Evaluation of five radiation schedules and prognostic factors for metastatic spinal cord compression.

PURPOSE: To study five radiotherapy (RT) schedules and potential prognostic factors for functional outcome in metastatic spinal cord compression (MSCC). PATIENTS AND METHODS: One thousand three hundred four patients who were irradiated from January 1992 to December 2003 were included in this retrospective review. The schedules of 1 x 8 Gy in 1 day (n = 261), 5 x 4 Gy in 1 week (n = 279), 10 x 3 Gy in 2 weeks (n = 274), 15 x 2.5 Gy in 3 weeks (n = 233), and 20 x 2 Gy in 4 weeks (n = 257) were compared for motor function, ambulatory status, and in-field recurrences. The following potential prognostic factors were investigated: age, sex, performance status, histology, number of involved vertebra, interval from cancer diagnosis to MSCC, pretreatment ambulatory status, and time of developing motor deficits before RT. A multivariate analysis was performed with the ordered logit model. RESULTS: Motor function improved in 26% (1 x 8 Gy), 28% (5 x 4 Gy), 27% (10 x 3 Gy), 31% (15 x 2.5 Gy), and 28% (20 x 2 Gy); and posttreatment ambulatory rates were 69%, 68%, 63%, 66%, and 74% (P = .578), respectively. On multivariate analysis, age, performance status, primary tumor, involved vertebra, interval from cancer diagnosis to MSCC, pretreatment ambulatory status, and time of developing motor deficits were significantly associated with functional outcome, whereas the RT schedule was not. Acute toxicity was mild, and late toxicity was not observed. In-field recurrence rates at 2 years were 24% (1 x 8 Gy), 26% (5 x 4 Gy), 14% (10 x 3 Gy), 9% (15 x 2.5 Gy), and 7% (20 x 2 Gy) (P < .001). Neither the difference between 1 x 8 Gy and 5 x 4 Gy (P = .44) nor between 10 x 3 Gy, 15 x 2.5 Gy, and 20 x 2 Gy (P = .71) was significant. CONCLUSION: The five RT schedules provided similar functional outcome. The three more protracted schedules seemed to result in fewer in-field recurrences. To minimize treatment time, the following two schedules are recommended: 1 x 8 Gy for patients with poor predicted survival and 10 x 3 Gy for other patients. Results should be confirmed in a prospective randomized trial.

Short-course radiotherapy is not optimal for spinal cord compression due to myeloma.

PURPOSE: To investigate the suitability of short-course radiotherapy (RT) for spinal cord compression (SCC) in myeloma patients. METHODS AND MATERIALS: Data for 172 myeloma patients irradiated between January 1994 and December 2004 for SCC were retrospectively evaluated. Short-course RT (1 x 8 Gy, 5 x 4 Gy, n = 61) and long-course RT (10 x 3 Gy, 15 x 2.5 Gy, 20 x 2 Gy, n = 111) were compared for functional outcome up to 24 months after RT. In addition, 10 potential prognostic factors were investigated. RESULTS: Improvement of motor function occurred in 90 patients (52%). Forty-seven percent of nonambulatory patients regained the ability to walk. Functional outcome was significantly influenced by the time of developing motor deficits before RT. Improvement of motor function was more frequent after long-course RT than after short-course RT: 59% vs. 39% (p = 0.10) at 1 month, 67% vs. 43% (p = 0.043) at 6 months, 76% vs. 40% (p = 0.003) at 12 months, 78% vs. 43% (p = 0.07) at 18 months, and 83% v 54% (p = 0.33) at 24 months. A subgroup analysis of the long-course RT group demonstrated a similar functional outcome for 10 x 3 Gy when compared with 15 x 2.5 Gy and 20 x 2 Gy. CONCLUSIONS: Long-course RT is preferable for SCC in myeloma patients because it resulted in better functional outcome than short-course RT. Treatment with 10 x 3 Gy can be considered appropriate.

Correlation between bone scintigraphy and tumor markers in patients with breast carcinoma.

A characteristic feature of many cancer types is their ability to metastasise to the skeleton. Bone is the most common site of metastatic invasion, after hematogenous spreading of breast cancer. Early detection of bone metastases is mandatory in the evaluation and management of these patients. Bone scintigraphy is commonly performed in detection and evaluation bone metastases. Tumor markers are present in healthy individuals as well as in patients with malignant diseases but in different concentration. Aim of study was to correlate serum levels of tumor marker Ca (15-3), CEA and presence of bone metastases detected by bone scintigraphy. Study included 25 patients with breast cancer, previously surgically treated. All patients underwent whole body scintigraphy. Ca (15-3) and CEA was measured by radioimmunoassay. Presence, number of bone metastases were correlated with Ca (15-3) and CEA levels. Median age of patients included in study was 50 varying from 30 to 67. Bone scintigraphy revealed bone metastases in 16 (64%) patients. A weak correlation was found between number of metastases and level of Ca (15-3) (r=0.139, p=0.254). Significant differences in Ca (15-3) level was found in patient with metastases compared to patients without metastases (chi square 0, p=1.0). Good correlation was found between number of metastases and serum level of CEA. Correlation between level of two tumor markers Ca (15-3) and CEA was a weak (r = 0.096 , p=0.323). Bone scintigraphy is a sensitive diagnostic toll for detecting breast cancer metastases to bone. Serum levels of tumor markes in isolation can not give complete accuracy about bone metastases.

Role of bone scintigraphy and tumor marker-Ca 15-3 in detection of bone metastases in patients with breast cancer.

Breast cancer is one of the most frequent types of cancer affecting women. After hematogenous spreading of cancer, axial skeleton is most frequently involved. Bone scintigraphy is commonly performed in detection and evaluation of bone metastases. In breast cancer, marker Ca 15-3 is widely accepted in follow-up and detection of disease recurrence. Aim of the study was to correlate levels of tumor marker Ca 15-3 and presence of bone metastases detected by bone scintigraphy. Study included 25 patients with breast cancer, previously surgically treated. All patients underwent total body scintigraphy. Ca 15-3 was measured by radioimmunoassay. Presence, number and location of bone metastases were correlated with Ca 15-3 levels. Bone scintigraphy revealed bone metastases in 16 (64%) patients. 11 (44%) patients with metastases and 1 patient (4%) without scintigraphically visible metastases had elevated Ca 15-3 levels. Significant difference in distribution of metastases was found for spine (t=3.930, p=0.008). Correlation between intensity of radiopharmaceutical uptake and level of Ca 15-3 in patients was positive (r =0.405). A weak correlation was found between number of metastases and level of Ca 15-3 (r=0.139). Significant differences in Ca 15-3 level was found in patients with metastases compared to patients without metastases (chi square 0, p =1.0). Since no significant correlation was found between level of Ca 15-3 and number of metastases, we consider scintigraphy an appropriate method for assessment of bone metastases in breast cancer.

High grade intraepithelial neoplasia of prostate is associated with values of prostate specific antigen related parameters intermediate between prostate cancer and normal levels.

High grade prostatic intraepithelial neoplasia (HGPIN) is widely regarded as the precancerous. The aim of this study was to determine PSA related parameters in patients with initial PSA values 2-10 ng/mL and diagnosis of HGPIN without finding carcinoma at the time of their first needle biopsy. Study groups consisted of 100 men who were diagnosed HGPIN, 84 with cancer and 183 with benign hyperplasia on first biopsy of prostate. Total PSA and free PSA were measured and ratio free/total PSA and PSA density calculated. Mean values of these parameters were compared, and receiver operating characteristic curves were used for comparison of PSA related parameters to discriminate groups of patients.Total PSA, free PSA level and PSA density in patients with HGPIN (6.388 ng/mL) did not differ significantly compared to prostate carcinoma (6.976 ng/mL) or benign prostatic hyperplasia (6.07 ng/mL) patients. Patients with HGPIN had significantly higher ratio free/total PSA than those with prostate carcinoma (0.168 vs 0.133), but significantly lower than patients with benign prostatic hyperplasia (0.168 vs 0.185). Ratio of free/total PSA significantly discriminate HGPIN from prostate carcinoma with sensitivity 84.52 and specify 45.00 at cut-off point of ≤ 0.18. Values of PSA, free PSA and ratio free/total PSA in cases of HGPIN appear to be intermediate between prostate cancer and normal levels. Ratio of free/total PSA may help in decision to repeat biopsies in the presence of HGPIN on biopsy, without concomitant prostate cancer, in patients suitable for curative treatment, with normal digito-rectal examination and trans-rectal sonography.

Extracapular extension predictors of prostate carcinoma for 2-10 ngr/ml PSA values.

UNLABELLED: Purpose of the research is to establish which clinical and biopsy parameters could predict extra-capsular spread of prostate carcinoma for 2-10 ng/ml PSA values, in patients submitted to radical retropubic prostatectomy. METHODOLOGY: In the period of 30 months, 80 patients were treated with radical retro-pubic prostatectomy with bilateral pelvic lymphadenectomy, for whom clinical, biopsy, radiological and biochemical analysis were positive to organ limited tumor. Serum PSA, fpsa/tpsa, PSAD,values are evaluated, and other parameters as number of positive biopsies, percentage of positive biopsies, localization of positive biopsies, and perineural invasion and biopsy Gleason score. RESULTS: from total number of 80 patients with 2-10 ng/ml PSA, 7 (9%) patients had extra-capsular spread of prostate carcinoma. Upon using multivariate regression analysis, following parameters were proved as significant predictors of extra-capsular spread: biopsy Gleason score, number of positive biopsy samples and invasion, while serum PSA, FPSA/TPSA ratio, PSAD, prostate age and volume have not shown as significant predictors for extra-capsular extension. CONCLUSION: Biopsy GS, perineural invasion and number of biopsy samples are statistically significant predictors of extra-capsular spread of prostate carcinoma for 2-10 ml PSA. Percentage of positive biopsies, tumor length in a sample and the localization of positive biopsies are on the borderline of statistical significance and as such should be taken into consideration.

Investigation of IVS14 + 1G > A polymorphism of DPYD gene in a group of Bosnian patients treated with 5-Fluorouracil and capecitabine.

Adverse drug reactions still pose an important clinical problem. Dihydropyrimidine dehydrogenase (DPD) is an enzyme that regulates 5-FU quantities available for anabolic processes and hence affects its pharmacokinetics, toxicity and efficacy. There are several studies describing a hereditary (pharmacogenetic) disorder in which individuals with absent or significantly reduced DPD activity may even develop a life-threatening toxicity following exposure to 5-FU. The most common mutation is known as the DPYD*2A or as the splice-site mutation (IVS14 + 1G A) leading to creation of a dysfunctional protein. An objective behind the study was to ascertain existence of the IVS14 + 1G A mutation among the population of Bosnia and Herzegovina. Our research has undeniably attested to existence of one heterozygote for the DPYD gene mutation, i.e. one heterozygote for IVS14 + 1 G > A, DPYD*2A mutation.

Values of prostate specific antigen in patients with operable prostate carcinoma.

BACKGROUND: Prostate specific antigen (PSA) has significance in diagnostics of the prostate cancer, establishing stage of the disease and follow up of results of the treatment with different methods. Increased PSA levels in serum is not characteristic only for persons who have prostate cancer but also of those with benign conditions, especially in range of 4.0 ng/mL to 10.0 ng/ml, where we see a lot of results superposition. Marker determination of free and total PSA-ratio FPSA/TPSA and total PSA and prostate volume--PSA density was introduced for improvement of the sensitivity of PSA. Purpose is to analyze demonstrators of the concentration of PSA and its fraction in patients with histologically confirmed and radically removed prostate cancer, and to establish its correlation with advancement and differentiation of the disease. WORK METHOD: The investigation was done in 80 patients with histologically confirmed, prostate cancer clinical stage T1-2, NO, MO, initial PSA level of 2-10 ng/ml and performed radical prostatectomy. RESULTS: Out of 80 patients, 6 of them (9%) had total serum PSA level within referral values (<4 ng/ml). There were 55 patients (68%) with values of ratio FPSA/TPSA from 0 to 0.15, 18 (23%) patients had values between 0.16-0.19 and 7 (9%) patients had values above 0.20 ratio FPSA/TPSA. Fifty patients (62%) had PSA density in values to 0, 15, and 30 patients (38%) had values above 0.15. According to completed multiple regression analysis values of PSA, ratio FPSA/TPSA and PSA density had no statistically significant correlation with extra-capsular invasion and lymphatic metastasis, which points out that as it is, they do not contribute to its prediction. CONCLUSION: Significant number of patients with histologically proven and radically removed prostate cancer had serum PSA level within normal referral values. PSA density and ratio FPSA/TPSA can help in differentiating malignant from benign changes in prostate in PSA values to 10 ng/ml but not with absolute safety since significant number of patients with proven cancer had these parameters in level range characteristic for benign diseases.

The relationship between the serum prostate specific antigen and whole body scintigraphy in prostate cancer patients after prostatectomy.

BACKGROUND AND AIM: Bone metastases are of the most frequent in prostate cancer. Serum prostate specific antigen--PSA has been suggested as an accurate means of monitoring prostate cancer. Whole body scintigraphy are currently the most widely used diagnostic procedures for metastases to the bone, the most common site of distant tumor spread. Aim of the study was to determinate relation between PSA level, number of metastases and 99mTc- MDP (methyl-diphosponate) uptake in patients with previous prostatectomy for prostate cancer. PATIENTS AND METHODS: Study enrolled 15 patients after previous prostatectomy for prostate cancer (histologically proven). Standard whole body scintigraphy (WBS) was performed 3 hours after intravenous application of 740 MBq 99mTc-MDP. Total PSA was measured by MEIA-Microparticle Enzyme Immunoassay. RESULTS: Group 1: 12/15 (80%) patients were with WBS detected metastases. Correlation of PSA level and number of detected bone metastases was good (r=0.79). Correlation of PSA level and uptake intensity of 99mTc-MDP (score 3) was positive and significant (r=0.706). CONCLUSION: PSA values were highly predictive for WBS results. PSA values correlated well with number of metastases. We propose no WBS in patients with normal PSA level. WBS is a sensitive diagnostic tool for detecting prostate cancer metastases to bone. PSA levels is good and simpler marker for disease progression, but that neither technique in isolation gives complete accuracy.

Short-course radiotherapy (RT) for metastatic spinal cord compression (MSCC) due to renal cell carcinoma: results of a retrospective multi-center study.

OBJECTIVE: For MSCC treatment, a short treatment time is desirable, especially if survival prognosis is poor. Survival depends on the primary tumor, extent of disease, performance status, ambulatory status, and the number of involved vertebrae. These factors may help to define the appropriate regimen for the individual patient. Our study compares short-course (1 x 8 Gy, 5 x 4 Gy) and long-course RT (10 x 3 Gy, 15 x 2.5 Gy, 20 x 2 Gy) for functional outcome in MSCC patients with renal cell carcinoma. METHODS: The following potential prognostic factors for functional outcome were retrospectively investigated: age, performance status, involved vertebra, ambulatory status, time of developing motor deficits before RT, radiation schedule (short-course RT, n=37; long-course RT, n=50). RESULTS: Eighty-seven patients were included in this retrospective study, 25 patients (29%) showed improvement of motor function, 52 patients (60%) no change, 10 patients (11%) deterioration. 25% of non-ambulatory patients became ambulatory after RT. Functional outcome was affected by the time of developing motor deficits before RT (p<0.001). The RT schedule had no significant impact (p=0.91). In the short-course RT sub-group, functional outcome was similar for 1 x 8 Gy and 5 x 4 Gy (p=0.99). CONCLUSION: Short-course and long-course RT appear similarly active for MSCC in patients with renal cell carcinoma. Short-course RT appears preferable, as it is means less patient discomfort. Because 1 x 8 Gy and 5 x 4 Gy were comparably effective, 1 x 8 Gy may be suggested the best actual choice.

The number of malignant neoplasm in Sarajevo region during the period 1998-2002.

UNLABELLED: Due to the specific war and post-war situation in Bosnia and Herzegovina it is possible to notice some differences in the number, type, advancement, biological course, treatment and its outcome. The actual situation which appeared in connection to depleted uranium has additionally raised questions about its influence on human health and about eventual increase in the number of malignant diseases in Bosnia and Herzegovina. In public, we often see that there are claims about enormous increase in the incidence of cancer. In order to achieve a realistic picture of actual condition and to avoid panic and ignorant attitude, correct and constant data of malignant tumors are necessary. THE AIM OF THE STUDY: To collect and analyze data on population with malignant tumors in the region of Sarajevo city, which represents a symbol of difficult times in our country in the recent past. MATERIAL AND METHODS: We have collected and analysed data on, population with malignant tumors which included persons with permanent residence in Sarajevo Canton during 5-year period, from 01.01.1998, until 31.12.2002. Results were compared to regional and world indicators, and were observed in the light of specific local situation. RESULTS: During period of 5 years (1998-2002) 7733 new cases of malignant tumors were registered in Sarajevo Canton; 3940 among men and 3809 among women. Mostly registered tumors were: lung cancer, amelanotic skin tumors, breast cancer, colorectal cancer, cervical and uterine cancer, urinary bladder cancer, prostate cancer and cancer of larynx. CONCLUSIONS: Number of all malignant tumors in the region of Sarajevo Canton correlates to those in South European countries and the one estimated by GLOBCAN 2000. High number was registered in 1998, possibly due to normalization of the health services (diagnostics and treatment of malignant tumors), which didn't exist during the war and early post-war period. After 2000, there is a gradual increase in the number of people with malignant tumors. The most common tumors are lung and breast cancer. Significant differences to estimation and data registrated in other South European counties is high number of laryngeal cancer, urinary bladder cancer, bone and cartilage sarcoma, brain tumors and malignant lymphomas among both genders. Cervical cancer is extremely high up on the list, which correlates with data in developing countries. The incidence of smoking in Bosnia and Herzegovina is extremely high, almost complete, which can influence not only the appearance of lung cancer but also laryngeal and urinary bladder cancer. It is hard to say whether the war and post-war stress, irregular and insufficient nutrition during and after the siege of the city or some other factor have influenced their appearance among exposed population and differences in the observed incidence.