Rituximab, Gemcitabine, Cisplatin and Methylprednisolone (R-GEM-P) is an effective regimen in relapsed diffuse large B-cell lymphoma.

BACKGROUND: Patients with relapsed diffuse large B-cell lymphoma (DLBCL) have a poor prognosis. Gemcitabine, methylprednisolone, cisplatin +/- rituximab (GEM-P+/-R) is a salvage regimen with limited overlap in toxicity with first-line therapy and short duration of inpatient delivery. METHODS: We assessed the efficacy and safety of GEM-P+/-R in a retrospective single-centre analysis including patients meeting criteria of ≥ 18 yr of age, histologically proven DLBCL, treated between 2001 and 2011 in second-line with gemcitabine 1000 mg/m(2) day 1, 8 and 15, methylprednisolone 1000 mg day 1-5, cisplatin 100 mg/m(2) day 15 (replaced with carboplatin AUC5 if contraindication/toxicity) +/- rituximab 375 mg/m(2) day 1 and 15, every 28 d. RESULTS: Forty-five patients aged 25-74 received a median of three cycles of GEM-P+/-R; 64% received rituximab. In 44 evaluable patients receiving GEM-P+/-R, overall response rate (ORR) was 48%; in 28 evaluable patients treated with rituximab + GEM-P (R-GEM-P), ORR was 61%. With median follow-up of 50.5 months (95% CI: 28.3-72.7), 3-yr overall survival (OS) from start of GEM-P+/-R was 31.4% (95% CI: 16.5-46.3); in patients treated with R-GEM-P, 3-yr OS was 49.1% (95% CI: 28.7-69.5). Predominant grade ≥ 3 toxicities were haematological; thrombocytopenia 69%, neutropenia 60% and febrile neutropenia 7%. CONCLUSION: R-GEM-P is a deliverable regimen with useful activity in second-line treatment of DLBCL. Our data suggest that rituximab should be given concurrently.

GEM-P chemotherapy is active in the treatment of relapsed Hodgkin lymphoma.

Hodgkin lymphoma (HL) is a relatively chemosensitive malignancy. However, for those who relapse, high-dose chemotherapy with autologous stem cell transplant is the treatment of choice which relies on adequate disease control with salvage chemotherapy. Regimens commonly used often require inpatient administration and can be difficult to deliver due to toxicity. Gemcitabine and cisplatin have activity in HL, non-overlapping toxicity with first-line chemotherapeutics, and may be delivered in an outpatient setting. In this retrospective single-centre analysis, patients with relapsed or refractory HL treated with gemcitabine 1,000 mg/m(2) day (D)1, D8 and D15; methylprednisolone 1,000 mg D1-5; and cisplatin 100 mg/m(2) D15, every 28 days (GEM-P) were included. Demographic, survival, response and toxicity data were recorded. Forty-one eligible patients were identified: median age 27. One hundred and twenty-two cycles of GEM-P were administered in total (median 3 cycles; range 1-6). Twenty of 41 (48 %) patients received GEM-P as second-line treatment and 11/41 (27 %) as third-line therapy. Overall response rate (ORR) to GEM-P in the entire cohort was 80 % (complete response (CR) 37 %, partial response 44 %) with 14/15 CR confirmed as a metabolic CR on PET and ORR of 85 % in the 20 second-line patients. The most common grade 3/4 toxicities were haematological: neutropenia 54 % and thrombocytopenia 51 %. Median follow-up from the start of GEM-P was 4.5 years. Following GEM-P, 5-year progression-free survival was 46 % (95 % confidence interval (CI), 30-62 %) and 5-year overall survival was 59 % (95 % CI, 43-74 %). Fourteen of 41 patients proceeded directly to autologous transplant. GEM-P is a salvage chemotherapy with relatively high response rates, leading to successful transplantation in appropriate patients, in the treatment of relapsed or refractory HL.

Conventional versus hypofractionated high-dose intensity-modulated radiotherapy for prostate cancer: preliminary safety results from the CHHiP randomised controlled trial.

BACKGROUND: Prostate cancer might have high radiation-fraction sensitivity, implying a therapeutic advantage of hypofractionated treatment. We present a pre-planned preliminary safety analysis of side-effects in stages 1 and 2 of a randomised trial comparing standard and hypofractionated radiotherapy. METHODS: We did a multicentre, randomised study and recruited men with localised prostate cancer between Oct 18, 2002, and Aug 12, 2006, at 11 UK centres. Patients were randomly assigned in a 1:1:1 ratio to receive conventional or hypofractionated high-dose intensity-modulated radiotherapy, and all were given with 3-6 months of neoadjuvant androgen suppression. Computer-generated random permuted blocks were used, with risk of seminal vesicle involvement and radiotherapy-treatment centre as stratification factors. The conventional schedule was 37 fractions of 2 Gy to a total of 74 Gy. The two hypofractionated schedules involved 3 Gy treatments given in either 20 fractions to a total of 60 Gy, or 19 fractions to a total of 57 Gy. The primary endpoint was proportion of patients with grade 2 or worse toxicity at 2 years on the Radiation Therapy Oncology Group (RTOG) scale. The primary analysis included all patients who had received at least one fraction of radiotherapy and completed a 2 year assessment. Treatment allocation was not masked and clinicians were not blinded. Stage 3 of this trial completed the planned recruitment in June, 2011. This study is registered, number ISRCTN97182923. FINDINGS: 153 men recruited to stages 1 and 2 were randomly assigned to receive conventional treatment of 74 Gy, 153 to receive 60 Gy, and 151 to receive 57 Gy. With 50·5 months median follow-up (IQR 43·5-61·3), six (4·3%; 95% CI 1·6-9·2) of 138 men in the 74 Gy group had bowel toxicity of grade 2 or worse on the RTOG scale at 2 years, as did five (3·6%; 1·2-8·3) of 137 men in the 60 Gy group, and two (1·4%; 0·2-5·0) of 143 men in the 57 Gy group. For bladder toxicities, three (2·2%; 0·5-6·2) of 138 men, three (2·2%; 0·5-6·3) of 137, and none (0·0%; 97·5% CI 0·0-2·6) of 143 had scores of grade 2 or worse on the RTOG scale at 2 years. INTERPRETATION: Hypofractionated high-dose radiotherapy seems equally well tolerated as conventionally fractionated treatment at 2 years. FUNDING: Stage 1 was funded by the Academic Radiotherapy Unit, Cancer Research UK programme grant; stage 2 was funded by the Department of Health and Cancer Research UK.

A risk prediction algorithm based on family history and common genetic variants: application to prostate cancer with potential clinical impact.

Genome wide association studies have identified several single nucleotide polymorphisms (SNPs) that are independently associated with small increments in risk of prostate cancer, opening up the possibility for using such variants in risk prediction. Using segregation analysis of population-based samples of 4,390 families of prostate cancer patients from the UK and Australia, and assuming all familial aggregation has genetic causes, we previously found that the best model for the genetic susceptibility to prostate cancer was a mixed model of inheritance that included both a recessive major gene component and a polygenic component (P) that represents the effect of a large number of genetic variants each of small effect, where . Based on published studies of 26 SNPs that are currently known to be associated with prostate cancer, we have extended our model to incorporate these SNPs by decomposing the polygenic component into two parts: a polygenic component due to the known susceptibility SNPs, , and the residual polygenic component due to the postulated but as yet unknown genetic variants, . The resulting algorithm can be used for predicting the probability of developing prostate cancer in the future based on both SNP profiles and explicit family history information. This approach can be applied to other diseases for which population-based family data and established risk variants exist.

Patterns of care in the management of seminoma stage I: results from a European survey.

UNLABELLED: Study Type - Therapy (practise pattern survey). Level of Evidence 3b. What's known on the subject? and What does the study add? The uncertainties about differences in relapse and rates of other late events such as second malignancy and cardiovascular events for the three post-orchidectomy strategies in seminoma stage I patients has led to debates about whether the three strategies are equally effective and safe. The differences in interpretation of the data as well as the debates are likely to result in differences in treatment after orchidectomy in seminoma stage I patient management. Current care patterns after orchidectomy are, however, unknown. We assessed patterns of care for seminoma stage I patients after orchidectomy by distributing a survey among doctors treating such patients across Europe. The 969 respondents showed large differences in care strategies between specialties and countries that indicate the need for research into long-term relapse rates and long-term adverse effects to standardize and optimize care for seminoma stage I patients. OBJECTIVE: • To assess precise patterns of care after orchidectomy in Europe for stage I seminoma patients, we aimed to perform a survey among doctors in the various European countries. PATIENTS AND METHODS: • We distributed a survey in 2009 and 2010 among American Society of Clinical Oncology and European Association of Urology members. RESULTS: • In total, 969 questionnaires were included in the analysis. More than half of the 969 physicians (58%) currently offer only one post-surgical treatment: 18% only surveillance, 19% only radiotherapy and 21% only chemotherapy. Thirteen percent of the 969 physicians currently offer all three strategies, 25% offer surveillance and adjuvant radiotherapy or chemotherapy, and 5% offer either adjuvant radiotherapy or chemotherapy without surveillance. • We found large differences in care patterns between specialties and countries. Even within countries, care after orchidectomy was not standardized. • Before 2005, 73% of the physicians offered only one treatment and of those 51% gave adjuvant radiotherapy. CONCLUSIONS: • Large differences in pattern of care after orchidectomy for stage I seminoma patients exist between specialties and countries within Europe. • More information on long-term relapse rates and long-term adverse effects of the three strategies is needed to standardize and optimize care after orchidectomy.

Diethylstilbestrol in castration-resistant prostate cancer.

UNLABELLED: What's known on the subject? and What does the study add? Diethylstilbestrol (DES) was the first hormone treatment used for prostate cancer and has also shown effectiveness in castration-resistant disease in small studies; however, concerns over thromboembolic toxicity have restricted its use in the past. Over 200 elderly men with castration-resistant prostate cancer were treated with 1-3 mg of DES, given with 75 mg aspirin and breast bud irradiation. Almost 30% of men showed a significant PSA response and the median time to PSA progression was 4.6 months. Almost 20% of patients with pain had a significant analgesic benefit. The most important toxicity was thromboembolism in 10% of men. Overall the drug has an acceptable toxicity profile and offers a palliative benefit in frail elderly men who may not be fit for chemotherapy. OBJECTIVE: • To assess the efficacy and toxicity of diethylstilbestrol (DES) in the management of castration-resistant prostate cancer (CRPC). PATIENTS AND METHODS: • A total of 231 patients with CRPC received treatment with DES at the Royal Marsden Hospital between August 1992 and August 2000. • The median pre-treatment prostate-specific antigen (PSA) level was 221 ng/mL. • DES was used at a dose of 1-3 mg daily, with aspirin 75 mg. • The primary endpoint was PSA response rate. RESULTS: • The PSA response rate (using PSA Working Group criteria) was 28.9%. • The median time to PSA progression was 4.6 months. • Of patients with bone pain, 18% had an improvement in their European Organisation for the Research and Treatment of Cancer pain score. • Thromboembolic complications were seen in 9.9% of all patients. CONCLUSIONS: • DES has significant activity in CRPC and can be of palliative benefit. • DES has an acceptable toxicity profile in the management of patients with symptomatic CRPC when used at a dose of 1-3 mg, combined with aspirin and prophylactic breast bud radiotherapy.

Prostate cancer segregation analyses using 4390 families from UK and Australian population-based studies.

Familial aggregation of prostate cancer is likely to be due to multiple susceptibility loci, perhaps acting in conjunction with shared lifestyle risk factors. Models that assume a single mode of inheritance may be unrealistic. We analyzed genetic models of susceptibility to prostate cancer using segregation analysis of occurrence in families ascertained through population-based series totaling 4390 incident cases. We investigated major gene models (dominant, recessive, general, X-linked), polygenic models, and mixed models of susceptibility using the pedigree analysis software MENDEL. The hypergeometric model was used to approximate polygenic inheritance. The best-fitting model for the familial aggregation of prostate cancer was the mixed recessive model. The frequency of the susceptibility allele in the population was estimated to be 0.15 (95% confidence interval (CI) 0.11-0.20), with a relative risk for homozygote carriers of 94 (95% CI 46-192), and a polygenic standard deviation of 2.01 (95% CI 1.72-2.34). These analyses suggest that one or more genes having a strong recessively inherited effect on risk, as well as a number of genes with variants having small multiplicative effects on risk, may account for the genetic susceptibility to prostate cancer. The recessive component would predict the observed higher familial risk for siblings of cases than for fathers, but this could also be due to other factors such as shared lifestyle by siblings, targeted screening effects, and/or non-additive effects of one or more genes.

The diagnostic utility of the flare phenomenon on bone scintigraphy in staging prostate cancer.

PURPOSE: Bone scintigraphy (BS) lacks sensitivity for detecting very early skeletal metastases (SM) in prostate cancer (PC) and is often limited by poor specificity. Also scintigraphic flare of SM can occur following effective treatment and mislead an early response assessment. We hypothesised that a flare reaction might amplify the signal from subclinical SM, increasing the sensitivity of BS and that the phenomenon may be specific for metastases. METHODS: We conducted a prospective study to determine the frequency of the flare phenomenon in patients with metastatic PC starting hormone therapy and to explore its utility in patients with negative staging scans but considered at high risk of SM and in those with equivocal baseline BS abnormalities. Ninety-nine patients commencing first-line hormone therapy had repeat BS at 6 weeks to score a flare reaction. RESULTS: Of 22 patients with unequivocal SM on the baseline scan, a flare occurred in 9 (41%). Of 36 high-risk localised prostate cancer patients with normal BS pre-treatment, the scan became positive for metastases at 6 weeks in 4 (11%). Of 41 patients with pre-treatment scintigraphic abnormalities of uncertain aetiology, a flare occurred in 8 cases (20%). All eight were confirmed to have SM by follow-up and imaging. Of the 33 remaining patients without a flare, 2 developed SM at 14 months and the remainder did not develop SM in a median follow-up period of 36 months. CONCLUSION: The flare phenomenon following initial hormone therapy can be used to improve both sensitivity and specificity of BS in PC.

Serum micronutrient and antioxidant levels at baseline and the natural history of men with localised prostate cancer on active surveillance.

The aim of this study was to determine whether serum concentrations of micronutrients, antioxidants and vitamins predict rate of disease progression in untreated, localised prostate cancer. Patients with localised prostatic adenocarcinoma on a prospective study of active surveillance underwent monitoring with serial PSA levels and repeat prostate biopsies. Disease progression was defined as either adverse histology on repeat biopsy (primary Gleason grade >or=4 or >50% positive cores of total) or radical treatment for PSA velocity >1 ng ml(-1) year(-1). Time to disease progression was analysed with respect to baseline levels of alpha-tocopherol, gamma-tocopherol, alpha-carotene and beta-carotene, lycopene, retinol and selenium. One hundred four patients were evaluable, with a median follow-up of 2.5 years. Thirty-eight patients experienced disease progression, 13 biochemical and 25 histologic progression. Median time to disease progression was 2.62 years. No significant association was seen between time to disease progression and baseline serum levels of alpha-tocopherol (p = 0.86), gamma-tocopherol (p = 0.84), alpha-carotenoid (p = 0.66), beta-carotene (p = 0.65), lycopene (p = 0.0.15), retinol (p = 0.76) or selenium (p = 0.76). No significant association was seen between serum levels of the micronutrients, antioxidants or vitamins and either adverse histology on repeat biopsy or PSA velocity. Our data do not support the hypothesis that high serum concentrations of micronutrients, antioxidants and vitamins prevent disease progression in men with localised prostate cancer.

Prostate-specific antigen (PSA) kinetics in untreated, localized prostate cancer: PSA velocity vs PSA doubling time.

OBJECTIVES: To compare the accuracy of prostate-specific antigen (PSA) velocity (PSAV) vs PSA doubling time (DT) for predicting the repeat biopsy results in men with localized prostate cancer on active surveillance (AS), as the utility of PSAV vs PSADT in untreated prostate cancer has not been well studied. PATIENTS AND METHODS: Eligible patients had favourable-risk localized prostate cancer (T1/2a, PSA level or=4, >50% cores positive, or initial Gleason score 3 + 3 upgraded to >or=3 + 4. Using all PSA values for the 2 years preceding repeat biopsy, the PSAV and PSADT were calculated using linear regression and the log-slope method (DT = ln2/slope), respectively. RESULTS: In all, 199 patients were assessable; the median PSAV and PSADT were 0.71 ng/mL/year and 5.29 years, respectively. Fifty-three patients (27%) had adverse histology on repeat biopsy. On univariate analyses, PSAV (P < 0.001) and PSADT (P = 0.019) were associated with adverse histology. The area under the receiver operating characteristic curve for predicting adverse histology was 0.70 and 0.63 for PSAV and PSADT, respectively. The mean difference was 0.07 (95% confidence interval 0.03-0.12; P < 0.001). CONCLUSIONS: PSAV is more accurate than PSADT for predicting adverse histology on repeat biopsies. These data suggest that PSAV should be used in preference to PSADT to describe PSA kinetics in untreated, localized prostate cancer.

Identification of new genetic risk factors for prostate cancer.

There is evidence that a substantial part of genetic predisposition to prostate cancer (PCa) may be due to lower penetrance genes which are found by genome-wide association studies. We have recently conducted such a study and seven new regions of the genome linked to PCa risk have been identified. Three of these loci contain candidate susceptibility genes: MSMB, LMTK2 and KLK2/3. The MSMB and KLK2/3 genes may be useful for PCa screening, and the LMTK2 gene might provide a potential therapeutic target. Together with results from other groups, there are now 23 germline genetic variants which have been reported. These results have the potential to be developed into a genetic test. However, we consider that marketing of tests to the public is premature, as PCa risk can not be evaluated fully at this stage and the appropriate screening protocols need to be developed. Follow-up validation studies, as well as studies to explore the psychological implications of genetic profile testing, will be vital prior to roll out into healthcare.

Intrinsic markers of tumour hypoxia and angiogenesis in localised prostate cancer and outcome of radical treatment: a retrospective analysis of two randomised radiotherapy trials and one surgical cohort study.

BACKGROUND: Expression of intrinsic markers of tumour hypoxia and angiogenesis are important predictors of radiotherapeutic, and possibly surgical, outcome in several cancers. Extent of tumour hypoxia in localised prostate cancer is comparable to that in other cancers, but few data exist on the association of extent of tumour hypoxia with treatment outcome. We aimed to study the predictive value of intrinsic markers of tumour hypoxia and angiogenesis in localised prostate cancer, both in patients treated with radiotherapy and in those treated surgically. METHODS: We applied a new, needle biopsy tissue microarray (TMA) technique to study diagnostic samples from men with localised, previously untreated prostate cancer treated in two randomised controlled trials of radiotherapy-dose escalation. Multivariate analysis by Cox proportional hazards was done to assess the association between clinical outcome, in terms of biochemical control, and immunohistochemical staining of hypoxia inducible factor-1 alpha (HIF-1 alpha), vascular endothelial growth factor (VEGF), and osteopontin expression. The analysis was repeated on an independent series of men with localised, previously untreated prostate cancer treated by radical prostatectomy. The main outcome was time to biochemical (ie, prostate-specific antigen [PSA]) failure. FINDINGS: Between Oct 12, 1995, and Feb 5, 2002, 308 patients were identified from two prospective, randomised trials at the Royal Marsden Hospital, London and Sutton, UK, for the radiotherapy cohort and diagnostic biopsies were available for 201 of these patients. Between June 6, 1995, and Nov 4, 2005, 329 patients were identified from the Aarhus University Hospital, Skejby, Denmark, for the prostatectomy cohort; of these, 40 patients were excluded because the tumour was too small to sample (19 patients), because the paraffin block was too thin (19 patients), or because the blocks were missing (two patients), leaving 289 patients for analysis. For patients treated with radiotherapy, increased staining for VEGF (p=0.008) and HIF-1 alpha (p=0.02) expression, but not increased osteopontin expression (p=0.978), were significant predictors of a shorter time to biochemical failure on multivariate analysis, independent of clinical tumour stage, Gleason score, serum PSA concentration, and dose of radiotherapy. For patients treated with surgery, increased staining for VEGF (p<0.0001) and HIF-1 alpha (p<0.0001) expression, and increased osteopontin expression (p=0.0005) were each significantly associated with a shorter time to biochemical failure on multivariate analysis, independent of pathological tumour stage, Gleason score, serum PSA concentration, and margin status. INTERPRETATION: To our knowledge, this is the largest study of intrinsic markers of hypoxia and angiogenesis in relation to the outcome of radical treatment of localised prostate cancer. Increased expression of VEGF, HIF-1 alpha, and, for patients treated with surgery, osteopontin, identifies patients at high risk of biochemical failure who would be suitable for enrolment into trials of treatment intensification.

Efficacy of low-dose dexamethasone in castration-refractory prostate cancer.

OBJECTIVE: To evaluate the prostate-specific antigen (PSA) response rate and duration of PSA response to dexamethasone in patients with castration-refractory prostate cancer (CRPC), as corticosteroids are frequently used as second-line hormonal treatment of CRPC and there is little published evidence concerning the efficacy of low-dose dexamethasone in this setting. PATIENTS AND METHODS: In all, 102 patients with progressive CRPC received oral dexamethasone (0.5 mg daily) between January 2003 and October 2006. The median pretreatment PSA level was 83 ng/mL. The main endpoint was the PSA response rate according to the PSA Working Group criteria. RESULTS: In all, 50 patients (49%) had a confirmed PSA response. The median (range) time to PSA progression for the entire cohort was 7.4 (1-28) months. In responders, the median duration of the PSA response was 11.6 (1-24) months. CONCLUSION: Low-dose dexamethasone has significant activity in CRPC. Subject to validation with more clinically meaningful endpoints, dexamethasone could become the corticosteroid of choice in the management of CRPC, and its potential for use in combination with novel agents should be explored.

Prostate-specific antigen velocity in untreated, localized prostate cancer.

OBJECTIVE: To report the results of a prospective study of active surveillance of untreated prostate cancer, with a focus on baseline predictors of prostate-specific antigen (PSA) velocity, as PSA velocity before treatment is an important predictor of prostate cancer mortality, and patients on active surveillance are monitored for several years to estimate the PSA velocity and thus select patients for radical treatment. PATIENTS AND METHODS: A prospective study of active surveillance for localized prostate cancer opened at the Royal Marsden Hospital in 2002. Eligible patients had clinical stage T1/T2a, N0/Nx, M0/Mx adenocarcinoma of the prostate with a serum PSA level of < 15 ng/mL, a Gleason score of < or = 7 with primary grade < or = 3, and less than half the biopsy cores positive. The PSA velocity before treatment was analysed in relation to baseline clinical characteristics. RESULTS: In all, 237 patients on surveillance were followed for a median of 24 months (median age 67 years; median initial PSA level 6.5 ng/mL; median pretreatment PSA velocity 0.44 ng/mL per year). On multivariate analysis, PSA density (i.e. serum PSA level/prostate volume) was the only significant determinant of PSA velocity (P < 0.001). Patients with a PSA density above or below the median (0.185 ng/mL/mL) had a median (interquartile range) PSA velocity of 0.92 (0.34-1.77) ng/mL per year and 0.35 (-0.06, 0.80) ng/mL per year, respectively. CONCLUSIONS: PSA density, which is readily available at the time of diagnosis, is an independent determinant of PSA velocity in untreated, localized prostate cancer. If this is confirmed, PSA density could be used to inform the often difficult choice between active surveillance and immediate radical treatment.

Efficacy of palliative low-dose involved-field radiation therapy in advanced lymphoma: a phase II study.

PURPOSE: To confirm the efficacy of low-dose involved-field radiation therapy (LD-IFRT) as palliative treatment in patients symptomatic from advanced lymphoma. PATIENTS AND METHODS: A total of 36 patients (47 sites), received 4 Gy in 2 fractions to the lymphoma with a 1.5-2-cm margin. Pathology subtypes included 29 (62%) sites with indolent lymphoma and 18 (36%) sites with aggressive lymphoma histology. Bulky disease was seen in 22 (48%) sites and, of these, 6 sites had disease > 10 cm. A median of 3 previous chemotherapy regimens (range, 0 to 9 regimens) preceded LD-IFRT. The primary endpoint of the study was in-field lymphoma control. Patients completed the European Organization for the Research and Treatment of Cancer QLQ-C30 quality of life (QOL) questionnaire before RT and at 3-4 weeks after treatment. RESULTS: The overall response rate (RR) at 1-3 months after the RT was 75%. A complete remission (CR) was observed in 13 patients (36%) lasting up to a maximum of 31.3 months and ongoing at analysis. A partial remission (PR) was achieved in 14 patients (39%) lasting up to 10 months. The response rate for non-diffuse large B-cell lymphoma (DLBCL) sites was 86%, while it was 50% for sites with DLBCL histology. Median time to local progression for the entire group was 15 months. There was no statistical difference between the QOL before and after LD-IFRT. CONCLUSION: LD-IFRT is an effective and easy treatment for patients with advanced lymphoma that can be repeated at previously irradiated sites, a particularly useful attribute because of the relapsing nature, especially of advanced follicular subtypes.

Clinical implications of introducing a new PSA assay.

BACKGROUND: A number of different prostate-specific antigen (PSA) assays are in common use. There has been little consideration of the possible clinical implications of interassay variation. The availability of two assays in the same laboratory provided an opportunity to audit the clinical implications of the interassay variation in PSA levels. METHODS: The same serum samples from patients with prostate cancer on follow-up were analyzed for PSA by the Abbott AxSYM assay and by the Abbott ARCHITECT assays. To assess within-patient reproducibility of the interassay variation, repeat analysis of PSA by both assays was conducted in a second sample obtained at least 1 month after the first. RESULTS: Samples from 156 cases were analyzed. The mean ratio of serum PSA values by the two assays (AxSYM assay/ARCHITECT assay) was 0.89 (range 0.5-2.27). The interassay coefficient of variation was 20%. In a subgroup of 50 cases with repeat samples available, the correlation coefficient, r, of the interassay variation in PSA between the first and second samples was 0.441. CONCLUSIONS: Interassay variation in serum PSA is clinically significant, both between patients and on repeated measurement within the same patient. Clinicians should be aware that simple correction factors may not accurately control for variation between PSA assays. Ideally, patients on follow-up for prostate cancer should be monitored using a single PSA assay.

Testicular germ-cell cancer.

Testicular germ-cell tumours (TGCTs) represent the model of a curable malignancy; sensitive tumour markers, accurate prognostic classification, logical series of management trials, and high cure rates in both seminomas and non-seminomas have enabled a framework of effective cancer therapy. Understanding the molecular biology of TGCT could help improve treatment of other cancers. The typical presentation in young adults means that issues of long-term toxicity become especially important in judging appropriate management. A focus of recent developments has been to tailor aggressiveness of treatment to the severity of the prognosis. Recent changes affect the most common subtypes and include the reduction of chemotherapy for patients who have metastastic non-seminomas and a good prognosis, and alternatives to adjuvant radiotherapy in stage I seminomas. We summarise advances in the understanding and management of TGCT during the past decade.

Assessing intra-fractional bladder motion using cine-MRI as initial methodology for Predictive Organ Localization (POLO) in radiotherapy for bladder cancer.

AIM: To assess the feasibility of using cine-MR to study intra-fractional time-volume and volume-deformity patterns of the bladder during radiotherapy as initial methodology for Predictive Organ Localization (POLO). METHODS: Nine patients receiving radiotherapy for localized muscle invasive bladder cancer were prospectively studied. Each had an MR scan performed on an empty bladder using a T1 weighted cine sequence over a period of 20 min. Scans were taken prior to, and repeated towards the end of, radiotherapy treatment. Time-volume sequences were determined and compared before and during radiotherapy. Absolute bladder volumes were then correlated with changes in bladder wall position. RESULTS: The mean post void residual bladder volume prior to radiotherapy at time 0 was 113 cm(3) [SD 53] and this did not differ significantly during radiotherapy -106 cm [SD 40] (p=0.24, paired t-test analysis). A linear relationship was observed for the rate bladder filling over a 20 min period, which did not significantly change on the cine-MR during radiotherapy (regression coefficient 2.1 vs 1.6, respectively, p=0.51). Significant positive relationships were seen between volume and anterior (p=0.02), superior (p<0.001), and inferior (p=0.03) wall motion. These relationships were complex, though linearity was observed for volumes up to 150 cm(3). The 1.5 cm CTV-PTV margin was sufficient to account for expansion in the majority of cases with the only breach occurring on the anterior wall in one patient. CONCLUSIONS: This study confirms the feasibility of using cine-MR for POLO. The development of such predictive methodology may compensate for the need to use an isotropic CTV-PTV margin to simply cover bladder filling when using image-guided radiotherapy.