Cronbachs alpha) for the proposed scales range from 0.48 to 0.92, and all item‐scale correlations and divergence correlations validate the use of the scales, ranging from 0.49 to 0.89. The validity of these scales is also confirmed by the rising median scores with rising reported levels of patient‐perceived “bother.” The different dimensions have differing quantitative influences on patients. We have developed a prostate‐specific HRQOL instrument that is an adequate and suitable tool for measuring HRQOL along three distinct dimensions for patients who have completed radiotherapy for PCa. Psychometric standards for reliability and validity were met for the proposed scales. Moreover, positive correlations were found between these dimensions and how bothered patients were by their symptoms, suggesting important relationships that should be followed in PCa patients after radiotherapy. Certain scales have strong influences on patient‐perceived “bothersomeness” of symptoms, such as loss of control of BF, urgency of BF, urgency of urination, and level of interest/satisfaction in sex. Compared to our earlier study on patients being treated with radiotherapy for PCa, this study produced very similar results. With some modification, the same questionnaire could be used for both groups of patients. Int. J. Cancer (Radiat. Oncol. Invest.) 90, 163–172 (2000).

Television and news print media are effective in recruiting potential participants in a prostate cancer chemoprevention trial.

The limiting factor for radiation (RT) dose-escalation is normal tissue toxicity. In dose-escalation studies, it is important to determine the factors associated with toxicity and the length of follow-up period after which a particular RT dose is considered safe.We analyzed 449 prostate cancer patients treated with RT at our institution and followed for a median of 27 months. Genitourinary (GU) and gastrointerological (GI) complications were graded and analyzed using three different statistical models. Univariate and multivariate analyses were conducted for factors associated with toxicity.There was no RTOG grade 4 or 5 toxicity. Only 23 patients (5%) experienced grade 3 toxicity. After treatment, there was an initial rapid decline in the risk of toxicity following treatment, followed by an increase or stabilization of the toxicity with time of follow-up. The breakpoints between the two periods were 2 y (any toxicity) and 1 y (high toxicity) for GU and 9 months (any toxicity, high toxicity) for GI. Age, dose, fraction size, duration of treatment and hospital of treatment emerge as important factors in the probability of developing toxicity.Our study shows that delivering conventional doses using conformal techniques is associated with minimal high-grade toxicity. However, even within a narrow dose range and fraction size used, differences do emerge which should lead one to be cautious in extending the results of dose escalation study to the community practice without a sufficient follow-up.

Potency probability following conformal megavoltage radiotherapy using conventional doses for localized prostate cancer

Theodore D.K. Chung, MD, PhD,1,2 Irwin I. Park,1 Lani Ignacio, BSN,3 Rose Catchatourian, MD,4 Mitchell Kopnick, MD,5 Evelyn Davison,3 Geraldine Conrad,6 Azhar M. Awan, MD,1,7 David Crawford, MD,8 and Srinivasan Vijayakumar, MD1,2,3,8* 1Department of Radiation and Cellular Oncology, The University of Chicago, Chicago, Illinois 2Department of Radiation Oncology, University of Illinois at Chicago, Chicago, Illinois 3Department of Radiation Oncology, Michael Reese Hospital and Medical Center, Chicago, Illinois 4Division of Hematology−Oncology, Michael Reese Hospital and Medical Center, Chicago, Illinois 5Division of Urology, Michael Reese Hospital and Medical Center, Chicago, Ilinois 6Office of Public Relations, Michael Reese Hospital and Medical Center, Chicago, Ilinois 7Department of Radiation Oncology, LaGrange Memorial Hospital, LaGrange, Ilinois 8Southwest Oncology Group, San Antonio, Texas