The majority of childhood, Adolescent and Young Adult (AYA) cancer survivors suffers from long-lasting health issues following cancer treatment. It is therefore critical to explore effective health ...promotion strategies to address their needs. Exposure to nature is a promising approach to support the needs of young cancer survivors. This study investigated whether it is feasible to conduct a randomized controlled trial (RCT) of a wilderness program for childhood and AYA cancer survivors.
Eligible participants were aged 16-39 years, had a cancer diagnosis, and met minimal criteria. Seventy-one individuals expressed interest and 59 were randomized to either a wilderness or a holiday program. The wilderness program involved an 8-day expedition including backpacking, sea kayaking, gorge climbing, camping, bush-craft skills, and mindfulness-practices. It was followed by a 4-day basecamp after 3 months. The comparison was an 8-day holiday program at a Spa-hotel followed by a 4-day holiday program at the same hotel after 3 months. Primary outcome was study feasibility and safety.
Ultimately, 19 AYAs participated in the wilderness and 23 in the holiday program. All completed the study at one-year follow-up. Participants were mostly female (70%) and represented diverse cancers. Clinical characteristics were similar between study arms excepting greater age at cancer diagnosis in the wilderness program (age 19.1 vs. 12.5; p = 0.024). Program adherence and data completeness was high (> 90%) in both arms. Adverse Effects (AEs) in the wilderness vs. the holiday program were similar (Relative Risk: 1.0, 95% Confidence Interval 0.8-1.3). The most frequent AE was tiredness, all were mild to moderate in severity, and serious AEs were not reported. Nature connectedness significantly increased over time in the wilderness program participants, but not in the holiday program (p < 0.001). No differences were found between the two study arms regarding quality of life, self-esteem, or self-efficacy.
It is feasible to conduct a RCT and a supervised wilderness adventure is equally safe for childhood and AYA cancer survivors as a holiday program. This pilot study lays the foundation for a larger RCT to investigate the effectiveness of wilderness programs on the health of young cancer survivors.
18/02/2021, NCT04761042 (clinicaltrials.gov).
Men with metastatic castration-resistant prostate cancer (mCRPC) have an incurable disease. Along with prolonging life, symptom management is one of the main goals with treatment. This is also ...important from a palliative care perspective where the life prolonging outcomes should be balanced with quality of life (QoL) in this late phase. It is also essential in symptom management to view different dimensions of symptoms, for example how severe or distressing symptoms are, to support best QoL. Therefore, more knowledge is needed about the symptom experience when these treatments are initiated and thus the aim of this study was to describe different dimensions of symptoms in men with mCRPC starting their first-line of life-prolonging treatment, and to describe the association between symptom burden and QoL.
Baseline data from a prospective longitudinal study of 143 men with mCRPC starting their first-line life-prolonging treatment were used. Symptoms were measured using the Memorial Symptom Assessment Scale (MSAS) and global QoL was measured by the EORTC QLQ C-30. Data was analyzed using descriptive- and multivariable linear regression analyses.
On average, the men had more than 10 symptoms (range 0-31 of 33). 50% or more reported sweats, lack of energy, pain, problems with sexual activity and sexual desire. The symptoms they reported as most severe, or most distressing were not always the ones that were reported as most frequent. There was an association between QoL and physical symptoms, and also between QoL, and analgesic use and prostate-specific antigen (PSA) values.
Even if some men with mCRPC report many symptoms, the dimensions of severity and distress levels vary, and the most frequent symptoms was not always the most burdensome or distressing. There was an association between high physical symptom burden and QoL, suggesting that it is not the number of symptoms that affects QoL but rather the subjective perceived impact of the physical symptoms experienced. The knowledge of how men with mCRPC experience and perceive their symptoms may help health care professionals in symptom management aiming to improve QoL, which is a cornerstone in integrating early palliative care.
Perirectal spacers may be beneficial to reduce rectal side effects from radiotherapy (RT). Here, we present the impact of a hyaluronic acid (HA) perirectal spacer on rectal dose as well as spacer ...stability, long-term gastrointestinal (GI) and genitourinary (GU) toxicity and patient-reported outcome (PRO).
In this phase II study 81 patients with low- and intermediate-risk prostate cancer received transrectal injections with HA before external beam RT (78 Gy in 39 fractions). The HA spacer was evaluated with MRI four times; before (MR0) and after HA-injection (MR1), at the middle (MR2) and at the end (MR3) of RT. GI and GU toxicity was assessed by physician for up to five years according to the RTOG scale. PROs were collected using the Swedish National Prostate Cancer Registry and Prostate cancer symptom scale questionnaires.
There was a significant reduction in rectal V70% (54.6 Gy) and V90% (70.2 Gy) between MR0 and MR1, as well as between MR0 to MR2 and MR3. From MR1 to MR2/MR3, HA thickness decreased with 28%/32% and CTV-rectum space with 19%/17% in the middle level. The cumulative late grade ≥ 2 GI toxicity at 5 years was 5% and the proportion of PRO moderate or severe overall bowel problems at 5 years follow-up was 12%. Cumulative late grade ≥ 2 GU toxicity at 5 years was 12% and moderate or severe overall urinary problems at 5 years were 10%.
We show that the HA spacer reduced rectal dose and long-term toxicity.
A genetic perspective of human history in Europe was derived from 22 binary markers of the nonrecombining Y chromosome (NRY). Ten lineages account for >95% of the 1007 European Y chromosomes studied. ...Geographic distribution and age estimates of alleles are compatible with two Paleolithic and one Neolithic migratory episode that have contributed to the modern European gene pool. A significant correlation between the NRY haplotype data and principal components based on 95 protein markers was observed, indicating the effectiveness of NRY binary polymorphisms in the characterization of human population composition and history.
In locally advanced prostate cancer (PC), androgen deprivation therapy (ADT) in combination with whole prostate radiotherapy (RT) is the standard treatment. ADT affects the prostate as well as the ...tumour on multiparametric magnetic resonance imaging (MRI) with decreased PC conspicuity and impaired localisation of the prostate lesion. Image texture analysis has been suggested to be of aid in separating tumour from normal tissue. The aim of the study was to investigate the impact of ADT on baseline defined MRI features in prostate cancer with the goal to investigate if it might be of use in radiotherapy planning.
Fifty PC patients were included. Multiparametric MRI was performed before, and three months after ADT. At baseline, a tumour volume was delineated on apparent diffusion coefficient (ADC) maps with suspected tumour content and a reference volume in normal prostatic tissue. These volumes were transferred to MRIs after ADT and were analysed with first-order -and invariant Haralick -features.
At baseline, the median value and several of the invariant Haralick features of ADC, showed a significant difference between tumour and reference volumes. After ADT, only ADC median value could significantly differentiate the two volumes.
Invariant Haralick -features could not distinguish between baseline MRI defined PC and normal tissue after ADT. First-order median value remained significantly different in tumour and reference volumes after ADT, but the difference was less pronounced than before ADT.
Hypofractionated radiotherapy for prostate cancer has gained increased attention due to its proposed high radiation-fraction sensitivity. Recent reports from studies comparing moderately ...hypofractionated and conventionally fractionated radiotherapy support the clinical use of moderate hypofractionation. To date, there are no published randomised studies on ultra-hypofractionated radiotherapy. Here, we report the outcomes of the Scandinavian HYPO-RT-PC phase 3 trial with the aim to show non-inferiority of ultra-hypofractionation compared with conventional fractionation.
In this open-label, randomised, phase 3 non-inferiority trial done in 12 centres in Sweden and Denmark, we recruited men up to 75 years of age with intermediate-to-high-risk prostate cancer and a WHO performance status between 0 and 2. Patients were randomly assigned to ultra-hypofractionation (42·7 Gy in seven fractions, 3 days per week for 2·5 weeks) or conventional fractionated radiotherapy (78·0 Gy in 39 fractions, 5 days per week for 8 weeks). No androgen deprivation therapy was allowed. The primary endpoint was time to biochemical or clinical failure, analysed in the per-protocol population. The prespecified non-inferiority margin was 4% at 5 years, corresponding to a critical hazard ratio (HR) limit of 1·338. Physician-recorded toxicity was measured according to the Radiation Therapy Oncology Group (RTOG) morbidity scale and patient-reported outcome measurements with the Prostate Cancer Symptom Scale (PCSS) questionnaire. This trial is registered with the ISRCTN registry, number ISRCTN45905321.
Between July 1, 2005, and Nov 4, 2015, 1200 patients were randomly assigned to conventional fractionation (n=602) or ultra-hypofractionation (n=598), of whom 1180 (591 conventional fractionation and 589 ultra-hypofractionation) constituted the per-protocol population. 1054 (89%) participants were intermediate risk and 126 (11%) were high risk. Median follow-up time was 5·0 years (IQR 3·1–7·0). The estimated failure-free survival at 5 years was 84% (95% CI 80–87) in both treatment groups, with an adjusted HR of 1·002 (95% CI 0·758–1·325; log-rank p=0·99). There was weak evidence of an increased frequency of acute physician-reported RTOG grade 2 or worse urinary toxicity in the ultra-hypofractionation group at end of radiotherapy (158 28% of 569 patients vs 132 23% of 578 patients; p=0·057). There were no significant differences in grade 2 or worse urinary or bowel late toxicity between the two treatment groups at any point after radiotherapy, except for an increase in urinary toxicity in the ultra-hypofractionation group compared to the conventional fractionation group at 1-year follow-up (32 6% of 528 patients vs 13 2% of 529 patients; (p=0·0037). We observed no differences between groups in frequencies at 5 years of RTOG grade 2 or worse urinary toxicity (11 5% of 243 patients for the ultra-hypofractionation group vs 12 5% of 249 for the conventional fractionation group; p=1·00) and bowel toxicity (three 1% of 244 patients vs nine 4% of 249 patients; p=0·14). Patient-reported outcomes revealed significantly higher levels of acute urinary and bowel symptoms in the ultra-hypofractionation group compared with the conventional fractionation group but no significant increases in late symptoms were found, except for increased urinary symptoms at 1-year follow-up, consistent with the physician-evaluated toxicity.
Ultra-hypofractionated radiotherapy is non-inferior to conventionally fractionated radiotherapy for intermediate-to-high risk prostate cancer regarding failure-free survival. Early side-effects are more pronounced with ultra-hypofractionation compared with conventional fractionation whereas late toxicity is similar in both treatment groups. The results support the use of ultra-hypofractionation for radiotherapy of prostate cancer.
The Nordic Cancer Union, the Swedish Cancer Society, and the Swedish Research Council.
The HYPO-RT-PC trial compared conventionally fractionated radiotherapy with ultra-hypofractionated radiotherapy in patients with localised prostate cancer. Ultra-hypofractionation was non-inferior to ...conventional fractionation regarding 5-year failure-free survival and toxicity. We aimed to assess whether patient-reported quality of life (QOL) differs between conventional fractionation and ultra-hypofractionation up to 6 years after treatment in the HYPO-RT-PC trial.
HYPO-RT-PC is a multicentre, open-label, randomised, controlled, non-inferiority, phase 3 trial done in 12 centres (seven university hospitals and five county hospitals) in Sweden and Denmark. Inclusion criteria were histologically verified intermediate-to-high-risk prostate cancer (defined as T1c–T3a with one or two of the following risk factors: stage T3a; Gleason score ≥7; and prostate-specific antigen 10–20 ng/mL with no evidence of lymph node involvement or distant metastases), age up to 75 years, and WHO performance status 0–2. Participants were randomly assigned (1:1) to conventional fractionation (78·0 Gy in 39 fractions, 5 days per week for 8 weeks) or ultra-hypofractionation (42·7 Gy in seven fractions, 3 days per week for 2·5 weeks) via a minimisation algorithm with stratification by trial centre, T-stage, Gleason score, and prostate-specific antigen. QOL was measured using the validated Prostate Cancer Symptom Scale (PCSS) and European Organization for Research and Treatment of Cancer Quality-of-Life Questionnaire (EORTC QLQ-C30) at baseline, the end of radiotherapy, months 3, 6, 12, and 24 after radiotherapy, every other year thereafter up to 10 years, and at 15 years. The primary endpoint (failure-free survival) has been reported elsewhere. Here we report QOL, a secondary endpoint analysed in the per-protocol population, up to 6 years after radiotherapy. The HYPO-RT-PC trial is registered with the ISRCTN registry, ISRCTN45905321.
Between July 1, 2005, and Nov 4, 2015, 1200 patients were enrolled and 1180 were randomly assigned (conventional fractionation n=591, ultra-hypofractionation n=589); 1165 patients (conventional fractionation n=582, ultra-hypofractionation n=583) were included in this QOL analysis. 158 (71%) of 223 patients in the conventional fractionation group and 146 (66%) of 220 in the ultra-hypofractionation group completed questionnaires at 6 years. The median follow-up was 48 months (IQR 25–72). In seven of ten bowel symptoms or problems the proportion of patients with clinically relevant deteriorations at the end of radiotherapy was significantly higher in the ultra-hypofractionation group than in the conventional fractionation group (stool frequency p<0·0001, rush to toilet p=0·0013, flatulence p=0·0013, bowel cramp p<0·0001, mucus p=0·0014, blood in stool p<0·0001, and limitation in daily activity p=0·0014). There were no statistically significant differences in the proportions of patients with clinically relevant acute urinary symptoms or problems (total 14 items) and sexual functioning between the two treatment groups at end of radiotherapy. Thereafter, there were no clinically relevant differences in urinary, bowel, or sexual functioning between the groups. At the 6-year follow-up there was no difference in the incidence of clinically relevant deterioration between the groups for overall urinary bother (43 33% of 132 for conventional fractionation vs 33 28% of 120 for ultra-hypofractionation; mean difference 5·1% 95% CI –4·4 to 14·6; p=0·38), overall bowel bother (43 33% of 129 vs 34 28% of 123; 5·7% –3·8 to 15·2; p=0·33), overall sexual bother (75 60% of 126 vs 59 50% of 117; 9·1% –1·4 to 19·6; p=0·15), or global health/QOL (56 42% of 134 vs 46 37% of 125; 5·0% –5·0 to 15·0; p=0·41).
Although acute toxicity was higher for ultra-hypofractionation than conventional fractionation, this long-term patient-reported QOL analysis shows that ultra-hypofractionation was as well tolerated as conventional fractionation up to 6 years after completion of treatment. These findings support the use of ultra-hypofractionation radiotherapy for intermediate-to-high-risk prostate cancer.
The Nordic Cancer Union, the Swedish Cancer Society, and the Swedish Research Council.
Background The HYPO-RT-PC trial compared conventionally fractionated radiotherapy with ultra-hypofractionated radiotherapy in patients with localised prostate cancer. Ultra-hypofractionation was ...non-inferior to conventional fractionation regarding 5-year failure-free survival and toxicity. We aimed to assess whether patient-reported quality of life (QOL) differs between conventional fractionation and ultra-hypofractionation up to 6 years after treatment in the HYPO-RT-PC trial. Methods HYPO-RT-PC is a multicentre, open-label, randomised, controlled, non-inferiority, phase 3 trial done in 12 centres (seven university hospitals and five county hospitals) in Sweden and Denmark. Inclusion criteria were histologically verified intermediate-to-high-risk prostate cancer (defined as T1c-T3a with one or two of the following risk factors: stage T3a; Gleason score &gt;= 7; and prostate-specific antigen 10-20 ng/mL with no evidence of lymph node involvement or distant metastases), age up to 75 years, and WHO performance status 0-2. Participants were randomly assigned (1:1) to conventional fractionation (78.0 Gy in 39 fractions, 5 days per week for 8 weeks) or ultra-hypofractionation (42.7 Gy in seven fractions, 3 days per week for 2.5 weeks) via a minimisation algorithm with stratification by trial centre, T-stage, Gleason score, and prostate-specific antigen. QOL was measured using the validated Prostate Cancer Symptom Scale (PCSS) and European Organization for Research and Treatment of Cancer Quality-of-Life Questionnaire (EORTC QLQ-C30) at baseline, the end of radiotherapy, months 3, 6, 12, and 24 after radiotherapy, every other year thereafter up to 10 years, and at 15 years. The primary endpoint (failure-free survival) has been reported elsewhere. Here we report QOL, a secondary endpoint analysed in the perprotocol population, up to 6 years after radiotherapy. The HYPO-RT-PC trial is registered with the ISRCTN registry, ISRCTN45905321. Findings Between July 1, 2005, and Nov 4, 2015, 1200 patients were enrolled and 1180 were randomly assigned (conventional fractionation n=591, ultra-hypofractionation n=589); 1165 patients (conventional fractionation n=582, ultra-hypofractionation n=583) were included in this QOL analysis. 158 (71%) of 223 patients in the conventional fractionation group and 146 (66%) of 220 in the ultra-hypofractionation group completed questionnaires at 6 years. The median follow-up was 48 months (IQR 25-72). In seven of ten bowel symptoms or problems the proportion of patients with clinically relevant deteriorations at the end of radiotherapy was significantly higher in the ultra-hypofractionation group than in the conventional fractionation group (stool frequency p&lt;0.0001, rush to toilet p=0.0013, flatulence p=0.0013, bowel cramp p&lt;0.0001, mucus p=0.0014, blood in stool p&lt;0.0001, and limitation in daily activity p=0.0014). There were no statistically significant differences in the proportions of patients with clinically relevant acute urinary symptoms or problems (total 14 items) and sexual functioning between the two treatment groups at end of radiotherapy. Thereafter, there were no clinically relevant differences in urinary, bowel, or sexual functioning between the groups. At the 6-year followup there was no difference in the incidence of clinically relevant deterioration between the groups for overall urinary bother (43 33% of 132 for conventional fractionation vs 33 28% of 120 for ultra-hypofractionation; mean difference 5.1% 95% CI -4.4 to 14.6; p=0.38), overall bowel bother (43 33% of 129 vs 34 28% of 123; 5.7% -3.8 to 15.2; p=0.33), overall sexual bother (75 60% of 126 vs 59 50% of 117; 9.1% -1.4 to 19.6; p=0.15), or global health/QOL (56 42% of 134 vs 46 37% of 125; 5.0% -5.0 to 15.0; p=0.41). Interpretation Although acute toxicity was higher for ultra-hypofractionation than conventional fractionation, this long-term patient-reported QOL analysis shows that ultra-hypofractionation was as well tolerated as conventional fractionation up to 6 years after completion of treatment. These findings support the use of ultra-hypofractionation radiotherapy for intermediate-to-high-risk prostate cancer.
This study was designed to investigate the possible relationship between the protein expression of basic fibroblast growth factor (bFGF) and vascular endothelial growth factor (VEGF) with p53 status, ...breast cancer prognostic factors, metastatic site, and survival after adjuvant therapy. Basic fibroblast growth factor and VEGF expression were determined by enzyme-linked immunosorbent assays in cytosol specimens obtained from 1307 patients with T1-3 primary breast cancer (789 node-negative, 518 node-positive) diagnosed between 1990 and 1997. The median follow-up time was 70 months. Increased bFGF expression was more frequently found in tumors with low VEGF expression (r = —0.286;
P = 0.095). Increased bFGF was associated with smaller tumors (
P < 0.001), absence of axillary metastasis (
P = 0.003), low S-phase fraction (
P < 0.001), and longer recurrencefree survival (RFS;
P = 0.0038) and overall survival (OS;
P = 0.0316). Vascular endothelial growth factor was a prognostic factor for RFS (
P < 0.0001) and OS (
P < 0.0001) in univariate and multivariate analyses (RFS: 95% CI, 1.1–1.7;
P = 0.036; OS: 95% CI, 1.2–2.2;
P = 0.002), whereas bFGF expression was not correlated with RFS or OS. Increased VEGF content was correlated with shorter survival after adjuvant endocrine therapy (RFS,
P = 0.0004; OS,
P = 0.0009). Patients with estrogen receptor—negative disease were excluded from the analysis. Basic fibroblast growth factor was not a prognostic factor after adjuvant systemic therapy, nor was it related to metastatic site. Expression of VEGF is an independent prognostic factor for patients with primary breast cancer. High bFGF expression was related to good prognostic features and longer survival times, but did not add prognostic information in multivariate analysis. The results might implicate that different angiogenic pathways exist in human breast cancer.
Adiposity traits have been associated with risk of many cancers in observational studies, but whether these associations are causal is unclear. Mendelian randomization (MR) uses genetic predictors of ...risk factors as instrumental variables to eliminate reverse causation and reduce confounding bias. We performed MR analyses to assess the possible causal relationship of birthweight, childhood and adult body mass index (BMI), and waist-hip ratio (WHR) on the risks of breast, ovarian, prostate, colorectal and lung cancers.
We tested the association between genetic risk scores and each trait using summary statistics from published genome-wide association studies (GWAS) and from 51 537 cancer cases and 61 600 controls in the Genetic Associations and Mechanisms in Oncology (GAME-ON) Consortium.
We found an inverse association between the genetic score for childhood BMI and risk of breast cancer odds ratio (OR) = 0.71 per standard deviation (s.d.) increase in childhood BMI; 95% confidence interval (CI): 0.60, 0.80; P = 6.5 × 10(-5)). We also found the genetic score for adult BMI to be inversely associated with breast cancer risk (OR = 0.66 per s.d. increase in BMI; 95% CI: 0.57, 0.77; P = 2.5 × 10(-7)), and positively associated with ovarian cancer (OR = 1.35; 95% CI: 1.05, 1.72; P = 0.017), lung cancer (OR = 1.27; 95% CI: 1.09, 1.49; P = 2.9 × 10(-3)) and colorectal cancer (OR = 1.39; 95% CI: 1.06, 1.82, P = 0.016). The inverse association between genetically predicted adult BMI and breast cancer risk remained even after adjusting for directional pleiotropy via MR-Egger regression.
Findings from this study provide additional understandings of the complex relationship between adiposity and cancer risks. Our results for breast and lung cancer are particularly interesting, given previous reports of effect heterogeneity by menopausal status and smoking status.
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