Developing and validating a simple urethra surrogate model to facilitate dosimetric analysis to predict genitourinary toxicity.

Purpose: The urethra is a critical structure in prostate radiotherapy planning; however, it is impossible to visualise on CT. We developed a surrogate urethra model (SUM) for CT-only planning workflow and tested its geometric and dosimetric performance against the MRI-delineated urethra (MDU). Methods: The SUM was compared against 34 different MDUs (within the treatment PTV) in patients treated with 36.25Gy (PTV)/40Gy (CTV) in 5 fractions as part of the PACE-B trial. To assess the surrogate's geometric performance, the Dice similarity coefficient (DSC), Hausdorff distance (HD), mean distance to agreement (MDTA) and the percentage of MDU outside the surrogate (UOS) were calculated. To evaluate the dosimetric performance, a paired t-test was used to calculate the mean of differences between the MDU and SUM for the D99, D98, D50, D2 and D1. The D(n) is the dose (Gy) to n% of the urethra. Results: The median results showed low agreement on DSC (0.32; IQR 0.21-0.41), but low distance to agreement, as would be expected for a small structure (HD 8.4mm (IQR 7.1-10.1mm), MDTA 2.4mm (IQR, 2.2mm-3.2mm)). The UOS was 30% (IQR, 18-54%), indicating nearly a third of the urethra lay outside of the surrogate. However, when comparing urethral dose between the MDU and SUM, the mean of differences for D99, D98 and D95 were 0.12Gy (p=0.57), 0.09Gy (p=0.61), and 0.11Gy (p=0.46) respectively. The mean of differences between the D50, D2 and D1 were 0.08Gy (p=0.04), 0.09Gy (p=0.02) and 0.1Gy (p=0.01) respectively, indicating good dosimetric agreement between MDU and SUM. Conclusion: While there were geometric differences between the MDU and SUM, there was no clinically significant difference between urethral dose-volume parameters. This surrogate model could be validated in a larger cohort and then used to estimate the urethral dose on CT planning scans in those without an MRI planning scan or urinary catheter.

Intensity-modulated radiotherapy versus stereotactic body radiotherapy for prostate cancer (PACE-B): 2-year toxicity results from an open-label, randomised, phase 3, non-inferiority trial.

BACKGROUND: Localised prostate cancer is commonly treated with external beam radiotherapy and moderate hypofractionation is non-inferior to longer schedules. Stereotactic body radiotherapy (SBRT) allows shorter treatment courses without impacting acute toxicity. We report 2-year toxicity findings from PACE-B, a randomised trial of conventionally fractionated or moderately hypofractionated radiotherapy versus SBRT. METHODS: PACE is an open-label, multicohort, randomised, controlled, phase 3 trial conducted at 35 hospitals in the UK, Ireland, and Canada. In PACE-B, men aged 18 years and older with a WHO performance status 0-2 and low-risk or intermediate-risk histologically-confirmed prostate adenocarcinoma (Gleason 4 + 3 excluded) were randomly allocated (1:1) by computerised central randomisation with permuted blocks (size four and six), stratified by centre and risk group to control radiotherapy (CRT; 78 Gy in 39 fractions over 7·8 weeks or, following protocol amendment on March 24, 2016, 62 Gy in 20 fractions over 4 weeks) or SBRT (36·25 Gy in five fractions over 1-2 weeks). Androgen deprivation was not permitted. Co-primary outcomes for this toxicity analysis were Radiation Therapy Oncology Group (RTOG) grade 2 or worse gastrointestinal and genitourinary toxicity at 24 months after radiotherapy. Analysis was by treatment received and included all patients with at least one fraction of study treatment assessed for late toxicity. Recruitment is complete. Follow-up for oncological outcomes continues. The trial is registered with ClinicalTrials.gov, NCT01584258. FINDINGS: We enrolled and randomly assigned 874 men between Aug 7, 2012, and Jan 4, 2018 (441 to CRT and 433 to SBRT). In this analysis, 430 patients were analysed in the CRT group and 414 in the SBRT group; a total of 844 (97%) of 874 randomly assigned patients. At 24 months, RTOG grade 2 or worse genitourinary toxicity was seen in eight (2%) of 381 participants assigned to CRT and 13 (3%) of 384 participants assigned to SBRT (absolute difference 1·3% [95% CI -1·3 to 4·0]; p=0·39); RTOG grade 2 or worse gastrointestinal toxicity was seen in 11 (3%) of 382 participants in the CRT group versus six (2%) of 384 participants in the SBRT group (absolute difference -1·3% [95% CI -3·9 to 1·1]; p=0·32). No serious adverse events (defined as RTOG grade 4 or worse) or treatment-related deaths were reported within the analysis timeframe. INTERPRETATION: In the PACE-B trial, 2-year RTOG toxicity rates were similar for five fraction SBRT and conventional schedules of radiotherapy. Prostate SBRT was found to be safe and associated with low rates of side-effects. Biochemical outcomes are awaited. FUNDING: Accuray.

Neoadjuvant Trastuzumab and Pertuzumab for Early HER2-Positive Breast Cancer: A Real World Experience.

Background: Randomized studies of neoadjuvant (NA) trastuzumab and pertuzumab combined with chemotherapy for HER2-positive breast cancers (BC) have reported pathological complete response (pCR) rates of 39 to 61%. This study aimed to determine the real-world efficacy and toxicity of NA trastuzumab and pertuzumab combined with chemotherapy in a UK tertiary referral cancer centre. Methods: HER2-positive early BC patients given neoadjuvant chemotherapy with trastuzumab and pertuzumab between October 2016 and February 2018 at our tertiary referral cancer centre were identified via pharmacy records. Clinico-pathological information, treatment regimens, treatment-emergent toxicities, operative details, and pathological responses and outcomes were recorded. Results: 78 female patients were identified; 2 had bilateral diseases and 48 of 78 (62%) were node positive at presentation. 55 of 80 (71%) tumours were ER-positive. PCR occurred in 37 of 78 (46.3%; 95% CI: 35.3-57.2%) patients. 14 of 23 (60.8%) patients with ER-negative tumours achieved pCR; 23 of 55 (41.8%) were ER-positive and 6 of 19 (31.6%) were ER-positive and PgR-positive. No cardiac toxicity was documented. Diarrhoea occurred in 53 of 72 (74%) patients. Grade 3-4 toxicity occurred in ≥2% patients. These were diarrhoea, fatigue, and infection. The Median follow up period was 45.2 months (95% CI 43.8-46.3) with 71 of 78 (91.0%) remaining disease-free and 72 of 78 (92.3%) alive. Estimated OS at 2 years 86% (95% CI: 75-99%). Conclusion: This data confirms the efficacy of neoadjuvant chemotherapy combined with dual HER2 directed therapy. While no cardiac toxicity was observed, diarrhoea occurred frequently. The low pCR rate observed in ER and PgR-positive BCs warrants further investigation and consideration of strategies to increase the pCR rate.

Docetaxel for Nonmetastatic Prostate Cancer: Long-Term Survival Outcomes in the STAMPEDE Randomized Controlled Trial.

BACKGROUND: STAMPEDE previously reported adding upfront docetaxel improved overall survival for prostate cancer patients starting long-term androgen deprivation therapy. We report long-term results for non-metastatic patients using, as primary outcome, metastatic progression-free survival (mPFS), an externally demonstrated surrogate for overall survival. METHODS: Standard of care (SOC) was androgen deprivation therapy with or without radical prostate radiotherapy. A total of 460 SOC and 230 SOC plus docetaxel were randomly assigned 2:1. Standard survival methods and intention to treat were used. Treatment effect estimates were summarized from adjusted Cox regression models, switching to restricted mean survival time if non-proportional hazards. mPFS (new metastases, skeletal-related events, or prostate cancer death) had 70% power (α = 0.05) for a hazard ratio (HR) of 0.70. Secondary outcome measures included overall survival, failure-free survival (FFS), and progression-free survival (PFS: mPFS, locoregional progression). RESULTS: Median follow-up was 6.5 years with 142 mPFS events on SOC (3 year and 54% increases over previous report). There was no good evidence of an advantage to SOC plus docetaxel on mPFS (HR = 0.89, 95% confidence interval [CI] = 0.66 to 1.19; P = .43); with 5-year mPFS 82% (95% CI = 78% to 87%) SOC plus docetaxel vs 77% (95% CI = 73% to 81%) SOC. Secondary outcomes showed evidence SOC plus docetaxel improved FFS (HR = 0.70, 95% CI = 0.55 to 0.88; P = .002) and PFS (nonproportional P = .03, restricted mean survival time difference = 5.8 months, 95% CI = 0.5 to 11.2; P = .03) but no good evidence of overall survival benefit (125 SOC deaths; HR = 0.88, 95% CI = 0.64 to 1.21; P = .44). There was no evidence SOC plus docetaxel increased late toxicity: post 1 year, 29% SOC and 30% SOC plus docetaxel grade 3-5 toxicity. CONCLUSIONS: There is robust evidence that SOC plus docetaxel improved FFS and PFS (previously shown to increase quality-adjusted life-years), without excess late toxicity, which did not translate into benefit for longer-term outcomes. This may influence patient management in individual cases.

Quality of Life in Men With Prostate Cancer Randomly Allocated to Receive Docetaxel or Abiraterone in the STAMPEDE Trial.

PURPOSE: Docetaxel and abiraterone acetate plus prednisone or prednisolone (AAP) both improve survival when commenced alongside standard of care (SOC) androgen deprivation therapy in locally advanced or metastatic hormone-sensitive prostate cancer. Thus, patient-reported quality of life (QOL) data may guide treatment choices. METHODS: A group of patients within the STAMPEDE trial were contemporaneously enrolled with the possibility of being randomly allocated to receive either docetaxel + SOC or AAP + SOC. A mixed-model assessed QOL in those who had completed at least one QLQ-C30 + PR25 questionnaire. The primary outcome measure was difference in global-QOL (QLQ-C30 Q29&30) between patients allocated to docetaxel + SOC or AAP + SOC over the 2 years after random assignment, with a predefined criterion for clinically meaningful difference of > 4.0 points. Secondary outcome measures included longitudinal comparison of functional domains, pain, and fatigue, plus global-QOL at defined timepoints. RESULTS: Five hundred fifteen patients (173 docetaxel + SOC and 342 AAP + SOC) were included. Baseline characteristics, proportion of missing data, and mean baseline global-QOL scores (docetaxel + SOC 77.8 and AAP + SOC 78.0) were similar. Over the 2 years following random assignment, the mean modeled global-QOL score was +3.9 points (95% CI, +0.5 to +7.2; P = .022) higher in patients allocated to AAP + SOC. Global-QOL was higher for patients allocated to AAP + SOC over the first year (+5.7 points, 95% CI, +3.0 to +8.5; P < .001), particularly at 12 (+7.0 points, 95% CI, +3.0 to +11.0; P = .001) and 24 weeks (+8.3 points, 95% CI, +4.0 to +12.6; P < .001). CONCLUSION: Patient-reported QOL was superior for patients allocated to receive AAP + SOC, compared with docetaxel + SOC over a 2-year period, narrowly missing the predefined value for clinical significance. Patients receiving AAP + SOC reported clinically meaningful higher global-QOL scores throughout the first year following random assignment.

Intensity-modulated fractionated radiotherapy versus stereotactic body radiotherapy for prostate cancer (PACE-B): acute toxicity findings from an international, randomised, open-label, phase 3, non-inferiority trial.

BACKGROUND: Localised prostate cancer is commonly treated with external-beam radiotherapy. Moderate hypofractionation has been shown to be non-inferior to conventional fractionation. Ultra-hypofractionated stereotactic body radiotherapy would allow shorter treatment courses but could increase acute toxicity compared with conventionally fractionated or moderately hypofractionated radiotherapy. We report the acute toxicity findings from a randomised trial of standard-of-care conventionally fractionated or moderately hypofractionated radiotherapy versus five-fraction stereotactic body radiotherapy for low-risk to intermediate-risk localised prostate cancer. METHODS: PACE is an international, phase 3, open-label, randomised, non-inferiority trial. In PACE-B, eligible men aged 18 years and older, with WHO performance status 0-2, low-risk or intermediate-risk prostate adenocarcinoma (Gleason 4 + 3 excluded), and scheduled to receive radiotherapy were recruited from 37 centres in three countries (UK, Ireland, and Canada). Participants were randomly allocated (1:1) by computerised central randomisation with permuted blocks (size four and six), stratified by centre and risk group, to conventionally fractionated or moderately hypofractionated radiotherapy (78 Gy in 39 fractions over 7·8 weeks or 62 Gy in 20 fractions over 4 weeks, respectively) or stereotactic body radiotherapy (36·25 Gy in five fractions over 1-2 weeks). Neither participants nor investigators were masked to allocation. Androgen deprivation was not permitted. The primary endpoint of PACE-B is freedom from biochemical or clinical failure. The coprimary outcomes for this acute toxicity substudy were worst grade 2 or more severe Radiation Therapy Oncology Group (RTOG) gastrointestinal or genitourinary toxic effects score up to 12 weeks after radiotherapy. Analysis was per protocol. This study is registered with ClinicalTrials.gov, NCT01584258. PACE-B recruitment is complete and follow-up is ongoing. FINDINGS: Between Aug 7, 2012, and Jan 4, 2018, we randomly assigned 874 men to conventionally fractionated or moderately hypofractionated radiotherapy (n=441) or stereotactic body radiotherapy (n=433). 432 (98%) of 441 patients allocated to conventionally fractionated or moderately hypofractionated radiotherapy and 415 (96%) of 433 patients allocated to stereotactic body radiotherapy received at least one fraction of allocated treatment. Worst acute RTOG gastrointestinal toxic effect proportions were as follows: grade 2 or more severe toxic events in 53 (12%) of 432 patients in the conventionally fractionated or moderately hypofractionated radiotherapy group versus 43 (10%) of 415 patients in the stereotactic body radiotherapy group (difference -1·9 percentage points, 95% CI -6·2 to 2·4; p=0·38). Worst acute RTOG genitourinary toxicity proportions were as follows: grade 2 or worse toxicity in 118 (27%) of 432 patients in the conventionally fractionated or moderately hypofractionated radiotherapy group versus 96 (23%) of 415 patients in the stereotactic body radiotherapy group (difference -4·2 percentage points, 95% CI -10·0 to 1·7; p=0·16). No treatment-related deaths occurred. INTERPRETATION: Previous evidence (from the HYPO-RT-PC trial) suggested higher patient-reported toxicity with ultrahypofractionation. By contrast, our results suggest that substantially shortening treatment courses with stereotactic body radiotherapy does not increase either gastrointestinal or genitourinary acute toxicity. FUNDING: Accuray and National Institute of Health Research.

Addition of Docetaxel to First-line Long-term Hormone Therapy in Prostate Cancer (STAMPEDE): Modelling to Estimate Long-term Survival, Quality-adjusted Survival, and Cost-effectiveness.

BACKGROUND: Results from large randomised controlled trials have shown that adding docetaxel to the standard of care (SOC) for men initiating hormone therapy for prostate cancer (PC) prolongs survival for those with metastatic disease and prolongs failure-free survival for those without. To date there has been no formal assessment of whether funding docetaxel in this setting represents an appropriate use of UK National Health Service (NHS) resources. OBJECTIVE: To assess whether administering docetaxel to men with PC starting long-term hormone therapy is cost-effective in a UK setting. DESIGN, SETTING, AND PARTICIPANTS: We modelled health outcomes and costs in the UK NHS using data collected within the STAMPEDE trial, which enrolled men with high-risk, locally advanced metastatic or recurrent PC starting first-line hormone therapy. INTERVENTION: SOC was hormone therapy for ≥2 yr and radiotherapy in some patients. Docetaxel (75mg/m2) was administered alongside SOC for six three-weekly cycles. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The model generated lifetime predictions of costs, changes in survival duration, quality-adjusted life years (QALYs), and incremental cost-effectiveness ratios (ICERs). RESULTS AND LIMITATIONS: The model predicted that docetaxel would extend survival (discounted quality-adjusted survival) by 0.89 yr (0.51) for metastatic PC and 0.78 yr (0.39) for nonmetastatic PC, and would be cost-effective in metastatic PC (ICER £5514/QALY vs SOC) and nonmetastatic PC (higher QALYs, lower costs vs SOC). Docetaxel remained cost-effective in nonmetastatic PC when the assumption of no survival advantage was modelled. CONCLUSIONS: Docetaxel is cost-effective among patients with nonmetastatic and metastatic PC in a UK setting. Clinicians should consider whether the evidence is now sufficiently compelling to support docetaxel use in patients with nonmetastatic PC, as the opportunity to offer docetaxel at hormone therapy initiation will be missed for some patients by the time more mature survival data are available. PATIENT SUMMARY: Starting docetaxel chemotherapy alongside hormone therapy represents a good use of UK National Health Service resources for patients with prostate cancer that is high risk or has spread to other parts of the body.

Addition of docetaxel, zoledronic acid, or both to first-line long-term hormone therapy in prostate cancer (STAMPEDE): survival results from an adaptive, multiarm, multistage, platform randomised controlled trial.

BACKGROUND: Long-term hormone therapy has been the standard of care for advanced prostate cancer since the 1940s. STAMPEDE is a randomised controlled trial using a multiarm, multistage platform design. It recruits men with high-risk, locally advanced, metastatic or recurrent prostate cancer who are starting first-line long-term hormone therapy. We report primary survival results for three research comparisons testing the addition of zoledronic acid, docetaxel, or their combination to standard of care versus standard of care alone. METHODS: Standard of care was hormone therapy for at least 2 years; radiotherapy was encouraged for men with N0M0 disease to November, 2011, then mandated; radiotherapy was optional for men with node-positive non-metastatic (N+M0) disease. Stratified randomisation (via minimisation) allocated men 2:1:1:1 to standard of care only (SOC-only; control), standard of care plus zoledronic acid (SOC + ZA), standard of care plus docetaxel (SOC + Doc), or standard of care with both zoledronic acid and docetaxel (SOC + ZA + Doc). Zoledronic acid (4 mg) was given for six 3-weekly cycles, then 4-weekly until 2 years, and docetaxel (75 mg/m(2)) for six 3-weekly cycles with prednisolone 10 mg daily. There was no blinding to treatment allocation. The primary outcome measure was overall survival. Pairwise comparisons of research versus control had 90% power at 2·5% one-sided α for hazard ratio (HR) 0·75, requiring roughly 400 control arm deaths. Statistical analyses were undertaken with standard log-rank-type methods for time-to-event data, with hazard ratios (HRs) and 95% CIs derived from adjusted Cox models. This trial is registered at ClinicalTrials.gov (NCT00268476) and ControlledTrials.com (ISRCTN78818544). FINDINGS: 2962 men were randomly assigned to four groups between Oct 5, 2005, and March 31, 2013. Median age was 65 years (IQR 60-71). 1817 (61%) men had M+ disease, 448 (15%) had N+/X M0, and 697 (24%) had N0M0. 165 (6%) men were previously treated with local therapy, and median prostate-specific antigen was 65 ng/mL (IQR 23-184). Median follow-up was 43 months (IQR 30-60). There were 415 deaths in the control group (347 [84%] prostate cancer). Median overall survival was 71 months (IQR 32 to not reached) for SOC-only, not reached (32 to not reached) for SOC + ZA (HR 0·94, 95% CI 0·79-1·11; p=0·450), 81 months (41 to not reached) for SOC + Doc (0·78, 0·66-0·93; p=0·006), and 76 months (39 to not reached) for SOC + ZA + Doc (0·82, 0·69-0·97; p=0·022). There was no evidence of heterogeneity in treatment effect (for any of the treatments) across prespecified subsets. Grade 3-5 adverse events were reported for 399 (32%) patients receiving SOC, 197 (32%) receiving SOC + ZA, 288 (52%) receiving SOC + Doc, and 269 (52%) receiving SOC + ZA + Doc. INTERPRETATION: Zoledronic acid showed no evidence of survival improvement and should not be part of standard of care for this population. Docetaxel chemotherapy, given at the time of long-term hormone therapy initiation, showed evidence of improved survival accompanied by an increase in adverse events. Docetaxel treatment should become part of standard of care for adequately fit men commencing long-term hormone therapy. FUNDING: Cancer Research UK, Medical Research Council, Novartis, Sanofi-Aventis, Pfizer, Janssen, Astellas, NIHR Clinical Research Network, Swiss Group for Clinical Cancer Research.

Utility of serum tumor markers during surveillance for stage I seminoma.

BACKGROUND: The serum tumor markers α-fetoprotein (AFP), ß-human chorionic gonadotropin (HCG), and lactate dehydrogenase (LDH) are often measured as part of surveillance protocols in patients with stage I seminoma. In this study, the authors evaluated the utility of routine measurement of these markers in the detection of disease relapse. METHODS: Data were gathered from a prospectively maintained database of patients who underwent surveillance for stage I testicular seminoma diagnosed between 1982 and 2005 at Princess Margaret Hospital. Patients were followed on a predefined schedule with physical examination (PE), serum tumor markers, abdominopelvic computed tomography, and chest x-rays. The records of patients who relapsed were examined for details of imaging and serum tumor markers throughout the period of follow-up until the time of relapse. RESULTS: Of the 527 patients who were managed by surveillance, 75 patients (14%) relapsed at a median follow-up of 72 months. Of these, 65 patients relapsed within the first 3 years and had routine serum tumor markers measured. In total, 11 patients had abnormal tumor markers at the time of relapse (AFP, 0 patients; HCG, 6 patients; LDH, 4 patients; and HCG and LDH, 1 patient). Only 1 patient had an elevated tumor marker (LDH) before relapse, as defined by an abnormal imaging study (n = 64) or physical examination (n = 1), for which the treatment and outcome were not affected. CONCLUSIONS: Serum tumor marker levels did not aid in the early diagnosis of disease relapse in patients with stage I seminoma who were managed with surveillance. The current results indicated that routine measurement of serum tumor markers can be discontinued safely in seminoma surveillance schedules.

Patient-specific PTV margins in radiotherapy for bladder cancer - a feasibility study using cone beam CT.

PURPOSE: To assess the feasibility of using cone beam computed tomography (CBCT) to generate patient-specific PTV margins for bladder cancer patients treated with radiation therapy (RT). METHODS: Eleven patients underwent CT simulation and daily RT (full bladder and empty rectum). CBCT was done prior to each fraction, and the whole bladder was contoured off-line. For the first 15 CBCTs of each patient, the bladder was aligned with CT-simulation bladder (pBladder) to create an occupancy volume (OV). A 5mm isotropic margin was added to OV (OV+5). A measurement-based PTV (mPTV) was generated by measuring maximal displacement between pBladder and OV in six directions. OV, OV+5, mPTV, and a standard PTV (2cm isotropic margin) were compared for absolute and relative volume differences. Using the final 10 CBCT of each patient, the ability of each study volume to encompass the entire CBCT bladder was determined. RESULTS: 161/165 CBCT images were of adequate quality for contouring. No daily trend in bladder volume variation was noted. The median absolute volumes (cm(3)) were: 221, 271, 426, 440, and 914 for pBladder, OV, OV+5, mPTV, and standard PTV, respectively. The median ratios of the study volumes/pBladder were: 1.4 OV, 2.1 OV+5, 2.4 mPTV, 4.1 standard PTV. OV+5 was smaller than mPTV in 9 patients. There was considerable inter-patient variability in study volumes and no apparent association of the magnitude of margin expansion and pBladder. The bladder was encompassed in 69%, 99%, 99%, and 100% of the final 10 fractions by OV, OV+5, mPTV, and standard PTV, respectively. CONCLUSIONS: The use of daily CBCT to generate patient-specific PTV margins is feasible and results in a marked reduction in the irradiated volume compared to population-based margins. As daily bladder volume varied unpredictably with considerable differences between patients, these findings support the use of patient-specific PTV margin expansions for bladder radiotherapy.

No role for routine chest radiography in stage I seminoma surveillance.

BACKGROUND: After orchidectomy, the standard management options available for stage I seminoma are surveillance, adjuvant radiotherapy, or adjuvant chemotherapy. The optimal follow-up protocol for surveillance is yet to be determined but includes frequent chest radiography (CXR) and computed tomography (CT) scan of the abdomen and pelvis (CT-AP). OBJECTIVE: The purpose of this study was to identify the modality that first detected relapse and to assess the value of the CXR in this setting. DESIGN, SETTING, AND PARTICIPANTS: Five hundred twenty-seven patients with histologically confirmed stage I testicular seminoma were managed with surveillance at our institution between 1982 and 2005. Routine CXRs were performed with each CT-AP and were done every 4-6 mo for 7 yr and annually thereafter. The median follow-up was 72 mo (range: 1-193). MEASUREMENTS: Measurements included the 5-yr relapse rate, overall survival, and disease-free survival to determine the modality that first detected relapse disease. RESULTS AND LIMITATIONS: The 5-yr actuarial relapse rate for the 527 patients was 14%. The 5-yr disease-free survival and overall survival were 85.7% and 98.6%, respectively. Seventy-three patients (97.3%) had an abnormal CT-AP and a normal CXR at relapse. One patient (1.3%) had an abnormal CT-AP with pulmonary metastasis on CXR and CT chest scan, and one patient (1.3%) had a biopsy-proven inguinal node metastasis with a normal CXR. No patient had a normal CT-AP or physical examination with an abnormal CXR at relapse. This is a single-center retrospective study based on a relatively small number of relapses and may be subject to bias. Confirmation of these results from other studies would be useful for wider clinical applicability. CONCLUSIONS: All except one relapse were detected by CT-AP with no relapses detected on CXR alone; therefore, CXR may be omitted as routine imaging in surveillance protocols.

Current treatment approaches for diffuse large B-cell lymphoma.

There have been two major developments over the last decade that has led to improvements in outcome and longer survival for patients with diffuse large B-cell lymphoma (DLBCL). These developments have been firstly to increase the dose of active cytotoxic drugs and shorten the time between cycles, resulting in dose-dense and/or dose-intense regimens and secondly the addition of the anti-CD20 monoclonal antibody rituximab to chemotherapy. Both strategies have been associated with higher response rates, lower relapse rates, longer event-free survival (EFS) and improved overall survival (OS), particularly in better prognostic groups. A combination of dose-dense and dose-intense chemotherapy regimens plus rituximab is currently being tested to confirm that the use of both approaches confers survival advantage. High-risk, poorer-prognosis DLBCL remains a challenge, and new treatment strategies are required for these patients. Improvements in outcome may potentially be achieved through a greater understanding of the genetic abnormalities specifically associated with poorer-prognosis disease, and factors that lead to unresponsiveness to chemotherapy. The role of radiotherapy is currently less clearly defined than at anytime in the management of DLBCL and the current evidence for using radiotherapy in this disease is therefore rigorously reviewed.