Clinical and imaging findings in cervical cancer and their impact on FIGO and TNM staging - An analysis from the EMBRACE study.

OBJECTIVE: To investigate differences in local tumour staging between clinical examination and MRI and differences between FIGO 2009, FIGO 2018 and TNM in patients with primary cervical cancer undergoing definitive radio-chemotherapy. METHODS: Patients from the prospective observational multi-centre study "EMBRACE" were considered for analysis. All patients had gynaecological examination and pelvic MRI before treatment. Nodal status was assessed by MRI, CT, PET-CT or lymphadenectomy. For this analysis, patients were restaged according to the FIGO 2009, FIGO 2018 and TNM staging system. The local tumour stage was evaluated for MRI and clinical examination separately. Descriptive statistics were used to compare local tumour stages and different staging systems. RESULTS: Data was available from 1338 patients. For local tumour staging, differences between MRI and clinical examination were found in 364 patients (27.2%). Affected lymph nodes were detected in 52%. The two most frequent stages with FIGO 2009 are IIB (54%) and IIIB (16%), with FIGO 2018 IIIC1 (43%) and IIB (27%) and with TNM T2b N0 M0 (27%) and T2b N1 M0 (23%) in this cohort. CONCLUSIONS: MRI and clinical examination resulted in a different local tumour staging in approximately one quarter of patients. Comprehensive knowledge of the differential value of clinical examination and MRI is necessary to define one final local stage, especially when a decision about treatment options is to be taken. The use of FIGO 2009, FIGO 2018 and TNM staging system leads to differences in stage distributions complicating comparability of treatment results. TNM provides the most differentiated stage allocation.

Predicting the presence of extracranial metastases in patients with brain metastases upon first diagnosis of cancer.

BACKGROUND AND PURPOSE: This study aimed to determine factors allowing the prediction of extracranial metastases in patients presenting with brain metastases at the first diagnosis of cancer. MATERIALS AND METHODS: Data from 659 patients with brain metastases upon first diagnosis of cancer were retrospectively analyzed. The parameters age, gender, Karnofsky performance score (KPS), primary tumor type and number of brain metastases were compared between 359 patients with extracranial metastases and 300 patients without extracranial metastases. Additional analyses were performed for patients with the most unfavorable and those with the most favorable characteristics. RESULTS: The comparison of patients with versus without extracranial metastases revealed significant differences between the groups in terms of KPS (p < 0.001) and number of brain metastases (p < 0.001). Of the study patients, 113 had both most unfavorable characteristics, i.e. KPS ≤ 50 and ≥ 4 brain metastases. The sensitivity for identifying patients with extracranial metastases was 82 %; specificity was 51 %. A total of 50 patients had KPS ≥ 90 and only one brain metastasis. The sensitivity for identifying patients without extracranial metastases was 86 %; specificity was 58 %. CONCLUSION: The combination of KPS and the number of brain metastases can help to predict the presence or absence of extracranial metastases.

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.

Brain metastasis from non-small cell lung cancer (NSCLC): prognostic importance of the number of involved extracranial organs.

BACKGROUND AND PURPOSE: This study investigated the potential prognostic value of the number of involved extracranial organs in patients with brain metastasis from non-small cell lung cancer (NSCLC). MATERIAL AND METHODS: A total of 472 patients who received whole-brain radiotherapy (WBRT) alone with 5 × 4 Gy or 10 × 3 Gy for brain metastasis from NSCLC were included in this retrospective study. In addition to the number of involved extracranial organs, 6 further potential prognostic factors were investigated including WBRT regimen, age, gender, Karnofsky Performance Score (KPS), number of brain metastases, and the interval from cancer diagnosis to WBRT. Subgroup analyses were performed for patients with metastatic involvement of one (lung vs. bone vs. other metastasis) and two (lung + bone vs. lung+lymph nodes vs. other combinations) extracranial organs. RESULTS: The survival rates at 6 months of the patients with involvement of 0, 1, 2, 3, and ≥ 4 extracranial organs were 52, 27, 17, 4, and 14%, respectively (p<0.001). On multivariate analysis, the number of involved extracranial organs remained significant (risk ratio 1.32; 95% confidence interval 1.19-1.46; p<0.001). Age <65 years (p=0.004), KPS ≥ 70 (p<0.001), and only 1-3 brain metastases (p=0.022) were also significantly associated with survival in the multivariate analysis. In the separate analyses of patients with involvement of one and two extracranial organs, survival was not significantly different based on the pattern of extracranial organ involvement. CONCLUSION: The number of involved extracranial organs is an independent prognostic factor of survival in patients with brain metastasis from NSCLC, irrespective of the pattern of extracranial organ involvement.

Brain metastasis. Prognostic value of the number of involved extracranial organs.

BACKGROUND AND PURPOSE: This study was performed to evaluate the prognostic role for survival of the number and the type of involved extracranial organs in patients with brain metastasis. MATERIAL AND METHODS: The data of 1146 patients who received whole-brain radiotherapy (WBRT) alone for brain metastasis have been retrospectively analyzed. In addition to the number of involved extra cranial organs, seven potential prognostic factors were investigated including WBRT regimen, age, gender, Karnofsky Performance Score (KPS), primary tumor type, number of brain metastases, and the interval from cancer diagnosis to WBRT. Additionally, subgroup analyses were performed for patients with involvement of one (lung vs. bone vs. liver vs. other metastasis) and two (lung + lymph nodes vs. lung + bone vs. lung + liver vs. liver + bone vs. other combinations) extracranial organs. RESULTS: The 6-month survival rates for the involvement of 0, 1, 2, 3, and ≥4 extracranial organs were 51, 30, 16, 13, and 10%, respectively (p<0.001). On multivariate analysis, the number of involved extracranial organs maintained significance (risk ratio 1.26; 95% confidence interval 1.18-1.34; p<0.001). According to the multivariate analysis, age (p<0.001), gender (p=0.002), and KPS (p<0.001) were also independent prognostic factors for survival. In the subgroup analyses of patients with involvement of one and two extracranial organs, survival was not significantly different based on the extracranial organ involved. CONCLUSION: The number of involved extracranial organs proved to be an independent prognostic factor in patients with brain metastasis, regardless of the organs involved. The number of involved extracranial organs should be considered in future trials designed for patients with brain metastasis.

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.

Phase I-II trial of low-dose gemcitabine in prolonged infusion and cisplatin for advanced non-small cell lung cancer.

After monotherapy with gemcitabine in low dose in long infusion, promising results in a variety of advanced chemoresistant tumors have been reported. In a previous phase I trial on heavily pre-treated patients, maximum tolerated dose (MTD) of gemcitabine in a 6 h infusion was 250 mg/m. The objective of our phase I-II trial was to test the combination of gemcitabine in a 6-h infusion and cisplatin in the treatment of advanced non-small cell lung cancer (NSCLC). Eligible patients were chemonaive, had locally advanced or metastatic NSCLC, Eastern Oncology Cooperative Oncology Group performance status 0-2 and normal organ function. Treatment consisted of gemcitabine in a 6-h infusion on days 1 and 8, and cisplatin at 75 mg/m on day 2 of a 3-week cycle. During phase I of the trial, the dose of gemcitabine was escalated from 130 to 170, 210 and 250 mg/m. After establishing dose-limiting toxicity (DLT) and MTD of the combination, the trial continued as phase II. Altogether, 61 patients were enrolled, of whom 54 had stage IV disease. In phase I of the trial, groups of six, seven, eight and eight patients were treated at the four dose levels of gemcitabine. In phase II, the remaining 32 patients all received gemcitabine at 250 mg/m. Serious toxicity included a patient with grade 5 ventricular arrhythmia and another with grade 4 cerebrovascular ischemia; four patients had grade 3 anemia. Reversible thrombocytosis with platelets over 500 was recorded in 32 patients; 42 patients had grade 2 alopecia. In general, tolerance to this treatment was good. One patient had complete response and 27 had partial responses, for a 28 of 61 (46%) response rate. Median progression-free survival, median survival and 1-year survival were 6 months, 9.5 months and 40%, respectively. We conclude that this treatment has an acceptable, yet distinct, toxicity profile; routine thromboprophylaxis is recommended. In our population of chemonaive patients, no DLT has been encountered. Due to the remarkable response rate, further research is warranted.

The basidiomycete ganoderma and asthma: collection, quantitation and immunogenicity of the spores.

Ganoderma fungal spores are a major component of the Auckland air-spora. Previous studies of ganoderma involvement in allergic asthma and rhinitis were extended by locating the sporophores (fruiting bodies) in the Auckland area and systematically collecting the ejected spores. Maximum production by one sporophore was 5 gram dry weight of spores in one week, equivalent to 11 billion spores. We have estimated that between 400 and 1200 sporophores would account for previously reported levels of ganoderma spores collected from the air by Burkhard spore traps. Both whole spores and extracts of spores were strongly immunogenic in rabbits. Of the 115 asthma patients who were skin prick tested with a variety of fungal extracts, 32 (28%) were positive to one or more fungi. Of these, 18 (16%) reacted positively to ganoderma extracts. A theory proposing how ganoderma might contribute to allergic hyperreactivity in susceptible patients is developed.

Allergy to basidiospores: immunologic studies.

Fruiting bodies of larger basidiomycetous fungi were collected over a 15 month period from natural habitats and a total of 67 different antigenic extracts were prepared from spores or tissue, in buffered saline, pH8, and standardised at 1:50 and 1:10 (W/V) concentrations. A number of heterogeneous and diagnosed allergic patients were tested by skin prick test method with the extracts of either individual species or mixtures of related species. Up to 22% patients reacted positively, indicating their possible IgE mediated reactions and the allergenic potency of the species involved. The potential allergenicity of many of these genera and/or species has not been reported previously. The findings suggest that basidiospores could be a possible major factor for the high respiratory allergy incidence in the Auckland region and necessitate further investigation.