A survival score for patients with brain metastases from less radiosensitive tumors treated with whole-brain radiotherapy alone.

BACKGROUND AND PURPOSE: This study aimed to develop and validate a scoring system to predict the survival of patients receiving whole-brain radiotherapy (WBRT) alone for brain metastases from less radiosensitive tumors. PATIENTS AND METHODS: The study included data from 176 patients with brain metastasis from renal cell carcinoma, malignant melanoma or colorectal cancer. Patients were divided into a test group (N=88) and a validation group (N=88). In the multivariate analysis of the test group, age, Karnofsky Performance Status and extracranial metastasis were significantly associated with survival. These three factors were included in the scoring system. The score for each factor was determined by dividing the 6-month survival rate (in %) by 10. The total score represented the sum of the three scores. According to the total scores-which ranged from 5 to 14 points-three prognostic groups were created. RESULTS: The 6-month survival rates in the test group were 11% for 5-8 points (N=47, group A), 38% for 9-11 points (N=29, group B) and 83% for 12-14 points (N=12, group C). In the validation group the 6-month survival rates were 12, 31 and 75%, respectively. Comparisons between the prognostic groups A, B and C of the test group with those of the validation group did not reveal any significant differences. CONCLUSION: The new scoring system based on three independent prognostic factors can help to estimate the survival of patients with brain metastases from a less radiosensitive tumor. The score appears to be valid and reproducible.

A new survival score for patients with brain metastases from non-small cell lung cancer.

BACKGROUND AND PURPOSE: Non-small cell lung cancer (NSCLC) is the most common primary tumor in patients developing brain metastasis. This study was performed to develop and validate a survival score particularly for this group of patients. PATIENTS AND METHODS: In this study, the data of 514 patients treated with whole-brain radiotherapy (WBRT) alone for brain metastasis from NSCLC were retrospectively analyzed. The patients were divided into a test group (n = 257) and a validation group (n = 257). In the multivariate analysis of the test group, gender, performance status, and extracranial metastases were independent predictors of survival and, therefore, included in the scoring system. The score for each of the three factors was obtained from the 6-month survival rate (in %) divided by 10. The total scores that represented the sum of the three scores were 5, 8, 9, 11, 12, or 15 points. Three prognostic groups were formed according to the total scores. RESULTS: The 6-month survival rates in the test group were 9 % for 5-9 points (group A), 54 % for 11-12 points (group B), and 79 % for 15 points (group C). In the validation group the 6-month survival rates were 14, 56, and 78 %, respectively. The comparisons between the prognostic groups A, B, and C of the test and the validation group did not reveal any significant differences. CONCLUSION: This new score appears valid and reproducible. It can help predict the survival of patients with brain metastasis from NSCLC.

A simple survival score for patients with brain metastases from breast cancer.

BACKGROUND AND PURPOSE: Personalized cancer treatment considers the patient's survival prognosis. Therefore, it is important to be able to estimate the patient's survival time, particularly in a palliative situation such as brain metastasis. This study aimed to create and validate a survival score for patients with brain metastasis from breast cancer, which is the second most common primary tumor in these patients. PATIENTS AND METHODS: Data of 230 patients treated with whole-brain radiotherapy (WBRT) alone for brain metastasis from breast cancer were retrospectively analyzed. Patients were assigned to a test (n = 115) or a validation group (n = 115). According to the results of the multivariate analysis of the test group, Karnofsky Performance Score and extracranial metastases were included in the scoring system. The score for each factor was obtained from the 6-month survival rate (in %) divided by 10. Total scores represented the sum of these scores and were 4, 7, 9, or 12 points. Three prognostic groups were formed. RESULTS: The 6-month survival rates in the test group were 10 % for 4-7 points, 55 % for 9 points, and 78 % for 15 points (p < 0.001). In the validation group the corresponding 6-month survival rates were 11, 54, and 75 %, respectively (p < 0.001). The comparisons between the prognostic groups of the test and the validation group did not show significant differences. CONCLUSION: This simple survival score appears valid and reproducible. It can be used to estimate the survival time of patients with brain metastasis from breast cancer receiving WBRT alone.

Validation of a survival score for patients treated with whole-brain radiotherapy for brain metastases.

BACKGROUND: This study was performed to validate a scoring system published in 2008 to predict the survival of patients receiving whole-brain radiotherapy (WBRT) alone for brain metastases. METHODS: The scoring system included four independent prognostic factors: age, performance status, extracranial metastases, and interval between first diagnosis of cancer and WBRT. The score for each prognostic factor was determined by dividing the 6-month survival rate (in %) by 10. The total score represented the sum of the scores for each prognostic factor. Total scores ranged from 9-18 points, and patients were divided into four groups. In the present study, 350 new patients were evaluated in order to validate the previously developed score. RESULTS: In the present validation study, the 6-month survival rates were 8 % for patients with a score of 9-10 points (group A), 24 % for those with a score of 11-13 points (group B), 51 % for those with a score of 14-16 points (group C), and 82 % for those with scores of 17-18 points (group D), respectively (p < 0.001). In our previous study published in 2008, the 6-month survival rates were 6 %, 15 %, 43 %, and 76 %, respectively (p < 0.001). The comparisons between each of the four prognostic groups of both series did not reveal a significant difference. CONCLUSION: In this study, the 6-month survival rates of the four prognostic groups were not significantly different from those of the preceding study. This demonstrates the validity and reproducibility of this score. The score can help select the appropriate treatment for the individual patient and help design prospective trials.

A phase II study of cetuximab, capecitabine and radiotherapy in neoadjuvant treatment of patients with locally advanced resectable rectal cancer.

BACKGROUND: Neoadjuvant chemoradiotherapy (CRT) reduces local tumor recurrence in locally advanced rectal cancer (LARC). This phase II study assessed neoadjuvant cetuximab with capecitabine-based CRT in LARC. METHODS: Patients with stage II/III LARC received capecitabine 1250 mg/m(2) twice daily for 2 weeks followed by intravenous cetuximab 400 mg/m(2) at week 3, then weekly intravenous 250 mg/m(2) cetuximab plus CRT including capecitabine 825 mg/m(2) twice daily (including weekends during radiotherapy) with radiotherapy of 45 Gy (25 x 1.8 Gy), 5 days a week for 5 weeks. Total mesorectal excision was scheduled 4-6 weeks following completion of CRT. The primary endpoint was pathological complete response (pCR). RESULTS: Thirty-seven patients were eligible for safety and efficacy. TMN staging at baseline was: T4N2, 11%; T3N2, 40%; T2N2, 3%; T3N1, 35%; T2N1, 3% and T3N0 8%. The most common adverse events included, grade 1/2 acneiform skin rash (86%), and grade 3 radiodermatitis, (16%), diarrhea (11%) and hypersensitivity (5%). pCR was achieved in 3 patients (8%). Overall-, T- and N-downstaging rates were 73%, 57% and 81% respectively. Total sphincter preservation rate was 76%, and 53% in 17 patients whose tumors were located within 5 cm from the anal verge. Non-fatal perioperative complications occurred in 13 patients (35%) with delayed wound healing occurring in 6 patients (16%). One death was recorded due to sepsis following colonic necrosis. CONCLUSION: Neoadjuvant cetuximab with capecitabine-based CRT is tolerable in patients with resectable LARC. Whilst the pCR rate was similar to recent reports, a high pathological downstaging rate was achieved.

Anal cancer chemoirradiation with curative intent - a single institution experience.

UNLABELLED: Results of radiochemotherapy in 50 patients with squamous cell carcinoma of the anal canal, treated with radical radiochemotherapy between January 2003 and September 2007, at the Institute of Oncology Ljubljana are presented. The treatment schedule consisted of 3-D conformal external beam radiotherapy (45 Gy in 25 fractions), with two cycles of concurrent chemotherapy (5-fluorouracil (5-FU) / Mitomycin C), followed by brachytherapy or external beam boost (15-30 Gy) to the primary tumor. Locoregional control (LRC), disease-free survival (DFS), disease-specific survival (DSS), overall survival (OS) and colostomy-free survival (CFS) rates and the rate of acute and chronic side-effects were estimated. The impact of individual tumor- and therapy-related factors on treatment outcome was assessed.

Treatment was completed according to the protocol in 72% of patients. The median follow-up time of 40 survivors was 22 months (range 1.7-53.2 months). At 2 years, LRC, DFS, DSS, OS and CFS rates were 68%, 67%, 87%, 76% and 85%, respectively. In the multivariate analysis, nodal stage was identified as an independent prognostic factor for LRC, DSS and CFS and application of Mitomycin C for OS. The most frequent acute side-effect of treatment was radiodermatitis (grade 3 in 66% of patients, grade 4 in 2%). Late anal stenosis, chronic ulceration and grade 2-3 incontinence developed in 3 (6 %), 2 (4 %) and 5 (10 %) of colostomy-free survivors, respectively.

Radiotherapy with concurrent 5-FU / Mitomycin C chemotherapy is feasible, with acceptable toxicity. The presented treatment outcome is comparable to other published results.

Results of adjuvant radiochemotherapy for gastric adenocarcinoma in Slovenia.

AIMS: To analyze the results of postoperative concomitant radiochemotherapy with 5-florouracil (5-FU) and leucovorin (LV) in patients with gastric carcinoma treated in a single institution. METHODS: During 2001-2004, 123 patients with the mean age of 60 years, were treated for adenocarcinoma of the stomach, stage Ib-IV, with postoperative concomitant radiochemotherapy. Radical (R0) and non-radical (R1) resection of the tumor was performed in 107 and 16 patients, respectively. Adjuvant treatment consisted of five cycles of five-day chemotherapy with 5-FU (425 mg/m(2)) and LV (20 mg/m(2)) and concomitant radiotherapy with the total dose of 45 Gy. RESULTS: The treatment was completed according to the protocol in 101 patients. Stomatitis, dysphagia, and nausea and vomiting of grade three occurred in 32, 27, and 23 patients, respectively. The median follow-up time of 87 survivors was 30.4 months (range 17.4-58.3 months). At two years, locoregional control (LRC), disease-free survival (DFS), disease-specific survival (DSS) and overall survival (OS) rates were 86%, 65%, 74%, and 73%, respectively. In the multivariate analysis, the initial Hb level was identified as independent prognostic factor for all survival four endpoints, the involvement of whole stomach with cancer for LRC, the total dose of 5-FU per five-day cycle for DFS, and pT stage for DSS. CONCLUSIONS: In operable gastric carcinoma, postoperative concomitant radiochemotherapy with 5-FU and LV is feasible and its toxicity acceptable. Its potential to improve the treatment outcome compared to the surgery alone is yet to be tested in well designed prospective randomized studies.

Cysteine proteinase inhibitor cystatin C in squamous cell carcinoma of the head and neck: relation to prognosis.

To determine the role of the cysteine proteinase inhibitor cystatin C in the invasive behavior of squamous cell carcinoma of the head and neck (SCCHN), Cystatin C protein level was measured in 82 pairs of primary tumour tissue and adjacent noncancerous mucosa, using the enzyme-linked immunosorbent assay. The median level of cystatin C in tumour tissue was 1.18 times lower than that in corresponding mucosa (P=0.031). In normal mucosa samples, the cystatin C level was influenced by the site of sampling: it was lower in nonlaryngeal tissue samples (oral cavity, oro- or hypopharynx) than in laryngeal samples (P=0.004). The tumour cystatin C level correlated inversely with pN-stage (P=0.047), whereas a trend of lower cystatin C levels was observed in the group with extranodal tumour extension compared to those with no extranodal spread (P=0.069). In univariate analysis, the patients with low tumour cystatin C levels exhibited poor disease-free survival (DFS, P=0.013) and disease-specific survival (DSS, P=0.013). In multivariate analysis, the most powerful predictor of survival was pN-stage (DFS: P=0.040, HR 2.78; DSS: P=0.011, HR 4.36,), followed by the cystatin C level (DFS: P=0.043, HR 0.22; DSS: P=0.067, HR 0.25). When comparing the prognostic strength of cystatin C to that of stefin A, another cysteine proteinase inhibitor, which emerged as the most significant prognosticator for survival in our previous study analysing the same cohort of patients, stefin A proved to be significantly more reliable predictor for both DFS and DSS than cystatin C. Our results indicate that cystatin C is implicated in the invasive behavior of SCCHN, and that there are variations in regulation of proteolytic pathways under nonmalignant conditions, inherent to individual subsites inside the upper aerodigestive tract. The correlation between high cystatin C levels and improved survival concurs with the concept of the protective role of high levels of cysteine proteinase inhibitors in tissue homogenates that has been previously suggested by the survival results in breast and lung carcinoma as well as SCCHN.

Hemoglobin as a factor influencing the outcome in inoperable oropharyngeal carcinoma treated by concomitant radiochemotherapy.

The aim of the study was to analyze the prognostic significance of hemoglobin (Hb) concentration for loco-regional control and survival of patients with inoperable carcinoma of the oropharynx. Seventy patients with inoperable squamous cell carcinoma of the oropharynx were prospectively treated by concomitant regimen of conventional radiotherapy and chemotherapy with Mitomycin C and Bleomycin. The prognostic value of Hb concentration before the therapy (Hb-S) and at the end of the therapy (Hb-E), the difference between both (DHb), and the average Hb concentration (Hb-Av) were analyzed. Hb concentration was falling significantly (median values, from 139 g/L to p<0.0001) during the first three weeks of the therapy; after that, it reached a plateau. In the last week of therapy, a slight increase (p=0.08) in Hb concentration was recorded. Significant correlation (p<0.0001) was found between Hb-S and other Hb-related parameters. The median follow-up of the patients alive on close-out date was 5.7 years (range 4-10.5 years). Longer disease-free survival (DFS) and disease-specific survival (DSS) correlated with higher values of Hb-S (p=0.0005, p=0.008) and Hb-E (p=0.02, p=0.02), while the Hb-Av was predictive for DFS only (p=0.004). The most significant difference between low- and high-Hb groups was calculated at cut-off concentrations of 122 (Hb-S), 116 (Hb-E), and 120 (Hb-Av) g/L. Only Hb-S was tested in multi- variate model where its independent value for predicting both, DFS (p=0.002; RR 3.6) and DSS (p=0.01; RR 2.9), was confirmed. In our patients, Hb-Swas proved to bean independent prognostic factor in predicting DFS and DSS. We believe that the concentration of Hb > or =120 g/L should be maintained during radiotherapy course.