Standardizing Integrated Oncology and Palliative Care Across Service Levels: Challenges in Demonstrating Effects in a Prospective Controlled Intervention Trial.

INTRODUCTION: Patients with cancer often want to spend their final days at home. In Norway, most patients with cancer die in institutions. We hypothesized that full integration of oncology and palliative care services would result in more time spent at home during end-of-life. METHODS: A prospective non-randomized intervention trial was conducted in two rural regions of Mid-Norway. The hospitals' oncology and palliative care outpatient clinics and surrounding communities participated. An intervention including information, education, and a standardized care pathway was developed and implemented. Adult non-curative patients with cancer were eligible. Proportion of last 90 days of life spent at home was the primary outcome. RESULTS: We included 129 patients in the intervention group (I) and 76 patients in the comparison group (C), of whom 82% of patients in I and 78% of patients in C died during follow-up. The mean proportion of last 90 days of life spent at home was 0.62 in I and 0.72 in C (p = 0.044), with 23% and 36% (p = 0.073), respectively, dying at home. A higher proportion died at home in both groups compared to pre-study level (12%). During the observation period the comparison region developed and implemented an alternative intervention to the study intervention, with the former more focused on end-of-life care. CONCLUSION: A higher proportion of patients with cancer died at home in both groups compared to pre-study level. Patients with cancer in I did not spend more time at home during end-of-life compared to those in C. The study intervention focused on the whole disease trajectory, while the alternative intervention was more directed towards end-of-life care. "Simpler" and more focused interventions on end-of-life care may be relevant for future studies on integration of palliative care into oncology. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02170168.

Palliative care is an important part of cancer care to improve patients' quality of life. To be cared for and die in the preferred place are quality markers in palliative care. Patients with cancer often want to spend their final days at home. In Norway, most patients with cancer die in institutions. We hypothesized that full integration of cancer and palliative care would result in more time spent at home during end-of-life. An intervention that included information, education, and a standardized care pathway was developed and implemented in a region of Mid-Norway (the intervention region, I). A similar region served as comparison region (C). Adult patients with cancer treated with non-curative intent were eligible. Altogether, 129 patients in I and 76 patients in C were included in the study, of whom 82% in I and 78% in C died during follow-up. The mean proportion of time spent at home last 90 days of life was 0.62 in I and 0.72 in C (p = 0.044), and 22.6% and 35.6% (p = 0.073) died at home, respectively. A higher proportion died at home in both groups compared to pre-study national levels (12%). During the study period, C developed and implemented an alternative intervention to the study intervention, with the former placing more focus on end-of-life care compared to the she study intervention that focused on the whole disease trajectory. This may explain why the intervention did not result in more time spent at home during end-of-life as compared to C. "Simpler" interventions directed towards the study's primary outcome may be relevant for future studies on integration of palliative care into oncology.

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.

Barriers and Facilitators When Implementing Electronic Patient-Reported Outcome Measures at a Municipal Cancer Care Unit: A Qualitative Study.

BACKGROUND: Few qualitative studies of barriers and facilitators when implementing electronic patient-reported outcome measure (ePROM) in municipal cancer care exist within the large body of symptom assessment research. Such data, gathered from healthcare professionals' (HCPs) perspective, are central to the development and design of sustainable interventions aiming for a systematic and patient-centered symptom assessment to patients with cancer. OBJECTIVE: The aim of this study was to identify and explore barriers and facilitators, as described by HCPs, in the implementation of the ePROM application "Eir" at a municipal cancer care unit in Norway. METHODS: The study applies a qualitative method, conducting an inductive data inquiry of semistructured individual interviews and focus groups with 14 Norwegian HCPs. Analysis was inspired by thematic analysis as described by Braun and Clarke. RESULTS: The analysis revealed 3 main themes affecting the implementation of ePROM in municipal cancer care: "achieving patient-centered care," "crucial management and training," and "technological barriers." CONCLUSION: The results from this study suggest that HCPs' motivation plays a significant role when implementing ePROM. Motivation of HCPs was strongly influenced by whether the application added value to previously used symptom assessment. Hands-on management and a multiprofessional approach enabled the implementation by facilitating adaptations, training, and resources. IMPLICATIONS FOR PRACTICE: The findings show that adapting the implementation of ePROMs to patient population could be of major importance. Early integration of ePROMs in cancer care could facilitate use throughout the disease trajectory.

Clinical experience of volumetric-modulated flattening filter free stereotactic body radiation therapy of lesions in the lung with deep inspiration breath-hold.

This clinical study aimed to evaluate lung cancer patients' ability to perform deep inspiration breath-hold (DIBH) during CT simulation and throughout the treatment course of stereotactic body radiation therapy (SBRT). In addition, target sizes, organ at risk (OAR) sizes, and doses to the respective volumes in filter-free volumetric-modulated arc therapy plans performed under free-breathing (FB) and DIBH conditions were evaluated. Twenty-one patients with peripheral lesions were included, of which 13 were eligible for SBRT. All patients underwent training for breath-hold during CT, and if they complied with the requirements, two CT scans were obtained: CT scan in DIBH and a four-dimensional CT scan in FB. The treatment plans in FB and DIBH were generated, and the dose parameters and volume sizes were compared. The endpoints for evaluation were patient compliance, target dose coverage, and doses to the OARs. This clinical study showed high patient DIBH compliance during both CT simulation and treatment for patients with lung cancer. A significant reduction in target volumes was achieved with SBRT in DIBH, in addition to significantly decreased doses to the heart, chest wall, and lungs. DIBH in SBRT of lung lesions is feasible, and a routine to manage intra-fractional deviation should be established upon implementation.

Improving public cancer care by implementing precision medicine in Norway: IMPRESS-Norway.

BACKGROUND: Matching treatment based on tumour molecular characteristics has revolutionized the treatment of some cancers and has given hope to many patients. Although personalized cancer care is an old concept, renewed attention has arisen due to recent advancements in cancer diagnostics including access to high-throughput sequencing of tumour tissue. Targeted therapies interfering with cancer specific pathways have been developed and approved for subgroups of patients. These drugs might just as well be efficient in other diagnostic subgroups, not investigated in pharma-led clinical studies, but their potential use on new indications is never explored due to limited number of patients. METHODS: In this national, investigator-initiated, prospective, open-label, non-randomized combined basket- and umbrella-trial, patients are enrolled in multiple parallel cohorts. Each cohort is defined by the patient's tumour type, molecular profile of the tumour, and study drug. Treatment outcome in each cohort is monitored by using a Simon two-stage-like 'admissible' monitoring plan to identify evidence of clinical activity. All drugs available in IMPRESS-Norway have regulatory approval and are funded by pharmaceutical companies. Molecular diagnostics are funded by the public health care system. DISCUSSION: Precision oncology means to stratify treatment based on specific patient characteristics and the molecular profile of the tumor. Use of targeted drugs is currently restricted to specific biomarker-defined subgroups of patients according to their market authorization. However, other cancer patients might also benefit of treatment with these drugs if the same biomarker is present. The emerging technologies in molecular diagnostics are now being implemented in Norway and it is publicly reimbursed, thus more cancer patients will have a more comprehensive genomic profiling of their tumour. Patients with actionable genomic alterations in their tumour may have the possibility to try precision cancer drugs through IMPRESS-Norway, if standard treatment is no longer an option, and the drugs are available in the study. This might benefit some patients. In addition, it is a good example of a public-private collaboration to establish a national infrastructure for precision oncology. Trial registrations EudraCT: 2020-004414-35, registered 02/19/2021; ClinicalTrial.gov: NCT04817956, registered 03/26/2021.

Implementing a Standardized Care Pathway Integrating Oncology, Palliative Care and Community Care in a Rural Region of Mid-Norway.

INTRODUCTION: To improve quality across levels of care, we developed a standardized care pathway (SCP) integrating palliative and oncology services for hospitalized and home-dwelling palliative cancer patients in a rural region. METHODS: A multifaceted implementation strategy was directed towards a combination of target groups. The implementation was conducted on a system level, and implementation-related activities were registered prospectively. Adult patients with advanced cancer treated with non-curative intent were included and interviewed. Healthcare leaders (HCLs) and healthcare professionals (HCPs) involved in the development of the SCP or exposed to the implementation strategy were interviewed. In addition, HCLs and HCPs exposed to the implementation strategy answered standardized questionnaires. Hospital admissions were registered prospectively. RESULTS: To assess the use of the SCP, 129 cancer patients were included. Fifteen patients were interviewed about their experiences with the patient-held record (PHR). Sixty interviews were performed among 1320 HCPs exposed to the implementation strategy. Two hundred and eighty-seven HCPs reported on their training in and use of the SCP. Despite organizational cultural differences, developing an SCP integrating palliative and oncology services across levels of care was feasible. Both HCLs and HCPs reported improved quality of care in the wake of the implementation process. Two and a half years after the implementation was launched, 28% of the HCPs used the SCP and 41% had received training in its use. Patients reported limited use and benefit of the PHR. CONCLUSION: An SCP may be a usable tool for integrating palliative and oncology services across care levels in a rural region. An extensive implementation process resulted in improvements of process outcomes, yet still limited use of the SCP in clinical practice. HCLs and HCPs reported improved quality of cancer care following the implementation process. Future research should address mandatory elements for usefulness and successful implementation of SCPs for palliative cancer patients.

When a patient has incurable cancer, it is beneficial to introduce palliative care early in the disease trajectory along with anti-cancer treatment. A standardized care pathway is a method to improve quality and reduce variation in healthcare. It can promote integrated healthcare services in palliative care, e.g. by specifying action points when the patient's situation is changing. In this study, a standardized care pathway for cancer patients with palliative care needs was developed in a rural region of Norway. The pathway focused on patients' needs and symptoms and on smooth transition between levels of care. An educational program and an information strategy were developed to ensure implementation. To evaluate the implementation, all activity regarding the implementation process was registered. Cancer patients and healthcare professionals were interviewed and answered questionnaires. One thousand three hundred and twenty healthcare professionals were exposed to the implementation strategy. One hundred and twenty-nine cancer patients were followed up according to the standardized care pathway. Despite different perspectives of care, it was feasible to develop a standardized care pathway for palliative cancer patients across care settings. A paper-based patient-held record was only found to be useful by a limited number of patients. An extensive implementation process was completed and resulted in improvements regarding healthcare professionals' experience with the quality of cancer care in the region, but limited use of the care pathway in clinical practice. Further research should identify the most important elements for usefulness and successful implementation of the care pathway.

Clinical Predictors for Analgesic Response to Radiotherapy in Patients with Painful Bone Metastases.

BACKGROUND: Radiotherapy (RT) reduces pain in about 60% of patients with painful bone metastases, leaving many patients without clinical benefit. This study assesses predictors for RT effectiveness in patients with painful bone metastases. MATERIALS AND METHODS: We included adult patients receiving RT for painful bone metastases in a multicenter, multinational longitudinal observational study. Pain response within 8 weeks was defined as ≥2-point decrease on a 0-10 pain score scale, without increase in analgesics; or a decrease in analgesics of ≥25% without increase in pain score. Potential predictors were related to patient demographics, RT administration, pain characteristics, tumor characteristics, depression and inflammation (C-reactive protein [CRP]). Multivariate logistic regression analysis with multiple imputation of missing data were applied to identify predictors of RT response. RESULTS: Of 513 eligible patients, 460 patients (90 %) were included in the regression model. 224 patients (44%, 95% confidence interval (CI) 39%-48%) responded to RT. Better Karnofsky performance status (Odds ratio (OR) 1.39, CI 1.15-1.68), breast cancer (OR 2.54, CI 1.12-5.73), prostate cancer (OR 2.83, CI 1.27-6.33) and soft tissue expansion (OR 2.00, CI 1.23-3.25) predicted RT response. Corticosteroids were a negative predictor (OR 0.57, CI 0.37-0.88). Single and multiple fraction RT had similar response. The discriminative ability of the model was moderate; C-statistic 0.69. CONCLUSION: This study supports previous findings that better performance status and type of cancer diagnosis predicts analgesic RT response, and new data showing that soft tissue expansion predicts RT response and that corticosteroids is a negative predictor for RT response in patients with painful bone metastases.

Fully Integrated Oncology and Palliative Care Services at a Local Hospital in Mid-Norway: Development and Operation of an Innovative Care Delivery Model.

INTRODUCTION: Early access to cancer palliative care is recommended. Descriptions of structures and processes of outpatient palliative care clinics operated within smaller hospitals are scarce. This paper presents the development and operation of a fully integrated cancer and palliative care outpatient clinic at a local hospital in a rural region of Mid-Norway offering palliative care concurrent with cancer treatment. A standardized care pathway was applied. METHODS: Palliative care is in Norway part of the public healthcare system. Official recommendations recent years point out action points to improve delivery of palliative care. An integrated cancer and palliative care outpatient clinic at a local hospital and an innovative care delivery model was developed and operated in this setting. Patients were recruited for a descriptive study of the patient population. Clinical data were collected by clinical staff and 13 symptom intensities were reported by the patients. RESULTS: Cancer and palliative care were provided by one team of healthcare professionals trained in both fields. There was a close collaboration with the other departments at the hospital, with its affiliated tertiary hospital, and with community health and care services to provide timely referral, enhanced continuity, and improved coordination of care. Eighty-eight patients were included. Mean age was 65.6 years, the most common cancer diagnoses were digestive organs (22.7%), male genital organs (20.5%) or breast (25.0%), 75.0% had metastatic or locally advanced cancer, 59.1% were treated with non-curative intention and 93.1% had Karnofsky Performance Status ≥ 80%. Median scores of individual symptoms ranged from 0 to 3 (numerical rating scale, 0-10) and 61.0% reported at least one clinically significant symptom rating (≥ 4). CONCLUSION: This delivery model of integrated outpatient cancer and palliative care is particularly relevant in rural regions allowing cancer patients access to palliative care earlier in the disease trajectory and closer to home.

Palliative care is an important part of cancer care which aims at improving cancer patients' symptom burden and quality of life and support their carers. Palliative care has traditionally been separated from cancer care. During the last decade, one has become aware of the benefits of introducing palliative care early and concurrent with cancer treatment. Most cancer patients are nowadays treated as outpatients. Availability of palliative care as a routine part of outpatient cancer clinics is therefore important. Most of the described models of early palliative care in cancer care are within large tertiary hospitals. Here it is described how early palliative care was delivered to cancer patients in an outpatient clinic in a smaller hospital in a rural region of Mid-Norway. In this integrated cancer and palliative care outpatient clinic, cancer and palliative care were provided by one team of healthcare professionals trained in both fields. The integrated outpatient clinic collaborated closely with the other hospital departments and with community health and care services. This was needed to be able to offer palliative care to all cancer patients in need of it, and closer to their home. Many of the patients attending the integrated outpatient clinic could not be cured for their cancer. They did not have many symptoms of their cancer, and they had a high functional status. This demonstrated that the integrated outpatient clinic in this local hospital was a relevant place to offer palliative care early and concurrent with cancer treatment before symptoms became severe.

Physical rehabilitation in patients with head and neck cancer: Impact on health-related quality of life and suitability of a post-treatment program.

OBJECTIVE: Physical rehabilitation programs hold the potential to mitigate deterioration in health-related quality of life (HRQoL) in patients with head and neck cancer. The objective was to assess development in relevant domains of HRQoL following a physical exercise and nutrition intervention administrated during or after treatment. METHODS: In a pilot study, 41 patients were randomized to resistance training and oral nutritional supplements during (EN-DUR, n = 20) or after (EN-AF, n = 21) radiotherapy. Global health status/QoL (GHS) and physical functioning (PF) were measured by the European Organization for Research and Treatment of Cancer (EORTC) quality of life questionnaire at baseline, week 6, and week 14. Differences between the groups were assessed by analysis of covariance. A difference of ≥10 points in GHS and PF was interpreted as clinically relevant. RESULTS: No statistically significant differences were detected between the groups; however, clinically relevant changes and differences in GHS and PF were observed. From baseline to week 6, GHS decreased 9 points in the EN-DUR group and 23 points in the EN-AF group and PF decreased 13 points and 21 points, respectively. From week 6 to week 14, GHS increased 14 points in the EN-DUR group and 26 points EN-AF group and PF did not change (0 points) in the EN-DUR group and increased 16 points in the EN-AF group. CONCLUSION: The findings from the present pilot study are promising and indicate that a physical rehabilitation program may have a positive impact on HRQoL during treatment and enhance recovery after treatment. A definitive randomized trial is warranted. LEVEL OF EVIDENCE: 1b-Individual randomized controlled trial.

Second Cancers in Patients With Locally Advanced Prostate Cancer Randomized to Lifelong Endocrine Treatment With or Without Radical Radiation Therapy: Long-Term Follow-up of the Scandinavian Prostate Cancer Group-7 Trial.

BACKGROUND: Curative radiation therapy (RT) constitutes a cornerstone in prostate cancer (PC) treatment. We present long-term follow-up estimates for second cancer (SC) risk and overall survival (OS) in patients randomized to hormone therapy (ET) alone or combined with 70 Gy prostatic RT in the Scandinavian Prostate Cancer Group-7 (SPCG-7) study. We explored the effect of salvage RT (≥60 Gy to the ET group) and reported causes of death. METHODS AND MATERIALS: The SPCG-7 study (1996-2002) was a randomized controlled trial that included 875 men with locally advanced nonmetastatic PC. In this analysis, including data from the Norwegian and Swedish Cancer and Cause of Death registries for 651 Norwegian and 209 Swedish study patients, we estimated hazard ratios (HRs) for SC and death, and cumulative incidences of SC. RESULTS: Median follow-up of the 860 (431 ET and 429) ET + RT patients was 12.2 years for SC risk analysis and 12.6 years for the OS analysis. Eighty-three of the Norwegian ET patients received salvage RT, and median time to salvage RT was 5.9 years. We found 125 and 168 SCs in the ET and ET + RT patients, respectively. With ET alone as reference, ET + RT patients had an HR of 1.19 (95% confidence interval [CI], 0.92-1.54) for all SCs and 2.54 (95% CI, 1.14-5.69) for urinary bladder cancer (UBC). The total number of UBC was 31 (23 in ET + RT; 8 in ET), and the vast majority (85%) were superficial. The HR for SC in salvage RT patients was 0.48 (95% CI, 0.24-0.94). Median OS was 12.8 (95% CI, 11.8-13.8) and 15.3 (95%, CI 14.3-16.4) years in the ET and ET + RT groups, respectively. Compared with ET alone, the risk of death was reduced in ET + RT patients (HR, 0.73; 95% CI, 0.62-0.86) and in ET patients receiving salvage RT (HR, 0.44; 95% CI, 0.30-0.65). CONCLUSIONS: Although the risk of UBC was increased in PC patients who received RT in addition to ET, this disadvantage is outweighed by the OS benefit of RT confirmed in our study. The risk of SC, and especially UBC, should be discussed with patients and be reflected in follow-up programs.

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.

Second cancers in radically treated Norwegian prostate cancer patients.

Introduction: The aim of this registry-based cohort study was to estimate second cancer (SC) risk following radical prostate cancer (PC) treatment and evaluate if the risk was influenced by radiotherapy. Materials and methods: We collected data from the Cancer Registry of Norway on all patients with PC as first cancer diagnosis, from 1997 to 2014. Standardized incidence ratios (SIRs) for SC were calculated by comparing our cohort to the standard male population. Subdistribution hazard ratios were estimated in treatment groups, using patients treated with radical prostatectomy (RP) as reference. Results: We analyzed 24,592 radically treated PC patients. The median follow-up was 7.75 and 6.25 years in the external beam radiotherapy (EBRT) and RP-groups, respectively. SIR for SC was indifferent from the reference population in 24,592 radically treated patients, higher following EBRT, SIR 1.12 (1.07-1.17), and lower following RP, SIR 0.93 (0.87-0.99). EBRT treated patients had higher rectal and urinary bladder cancer incidences, SIR 1.38 (1.16-1.64) and 1.49 (1.31-1.69), respectively. The EBRT patients and the patients treated with radiation after RP (RT after RP) had 38 and 27% higher risk of any SC. We found higher risk of bladder cancer for all treatment groups as compared to RP patients. Only EBRT treated patients showed higher risk of rectal and lung cancer. Discussion/conclusions: In our study, we found that PC patients treated with EBRT had an increased incidence of SC compared to the general population. Patients treated with EBRT and RT after RP were found to have increased risk of SCs, using RP patients as reference. The risks of rectal and urinary bladder cancer in patients receiving EBRT were higher compared to both the general population and to patients treated with radical prostatectomy. The risk of SC should be taken into account when discussing treatment for patients and designing follow-up.

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.

The Palliative Radiotherapy and Inflammation Study (PRAIS) - protocol for a longitudinal observational multicenter study on patients with cancer induced bone pain.

BACKGROUND: Radiation therapy (RT) results in pain relief for about 6 of 10 patients with cancer induced bone pain (CIBP) caused by bone metastases. The high number of non-responders, the long median time from RT to pain response and the risk of adverse effects, makes it important to determine predictors of treatment response. Clinical features such as cancer type, performance status and pain intensity, and biomarkers for osteoclast activity are proposed as predictors of response to RT. However, results are inconsistent and there is a need for better predictors of RT response. A similar argument can be stated for the development of cachexia; there are currently no predictors that can identify patients who will develop cachexia later in the cancer disease trajectory. Experimental and preclinical studies show that pain, depression and cachexia are related to inflammation. However, it is not known if inflammatory biomarkers can predict CIBP, depression or development of cachexia. METHODS: This multicenter, multinational longitudinal observational study will include 600 adult patients receiving RT for CIBP. Demographic data, clinical variables, osteoclast and inflammatory biomarkers will be assessed before start of RT, and 3, 8, 16, 24 and 52 weeks after last course of RT. The primary aim of the study is to identify potential predictors for pain relief from RT. Secondary aims are to explore potential predictors for development of cachexia, the longitudinal relationship between pain intensity and depression, and if inflammatory biomarkers are associated with changes in pain intensity, cachexia and depression during one-year follow up. DISCUSSION: The immediate clinical implication of the PRAIS study is to identify potential predictive factors for a RT response on CIBP, and thereby reduce non-efficacious RT. Patient benefits are fewer hospital visits, reduced risk of adverse effects and more individualized pain treatment. The long-term clinical implication of the PRAIS study is to improve the knowledge about inflammation in relation to CIBP, cachexia and depression and potentially identify associations and mechanisms that can be targeted for treatment. TRIAL REGISTRATION: ClinicalTrials.gov NCT02107664 , date of registration April 8, 2014 (retrospectively registered). TRIAL SPONSOR: The European Palliative Care Research Centre (PRC), Department of Clinical and Molecular Medicine, NTNU, Faculty of medicine and Health Sciences, Trondheim, N-7491, Norway.

International validation of the EORTC QLQ-PRT20 module for assessment of quality of life symptoms relating to radiation proctitis: a phase IV study.

BACKGROUND: Although patients experience radiation proctitis post radiotherapy no internationally tested instruments exist to measure these symptoms. This Phase IV study tested the scale structure, reliability and validity and cross-cultural applicability of the EORTC proctitis module (QLQ-PRT23) in patients who were receiving pelvic radiotherapy. METHODS: Patients (n = 358) from six countries completed the EORTC QLQ-C30, QLQ-PRT23 and EORTC Quality of Life Group debriefing questions. Clinicians completed the EORTC Radiation Therapy Oncology Group scale. Questionnaires were completed at four time-points. The module's scale structure was examined and validated using standard psychometric analysis techniques. RESULTS: Three items were dropped from the module (QLQ-PRT23 → QLQ-PRT20). Factor analysis identified five factors in the module: bowel control; bloating and gas; emotional function/lifestyle; pain; and leakage. Inter-item correlations were within r = 0.3-0.7. Test-Retest reliability was high. All multi-item scales discriminated between patients showing symptoms and those without symptomology. The module discriminated symptoms from the clinician completed scoring and for age, gender and comorbidities. CONCLUSION: The EORTC QLQ-PRT20 is designed to be used in addition to the EORTC QLQ-C30 to measure quality of life in patients who receive pelvic radiotherapy. The EORTC QLQ-PRT20 is quick to complete, acceptable to patients, has good content validity and high reliability. TRIAL REGISTRATION: Australian and New Zealand Clinical Trials Registry (ANZCTR) ACTRN12609000972224 .

Does Prophylactic Radiation Therapy to Avoid Gynecomastia in Patients With Prostate Cancer Increase the Risk of Breast Cancer?

PURPOSE: Prostate cancer (PC) patients who undergo antiandrogen monotherapy are offered prophylactic radiation therapy (PRT) to the breast buds to avoid gynecomastia. The aim of the present study was to evaluate whether the risk of breast cancer (BC) in men with PC as their first cancer diagnosis was influenced by PRT. METHODS AND MATERIALS: From the Norwegian Cancer Registry, we collected data from all patients with PC as their first cancer diagnosis from 1997 to 2014. We registered all RT given to the patients in the same period and the occurrence of BC diagnosed ≥3 months after the PC diagnosis. The histopathologic diagnoses of all BC cases were collected. Subdistribution hazard ratios for the risk of BC in the PRT and non-PRT groups were estimated. A standardized incidence ratio for BC was calculated by comparing our cohort to the standard male population. RESULTS: We analyzed 59,169 patients with PC, of whom 7864 (13.3%) had received PRT. The median follow-up time was 4 years. Of the 12 men with a diagnosis of BC, 3 had received PRT, and 2 of the 3 were phyllodes tumors. The risk of BC was not significantly different statistically for the patients given PRT compared with the non-PRT group (subdistribution hazard ratio 1.62, 95% confidence interval 0.41-5.62, adjusted for age and time of diagnosis). The standardized incidence ratio was 0.996 (95% confidence interval 0.57-1.75). CONCLUSIONS: In this registry-based study, we did not find an increased risk of BC in PC patients who received PRT. The number of BC cases in our study was low, and the risk of secondary BC after PRT seems to be negligible. The incidence of BC could, however, increase with additional follow-up. Also, 2 patients who had received PRT developed a malignant phyllodes tumor, an extremely rare type of BC associated with gynecomastia.

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.