Image guided radiotherapy in curative treatment for prostate cancer. 5-year results from a randomized controlled trial (RIC-trial).

BACKGROUND: Between 2012 and 2015 we conducted a randomized controlled trial in prostate cancer patients comparing weekly 2-D portal imaging versus daily 3-D verification. AIM: To evaluate the clinical outcomes of image guided radiotherapy by presenting rectal and urinary side effects, health related quality of life and progression free survival after 5-years follow up of a randomized controlled trial. METHODS: We randomized 260 men with intermediate or high-risk prostate cancer to weekly 2-D portal imaging with 15 mm margin from CTV to PTV (Arm A) or daily 3-D cone-beam computer tomography with 7 mm margins (Arm B). Prescribed doses were 78 Gy/39 fractions. All patients received hormonal therapy. Primary end point was patient reported bowel symptoms and secondary outcomes were patient reported urinary symptoms, health- related quality of life and progression free survival. RESULTS: Of the 216 patients available for analyses at 5 years more than 90 % completed patient reported outcome measures. There were no significant differences between study arms for any single items nor scales evaluating bowel symptoms. There were also no differences in self-reported urinary symptoms nor in health-related quality of life. Symptom scores were low in both study arms. Progression free survival was similar in Arm B as compared to arm A (Hazard ratio 1.01; 95 % CI 0.57 to 1.97). CONCLUSIONS: Our results support that both 2-D weekly and 3-D daily image guided radiotherapy are safe and efficient treatments for PC and emphasize the need to evaluate technological progress in clinical trials with long follow-up.

The effect of a smoking cessation program for patients in cancer treatment: a quasi-experimental intervention study.

BACKGROUND: Compared to non-smokers, smokers have reduced effects of cancer treatment, and increased risk of treatment-related toxicity. Quitting smoking can improve treatment effects and reduce side effects. This study reports on the potential impact of a smoking cessation program on smoking cessation rates among patients in cancer treatment. MATERIAL AND METHODS: Cancer patients 18 years and older who smoked, with survival prognosis ≥12 months, not suffering dementia or other mental illness, and who were referred to cancer treatment at six Norwegian hospitals were invited to participate. The study took place from 2017 to 2020 and used a pre-test-posttest non-equivalent control group design. The intervention group received structured smoking cessation guidance based on Motivational Interviewing combined with cost-free nicotine replacement products, while the control group received standard smoking cessation treatment. Self-reported smoking status were registered at baseline and at 6 months' follow up. RESULTS: 76% of patients smoked at baseline and 44% at follow-up in the intervention group, correspondingly 72% and 49% in the control group. In an analysis of differences in within-person change, the reduction in the intervention group was 13 percentage points larger (95% CI = (0.25, -0.005), p = 0.041). Adjusting for gender, age, education, labour market participation and partnership status did not attenuate the estimated effect (18 percentage point difference, 95% CI = (-0.346, -0.016), p = 0.032). Demographic factors and dropout rate differed somewhat between the groups with a higher dropout rate in the intervention group, 54% vs. 51%, respectively). CONCLUSION: Offering a structured smoking cessation program based on Motivational Interviewing and cost-free nicotine replacement products to cancer patients can increase cessation rates in comparison to standard smoking cessation care.

Training, validation, and clinical implementation of a deep-learning segmentation model for radiotherapy of loco-regional breast cancer.

AIM: To train and validate a comprehensive deep-learning (DL) segmentation model for loco-regional breast cancer with the aim of clinical implementation. METHODS: DL segmentation models for 7 clinical target volumes (CTVs) and 11 organs at risk (OARs) were trained on 170 left-sided breast cancer cases from two radiotherapy centres in Norway. Another 30 patient cases were used for validation, which included the evaluation of Dice similarity coefficient and Hausdorff distance, qualitative scoring according to clinical usability, and relevant dosimetric parameters. The manual inter-observer variation (IOV) was also evaluated and served as a benchmark. Delineation of the target volumes followed the ESTRO guidelines. RESULTS: Based on the geometric similarity metrics, the model performed significantly better than IOV for most structures. Qualitatively, no or only minor corrections were required for 14% and 71% of the CTVs and 72% and 26% of the OARs, respectively. Major corrections were required for 15% of the CTVs and 2% of the OARs. The most frequent corrections occurred in the cranial and caudal parts of the structures. The dose coverage, based on D98 > 95%, was fulfilled for 100% and 89% of the breast and lymph node CTVs, respectively. No differences in OAR dose parameters were considered clinically relevant. The model was implemented in a commercial treatment planning system, which generates the structures in 1.5 min. CONCLUSION: Convincing results from the validation led to the decision of clinical implementation. The clinical use will be monitored regarding applicability, standardization and efficiency.

Rectal volume variations and estimated rectal dose during 8 weeks of image-guided radical 3D conformal external beam radiotherapy for prostate cancer.

•Modern IGRT has given new insight regarding organ motion in radiotherapy.•Rectal volume variation may increase the risk of biochemical and local failure.•Rectal volume decreased significantly during eight weeks of radiotherapy.•The percentage of irradiated rectal volume did not change statistically significant.•Our study shows that IGRT ensures a close to stable dose to the rectum.

Dose to penile bulb is not associated with erectile dysfunction 18 months post radiotherapy: A secondary analysis of a randomized trial.

BACKGROUND: Erectile dysfunction is a common side effect of prostate cancer (PC) therapy. In this randomized study (The RIC-study) we used patient reported outcomes to evaluate sexual function 18 months after combined endocrine therapy and radical radiotherapy (RT) given with either wide or tight planning target volume (PTV) margins. We also analyzed the impact of radiation dose to penile bulb on sexual function. METHODS: The RIC-study included 257 men with intermediate and high-risk PC. All patients received 6 months of total androgen blockage started 3 months prior to randomization. In high-risk patients, an oral anti-androgen (Bicalutamide) was administered for an additional 2.5 years. Patients were randomized to receive 78 Gy in 39 fractions guided either by weekly offline orthogonal portal imaging or by daily online cone beam computed tomography image-guided RT. Sexual function was evaluated at 18 months after start of RT using the Questionnaire Umeå Fransson Widmark 1994. Ability to have an erection was assessed on an 11-point scale numerical rating scale (0 = no and 10 = very much) as the primary outcome. In addition, the association between penile bulb (PB) radiation dose and erectile function was analyzed. FINDINGS: Of 250 evaluable patients, 228 (mean age 71.8 years) returned the questionnaires. The patients reported a high degree of sexual related problems with mean scores to the primary outcome question (221 respondents) of 7.44 and 7.39 in the 2D weekly IGRT-arm and 3D daily IGRT-arm (p = 0.93) respectively. For four additional questions (scale 0-10) regarding sexual function resulted in mean scores >6.5 with no difference between study arms. The mean dose to PB was substantially larger in the 2D weekly IGRT-arm vs the 3D daily IGRT-arm (mean 59.8 Gy vs mean 35.1 Gy).We found no effect of mean PB-dose on the primary outcome adjusted for study-site, risk-group and age. When adjusting for serum-testosterone level at 18 months in addition, the effect of mean PB-dose remained insignificant. INTERPRETATION: IGRT protocol or PB dose had no effect on ED 18 months after RT in this study population. The low potency rates can partly be explained by the prolonged use of anti-androgen in high risk patients. Longer follow-up is needed to confirm the results from the RIC-study.

Radiotherapy for prostate cancer - Does daily image guidance with tighter margins improve patient reported outcomes compared to weekly orthogonal verified irradiation? Results from a randomized controlled trial.

BACKGROUND: Novel cancer drugs are subject to strict scientific evaluation of safety and efficacy and usually undergo a cost effectiveness analysis before approval for use in clinical practice. For new techniques in radiotherapy (RT) such as image-guided radiotherapy (IGRT), this is often not the case. We performed a randomized controlled trial to compare daily cone beam computer tomography (CBCT) IGRT with reduced planning target volume (PTV) margins vs weekly orthogonal portal imaging with conventional PTV margins. The primary aim of the study was to investigate the effect of two different image guidance techniques on patient reported outcome (PRO) using early side effects as proxy outcome of late rectal side effects in patients receiving curative RT for prostate cancer. METHODS: This open label, phase 3 trial conducted at two RT centers in Norway enrolled men aged 18 years or older with previously untreated histologically proven intermediate or high-risk adenocarcinoma of the prostate. Patients eligible for radical RT received it after 3 months of total androgen blockage and were randomly assigned to 78 Gy in 39 fractions guided either by weekly offline orthogonal portal imaging (15 mm margins to PTV) or by daily online CBCT IGRT (7 mm margins to PTV). Based on previous results indicating that acute rectal side effects are a valid proxy outcome for late rectal side effects, the primary outcome was acute rectal toxicity at end of RT as evaluated by rectal bother scale (five of the items from PRO's QUFW94). The RIC-trial is registered with ClinicalTrials.gov, number NCT01550237. FINDINGS: Between October 2012 and June 2015, 257 patients were randomly assigned to weekly offline portal imaging (n = 129) or daily online CBCT IGRT (n = 128). Out of 250 evaluable patients, 96% completed PROs at baseline and 97% at end of RT. Baseline analyses demonstrated balance between groups for baseline characteristics as well as for PROs. In general, patients reported a small degree of side effects at end of RT, and there was no difference between groups for primary outcome (rectal bother scale of QUFW94 1.871 vs 1.884, p = 0.804). In addition, there were no significant differences between groups for any other gastrointestinal or urinary symptom as reported by QUFW94. Health related quality of life analyses (EORTC QLQ 30) demonstrated no differences between groups. INTERPRETATION: In radical RT for prostate cancer, daily CBCT IGRT with reduced PTV margins demonstrated no advantage with respect to patient reported side effects at end of RT as compared to weekly orthogonal offline portal imaging with standard PTV margins.

[Treatment of acute pancreatitis]. / Behandling av akutt pankreatitt.

BACKGROUND: The role of surgery in the treatment of acute pancreatitis is still unclear. The aim of this study was to evaluate and compare our results with different treatment strategies described in the literature. MATERIAL AND METHODS: From 1980 to 1998, 376 patients, 195 women and 181 men, median age of 62.5 years (15-96 years) with acute pancreatitis were treated in our hospital. The classification of the pancreatitis was based on Ranson signs (more than four defined as serious). Patients with septic necrosis/abscesses were treated with percutaneous drainage and irrigation. RESULTS: The disease was caused by gallstone in 58%, ethyl in 13%, unknown cause in 14%, and miscellaneous in 15%. In 50 patients (13%) the pancreatitis was serious. Ten patients (2.6%) died in hospital. Among all patients with serious/haemorrhagic pancreatitis the mortality was 18%. INTERPRETATION: Intensive supportive care and broad spectrum antibiotics combined with percutaneous drainage and irrigation of infected intraabdominal content in haemorrhagic pancreatitis seem to give the same results as open surgery.

[Acute gallstone pancreatitis--when should the clearance of biliary tract be performed?]. / Akutt gallesteinspankreatitt--når skal galleveiene saneres?

BACKGROUND: On the basis of a 19-year material we discuss early or delayed surgery for definitive clearance of the biliary tract after acute gallstone pancreatitis. MATERIAL AND METHODS: During 1980-98, 218 patients, 133 women and 85 men, median age 69.5 years (16-96 years) with acute gallstone pancreatitis were treated at Levanger hospital, Norway. During 1980-89 (period 1), 111 patients were mainly treated by open operations as soon as the acute pancreatitis had settled, while during 1990-98 (period 2), 107 patients were mainly treated conservatively and the biliary operations performed laparoscopically/endoscopically later. RESULTS: In period 1 two patients died, one of them after open surgery (2%). In period 2 four patients died. 21 patients were readmitted due to a new attack, two of whom died. Two patients developed acute cholecystitis. INTERPRETATION: Early surgery for the gallstone disease in patients with acute gallstone pancreatitis is well tolerated, recurrent attacks are rare and the mortality low.