Long-term Overall Survival after External Beam Radiotherapy for Localised Prostate Cancer.

AIMS: Knowledge on survival probabilities is essential for determining optimal treatment strategies. We studied overall survival and associated prognostic factors in Dutch patients with localised prostate cancer (PCa) selected for external beam radiotherapy. MATERIALS AND METHODS: For this single-centre retrospective cohort study, we identified all T1-T3 PCa patients (aged 55-80 years) in the radiotherapy planning database with a start date between January 2006 and December 2013, treated with 72-78 Gy in 2 Gy fractions to the prostate ± seminal vesicles (n = 1536). Long-term androgen deprivation therapy (ADT) was predominantly prescribed in the case of extracapsular disease (>T3). Overall survival was estimated using the Kaplan-Meier method. Prognostic factors were evaluated in Cox regression models for the intermediate-risk and high-risk groups. RESULTS: The median follow-up was 12 years for patients who were alive. Ten-year survival rates were 79.0% for low-risk (n = 120), 59.9% for intermediate-risk (n = 430) and 56.8% for high-risk patients (n = 986). A higher age, higher comorbidity score, active smoking and Gleason score ≥8 had a statistically significant negative impact on overall survival at multivariable analysis. ADT was associated with superior overall survival in the high-risk group translating into overall survival rates similar to the intermediate-risk group. CONCLUSIONS: Although PCa patients selected for external beam radiotherapy are typically in good health, their comorbidity score and smoking habits appeared to be dominant predictors for overall survival. Overall survival rates within the high-risk group varied, showing improved overall survival with ADT prescription and worse overall survival in the case of Gleason score ≥8.

Acute and late toxicity patterns of moderate hypo-fractionated radiotherapy for prostate cancer: A systematic review and meta-analysis.

Introduction: Moderate hypofractionated (HF) radiotherapy is becoming the new standard in radiotherapy for prostate cancer patients. It is established as safe, but it might be associated with increased acute toxicity levels. We conducted a systematic review on moderate HF to establish acute toxicity levels and their required clinical management; late toxicity was reported as a secondary outcome. Material and methods: Using PRISMA guidelines, we conducted a systematic review for studies published until June 2022. We identified 17 prospective studies, with 7796 localised prostate cancer patients, reporting acute toxicity of moderate hypofractionation (2.5-3.4 Gy/fraction). A meta-analysis was done for 10/17 studies with a control arm (standard fractionation (SF)), including evaluation of late toxicity rates. We used Cochrane bias assessment and Newcastle-Ottawa bias assessment tools for randomized controlled trials (RCTs) RCT and non-RCTs, respectively. Results: Pooled results showed that acute grade ≥ 2 gastro-intestinal (GI) toxicity was increased by 6.3 % (95 % CI for risk difference = 2.0 %-10.6 %) for HF vs SF. Acute grade ≥ 2 Genito-urinary (GU) and late toxicity were not significantly increased. The overall risk of bias assessment revealed a low risk in the meta-analysis of included studies. Data on management of toxicity (medication, interventions) was only reported in 2/17 studies. Conclusion: HF is associated with increased acute GI symptoms, needing adequate monitoring and management. Reports on toxicity management were very limited. Pooled late GI and GU toxicity showed similar levels for SF and HF.

Impact of Advanced External Beam Radiotherapy on Second Haematological Cancer Risk in Prostate Cancer Survivors.

AIMS: External beam radiotherapy (EBRT) for prostate cancer (PCa) has rapidly advanced over the years. Advanced techniques with altered dose distributions may have an impact on second haematological cancer (SHC) risks. We assessed SHC risk after EBRT for PCa and explored whether this risk has changed over the years. MATERIALS AND METHODS: Patients diagnosed with a T1-T3 PCa between 1990 and 2015 were selected from the Netherlands Cancer Registry. Patients treated with EBRT were assigned to EBRT eras based on the date of diagnosis. These eras represented two-dimensional radiotherapy (2D-RT; 1991-1996), three-dimensional conformal radiotherapy (3D-CRT; 1998-2005) or advanced EBRT (2008-2015). Standardised incidence ratios (SIR) and absolute excess risks (AER) were calculated overall and by EBRT era. Sub-hazard ratios (sHRs) were calculated for the comparison of EBRT versus radical prostatectomy and active surveillance. RESULTS: PCa patients with EBRT as the primary treatment (n = 37 762) had an increased risk of developing a SHC (SIR = 1.20; 95% confidence interval 1.13-1.28) compared with the Dutch male general population. Estimated risks were highest for the 2D-RT era (SIR = 1.32; 95% confidence interval 1.14-1.67) compared with the 3D-CRT era (SIR = 1.16; 95% confidence interval 1.05-1.27) and the advanced EBRT era (SIR = 1.21; 95% confidence interval 1.07-1.36). AER were limited, with about five to six extra cases per 10 000 person-years. Relative risk analysis (EBRT versus radical prostatectomy/active surveillance) showed significant elevation with EBRT versus active surveillance (sHR = 1.17; 95% confidence interval 1.03-1.33; P = 0.017), but not for EBRT versus radical prostatectomy (sHR = 1.08; 95% confidence interval 0.94-1.23; P = 0.281). CONCLUSION: Increased SHC risks after EBRT for PCa cancer were observed for all EBRT eras compared with the general Dutch male population. Excess risks for EBRT versus other PCa treatment groups were found for only EBRT versus active surveillance.

Circulating tumor cell detection in advanced non-small cell lung cancer patients by multi-marker QPCR analysis.

BACKGROUND: The aim of this study was to explore circulating tumor cell (CTC) detection in advanced non-small cell lung cancer (NSCLC). CTCs may not only serve as a prognostic marker in selected tumor types, but may also be useful as pharmacodynamic marker in drug development. METHODS: Fourty-six advanced NSCLC patients and fourty-six healthy controls were included in the study and 8.0 ml of peripheral blood was obtained from each of the participants. Immunomagnetic bead enrichment for cells expressing epithelial cell adhesion molecule (EpCAM) was performed, followed by multi-marker quantitative real-time PCR of a panel of marker genes: cytokeratin 7 (CK7), cytokeratin 19 (CK19), human epithelial glycoprotein (EGP) and fibronectin 1 (FN1). Using quadratic discriminant analysis (QDA), expression values were combined into a single score, which indicated CTC-positivity or -negativity. Test characteristics were assessed using receiver operating characteristic (ROC) curve analysis. RESULTS: ROC curve analysis showed capability of discrimination between advanced NSCLC patients and healthy controls (area=0.712; 95% CI 0.606-0.819; P<0.001). A cut-off minimizing overall misclassification for QDA-positivity reached a sensitivity of 46% (95% CI 31-61) and a specificity of 93% (95% CI 82-99). CONCLUSIONS: In this exploratory study, an assay was developed for discriminating CTCs in peripheral blood samples of advanced NSCLC patients from healthy controls. The assay demonstrated an acceptable sensitivity in combination with good specificity. Further validation studies should take place in NSCLC patients and a matched control group.

Parotid gland sparing IMRT for head and neck cancer improves xerostomia related quality of life.

BACKGROUND AND PURPOSE: To assess the impact of intensity modulated radiotherapy (IMRT) versus conventional radiation on late xerostomia and Quality of Life aspects in head and neck cancer patients. PATIENTS AND NETHODS: Questionnaires on xerostomia in rest and during meals were sent to all patients treated between January 1999 and December 2003 with a T1-4, N0-2 M0 head and neck cancer, with parotid gland sparing IMRT or conventional bilateral neck irradiation to a dose of at least 60 Gy, who were progression free and had no disseminated disease (n = 192). Overall response was 85% (n = 163); 97% in the IMRT group (n = 75) and 77% in the control group (n = 88) the median follow-up was 2.6 years. The prevalence of complaints was compared between the two groups, correcting for all relevant factors at multivariate ordinal regression analysis. RESULTS: Patients treated with IMRT reported significantly less difficulty transporting and swallowing their food and needed less water for a dry mouth during day, night and meals. They also experienced fewer problems with speech and eating in public. Laryngeal cancer patients in general had fewer complaints than oropharynx cancer patients but both groups benefited from IMRT. Within the IMRT group the xerostomia scores were better for those patients with a mean parotid dose to the "spared" parotid below 26 Gy. CONCLUSION: Parotid gland sparing IMRT for head and neck cancer patients improves xerostomia related quality of life compared to conventional radiation both in rest and during meals. Laryngeal cancer patients had fewer complaints but benefited equally compared to oropharyngeal cancer patients from IMRT.