Harri Visapää

Implementation of adaptive radiation therapy for urinary bladder carcinoma: Imaging, planning and image guidance

Abstract Background. Adaptive radiation therapy (ART) for urinary bladder cancer has emerged as a promising alternative to conventional RT with potential to minimize radiation-induced toxicity to healthy tissues. In this work we have studied bladder volume variations and their effect on healthy bladder dose sparing and intrafractional margins, in order to refine our ART strategy. Material and methods. An online ART treatment strategy was followed for five patients with urinary bladder cancer with the tumors demarcated using Lipiodol®. A library of 3–4 predefined treatment plans for each patient was created based on four successive computed tomography (CT) scans. Cone beam CT (CBCT) images were acquired before each treatment fraction and after the treatment at least weekly. In partial bladder treatment the sparing of the healthy part of the bladder was investigated. The bladder wall displacements due to bladder filling were determined in three orthogonal directions (CC, AP, DEX-SIN) using the treatment planning CT scans. An ellipsoidal model was applied in order to find the theoretical maximum values for the bladder wall displacements. Moreover, the actual bladder filling rate during treatment was evaluated using the CBCT images. Results. In partial bladder treatment the volume of the bladder receiving high absorbed doses was generally smaller with a full than empty bladder. The estimation of the bladder volume and the upper limit for the intrafractional movement of the bladder wall could be represented with an ellipsoidal model with a reasonable accuracy. Observed maximum growth of bladder dimensions was less than 10 mm in all three orthogonal directions during 15 minute interval. Conclusion. The use of Lipiodol contrast agent enables partial bladder treatment with reduced irradiation of the healthy bladder volume. The ellipsoidal bladder model can be used for the estimation of the bladder volume changes and the upper limit of the bladder wall movement during the treatment fraction.

Renal tumour invasion index as a novel anatomical classification predicting urological complications after partial nephrectomy

Abstract Objective. The goal of anatomical classification systems (ACSs) is to assess renal tumour complexity and predict surgical complications. However, the present ACSs may include some relatively unimportant components and may be complicated to use. This study introduces the invasion depth of the renal tumour divided by the parenchymal thickness, called the renal tumour invasion index (RTII), as a novel ACS and compares it with previous ACSs in predicting urological complications after partial nephrectomy. Material and methods. This retrospective single-institution study assessed 280 consecutive patients subjected to a planned partial nephrectomy. The main outcome was perioperative 30-day urological complications. RTII was compared with the PADUA (preoperative aspects and dimensions used for an anatomical) classification score, RENAL (radius, exophytic/endophytic, nearness to collecting system or sinus, anterior/posterior and location relative to polar lines) nephrometry score and C (centrality) index to predict urological complications, using statistical methods of receiver operating curve and logistic binary regression. Results. Areas under the curve for RTII, RENAL, C index and PADUA were 0.64 (95% CI 0.57–0.72, p < 0.001), 0.61 (95% CI 0.54–0.69, p = 0.004), 0.64 (95% CI 0.57–0.71, p < 0.001) and 0.57 (95% CI 0.49–0.65, p = 0.06), respectively, indicating that all the ACSs studied are able to predict urological complications. Similarly, in a multivariate logistic regression model adjusted for comorbidity and surgical approach, all ACSs were statistically significant predictors of urological complications. Conclusions. RTII is as good as the previous more complicated ACSs in predicting urological complications after partial nephrectomy. As a simple measurement with a straightforward anatomical interpretation, RTII may be useful in counselling patients and stratifying patients in studies.

Papillary renal cell cancer is strongly associated with simple renal cysts.

Introduction: The purpose of this study was to evaluate the prevalence of simple renal cysts (SRCs) in patients with renal neoplasia. Patients and Methods: The study population consisted of 482 patients who underwent partial or radical nephrectomy for kidney tumour between 2006 and 2010. Prevalence of cysts was evaluated retrospectively on a preoperative CT or MRI scan. Results: SRCs are more prevalent in patients with papillary renal cell cancer (RCC) than patients with clear cell RCC. All obese (BMI ≥30) patients in our study population had SRCs. Conclusions: This is the first study to show an association between SRCs and papillary RCC.

Hand-assisted laparoscopic versus open partial nephrectomy in patients with T1 renal tumor: Comparative perioperative, functional and oncological outcome

Abstract Objective: Studies comparing hand-assisted laparoscopic partial nephrectomy (HALPN) and open partial nephrectomy (OPN) for T1 kidney tumors are scarce. This study investigated the perioperative, functional and oncological outcomes of these methods. Materials and methods: A prospective institutional kidney tumor register was used to identify patients between January 2006 and May 2014 undergoing HALPN (n = 139) or OPN (n = 165) for tumors 7 cm or smaller with non-absolute indication for nephron-sparing surgery. The outcomes were compared using univariate and multivariate statistical methods. Results: HALPN and OPN groups were similar with regard to tumor characteristics but HALPN patients were 2 years younger (p = 0.001) and had less comorbidity. Fewer intraoperative complications were encountered in HALPN than in OPN patients (7.2% vs 12.7%, p = 0.043). HALPN patients had less all-grade postoperative 30 day complications than OPN patients (27% vs 41%, p = 0.037), but there was no significant difference in Clavien 3–5 complications. Glomerular filtration rate 3 months after operation was lower in the HALPN than in the OPN group (7.1 ± 12.7% vs 10.0 ± 12.4%, p = 0.054). There was no difference in overall survival or recurrence-free survival during the median follow-up of 35 months. Conclusions: HALPN is a feasible method to achieve equal perioperative, functional and oncological outcomes compared to OPN in patients with tumors 7 cm or smaller in diameter.

Gold seed fiducials in analysis of linear and rotational displacement of the prostate bed

BACKGROUND AND PURPOSE This study aimed to investigate the magnitude of interfraction prostate bed motion during radiotherapy using both the implanted gold seed fiducials and the soft tissue registration and to define reasonable planning target volume (PTV) margins for different localization methods. MATERIAL AND METHODS Thirteen prostatectomized prostate cancer patients, after implanting four gold seed fiducials into their prostate bed, were imaged daily using a pretreatment cone-beam computed tomography (CBCT). Linear and the rotational prostate bed motion (PBM) was measured for 466 CBCTs. RESULTS The linear PBM mean and standard deviation values in millimeters are 0.0 ± 0.5, 0.7 ± 2.1 and 0.8 ± 1.6 in the LR, SI and AP axes, respectively. In 20% of the fractions the rotation of the prostate bed in sagittal plane exceeds ±6° and in 5% it exceeds ±10° from the position on the planning CT. In the transversal and coronal planes 1% and 2% of it exceeds ±6°. The PTV margins are 2.4, 6.5 and 6.6mm in the LR, SI and AP axes, respectively, if imaging is performed for the first three treatment fractions. CONCLUSION The linear PBM is largest in the SI and AP axis, whereas the rotation is largest in the sagittal plane. Bone localization during the first three treatment fractions can reduce PTV margins by 52%, 18% and 10% in the LR, SI and AP axes, respectively, whereas in daily CBCT the use of the gold seed fiducials seems profitable.

Renal tumour anatomical characteristics and functional outcome after partial nephrectomy

Abstract Objective. Anatomical features of renal tumours may be useful in predicting glomerular filtration rate (GFR) after partial nephrectomy. In this study, anatomical classification systems (ACSs) were compared to predict changes in renal function after surgery. Materials and methods. A group of 294 patients with T1 renal tumours receiving partial nephrectomy between January 2006 and June 2013 were identified from the institutional kidney tumour database. Preoperative images from computed tomography or magnetic resonance imaging were reviewed to assess diameter, PADUA (preoperative aspects and dimensions used for an anatomical) classification score, RENAL (radius, exophytic/endophytic properties of the tumour, nearness of tumour deepest portion to the collecting system or sinus, anterior/posterior descriptor and location relative to polar lines) nephrometry score, centrality index (C index) and renal tumour invasion index (RTII). GFR was estimated using the Modification of Diet in Renal Disease equation preoperatively and 3 months after operation. Linear and logistic regression were applied as statistical methods. Results. Mean tumour diameter was 3.0 ± 2.2 cm (range 1.0–7.0 cm). GFR was 85 ± 22 ml/min/1.73 m² before the operation and 77 ± 21 ml/min/1.73 m² (–8% change) 3 months after the operation. In univariate linear regression, the percentage change in GFR was weakly but statistically significantly associated with surgical approach (p = 0.04), indication for nephron sparing (p = 0.02), preoperative GFR (p < 0.001), PADUA (p = 0.02), RENAL (p = 0.01) and RTII (p = 0.003). In multivariate logistic regression analysis among patients with tumours 3 cm or larger, PADUA (odds ratio 1.55, p = 0.021) and RTII (odds ratio 3.87, p = 0.037) predicted at least a 20% reduction in GFR. Conclusions. Renal tumour ACSs may be clinically useful in predicting changes in renal function after partial nephrectomy in patients with larger tumours. The performance of RTII is equal to that of other ACSs in predicting changes in GFR.

Renal Tumor Invasion Depth and Diameter are the Two Most Accurate Anatomical Features Regarding the Choice of Radical Versus Partial Nephrectomy

Background and Aims: To evaluate simple tumor characteristics (renal tumor diameter and parenchymal invasion depth) compared with more complex classifications, that is, Renal Tumor Invasion Index (RTII) and Preoperative Aspects and Dimensions Used for an Anatomical classification, in predicting the type of nephrectomy (radical vs partial) performed. Material and Methods: A total of 915 patients who had undergone either partial nephrectomy (n = 388, 42%) or radical nephrectomy (n = 527, 58%) were identified from the Helsinki University Hospital kidney tumor database between 1 January 2006 and 31 December 2014. Tumor maximum diameter and depth of invasion into the parenchyma were estimated from computed tomography or magnetic resonance imaging images and compared with Preoperative Aspects and Dimensions Used for an Anatomical and Renal Tumor Invasion Index. Logistic regression and receiver operating curves were used to compare the parameters at predicting the type of nephrectomy. Results and conclusion: All the anatomical variables of receiver operating curve/area under the curve analyses were significant predictors for the type of nephrectomy. Parenchymal invasion (area under the curve 0.91; 95% confidence interval, 0.89–0.93), RTII (area under the curve 0.91; 95% confidence interval, 0.89–0.93), and diameter (area under the curve 0.91; 95% confidence interval, 0.89–0.93) performed significantly better than Preoperative Aspects and Dimensions Used for an Anatomical classification (area under the curve 0.88; 95% confidence interval, 0.85–0.89). In multivariable analysis, invasion depth was the best predictor of nephrectomy type (percentage correct, 85.6%). Addition of one anatomic parameter into the model of non-anatomical cofactors improved the accuracy of the model significantly, but the addition of more parameters did not. Parenchymal invasion depth and tumor diameter are the most accurate anatomical features for predicting the nephrectomy type. All potential anatomical classification systems should be tested against these two simple characteristics.

The complex interplay of sex steroids manifested by endocrine treatment of prostate cancer

The human fetus is initially capable of differentiating both to female or male fenotype irrespective of the genotype. Subsequent development of sexual characteristics in both genders is highly dependent on the proper, timely and balanced secretion of sex steroids. A remnant of this peculiar phenomenon is underlying the observations made by Alfthan and Holsti in their article dating from the early issues of SJU [1]. In their paper, they examined prevention of gynecomastia by roentgen irradiation in men who were treated with estrogen to treat their prostate cancer. High levels of parenteral estrogen not only caused suppression of gonadotropin release from the pituitary and subsequent castrate levels of testosterone, but also secondary indirect feminizing effects such as gynecomastia. In their prospective study, Alfthan and Holsti elegantly demonstrate the powerful effect of local irradiation in preventing hyperplasia of the male mammary glandular tissue. However, the secondary effects of estrogen in the male were not entirely unwanted: estrogens are trophic on the bone and prevent climacteric symptoms otherwise common among castrates. Estrogen treatment for prostate cancer as a means of ADT is nowadays rare, but the advantageous effects of estrogens particularly on the bone are still of interest [2,3]. Furthermore, combining estrogen therapy with novel therapies in treating castration-resistant prostate cancer is showing promise [3]. At present, a shifted balance between androgen and estrogen action is still seen in different conditions: Pure antiandrogens such as bicalutamide exert their anti-androgenic effect at their main target tissue, the prostate. However, when used as monotherapy they also block the negative androgen feedback on the hypothalamic and pituitary level resulting in increased LH and subsequently testosterone production. Abundance of testosterone in turn results in increased estrogen turnover by aromatase action resulting in gynecomastia and analogously to protection of bone mass. The recently developed antiandrogens such as enzalutamide share the endocrine effects of bicalutamide and when used as monotherapy their use also warrants prophylactic irradiation of mammary tissue [5]. In addition to hormonal manipulations for prostate cancer, a shift of hormonal balance may be a contributing factor to changes seen in the normal aging of males, but these changes are subtle and not well understood [6,7]. As a part of metabolic syndrome, accumulation of body fat contributes to increased aromatization of testosterone to estrogen, which is mainly responsible for negative feedback in the pituitary level, also in the male. This results in decreased testosterone production which further contributes to the vicious circle seen in obesity [8]. The paper by Alfthan and Holsti exemplifies one aspect of how the interplay of sex steroids can affect various organ systems. However, our understanding of this complex system is still incomplete. Understanding of the male endocrinology gives us urologists a unique position in the study of male hormonal changes seen during normal aging and sickness.