A.C.M. van den Bergh

The influence of respiration induced motion of the kidneys on the accuracy of radiotherapy treatment planning, a magnetic resonance imaging study

An MRI study has been performed to determine the respiration induced motion of the kidneys. Under normal respiration conditions displacements of the left and right kidney varied from 2 to 24 mm and 4 to 35 mm, respectively. Under forced respiration conditions displacements were larger and ranged from 10 to 66 mm for the left kidney and 10 to 86 mm for the right kidney. The influence of kidney motion on the radiation dose was determined for patients irradiated on the total abdomen for ovarian cancer with shielding of the kidneys during part of the treatment. The kidney motion resulted in a larger fraction of the kidney volume receiving a dose between 20 and 22 Gy.

Acute toxicity of curative radiotherapy for intermediate- and high-risk localised prostate cancer in the EORTC trial 22991

INTRODUCTION This trial randomly assessed short-term adjuvant hormonal therapy added to radiotherapy (RT) for intermediate- and high-risk (UICC 1997 cT2a or cT1b-c with high PSA or Gleason score) localised prostate cancer. We report acute toxicity (CTCAE v2) assessed weekly during RT in relation to radiation parameters. PATIENTS AND METHODS Centres selected the RT dose (70, 74 or 78Gy) and RT technique. Statistical significance is at 0.05. RESULTS Of 791 patients, 652 received 3D-CRT (70Gy: 195, 74Gy: 376, 78Gy: 81) and 139 received IMRT (74Gy: 28, 78Gy: 111). During RT, grade 3 gastrointestinal (GI) and genitourinary (GU) toxicities were reported by 7 (0.8%) and 50 (6.3%) patients, respectively. No grade 4 was reported. The risk of grade 2 GI toxicity increased significantly with increasing D50%-rectum (p=0.004) and that of grade 2 GU toxicity correlated only to Dmax-bladder (p=0.051). 3D-RT technique, increasing total dose and V95% >400 cc increased D50% and Dmax. One month after RT, only 14 patients (1.8%) reported grade 3 toxicity. AST did not seem to influence the risk of GU or GI acute toxicity. CONCLUSION RT up to 78Gy was well tolerated. Dmax-bladder and D50%-rectum influenced the risk of grade 2 GU toxicity and GI toxicity, respectively. Both were lower with IMRT but remained high for an irradiated RT volume>400 cc for 3D-RT and for a dose of 78Gy. Hormonal treatment did not influence acute toxicity.

Quality of life is impaired in association with the need for prolonged postoperative therapy by somatostatin analogs in patients with acromegaly.

OBJECTIVE To assess the influence of long-acting somatostatin analogs (SSTA) after initial pituitary surgery on long-term health-related quality of life (HR-QoL) in relation to disease control in patients with acromegaly. DESIGN This is a cross-sectional study in two tertiary referral centers in The Netherlands. PATIENTS AND METHODS One hundred and eight patients with acromegaly, in whom transsphenoidal (n=101, 94%) or transcranial (n=7, 6%) surgery was performed. Subsequently, 46 (43%) received additional radiotherapy and 41 (38%) were on postoperative treatment with SSTA because of persistent or recurrent disease at the time of study. All subjects filled in standardized questionnaires measuring HR-QoL. Disease control at the time of study was assessed by local IGF1 SDS. RESULTS IGF1 SDS were slightly higher in patients treated with SSTA in comparison with patients without use of SSTA (0.85±1.52 vs 0.25±1.21, P=0.026), but the percentage of patients with insufficient control (IGF1 SDS >2) was not different (17 vs 9%, P=0.208). Patients using SSTA reported poorer scores on most subscales of the RAND-36 and the acromegaly QoL and on all subscales of the multidimensional fatigue inventory-20. A subgroup analysis in patients with similar IGF1 levels (SSTA+, n=26, IGF1 SDS 0.44±0.72 vs SSTA-, n=44, IGF1 SDS 0.41±0.65) revealed worse scores on physical functioning, physical fatigue, reduced activity, vitality, and general health perception across all HR-QoL questionnaires in patients treated with SSTA. CONCLUSION QoL is impaired in association with the need for prolonged postoperative therapy by SSTA in patients with acromegaly despite similar IGF1 levels.

Cognitief functioneren bij patiënten die behandeld zijn voor een niet functionerende hypofysemacro-adenoom en de effecten van hypofysebestraling

Niet functionerende hypofysemacro-adenomen (NFA) zijn goedaardige tumoren van de hypofyse die door druk op de oogzenuwen uitval van het gezichtvermogen kunnen geven en tevens kunnen leiden tot verlies van de hypofysefunctie. De aanbevolen behandeling bestaat uit transsfenoïdale chirurgie soms gevolgd door radiotherapie indien er sprake is van een tumorrest of hergroei. De lokale tumorcontrole verbetert sterk door de toepassing van radiotherapie op de hypofyse (Van den Bergh et al., 2007). Naast deze positieve effecten op tumorcontrole, worden er cognitieve veranderingen gevonden in het geheugen en executieve functies (o.a. planning, cognitieve flexibiliteit en inhibitie) bij behandelde hypofysepatiënten (Guinan et L., 1998; Noad et al., 2004; Peace et al., 1997; Peace et al., 1998). Eerdere studies hadden echter als nadeel dat de patiëntenpopulaties heterogeen waren ten aanzien van de hypofyse aandoening en bovendien vaak klein waren.

No negative impact of radiotherapy on the incidence of second tumours and mortality in pituitary adenoma patients

Purpose: Postoperative radiotherapy (PORT) results in excellent local tumour control and improvement of excessive hormonal secretion in pituitary adenoma patients where (repeated) surgery was unsuccessful. Despite this benefit, concerns related to possible long term side effects are often quoted to delay or reject this treatment. In previous studies. the incidence of second tumours and mortality in pituitary adenoma patients treated with PORT were compared with a normal reference population. For proper evaluation however, a direct comparison with similar patients treated with surgery alone should be made. The purpose of this study was to assess the impact of PORT on developing second tumours and mortality in pituitary adenoma patients by comparing the incidence with patients treated with surgery alone. Materials: A retrospective study was performed in 462 pituitary adenoma patients (non-functioning adenoma n=256. growth-hormone secreting n=139 and adrenocorticotropic-hormone secreting adenoma n= 67) treated between t959 and 2008 at the University Medical Center Groningen. PORT was performed in 236 pituitary adenoma patients. The different radiotherapy techniques used in this period were divided into techniques with (n=80) or without (n=153) a beam configuration directed into the central body axis of the patient. Most patients received a radiation fractionation scheme of 25 daily fractions of 1.8 Gy in 5 weeks.After pituitary adenoma diagnosis the incidence of tumours and death were investigated using median life expectancy (MLE). MLE was used to correct for year of birth and gender and with the application of years of follow up as a time base for a left-censored log-rank test. Results: Median age at diagnosis was 47 (range 10-83) years and median overall follow-up time was 9 (range 1-49) years. The median follow-up time of patients treated with PORT was 14 (range 1-49) years and 6 (range 134) years in patients treated with surgery alone. Four patients developed an intracranial tumour, 3 of them were treated with PORT. Twenty-one patients treated with PORT developed an extracranial tumour compared to 11 patients treated with surgery alone (RR 1.04 CI 95%, 0.50-2.17, P = 0.917). In 11 out of the 21 patients treated with PORT and diagnosed with an extracranial tumour a central body axis radiotherapy technique was used (RR 1.43 CI 95%, 0.60-3.41, P = 0.425).Forty-five patients treated with PORT died compared to 24 patients treated with surgery alone (RR 1.26 CI 95%, 0.77-2.08, P = 0.358). Conclusions: Postoperative radiotherapy did not increase the incidence of second tumours and mortality in pituitary adenoma patients. Central body axis radiotherapy technique was not associated with an increase in extracranlal tumours.

The morbidity of treatment for patients with stage I endometrial cancer: results from a randomized trial

Purpose: To compare the treatment complications for patients with Stage I endometrial cancer treated with surgery and pelvic radiotherapy (RT) or surgery alone in a multicenter randomized trial. Methods and Materials: The Postoperative Radiation Therapy in Endometrial Carcinoma (PORTEC) trial included patients with endometrial cancer confined to the uterine corpus, either Grade 1 or 2 with more than 50% myometrial invasion, or Grade 2 or 3 with less than 50% myometrial invasion. Surgery consisted of an abdominal hysterectomy and oophorectomy, without lymphadenectomy. After surgery, patients were randomized to receive pelvic RT (46 Gy), or no further treatment. A total of 715 patients were randomized. Treatment complications were graded using the French‐Italian glossary. Results: The analysis was done at a median follow-up duration of 60 months. 691 patients were evaluable. Five-year actuarial rates of late complications (Grades 1‐ 4) were 26% in the RT group and 4% in the control group (p < 0.0001). Most were Grade 1 complications, with 5-year rates of 17% in the RT group and 4% in the control group. All severe (Grade 3‐ 4) complications were observed in the RT group (3%). Most complications were of the gastrointestinal tract. The symptoms resolved after some years in 50% of the patients. Grade 1‐2 genitourinary complications occurred in 8% of the RT patients, and 4% of the controls. Bone complications occurred in 4 RT patients (1%). Seven patients (2%) discontinued their RT due to acute RT-related symptoms. Patients with acute morbidity had an increased risk of late RT complications (p 0.001). The 4-field box technique was associated with a lower risk of late complications (p 0.06). Conclusion: Pelvic RT increases the morbidity of treatment in Stage I endometrial cancer. In the PORTEC trial, severe complications occurred in 3% of treated patients, and over 20% experienced mild (mostly Grade 1) symptoms. Patients with acute RT-related morbidity had an increased risk of late complications. As pelvic RT in Stage I endometrial carcinoma was shown to significantly reduce the rate of locoregional recurrence, but without a survival benefit, its use in the adjuvant setting requires careful patient selection (treating those at increased risk of relapse), and the use of treatment schemes with the lowest risk of morbidity.