Significantly reduced incidence and improved survival from prostate cancer over 25 years.

BACKGROUND: Prostate cancer (PCa) was the second most frequent cancer and the fifth leading cause of cancer death among men in 2020. The aim of this study was to analyze trends in the incidence, mortality and survival of PCa in Girona, Spain, over 25 years. METHODS: Population-based study of PCa collected in the Girona Cancer Registry, 1994-2018. Age-adjusted incidence and mortality rates were calculated per 100,000 men-year. Joinpoint regression models were used for trends, calculating the annual percentage changes (APC). Observed and net survival were analyzed using Kaplan-Meier and Pohar-Perme estimations, respectively. RESULTS: A total of 9,846 cases of PCa were registered between 1994-2018. The age-adjusted incidence and mortality rates were 154.7 (95%CI: 151.7 157.8) and 38.9 (95%CI: 37.3 -40.6), respectively. An increased incidence of 6.2% was observed from 1994 to 2003 (95%CI: 4.4 -8.1), and a decrease of -2.7% (95%CI: -3.5 -;-1.9) between 2003 and 2018. Mortality APC was -2.6% (95%CI: -3.3 --2.0). Five-year observed and net survival were 72.8% (95%CI: 71.8 - 73.7) and 87.2% (95%CI: 85.9 - 88.4), respectively. Five-year net survival increased over time from 72.9% (1994-1998) to 91.3% (2014-2018). CONCLUSIONS: The analyses show a clear reduction in PCa incidence rates from 2003 on, along with an increase in overall survival when comparing the earlier period with more recent years.

Impact of the dose quantity used in MV photon optimization on dose distribution, robustness, and complexity.

PURPOSE: Convolution/superposition algorithms used in megavoltage (MV) photon radiotherapy model radiation transport in water, yielding dose to water-in-water (Dw,w ). Advanced algorithms constitute a step forward, but their dose distributions in terms of dose to medium-in-medium (Dm,m ) or dose to water-in-medium (Dw,m ) can be problematic when used in plan optimization due to their different dose responses to some atomic composition heterogeneities. Failure to take this into account can lead to undesired overcorrections and thus to unnoticed suboptimal and unrobust plans. Dose to reference-like medium (Dref,m* ) was recently introduced to overcome these limitations while ensuring accurate transport. This work evaluates and compares the performance of these four dose quantities in planning target volume (PTV)-based optimization. METHODS: We considered three cases with heterogeneities inside the PTV: virtual phantom with water surrounded by bone; head and neck; and lung. These cases were planned with volumetric modulated arc therapy (VMAT) technique, optimizing with the same setup and objectives for each dose quantity. We used different algorithms of the Varian Eclipse treatment planning system (TPS): Acuros XB (AXB) for Dm,m and Dw,m , and Analytical Anisotropic Algorithm (AAA) for Dw,w . Dref,m* was obtained from Dm,m distributions using an in-house software considering water as the reference medium (Dw,m* ). The optimization process consisted of: (1) common first optimization, (2) dose distribution computed for each quantity, (3) re-optimization, and (4) final calculation for each dose quantity. The dose distribution, robustness to patient setup errors, and complexity of the plans were analyzed and compared. RESULTS: The quantities showed similar dose distributions after the optimization but differed in terms of plan robustness. The cases with soft tissue and high-density heterogeneities followed the same pattern. For AXB Dm,m , cold regions appeared in the heterogeneities after the first optimization. They were compensated in the second optimization through local fluence increases, but any positional mismatch impacted robustness, with clinical target volume (CTV) variations from the nominal scenario around +3% for bone and up to +7% for metal. For AXB Dw,m the pattern was inverse (hot regions compensated by fluence decreases) and more pronounced, with CTV dose variations around -7% for bone and up to -17% for metal. Neither AXB Dw,m* nor AAA Dw,w presented these dose inhomogeneities, which resulted in more robust plans. However, Dw,w differed markedly from the other quantities in the lung case because of its lower radiation transport accuracy. AXB Dm,m was the most complex of the four dose quantities and AXB Dw,m* the least complex, though we observed no major differences in this regard. CONCLUSIONS: The dose quantity used in MV photon optimization can affect plan robustness. Dw,w distributions from convolution/superposition algorithms are robust but may not provide sufficient radiation transport accuracy in some cases. Dm,m and Dw,m from advanced algorithms can compromise robustness because their different responses to some composition heterogeneities introduce additional fluence compensations. Dref,m* offers advantages in plan optimization and evaluation, producing accurate and robust plans without increasing complexity. Dref,m* can be easily implemented as a built-in feature of the TPS and can facilitate and simplify the treatment planning process when using advanced algorithms. Final reporting can be kept in Dm,m or Dw,m for clinical correlations.

Dosimetric Impact of Acuros XB Dose-to-Water and Dose-to-Medium Reporting Modes on Lung Stereotactic Body Radiation Therapy and Its Dependency on Structure Composition.

PURPOSE: Our purpose was to assess the dosimetric effect of switching from the analytical anisotropic algorithm (AAA) to Acuros XB (AXB), with dose-to-medium (Dm) and dose-to-water (Dw) reporting modes, in lung stereotactic body radiation therapy patients and determine whether planning-target-volume (PTV) dose prescriptions and organ-at-risk constraints should be modified under these circumstances. METHODS AND MATERIALS: We included 54 lung stereotactic body radiation therapy patients. We delineated the PTV, the ipsilateral lung, the contralateral lung, the heart, the spinal cord, the esophagus, the trachea, proximal bronchi, the ribs, and the great vessels. We performed dose calculations with AAA and AXB, then compared clinically relevant dose-volume parameters. Paired t tests were used to analyze differences of means. We propose a method, based on the composition of the involved structures, for predicting differences between AXB Dw and Dm calculations. RESULTS: The largest difference between the algorithms was 4%. Mean dose differences between AXB Dm and AXB Dw depended on the average composition of the volumes. Compared with AXB, AAA underestimated all PTV dose-volume parameters (-0.7 Gy to -0.1 Gy) except for gradient index, which was significantly higher (4%). It also underestimated V5 of the contralateral lung (-0.3%). Significant differences in near-maximum doses (D2) to the ribs were observed between AXB Dm and AAA (1.7%) and between AXB Dw and AAA (-1.6%). AAA-calculated D2 was slightly higher in the remaining organs at risk. CONCLUSIONS: Differences between AXB and AAA are below the threshold of clinical detectability (5%) for most patients. For a small subgroup, the difference in maximum doses to the ribs between AXB Dw and AXB Dm may be clinically significant. The differences in dose volume parameters between AXB Dw and AXB Dm can be predicted with reference to structure composition.

A Novel Device for Deep-Inspiration Breath Hold (DIBH): Results from a Single-Institution Phase 2 Clinical Trial for Patients with Left-Sided Breast Cancer.

PURPOSE: To validate a novel device developed at our institution for deep inspiration breath hold (DIBH) within a phase 2 clinical trial for left-sided breast cancer and to evaluate the dosimetric benefits of its use. METHODS AND MATERIALS: The device uses an external mechanical reference for guiding the patient to the desired breath level and gives acoustic and visual feedback to the patient and the radiation therapists, respectively. A phase 2 clinical trial was performed for its validation. The thoracic amplitude was used as a surrogate of the inspiration level. The stability, repeatability, reproducibility, and reliability of DIBH using the device were analyzed. The dosimetric parameters of the heart, the left anterior descending coronary artery, the ipsilateral lung, the contralateral breast, and the target coverage using free breathing and DIBH were compared. RESULTS: Thirty-eight patients were included in the analysis. The maximum population value of stability and repeatability were 1.7 mm and 3.3 mm, respectively. The reproducibility mean value was 1.7 mm, and population systematic and random errors were 0.3 mm and 0.9 mm, respectively. The reliability was 98.9%. Statistically significant dose reductions were found for the heart, the left anterior descending coronary artery, and the ipsilateral lung dosimetric parameters in DIBH, without losing dose coverage to the planning target volumes. CONCLUSIONS: The validation of the device within the phase 2 clinical trial demonstrates that it offers reliable, stable, repeatable, and reproducible breast cancer treatments in DIBH with its dosimetric benefits.

Descriptive epidemiology of primary malignant and non-malignant central nervous tumors in Spain: Results from the Girona Cancer Registry (1994-2013).

BACKGROUND: Systematic registration of non-malignant central nervous system (CNS) tumors is a rare practice among European cancer registries. Thus, the real burden of all CNS tumors across Europe is underestimated. The Girona Cancer Registry provides here the first data on CNS tumor incidence and survival trends in Spain for all histological types, including malignant and non-malignant tumors. METHODS: Data on all incident cases of primary CNS tumors notified to the Girona population-based cancer registry from 1994 to 2013 (n=2,131) were reviewed. Incidences rates (IRs) were standardized to the 2013 European population and annual percentage changes (EAPC) were estimated using a piecewise log linear model. 1- and 5-year observed (OS) and relative survival (RS) were also calculated. Results were expressed by sex, age-group, histological subtype and behavior. RESULTS: The overall IR was 16.85 and increased across the period of study (EAPC=+2.2%). The proportion and IRs of malignant (50.2%; IR=9.35) and non-malignant cases (49.8%; IR=9.14) were similar; however, non-malignant tumors were more frequent in women (sex ratio=0.63). The most frequently reported histologies were meningioma (27.6%; IR=5.11) and glioblastoma (22.2%; IR=4.15), which also accounted for the highest and lowest 5-year RS (80.2%; 3.7%, respectively). Globally, 5-year RS was lower in men (42.6% vs. 58.3%, respectively) and in the elderly (64.9% for 0-14years vs. 23.0% for >74years). CONCLUSION: This study presents a comprehensive overview of the epidemiology of malignant and non-malignant CNS primary tumors from the well-established region-wide Girona Cancer Registry (1994-2013). Incidence rates were recovered for all histologies. Survival is still dramatically associated to both age and histological subtype.

Trends in net survival from prostate cancer in six European Latin countries: results from the SUDCAN population-based study.

Cancer survival is a key measure of the effectiveness of a health-care system. European Latin countries have some differences in their health system; therefore, it is of interest to compare them in terms of survival from cancer. Prostate cancer data from six countries (Belgium, France, Italy, Portugal, Spain, and Switzerland) were extracted from the EUROCARE-5 database (end of follow-up: 1 January 2009). First, the net survival (NS) was studied over the 2000-2004 period using the Pohar-Perme estimator. For trend analyses, the study period was specific to each country. Trends in NS over the 1989-2004 period and changes in the pattern of cancer excess mortality rate until 5 years after the diagnosis were examined using a multivariate excess mortality rate model. A striking increase in survival from prostate cancer occurred in European Latin countries at all ages studied. In the last period of the study, there was little difference in age-standardized NSs from prostate cancer between the six countries. The trends of the survival followed those of the incidence (except in Spain in the elderly); the increases in incidence were the highest at ages 60-70 years and, in the elderly (around 80 years), the incidence did not increase in Switzerland. The increases in NS can mainly be explained by lead-time and overdiagnosis effects. The epidemiological interpretability of the changes in prostate cancer survival in Latin countries is strongly compromised by the biases inherent to the extensive prostate-specific antigen testing.

Survival of male genital cancers (prostate, testis and penis) in Europe 1999-2007: Results from the EUROCARE-5 study.

BACKGROUND: We provide updated estimates of survival and survival trends of male genital tumours (prostate, testicular and penis cancers), in Europe and across European areas. METHODS: The complete approach was used to obtain relative survival estimates for patients diagnosed in 2000-2007, and followed up through 2008 in 29 countries. Data came from 87 cancer registries (CRs) for prostate tumours and from 86 CRs for testis and penis tumours. Relative survival time trends in 1999-2007 were estimated by the period approach. Data came from 49 CRs in 25 countries. RESULTS: We analysed 1,021,275 male genital cancer cases. Five-year relative survival was high and decreased with increasing age for all tumours considered. We found limited variation in survival between European regions with Eastern Europe countries having lower survival than the others. Survival for penile cancer patients did not improve from 1999 to 2007. Survival for testicular cancer patients remained stable at high levels since 1999. Survival for prostate cancer patients increased over time. CONCLUSIONS: Treatment standardisation and centralisation for very rare diseases such as penile cancers or advanced testicular tumours should be supported. The high survival of testicular cancer makes long-term monitoring of testicular cancer survivors necessary and CRs can be an important resource. Prostate cancer patients' survival must be interpreted considering incidence and mortality data. The follow-up of the European Randomised Study of Screening for Prostate Cancer should continue to clarify the impact of screening on prostate cancer mortality together with population based studies including information on stage and treatments.

Population-based survival analyses of central nervous system tumors from 1994 to 2008. An up-dated study in the temozolomide-era.

The present population-based study describes the survival of malignant central nervous system (CNS) tumors diagnosed during 15 years. Also, we obtained individual data regarding the use of temozolomide to analyze the impact of this drug on the survival of patients diagnosed with glioblastoma. From 1994 to 2008, a total of 679 incident cases of primary CNS tumors were reported by the Girona Cancer Registry after excluding 39 cases diagnosed by death certificate only. Number of cases and the corresponding proportion for each CNS histological subtype in the study population were: 25 oligodendroglial and oligoastrocytics (3.7%), 22 ependymal tumors (3.2%), 24 embryonal (3.5%), 372 astrocytic (54.8%), 1 choroid plexus (0.1%) and 235 without histological confirmation (34.6%). Observed survival after 5 years since diagnosis for the histological subtype were: 58.8%; 47.5%; 37.0%; 14.5% and 6.5%, respectively (p<0.001). Survival of patients diagnosed with glioblastoma according to temozolomide treatment (yes/no) was 60.8% vs. 13.6% and 5.9% vs. 2.5% after 1 and 5 years since diagnosis, respectively. Short-term survival was higher for patients diagnosed with glioblastoma and treated with temozolomide than patients not treated with temozolomide.

Late rectal and bladder toxicity following radiation therapy for prostate cancer: Predictive factors and treatment results.

AIM: This study aimed at investigating factors associated to late rectal and bladder toxicity following radiation therapy and the effectiveness of Hyperbaric Oxygen Therapy (HBOT) when toxicity is grade ≥2. BACKGROUND: Radiation is frequently used for prostate cancer, but a 5-20% incidence of late radiation proctitis and cystitis exists. Some clinical and dosimetric factors have been defined without a full agreement. For patients diagnosed of late chronic proctitis and/or cystitis grade ≥2 treatment is not well defined. Hyperbaric Oxygen Therapy (HBOT) has been used, but its effectiveness is not well known. MATERIALS AND METHODS: 257 patients were treated with radiation therapy for prostate cancer. Clinical, pharmacological and dosimetric parameters were collected. Patients having a grade ≥2 toxicity were treated with HBOT. Results of the intervention were measured by monitoring toxicity by Common Toxicity Criteria v3 (CTCv3). RESULTS: Late rectal toxicity was related to the volume irradiated, i.e. V50 > 53.64 (p = 0.013); V60 > 38.59% (p = 0.005); V65 > 31.09% (p = 0.002) and V70 > 22.81% (p = 0.012). We could not correlate the volume for bladder. A total of 24 (9.3%) patients experienced a grade ≥2. Only the use of dicumarinic treatment was significant for late rectal toxicity (p = 0.014). A total of 14 patients needed HBOT. Final percentage of patients with a persistent toxicity grade ≥2 was 4.5%. CONCLUSION: Rectal volume irradiated and dicumarinic treatment were associated to late rectal/bladder toxicity. When toxicity grade ≥2 is diagnosed, HBOT significantly ameliorate symptoms.

Population-based incidence and survival of central nervous system (CNS) malignancies in Girona (Spain) 1994-2005.

The purpose of this study was to describe the incidence and survival of primary Central Nervous System (CNS) malignancies using data from the population-based cancer registry for Girona province (north-east Spain).We included all cases of primary CNS malignancies registered between 1994 and 2005. Pathological diagnoses were reviewed and grouped according to the 2007 WHO Classification. Meningeal, soft tissue tumours, spinal cord tumours and primary CNS lymphoma were not included. Cases notified only by death certificate were excluded from the survival analysis. Kaplan and Meier survival curves were calculated from date of diagnosis to death or end of study (31 December 2005), as was relative survival. A total of 493 new CNS cancer patients were registered during the study period: 49.3% astrocytic, 3.4% oligodendroglial and oligoastrocytic tumours, 2.6% ependimal tumours, 3.7% embryonal tumours, 0.2% choroid plexus and 41% without histological confirmation. The mean age (in years) for embryonal tumours was 18.17 years, these being the younger patients in the sample, and 66.34 years for those without histological confirmation, the older patients. Overall, the age standardised incidence rate was 5.88 cases/100,000 people/year (men = 6.81; women = 4.99) with an increasing trend by age until the 70-74 age group. Five-year observed survival rates were: 14.6% for astrocytic tumours, 35.7% for oligodendroglial and oligoastrocytic tumours, 41.0% for ependymal tumours, 32.4% for embryonal tumours and 7.5% for those without histological confirmation (log rank test: P < 0.001). Five-year observed survival rates for astrocytic tumours were analyzed separately by tumour grading, with 37% for diffuse astrocytoma, 7.1% for anaplastic astrocytoma and 4.7% for glioblastoma (log rank test: P < 0.001).Our results show that astrocytic tumours are most frequently diagnosed and glioblastoma patients have the worst survival figures for the area covered by our population cancer registry.The high observed incidence of histologically unverified tumours is most probably due to easy access to state of the art CNS imaging in our area.