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author:("fossa, S. D.")
1.  Sperm counts and endocrinological markers of spermatogenesis in long-term survivors of testicular cancer 
British Journal of Cancer  2012;107(11):1833-1839.
Background:
The objective of this study was to assess markers of spermatogenesis in long-term survivors of testicular cancer (TC) according to treatment, and to explore correlations between the markers and associations with achieved paternity following TC treatment.
Methods:
In 1191 TC survivors diagnosed between 1980 and 1994, serum-follicle stimulating hormone (s-FSH; n=1191), s-inhibin B (n=441), and sperm counts (millions per ml; n=342) were analysed in a national follow-up study in 1998–2002. Paternity was assessed by a questionnaire.
Results:
At median 11 years follow-up, 44% had oligo- (<15 millions per ml; 29%) or azoospermia (15%). Sperm counts and s-inhibin B were significantly lower and s-FSH was higher after chemotherapy, but not after radiotherapy (RT), when compared with surgery only. All measures were significantly more abnormal following high doses of chemotherapy (cisplatin (Cis)>850 mg, absolute cumulative dose) compared with lower doses (Cis ⩽850 mg). Sperm counts were moderately correlated with s-FSH (−0.500), s-inhibin B (0.455), and s-inhibin B : FSH ratio (−0.524; all P<0.001). All markers differed significantly between those who had achieved post-treatment fatherhood and those with unsuccessful attempts.
Conclusion:
The RT had no long-term effects on the assessed markers of spermatogenesis, whereas chemotherapy had. At present, the routine evaluation of s-inhibin B adds little in the initial fertility evaluation of TC survivors.
doi:10.1038/bjc.2012.471
PMCID: PMC3504949  PMID: 23169336
germ cell tumour; inhibin B; late effects; paternity; spermatogenesis; testicular cancer
2.  Why do patients with radiation-induced sarcomas have a poor sarcoma-related survival? 
British Journal of Cancer  2011;106(2):297-306.
Background:
This study aims to provide reasons for the poor sarcoma-related survival in patients with radiation-induced sarcoma (RIS).
Methods:
We performed a case–control study comparing sarcoma-related survival of 98 patients with RIS to that of 239 sporadic high-grade malignant sarcomas.
Results:
The cumulative sarcoma-related 5-year survival was 32% (95% confidence interval (CI): 22–42) for patients with RIS vs 51% (95% CI: 44–58) for controls (P<0.001). Female gender, central tumour site and incomplete surgical remission were significantly more frequent among RIS patients than in controls. In multivariate analysis incomplete surgical remission (hazard ratio (HR) 4.48, 95% CI: 3.08–6.52), metastases at presentation (HR 2.93, 95% CI: 1.95–4.41), microscopic tumour necrosis (HR 1.88, 95% CI: 1.27–2.78) and central tumour site (HR 1.71, 95% CI: 1.18–2.47) remained significant adverse prognostic factors, but not sarcoma category (RIS vs sporadic).
Conclusion:
The poor prognosis of RIS patients are not due to the previous radiotherapy per se, but related to the unfavourable factors – central tumour site, incomplete surgical remission, microscopic tumour necrosis and the presence of metastases, the two former factors overrepresented in RIS.
doi:10.1038/bjc.2011.559
PMCID: PMC3261679  PMID: 22173669
radiation; radiation-induced; sarcoma; secondary malignancies; prognosis; treatment-related morbidity
3.  Valvular dysfunction and left ventricular changes in Hodgkin's lymphoma survivors. A longitudinal study 
British Journal of Cancer  2009;101(4):575-581.
Purpose:
Hodgkin's lymphoma survivors (HLSs) have an elevated risk for cardiovascular diseases that appear several years after radiotherapy. This study examined the time-dependent development and evolution of valvular and myocardial function related to treatment with mediastinal radiotherapy and anthracyclines in HLSs.
Patients and methods:
In 1993, echocardiography was performed in 116 HLSs median 10 years (range 6–13 years) after treatment with mediastinal radiotherapy. None of the 116 patients had valvular stenosis in 1993 whereas 36 (31%) had moderate valvular regurgitation. In 2005–2007, 51 of 57 invited patients were included in a second echocardiographic study – median 22 years (range 11–27 years) after treatment. Of these patients, 28 (55%) had also received anthracyclines. The patients were selected on the basis of the presence or absence of moderate valvular regurgitation in 1993.
Results:
The second echocardiographic study demonstrated that 10 out of 27 (37%) patients with only mild or no aortic or mitral regurgitation in 1993 had developed moderate regurgitation in either or both the aortic or mitral valve. Of the 24 patients with moderate (n=23) or severe (n=1) regurgitation in the aortic or mitral valve in 1993, 8 (33%) had progressed to severe regurgitation, developed moderate regurgitation in a previously normal or mild regurgitant valve or had received valvular replacement. In total, of all patients, 20 (39%) had developed mild to severe aortic stenosis and 3 patients had received valvular replacement. In a multiple linear regression the use of anthracyclines predicted left ventricular remodelling between ECHO 1993 and 2005 as demonstrated by increased left ventricular end systolic diameter (β =0.09 (95% CI 0.01–0.17), P=0.04) and reduced thickness of the left ventricular posterior wall (β =−0.18 (95% CI −0.33 to −0.03), P=0.02) and interventricular septum (β =−0.16 (95% CI −0.30 to −0.03), P=0.02).
Conclusion:
Given the progressive nature of valvular dysfunction and left ventricular remodelling 20–30 years after diagnosis, we recommend life-long cardiological follow-up of HLSs treated with mediastinal radiotherapy.
doi:10.1038/sj.bjc.6605191
PMCID: PMC2736805  PMID: 19623176
lymphoma; cardiac valves; cardiomyopathy
4.  Gonadal function in male patients after treatment for malignant lymphomas, with emphasis on chemotherapy 
British Journal of Cancer  2009;100(3):455-463.
Gonadal function was assessed in male lymphoma survivors based on serum hormone levels (LH, FSH, testosterone, SHBG), and was related to treatment, age and observation time. Male patients ⩽50 years at diagnosis treated for Hodgkin's (HL) and/or non-Hodgkin's lymphoma (NHL) at the Norwegian Radium Hospital from 1 January 1980 to 31 December 2002 were included. Five treatment groups were defined: 1: radiotherapy only and/or low gonadotoxic chemotherapy (both HL and NHL)(‘No/low'), 2: medium gonadotoxicity chemotherapy for NHL (‘med-NHL'), 3: medium gonadotoxicity chemotherapy for HL (‘med-HL'), 4: highly gonadotoxic chemotherapy for NHL (‘high-NHL'), 5: highly gonadotoxic chemotherapy for HL (‘high-HL'). Gonadal hormone levels were categorised into three groups: 1: All gonadal hormones within normal range (normal), 2: Isolated elevated FSH, with LH, SHBG and testosterone within normal range (exocrine hypogonadism), 3: Testosterone below and/or LH above normal range (endocrine hypogonadism). One hundred and forty-four (49%) of the patients had normal gonadal hormones, 60 (20%) displayed exocrine hypogonadism and almost one-third (n=90, 30%) had endocrine hypogonadism. Compared to those treated with no/low gonadotoxic chemotherapy patients from all other treatment groups had significantly elevated risk for exocrine hypogonadism. Patients from the other treatment groups, except those in the med-NHL group, also had significantly elevated risk for endocrine hypogonadism compared with the group treated with no/low gonadotoxic chemotherapy. Men aged above 50 years at survey were about five times more likely to have endocrine hypogonadism compared with those less than 40 years. Because of the adverse health effects following long-lasting endocrine hypogonadism, gonadal hormones should be assessed regularly in male lymphoma survivors, especially after treatment with alkylating agents and high-dose chemotherapy with autologous stem cell support and in male patients who are 50 years and older.
doi:10.1038/sj.bjc.6604892
PMCID: PMC2658535  PMID: 19156143
male lymphoma survivors; chemotherapy; gonadal function
5.  Post-treatment parenthood in Hodgkin's lymphoma survivors 
British Journal of Cancer  2007;96(9):1442-1449.
Attempted and achieved post-treatment parenthood, with or without use of assisted reproduction techniques (ARTs), was assessed in Hodgkin's lymphoma survivors treated from 1971–1998, aged below 50 (females) or 65 (males) at diagnosis, aged 18 to 75 at survey. Four treatment groups were constructed: radiotherapy only, low -, medium - and high gonadotoxic chemotherapy (with or without radiotherapy in the three chemotherapy groups). Using Kaplan–Meier estimates, log-rank tests and Cox regression analyses, factors influencing post-treatment parenthood were investigated, with birth of the first child after treatment as the end point. Forty-five per cent (120/269) of males and 50% (91/184) of females reported attempted post-treatment parenthood. Of these, 76 (63%) males and 68 (75%) females had a child without use of ARTs. In addition 10 males and one female achieved post-treatment parenthood with use of ARTs. Treatment group was significantly associated with post-treatment parenthood, with highest probabilities after radiotherapy only and low gonadotoxic chemotherapy. In univariate analyses, age at diagnosis was a significant factor related to post-treatment parenthood in females.
doi:10.1038/sj.bjc.6603711
PMCID: PMC2360165  PMID: 17406362
Hodgkin's lymphoma; chemotherapy; radiotherapy; post-treatment parenthood
6.  Late recurrences of germ cell malignancies: a population-based experience over three decades 
British Journal of Cancer  2006;94(6):820-827.
The purpose of this study was to explore the incidence of late relapse in patients with malignant germ cell tumour (MGCT) in a population-based series, with emphasis on the mode of detection, survival, and the relevance of histological findings. The clinical records from a population-based cohort of patients with seminoma (n=1123) or non-seminoma (n=826) were evaluated for late relapses. Twenty-five patients developed a late relapse. The cumulative 10-year incidence rate was 1.3%. All 10 seminoma patients, but only eight of 15 non-seminoma patients relapsed with vital malignant tumour (P=0.02). Teratoma or necrosis was found in seven of nine primarily chemotherapy-treated non-seminoma patients with normal tumour markers at late relapse. Six of nine patients operated with limited retroperitoneal lymph node dissection as part of the primary treatment had relapsed retroperitoneally outside the original operation field. The 10-year cause-specific survival was 68% in all patients, 50% in patients relapsing with vital malignant tumour and 100% in those with teratoma/ necrosis before or after salvage chemotherapy. The 10-year incidence rate of late relapses of 1.3% might reflect the true incidence rate in a population-based cohort of MGCT patients, with cure in at least half of them.
doi:10.1038/sj.bjc.6603014
PMCID: PMC3216420  PMID: 16508636
late relapse; late recurrence; testicular cancer; extragonadal germ cell cancer; EGGCT; seminoma; non-seminoma; retroperitoneal lymph node dissection
7.  Intensive induction chemotherapy with C-BOP/BEP for intermediate- and poor-risk metastatic germ cell tumours (EORTC trial 30948) 
British Journal of Cancer  2005;93(11):1209-1214.
New chemotherapy regimens are continuously explored in patients with high-risk malignant germ cell tumours (MGCTs). This multicentre phase II trial assessed the efficacy and toxicity of C-BOP/BEP chemotherapy in intermediate and poor prognosis MGCT (IGCCCG criteria). C-BOP/BEP treatment consisted of cycles of cisplatin, vincristine, bleomycin and carboplatin, followed by one cycle of vincristine and bleomycin and three cycles of BEP (bleomycon, etoposide, cisplatin). The trial was designed to demonstrate a 1-year progression-free survival rate of 80%, that is, to exclude a 1-year rate of 70% or less, with a one-sided significance level of 5%. Secondary end points included toxicity, overall survival and the postchemotherapy complete response rate. In total, 16 European hospitals entered 66 eligible patients (intermediate prognosis group: 37; poor prognosis group: 29). A total of 45 patients (68.2%, 95% confidence interval (95% CI): 56.9–79.4%) achieved a complete response (intermediate prognosis: 30; poor prognosis: 15). After a median observation time of 40.4 months (range: 13.7–66.3), the 1-year progression-free survival rate was 81.8% 95% CI: 72.5–91.1%). The 2-year overall survival was 84.5% (95% CI: 75.6–93.3%). In all, 51 patients experienced at least one episode of WHO grade 3/4 leucopenia, and at least one event of grade 3/4 thrombocytopenia occurred in 30 patients. There was no toxic death. With an 82% 1-year progression-free survival and a lower limit of the 95% CI above 70%, the efficacy of C-BOP/BEP is comparable to that of published alternative chemotherapy schedules in high-risk MGCT patients. The treatment's toxicity is manageable in a multicentre setting. In poor prognosis patients, C-BOP/BEP should be compared to standard chemotherapy of four cycles of BEP.
doi:10.1038/sj.bjc.6602830
PMCID: PMC2361516  PMID: 16251877
intermediate and poor prognosis metastatic germ cell tumours; bleomycin; carboplatin; vincristine; cisplatin; etoposide
9.  Increased mortality rates in young and middle-aged patients with malignant germ cell tumours 
British Journal of Cancer  2004;90(3):607-612.
doi:10.1038/sj.bjc.6601558
PMCID: PMC2409607  PMID: 14760372
malignant germ cell tumours; mortality; nongerm cell cancer; cardiovascular diseases
10.  Expression of the epidermal growth factor receptor family in prostate carcinoma before and during androgen-independence 
British Journal of Cancer  2004;90(2):449-454.
doi:10.1038/sj.bjc.6601536
PMCID: PMC2410152  PMID: 14735192
prostatic neoplasms/receptor; epidermal growth factor/receptor; erbB-2/receptor; erbB-3
12.  Excessive annual BMI increase after chemotherapy among young survivors of testicular cancer 
British Journal of Cancer  2003;88(1):36-41.
doi:10.1038/sj.bjc.6600714
PMCID: PMC2376769  PMID: 12556956
testicular cancer; treatment; BMI
13.  Identification of nucleolar protein No55 as a tumour-associated autoantigen in patients with prostate cancer 
British Journal of Cancer  2000;83(6):743-749.
Four different genes were identified by immunoscreening of a cDNA expression library from the human prostate cancer cell line DU145 with allogeneic sera from four prostate cancer patients. A cDNA encoding the nucleolar protein No55 was further analysed and shown to be expressed at the mRNA level in several normal tissues, including ovaries, pancreas and prostate and in human prostate cancer cell lines PC-3, PC-3m and LNCaP. By reverse transcriptase/polymerase chain reaction, expression of No55 was several-fold higher in two out of nine prostate cancer primary tumours and two out of two metastatic lesions, compared to normal prostate tissue. Antibodies to No55 were detected in sera from seven out of 47 prostate cancer patients but not in sera from 20 healthy male controls. Sequence analysis of the No55 open reading frame from normal and tumour tissues revealed no tumour-specific mutations. The No55 gene was located to chromosome 17q21, a region reported to be partially deleted in prostate cancer. Considering the immunogenicity of the No55 protein in the tumour host, the expression profile and chromosomal localization of the corresponding gene, studies evaluating No55 as a potential antigen for immunological studies in prostate cancer may be warranted. © 2000 Cancer Research Campaign
doi:10.1054/bjoc.2000.1365
PMCID: PMC2363543  PMID: 10952778
SEREX; prostate cancer; No55
14.  Fertility in Norwegian testicular cancer patients 
British Journal of Cancer  2000;82(3):737-741.
The intention was to explore the relationship between fertility and testicular cancer, including the possibly treatment-induced changes over time in the post-diagnostic fertility. Data are from the Norwegian Cancer Registry, The Norwegian Population Register and the Population Censuses. By estimating Poisson regression models, birth rates among testicular cancer patients were compared with those of other men who had the same age, parity and duration since previous birth. Poisson regression models were also estimated to check whether men's parity has an effect on the cancer incidence. Fertility rates among testicular cancer patients born after 1935 and treated before 1991 decreased by roughly 30% when compared with the normal population. The introduction of cisplatin chemotherapy and of nerve-sparing RPLND in the 1980s seems to have enabled more patients with non-seminoma to father a child after treatment, or at least shortened the time to conception. Moreover, the risk of being diagnosed with seminoma is reduced with increasing parity. This suggests that the relatively low fertility after diagnosis may be partly due to the continuing inherent influence of a sub- or infecundity that also had a bearing on the development of the disease. © 2000 Cancer Research Campaign
doi:10.1054/bjoc.1999.0989
PMCID: PMC2363334  PMID: 10682691
fecundity; incidence; infecundity; infertility; parity; treatment
15.  Prognostic factors in patients progressing after cisplatin-based chemotherapy for malignant non-seminomatous germ cell tumours 
British Journal of Cancer  1999;80(9):1392-1399.
The aim of this study was to define prognostic parameters for survival in patients with malignant germ cell tumours progressing after platinum-based induction chemotherapy with or without surgery. A total of 164 progressing patients (testicular: 83%, extragonadal: 17%) were identified out of 795 patients treated with platinum-based induction chemotherapy for metastatic germ cell malignancy with or without surgery. ‘Progressive disease’ included patients who had progressed after a previous partial or complete remission as well as patients who failed primary therapy. Salvage chemotherapy consisted of ‘conventional’ platinum-based chemotherapy. Prognostic factors for survival were assessed by uni- and multivariate analyses. The resulting prognostic model was validated in an independent data set of 66 similar patients. For all 164 patients the median time from start of induction chemotherapy to progression was 10 months (range: 0–99). Thirty-eight (23%) patients relapsed after 2 years. The 5-year survival rate for all progressing patients was 30% (95% confidence interval 23–38%). In the univariate analysis the following factors most importantly predicted a poor prognosis: progression-free interval < 2 years: initial poor prognosis category (MRC criteria), < CR to induction chemotherapy, initial treatment early in the 1980s and treatment given at a ‘small’ centre. Three prognostic factors remained in the multivariate analysis: progression-free interval, response to induction treatment and the level of serum human chronic gonadotrophin (hCG) and alpha fetoprotein (AFP) at relapse. One hundred and twenty-four patients could be classified on the basis of these characteristics, Those patients with progression-free interval < 2 years, < CR to induction chemotherapy and high markers at relapse (AFP >100 kU l−1 or hCG >100 IU l−1) formed a poor prognosis group of 30 patients, none of whom survived after 3 years. Patients with at most two of these three risk factors formed a good prognosis group of 94 patients (76%) with a 47% (37–56%) 5-year survival. Thirty-eight patients from the good prognosis group with a progression-free interval of >2 years had a 2-year survival of 74% (60–88%) and 5-year survival of 61%. These prognostic groups were validated in the independent data set, in which 5-year survival rates in the good and poor risk groups were 51% and 0% respectively. One-third of patients progressing during or after platinum-based induction chemotherapy for metastatic germ cell malignancy may be cured by repeated ‘conventional’ platinum-based chemotherapy. Good prognosis parameters are: progression-free interval of > 2 years, CR to induction treatment and normal or low serum markers at relapse (hCG < 100 IU l−1 and AFP < 100 kU l−1). The results of high-dose salvage chemotherapy should be interpreted on the background of these prognostic factors. © 1999 Cancer Research Campaign
doi:10.1038/sj.bjc.6690534
PMCID: PMC2363071  PMID: 10424741
germ cell malignancy; relapse; cisplatin-based chemotherapy; survival
16.  Resection of residual retroperitoneal masses in testicular cancer: evaluation and improvement of selection criteria. The ReHiT study group. Re-analysis of histology in testicular cancer. 
British Journal of Cancer  1996;74(9):1492-1498.
Residual retroperitoneal masses may remain after chemotherapy for metastatic non-seminomatous testicular cancer, which harbour residual tumour or totally benign tissue (necrosis/fibrosis). These residual masses may be effectively removed by a surgical resection. We evaluated current selection criteria and tried to develop alternative criteria in a data set of 544 patients, who had retroperitoneal lymph node dissection of residual masses. Six resection policies were identified from the literature. Two alternative policies were developed with logistic regression analysis. Evaluation of the policies focused on the true-positive rate (resection in case of tumour), and the false-positive rate (resection in case of necrosis). It appeared that most current policies use the size of the residual mass (> or = 10 mm or > or = 20 mm) as the predominant selection criterion. This resulted in high true-positive rates (most > 90%), but false-positive rates between 37% and 87%. The alternative policies included five well-known predictors of necrosis in addition to residual mass size (primary tumour histology, prechemotherapy levels of the three tumour markers alphafetoprotein (AFP), human chorionic gonadotropin (HCG) and lactate dehydrogenase (LDH) and mass shrinkage during chemotherapy). This strategy resulted in improved true- and false-positive rates, even when categories of the predictors were simplified for practical application. We conclude that a simple statistical model, based on a limited number of patient characteristics, provides better guidelines for patient selection than those currently used in clinical practice.
PMCID: PMC2074767  PMID: 8912551
17.  Survival of patients with advanced urothelial cancer treated with cisplatin-based chemotherapy. 
British Journal of Cancer  1996;74(10):1655-1659.
The aim of the present retrospective study was to assess long-term survival after cisplatin-based chemotherapy in 398 patients with advanced urothelial transitional cell carcinoma (TCC) treated at seven international oncological units. Various combinations of cisplatin, methotrexate, vinblastine (or vincristine) and doxorubicin were used. The complete response rate according to the WHO criteria was 17%. Partial responses were obtained in 42% of the patients. The overall cancer-related 2 year and 5 year survival rates were 21% and 11% respectively. Based on multivariate analyses, a good prognosis group could be identified comprising patients with a good performance status with disease confined to lymph nodes (14%) or patients with T4b disease only. These patients had a 28% 5 year survival rate, which, in part, has to be related to post-chemotherapy consolidation treatment in patients with pelvis-confined disease (radiotherapy, 26%; total cystectomy, 11%). Fifteen patients died of chemotherapy-related complications and in 16% of the patients toxicity led to discontinuation of treatment. Modern cisplatin-based chemotherapy leads to long-term survival and cure of selected patients with advanced urothelial transitional cancer. In routine clinical practice, chemotherapy should be offered to good prognosis patients; those presenting with a good performance status and a non-metastasising T4b tumour or with metastases confined to lymph nodes. Post-chemotherapy consolidation treatment by surgery or radiotherapy should always be considered. Such chemotherapy requires oncological expertise in order to avoid unnecessary toxicity.
PMCID: PMC2074866  PMID: 8932351
18.  Cisplatin, vincristine and ifosphamide combination chemotherapy of metastatic seminoma: results of EORTC trial 30874. EORTC GU Group. 
British Journal of Cancer  1995;71(3):619-624.
The aims of the trial were to establish the response rate and determine the toxicity of combination chemotherapy with ifosphamide, vincristine and cisplatin (HOP regimen) in advanced metastatic seminoma and to study the role of post-chemotherapy consolidation treatment. Patients with bulky metastatic non-alpha-fetoprotein-producing seminomas were eligible for this phase II study [serum human chorionic gonadotropin < 200 U l-1 (< 40 ng l-1)] if they presented with abdominal masses > or = 10 cm or had extra-gonadal seminoma or had relapsed after previous radiotherapy. The HOP regimen consisted of four 3-weekly cycles of the following drug combination: ifosphamide (days 1-5, 1.2 mg m-2 day-1), vincristine (day 1, 2 mg) and cisplatin (days 1-5, 20 mg m-2 day-1). Residual masses persisting 6 months after chemotherapy could be considered for consolidation surgery or radiotherapy. Maximal response to the HOP chemotherapy (evaluated at any time) was based on the WHO criteria. The median observation time was 2.5 years (range 1.8-5.5 years). Thirteen institutions treated 42 eligible patients within the study (testicular cancer stage > or = IID, 25; extragonadal, 5; relapse after previous radiotherapy, 12). Two patients were not evaluable for response owing to premature treatment discontinuation. Maximal response was as follows: complete remission (CR), 26 (65%); partial remission (PR) 11 (28%); no change (NC), 2 (5%); progressive disease (PD), 1 (3%). Four patients have died, three from their malignancy (two without previous irradiation and one with prior radiotherapy). The fourth patient died of treatment-related toxicity. The 3 year survival for all 42 eligible patients was 90%. Dose reduction and treatment postponement were necessary in 25 and 14 patients respectively. Ten patients experienced granulocytic fever. Previously irradiated patients tolerated chemotherapy as well as non-irradiated patients. Immediately after HOP chemotherapy a mass persisted in 16 of 17 patients with retroperitoneal masses of > or = 100 mm at presentation. Three of these residual lesions were resected within the following 6 months showing complete necrosis. Four lesions dissolved spontaneously during the first year of follow-up. Nine lesions persisted for > or = 1 year (one after consolidation radiotherapy) without leading to relapse. Four of seven patients with mediastinal lesions achieved CR and three a PR after HOP chemotherapy. The HOP chemotherapy regimen is highly effective in patients with advanced metastatic seminoma or those relapsing after previous radiotherapy, but is associated with a high risk of toxicity, in particular myelotoxicity.
PMCID: PMC2033625  PMID: 7880748
19.  How safe is surveillance in patients with histologically low-risk non-seminomatous testicular cancer in a geographically extended country with limited computerised tomographic resources? 
British Journal of Cancer  1994;70(6):1156-1160.
In patients with clinical stage I non-seminomatous testicular cancer only limited information is available about the administrative problems with the surveillance programme, in particular if this policy is to be implemented in a geographically extended country with limited computerised tomography (CT) resources. One hundred and two patients with non-seminomatous testicular cancer clinical stage I and low-risk histology (MRC criteria, UK) were followed by the surveillance policy for at least 1 year after orchiectomy (median 47 months, range 21-81 months). Twenty-two patients (22%) relapsed after a median time of 5 months (range 2-18 months), 14 of them in the retroperitoneal space. Serum alpha-fetoprotein and/or human chorionic gonadotrophin were elevated in eight of the 22 relapsing patients. The progression-free and cancer-corrected survival rates were 78% and 99% respectively. Patient non-compliance did not represent a major problem, whereas the regular and adequate performance of necessary CT examinations yielded some administrative difficulties. One and 3 years after orchiectomy about 50% of the relapse-free patients had no psychological problems and were satisfied with the surveillance programme, whereas 46% reported minor and 4% major psychological distress. Despite non-negligible administrative difficulties in geographically extended countries, surveillance is feasible and safe in compliant patients with low-risk non-seminomatous testicular cancer stage I. The responsible cancer centre and the local hospitals should establish a high degree of cooperation and enable adequate follow-up examinations in these patients.
PMCID: PMC2033670  PMID: 7981068
20.  Prostatic carcinoma: a multivariate analysis of prognostic factors. 
British Journal of Cancer  1994;69(5):924-930.
Tissue specimens from 150 patients with localised prostatic carcinomas and 116 patients with prostatic carcinomas with distant metastases were analysed for histological grade (WHO and Gleason) and immunoreactivity for prostate acid phosphatase (PAP), prostate-specific antigen (PSA), neurone-specific enolase (NSE), p53 protein, c-erbB-2 protein, cytokeratins (AE1/AE3) and vimentin. After stratification for the presence or absence of distant metastases, multivariate regression analysis revealed that WHO grading was the most powerful independent prognosticator, followed by age and prostate acid phosphatase expression. There was a trend towards reduced survival with decreasing prostate-specific antigen reactivity. The Gleason system showed poor prognostic ability. The analysis predicted reduced survival in the presence of extensive neurone-specific enolase reactivity, mostly because of one case of small-cell carcinoma.
PMCID: PMC1968899  PMID: 7514029
21.  Clinical significance of DNA ploidy and S-phase fraction and their relation to p53 protein, c-erbB-2 protein and HCG in operable muscle-invasive bladder cancer. 
British Journal of Cancer  1993;68(3):572-578.
DNA ploidy and S-phase fraction (SPF), determined by flow cytometry were studied in 118 patients with muscle-invasive transitional cell carcinoma (TCC) of the urinary bladder, scheduled for cystectomy after pre-operative radiotherapy (20 Gy/1 week) with or without systemic cisplatin-based neo-adjuvant chemotherapy. The correlation between these parameters and immunohistochemically demonstrated p53, c-erbB-2 and HCG was also investigated. There were 16 DNA diploid and 102 DNA non-diploid tumours. DNA ploidy was not related to the T (all 118 patients) or pN (58 patients) category, occurrence of stage reduction or cancer-related 5 years survival. Patients with high SPF tumours tended, however, to have a better prognosis than those with low SPF TCC reaching the level of significance (P < 0.05) for those patients who had high SPF tumours and received neo-adjuvant chemotherapy. Fifty-one of the tumours were p53 positive. p53 positive tumours were significantly more often found in TCC with low SPFs than in those with high SPFs. Respectively 12 and 9% of the tumours were HCG and c-erbB-2 positive, without correlation to DNA ploidy or SPF. We conclude that DNA ploidy does not represent a prognostic parameter in muscle-invasive operable bladder carcinomas. A high SPF, determined by FCM, may be helpful to identify patients with chemotherapy-sensitive TCC of the urinary bladder.
PMCID: PMC1968394  PMID: 8102536
22.  Long-term follow-up of pulmonary function in patients cured from testicular cancer with combination chemotherapy including bleomycin. 
British Journal of Cancer  1993;68(3):555-558.
A follow-up study of pulmonary function in two groups of patients with testicular cancer was performed 6-12 years after treatment. Both groups, 47 patients in each, had undergone retroperitoneal lymph node dissection (RPLND). Patients with pathological stage (ps) II had also received bleomycin (median 270 mg) and cisplatin (median 540 mg) in three or four courses which included vinblastine or etoposide. Patients in ps I and II were similar with respect to age, general health, observation period, inspired oxygen fraction (FiO2) and maximal arterial oxygen pressure (pO2) at RPLND, but four (8.2%) with psII disease developed densities on chest X-ray during chemotherapy. At the long-term follow-up the groups were similar with respect to physical exercise, smoking pattern, present drug treatment and history of cardiopulmonary disease. In both groups forced vital capacity (FVC), forced expiratory volume in one second (FEV1), and single breath transfer factor for carbon monoxide (TLCO) were within normal limits, and no difference was found between the groups. The combined data for both groups showed that smoking was highly associated with impairment in TLCO (P = 0.005), and smoking frequency was negatively correlated to TLCO (P = 0.002). We conclude that 3-4 courses with bleomycin, cisplatin and etoposide/vinblastine in testicular cancer patients do not lead to long-term impairment of pulmonary function.
PMCID: PMC1968399  PMID: 7688978
23.  Hormone resistant prostatic adenocarcinoma. An evaluation of prognostic factors in pre- and post-treatment specimens. 
British Journal of Cancer  1993;68(2):380-384.
Pre- and post-treatment specimens from 47 patients with hormone resistant prostatic carcinoma were compared with each other regarding histological grade and immunoreactivity for p53 protein, neuron specific enolase and c-erbB-2 protein. Significantly more specimens expressed a high malignancy grade when the tumour had become hormone resistant than at the time of initial diagnosis (Gleason P: < 0.0001, WHO P:0.0003). p53 protein immunoreactivity increased significantly with disease progression (P:0.006), while tissue PSA immunoreactivity was reduced in post-treatment specimens (P:0.011). p53 protein expression did not correlate with histological grade or PSA expression and seems to be an independent parameter which participates late in the neoplastic transformation. Thirty-two percent of the tumours were neuron specific enolase positive, but this parameter did not correlate with development of hormone resistance. c-erbB-2 protein reactivity was not recognised.
Images
PMCID: PMC1968568  PMID: 7688548
24.  Pre- and post-treatment sexual life in testicular cancer patients: a descriptive investigation. 
British Journal of Cancer  1993;67(5):1113-1117.
Aspects of sexuality were assessed by questionnaires in 76 testicular cancer patients after orchiectomy before further treatment and, respectively, 6, 12 and 36 months after therapy. Before treatment 11% of the patients reported dissatisfaction with sexual life. About 20% of the patients sometimes experienced reduced libido and erectile difficulties. Six months after therapy significantly more patients (27%) recorded an unsatisfactory sexual life as compared to the pretreatment situation. At the 36 months' evaluation 22 of 76 evaluable patients (18%) still stated that their sexual life was inferior to the pretreatment experience. Libido and erectile function decreased transiently during the first year after treatment in most patients. Twelve patients reported permanent 'dry ejaculation' after bilateral retroperitoneal lymph node dissection. Other sexual disturbances could not be related to specified treatment modalities. Increased age at the time of diagnosis and psychological distress tended to correlate with the incidence of sexual problems. For about 60% of the patients the discussion of expected and experienced sexual life problems was an important issue to be discussed before their treatment for testicular cancer and during follow-up. The high frequency of any kind of long-lasting sexual problems (30%), though often of minor degree, warrants an adequate counselling of these patients before and after treatment.
PMCID: PMC1968446  PMID: 8494708
25.  Salvage treatment in male patients with germ cell tumours. 
British Journal of Cancer  1993;67(3):568-572.
The outcome of salvage treatment was reviewed in 55 patients relapsing during or after their primary chemotherapy for advanced malignant germ cell tumours. Fifty-two patients had been given cisplatin-based chemotherapy as their primary treatment, whereas three patients had received carboplatin-based chemotherapy. The median time to relapse was 2 months (range: 0-96 months) from discontinuation of the primary treatment. Two patients underwent radical surgery only, and one patient had radiotherapy to a brain metastasis as his only curatively intended salvage treatment. Six patients did not receive any treatment for their recurrent malignancy (refusal, terminal condition) except for purely palliative measures. The disease-free survival for the total group was 27% at 5 years. Complete response to primary treatment lasting for > or = 6 months was the only parameter which significantly predicted a favourable outcome (45% 5 year disease-free survival in 12 eligible patients).
PMCID: PMC1968255  PMID: 8382512

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