Patient reported outcomes following MR-guided radiotherapy for prostate cancer: a systematic review and meta-analysis.

PURPOSE: This systematic review provides an overview of literature on the impact of MR-guided radiotherapy (MRgRT) on patient reported outcomes (PROs) in patients with prostate cancer (PC). METHODS: A systematic search was performed in October 2023 in PubMed, EMBASE and Cochrane Library. The PICOS framework (i.e., patient, intervention, comparison, outcome, study design) was used to determine eligibility criteria. Included were studies assessing PROs following MRgRT for PC with sample size >10. Methodological quality was assessed using the ROBINS-I and RoB 2. Relevant mean differences (MD) compared to pre-RT were interpreted using minimal important differences (MID). Meta-analyses were performed using random-effects models. Between-study heterogeneity was assessed using the I2-statistic. RESULTS: Eleven observational studies and one randomized controlled trial (n=897) were included. Nine studies included patients with primary PC with MRgRT as first-line treatment (n=813) and three with MRgRT as second-line treatment (n=84). Substantial risk of bias was found in five studies. EORTC QLQ-C30 and EORTC QLQ-PR25 scores were pooled from three studies, and EPIC-26 scores from four studies. Relevant MDs for the urinary domain were found with the EPIC-26 (MD-10.0 [95%CI -12.0 - -8.1]; I20%) and the EORTC QLQ-PR25 (MD8.6 [95%CI -4.7-22.0]; I297%), both at end-RT to one month follow-up. Relevant MDs for the bowel domain were found with the EPIC-26 (MD-4.7 [95%CI -9.2 - -0.2]; I282%), at end-RT or one month follow-up, but not with the EORTC QLQ-PR25. For both domains, no relevant MDs were found after three months of follow-up. No relevant MDs were found in the general QoL domains of the EORTC QLQ-C30. CONCLUSION: MRgRT for PC results in a temporarily worsening of patient-reported urinary and bowel symptoms during the first month after treatment compared to pre-RT, resolving at 3 months. No clinically relevant changes were found for general QoL domains. These results provide important information for patient counseling and can serve as a benchmark for future studies.

Quality of life and clinical outcomes in rectal cancer patients treated on a 1.5T MR-Linac within the MOMENTUM study.

Background and purpose: This study assessed quality of life (QoL) and clinical outcomes in rectal cancer patients treated with magnetic resonance (MR) guided short-course radiation therapy (SCRT) on a 1.5 Tesla (T) MR-Linac during the first 12 months after treatment. Materials and methods: Rectal cancer patients treated with 25 Gy SCRT in five fractions with curative intent in the Netherlands (2019-2022) were identified in MOMENTUM (NCT04075305). Toxicity (CTCAE v5) and QoL (EORTC QLQ-C30 and -CR29) was primarily analyzed in patients without metastatic disease (M0) and no other therapies after SCRT. Patients who underwent tumor resection were censored from surgery. A generalized linear mixed-model was used to investigate clinically meaningful (≥10) and significant (P < 0.05) QoL changes. Clinical and pathological complete response (cCR and pCR) rates were calculated in patients in whom response was documented. Results: A total of 172 patients were included, of whom 112 patients were primarily analyzed. Acute and late radiation-induced high-grade toxicity were reported in one patient, respectively. CCR was observed in 8/64 patients (13 %), 14/37 patients (38 %) and 13/16 patients (91 %) at three, six and twelve months; pCR was observed in 3/69 (4 %) patients. After 12 months, diarrhea (mean difference [MD] -17.4 [95 % confidence interval [CI] -31.2 to -3.7]), blood and mucus in stool (MD -31.1 [95 % CI -46.4 to -15.8]), and anxiety (MD -22.4 [95 % CI -34.0 to -10.9]) were improved. Conclusion: High-field MR-guided SCRT for the treatment of patients with rectal cancer is associated with improved disease-related symptom management and functioning one year after treatment.

Patient expectation and experience of MR-guided radiotherapy using a 1.5T MR-Linac.

Background and Purpose: Online adaptive MR-guided radiotherapy (MRgRT) is a relatively new form of radiotherapy treatment, delivered using a MR-Linac. It is unknown what patients expect from this treatment and whether these expectations are met. This study evaluates whether patients' pre-treatment expectations of MRgRT are met and reports patients' on-table experience on a 1.5 T MR-Linac. Materials and methods: All patients treated on the MR-Linac from November 2020 until April 2021, were eligible for inclusion. Patient expectation and experience were captured through questionnaires before, during, and three months after treatment. The on-table experience questionnaire included patient' physical and psychological coping. Patient-expected side effects, participation in daily and social activity, disease outcome and, disease related symptoms were compared to post-treatment experience. Results: We included 113 patients who were primarily male (n = 100, 89 %), with a median age of 69 years (range 52-90). For on-table experience, ninety percent of patients (strongly) agreed to feeling calm during their treatment. Six and eight percent of patients found the treatment position or bed uncomfortable respectively. Twenty-eight percent of patients felt tingling sensations during treatment. After treatment, 79 % of patients' expectations were met. Most patients experienced an (better than) expected level of side effects (75 %), participation in daily- (83 %) and social activity (86 %) and symptoms (78 %). However, 33 % expected more treatment efficacy than experienced. Conclusion: Treatment on the 1.5 T MR-Linac is well tolerated and meets patient expectations. Despite the fact that some patients expected greater treatment efficacy and the frequent occurrence of tingling sensations during treatment, most patient experiences were comparable or better than previously expected.

Realizing the value of complex medical technology: Demonstrating cost-effectiveness is not enough.

The main factors driving the value of medical treatments are proven effectiveness and cost-effectiveness. This is different for complex medical technologies that combine scientific disciplines, functions or tools in a single solution-oriented method. This short communication provides three recommendations to realize the value of complex medical technologies. It is important to engage stakeholders before technology implementation to promote its relevance from multiple perspectives, to explore opportunities for professional development and collaboration, and to demonstrate the societal effects over the entire life-cycle.

Stereotactic Body radiotherapy and pedicLE screw fixatioN During one hospital visit for patients with symptomatic unstable spinal metastases: a randomized trial (BLEND RCT) using the Trials within Cohorts (TwiCs) design.

BACKGROUND: Spinal metastases can lead to unremitting pain and neurological deficits, which substantially impair daily functioning and quality of life. Patients with unstable spinal metastases receive surgical stabilization followed by palliative radiotherapy as soon as wound healing allows. The time between surgery and radiotherapy delays improvement of mobility, radiotherapy-induced pain relief, local tumor control, and restart of systemic oncological therapy. Stereotactic body radiotherapy (SBRT) enables delivery of preoperative high-dose radiotherapy while dose-sparing the surgical field, allowing stabilizing surgery within only hours. Patients may experience earlier recovery of mobility, regression of pain, and return to systemic oncological therapy. The BLEND RCT evaluates the effectiveness of SBRT followed by surgery within 24 h for the treatment of symptomatic, unstable spinal metastases. METHODS: This phase III randomized controlled trial is embedded within the PRospective Evaluation of interventional StudiEs on boNe meTastases (PRESENT) cohort. Patients with symptomatic, unstable spinal metastases requiring stabilizing surgery and radiotherapy will be randomized (1:1). The intervention group (n = 50) will be offered same-day SBRT and surgery, which they can accept or refuse. According to the Trial within Cohorts (TwiCs) design, the control group (n = 50) will not be informed and receive standard treatment (surgery followed by conventional radiotherapy after 1-2 weeks when wound healing allows). Baseline characteristics and outcome measures will be captured within PRESENT. The primary outcome is physical functioning (EORTC-QLQ-C15-PAL) 4 weeks after start of treatment. Secondary endpoints include pain response, time until return to systemic oncological therapy, quality of life, local tumor control, and adverse events up to 3 months post-treatment. DISCUSSION: The BLEND RCT evaluates the effect of same-day SBRT and stabilizing surgery for the treatment of symptomatic, unstable spinal metastases compared with standard of care. We expect better functional outcomes, faster pain relief, and continuation of systemic oncological therapy. The TwiCs design enables efficient recruitment within an ongoing cohort, as well as prevention of disappointment bias and drop-out as control patients will not be informed about the trial. TRIAL REGISTRATION: ClinicalTrials.gov NCT05575323. Registered on October 11, 2022.

Hyperbaric oxygen therapy for local late radiation toxicity in breast cancer patients: A systematic review.

PURPOSE: This systematic review aims to provide an overview of the literature on the effect of hyperbaric oxygen therapy (HBOT) on symptoms of local late radiation toxicity (LRT) in patients treated for breast cancer. METHODS: A systematic search was performed in September 2021. All studies with a sample size of ≥10 patients reporting the effect of HBOT for symptoms of LRT after radiotherapy of the breast and/or chest wall were included. The ROBINS-I tool was used for critical appraisal of methodological quality. The toxicity outcomes pain, fibrosis, lymphedema, necrosis/skin problems, arm and shoulder mobility, and breast and arm symptoms were evaluated. RESULTS: Nine studies concerning a total of 1308 patients were included in this review. Except for one study, sample sizes were small. Most studies had inadequate methodology with a substantial risk of bias. Post-HBOT, a significant reduction of pain was observed in 4/5 studies, of fibrosis in 1/2 studies, and of lymphedema of the breast and/or arm in 4/7 studies. Skin problems of the breast were significantly reduced in 1/2 studies, arm- and shoulder mobility significantly improved in 2/2 studies, and breast- and arm symptoms were significantly reduced in one study. CONCLUSION: This systematic review indicates that HBOT might be useful for reducing symptoms of LRT in breast cancer patients, however evidence is limited. A randomized controlled trial in a larger cohort of patients including a combination of patient- and clinician-reported outcome measures would be valuable to assess the effect of HBOT on symptoms of LRT.

Patient-Reported Symptoms of Late Toxicity in Patients With Breast Cancer Treated With Hypofractionated Radiation Therapy and the Association With Quality of Life.

PURPOSE: Our purpose was to assess the prevalence of patient-reported symptoms of local late toxicity in patients with irradiated breast cancer and determine the association between late toxicity and quality of life. METHODS: Within the prospective Utrecht cohort for Multiple BReast cancer intErvention studies and Long-term evaluation cohort, a survey on self-reported late toxicity was sent to all patients with breast cancer with ≥12 months interval since radiation therapy treated with curative intent. Patients were treated with hypofractionated radiation therapy of 40 Gy/15 fractions or 42.5 Gy/16 fractions, with or without a simultaneous integrated boost. Symptoms of late toxicity were evaluated on a 4-point Likert scale. Late toxicity was defined as moderate-severe breast or chest wall pain combined with at least 1 other mild-severe late toxicity symptom, that is, breast or arm/hand lymphedema, firmness of the breast, or impaired arm movement. Physical, role, and social functioning were measured before, during, and after the late toxicity survey using the European Organization for Research and Treatment of Cancer Quality of Life Core questionnaire-C30 and compared with a Dutch normative population. RESULTS: In the study, 1613/2248 patients (72%) were included. Of those, 16% (n = 265) reported late toxicity. The median time interval between radiation therapy and survey was 38 months (interquartile range, 21-55). Moderate/severe firmness of the breast, chest wall pain, and breast pain were reported by, respectively, 18% (n = 295), 14% (n = 225), and 10% (n = 140) of all patients. Physical, role, and social functioning were below the clinical threshold (ie, clinically relevant impairment) in 13% to 52% of patients with late toxicity and 2% to 26% of patients without late toxicity. Patients with late toxicity significantly more often received analgesics, physiotherapy, and lymphedema therapy compared with patients without late toxicity. CONCLUSIONS: This study provided insight into the prevalence of patient-reported late toxicity after hypofractionated radiation therapy and the influence of late toxicity on quality of life after breast cancer. These results may help health care professionals to inform their patients about long-term effects of breast cancer treatment including hypofractionated radiation therapy.

Stereotactic ablative radiotherapy or best supportive care in patients with localized pancreatic cancer not receiving chemotherapy and surgery (PANCOSAR): a nationwide multicenter randomized controlled trial according to a TwiCs design.

BACKGROUND: Significant comorbidities, advanced age, and a poor performance status prevent surgery and systemic treatment for many patients with localized (non-metastatic) pancreatic ductal adenocarcinoma (PDAC). These patients are currently treated with 'best supportive care'. Therefore, it is desirable to find a treatment option which could improve both disease control and quality of life in these patients. A brief course of high-dose high-precision radiotherapy i.e. stereotactic ablative body radiotherapy (SABR) may be feasible. METHODS: A nationwide multicenter trial performed within a previously established large prospective cohort (the Dutch Pancreatic cancer project; PACAP) according to the 'Trial within cohorts' (TwiCs) design. Patients enrolled in the PACAP cohort routinely provide informed consent to answer quality of life questionnaires and to be randomized according to the TwiCs design when eligible for a study. Patients with localized PDAC who are unfit for chemotherapy and surgery or those who refrain from these treatments are eligible. Patients will be randomized between SABR (5 fractions of 8 Gy) with 'best supportive care' and 'best supportive care' only. The primary endpoint is overall survival from randomization. Secondary endpoints include preservation of quality of life (EORTC-QLQ-C30 and -PAN26), NRS pain score response and WHO performance scores at baseline, and, 3, 6 and 12 months. Acute and late toxicity will be scored using CTCAE criteria version 5.0: assessed at baseline, day of last fraction, at 3 and 6 weeks, and 3, 6 and 12 months following SABR. DISCUSSION: The PANCOSAR trial studies the added value of SBRT as compared to 'best supportive care' in patients with localized PDAC who are medically unfit to receive chemotherapy and surgery, or refrain from these treatments. This study will assess whether SABR, in comparison to best supportive care, can relieve or delay tumor-related symptoms, enhance quality of life, and extend survival in these patients. TRIAL REGISTRATION: Clinical trials, NCT05265663 , Registered March 3 2022, Retrospectively registered.

A nationwide randomized controlled trial on additional treatment for isolated local pancreatic cancer recurrence using stereotactic body radiation therapy (ARCADE).

BACKGROUND: Disease recurrence is the main cause of mortality after resection of pancreatic ductal adenocarcinoma (PDAC). In 20-30% of resected patients, isolated local PDAC recurrence occurs. Retrospective studies have suggested that stereotactic body radiation therapy (SBRT) might lead to improved local control in these patients, potentially having a beneficial effect on both survival and quality of life. The "nationwide randomized controlled trial on additional treatment for isolated local pancreatic cancer recurrence using stereotactic body radiation therapy" (ARCADE) will investigate the value of SBRT in addition to standard of care in patients with isolated local PDAC recurrence compared to standard of care alone, regarding both survival and quality of life outcomes. METHODS: The ARCADE trial is nested within a prospective cohort (Dutch Pancreatic Cancer Project; PACAP) according to the 'Trials within Cohorts' design. All PACAP participants with isolated local PDAC recurrence after primary resection who provided informed consent for being randomized in future studies are eligible. Patients will be randomized for local therapy (5 fractions of 8 Gy SBRT) in addition to standard of care or standard of care alone. In total, 174 patients will be included. The main study endpoint is survival after recurrence. The most important secondary endpoint is quality of life. DISCUSSION: It is hypothesized that additional SBRT, compared to standard of care alone, improves survival and quality of life in patients with isolated local recurrence after PDAC resection. TRIAL REGISTRATION: ClinicalTrials.gov registration NCT04881487 . Registered on May 11, 2021.

Factors Associated with Late Local Radiation Toxicity after Post-Operative Breast Irradiation.

Purpose: To assess determinants associated with late local radiation toxicity in patients treated for breast cancer. Methods: A systematic review was performed. All studies reporting ≥2 variables associated with late local radiation toxicity after treatment with postoperative whole breast irradiation were included. Cohort studies, randomized controlled trials, and cross-sectional studies were eligible designs. Study characteristics and definitions of determinants and outcome measures were extracted. If possible, the measure of association was extracted. Results: Twenty-one studies were included in this review. Six out of seven studies focused on the association between radiotherapy (boost) dose or irradiated breast volume and late radiation toxicity found significant results. Tumor bed boost was associated with late radiation toxicity, fibrosis, and/or edema in six out of twelve studies. Lower age was associated with late breast toxicity in one study, while in another study, higher age was significantly associated with breast fibrosis. Also, no association between age and late radiation toxicity was found in eight out of twelve studies. Similar inconsistent results were found in the association between late radiation toxicity and other patient-related factors (i.e., breast size, diabetes mellitus) and surgical and systemic treatment-related factors (i.e., complications after surgery, chemotherapy, and time between surgery and radiotherapy). Conclusion: In modern 3D radiotherapy, radiotherapy (boost) dose and volume are-like in 2D radiotherapy-associated with late local radiation toxicity, such as breast fibrosis and edema. Treatment de-escalation, for example, partial breast irradiation in selected patients might be important to decrease late local toxicity without compromising locoregional control and survival.

Interrater agreement of contouring of the neurovascular bundles and internal pudendal arteries in neurovascular-sparing magnetic resonance-guided radiotherapy for localized prostate cancer.

BACKGROUND AND PURPOSE: Radiation damage to neural and vascular tissue, such as the neurovascular bundles (NVBs) and internal pudendal arteries (IPAs), during radiotherapy for prostate cancer (PCa) may cause erectile dysfunction. Neurovascular-sparing magnetic resonance-guided adaptive radiotherapy (MRgRT) aims to preserve erectile function after treatment. However, the NVBs and IPAs are not routinely contoured in current radiotherapy practice. Before neurovascular-sparing MRgRT for PCa can be implemented, the interrater agreement of the contouring of the NVBs and IPAs on pre-treatment MRI needs to be assessed. MATERIALS AND METHODS: Four radiation oncologists independently contoured the prostate, NVB, and IPA in an unselected consecutive series of 15 PCa patients, on pre-treatment MRI. Dice similarity coefficients (DSCs) for pairwise interrater agreement of contours were calculated. Additionally, the DCS of a subset of the inferior half of the NVB contours (i.e. approximately prostate midgland to apex level) was calculated. RESULTS: Median overall interrater DSC for the left and right NVB was 0.60 (IQR: 0.54 - 0.68) and 0.61 (IQR: 0.53 - 0.69) respectively and for the left and right IPA 0.59 (IQR: 0.53 - 0.64) and 0.59 (IQR: 0.52 - 0.64) respectively. Median overall interrater DSC for the inferior half of the left NVB was 0.67 (IQR: 0.58 - 0.74) and 0.67 (IQR: 0.61 - 0.71) for the right NVB. CONCLUSION: We found that the interrater agreement for the contouring of the NVB and IPA improved with enhancement of the MRI sequence as well as further training of the raters. The agreement was best in the subset of the inferior half of the NVB, where a good agreement is clinically most relevant for neurovascular-sparing MRgRT for PCa.

[Proton therapy and the importance of RCT]. / Protonentherapie en het belang van RCT's.

The pace of innovation within radiotherapy is high. In recent years, two major innovations have made their appearance in the Netherlands: proton therapy and MRI-guided radiotherapy. Both are, in theory, a promising addition to the arsenal of cancer therapies. Financial incentives, industry pressure, and patient demand for high-tech treatments have led, or are likely to lead, to widespread implementation of these innovations, without clinical evidence of superiority over existing techniques. Using proton therapy, the most advanced of both innovations, this article describes that RCTs are necessary to investigate whether, and for whom, the theoretical benefits of radiotherapy innovations actually translate into clinically relevant benefits. With a good national network from the Dutch Society for Radiotherapy and Oncology (NVRO) with collaborating radiation oncologists and clinical physicists, the Netherlands is in the unique position to perform these important RCTs.

Impact of the COVID-19 pandemic on quality of life and emotional wellbeing in patients with bone metastases treated with radiotherapy: a prospective cohort study.

Implementation of COVID-19 measures may have induced concerns about access and quality of health care for cancer patients with bone metastases, and it may have affected their quality of life. In this study, we evaluated the effect of the first COVID-19 lockdown on quality of life and emotional functioning of patients with stage IV cancer treated for painful bone metastases in the UMC Utrecht, the Netherlands. A COVID-19 specific questionnaire was sent to active participants in the Prospective Evaluation of interventional StudiEs on boNe meTastases (PRESENT) cohort, consisting of patients irradiated for metastatic bone disease. Patient reported outcomes (PROs) were compared with the last two PROs collected within the PRESENT cohort before the COVID-19 lockdown in the Netherlands on the 16th of March. For the 169 (53%) responders, median age at start of lockdown was 68 years (range 38-92) and 62% were male. Patients reported a statistically significant decrease in emotional functioning (83.6 to 79.2, P = 0.004) and in general quality of life score during the COVID-19 lockdown (72.4 to 68.7, P = 0.007). A steep increase in feeling isolated was reported (18% before and 67% during lockdown). This study has shown a strong increase in the experience of isolation and a decrease of emotional functioning and general quality of life during the COVID-19 lockdown in cancer patients with bone metastases. Due to the nature of the treatment of this patient population, efforts should be made to minimize these changes during future lockdowns.

Pain Response After Stereotactic Body Radiation Therapy Versus Conventional Radiation Therapy in Patients With Bone Metastases-A Phase 2 Randomized Controlled Trial Within a Prospective Cohort.

PURPOSE: Pain response after conventional external beam radiation therapy (cRT) in patients with painful bone metastases is observed in 60% to 70% of patients. The aim of the VERTICAL trial was to investigate whether stereotactic body radiation therapy (SBRT) improves pain response. METHODS AND MATERIALS: This single-center, phase 2, randomized controlled trial was conducted within the PRESENT cohort, which consists of patients referred for radiation therapy of bone metastases to our tertiary center. Cohort participants with painful bone metastases who gave broad informed consent for randomization were randomly assigned to cRT or SBRT. Only patients in the intervention arm received information about the trial and were offered SBRT (1 × 18 Gy, 3 × 10 Gy, or 5 × 7 Gy), which they could accept or refuse. Patients who refused SBRT underwent standard cRT (1 × 8 Gy, 5 × 4 Gy, or 10 × 3 Gy). Patients in the control arm were not informed. Primary endpoint was pain response at 3 months after radiation therapy. Secondary outcomes were pain response at any point within 3 months, mean pain scores, and toxicity. Data were analyzed intention to treat (ITT) and per protocol (PP). This trial was registered with Clinicaltrials.gov, NCT02364115. RESULTS: Between January 29, 2015, and March 20, 2019, 110 patients were randomized. ITT analysis included 44 patients in the cRT arm and 45 patients in the SBRT arm. In the intervention arm, 12 patients (27%) declined SBRT, and 7 patients (16%) were unable to complete the SBRT treatment. In ITT, 14 of 44 patients (32%; 95% confidence interval [CI], 18%-45%) in the control arm and 18 of 45 patients (40%; 95% CI, 26%-54%) in the SBRT arm reported a pain response at 3 months (P = .42). In PP, these proportions were 14 of 44 (32%; 95% CI, 18%-45%) and 12 of 23 patients (46%; 95% CI, 27%-66%), respectively (P = .55). In ITT, a pain response within 3 months was reported by 30 of 44 control patients (82%; 95% CI, 68%-90%) and 38 of 45 patients (84%; 95% CI, 71%-92%) in the SBRT arm (P = .12). In PP, these proportions were 36 of 44 (82%; 95% CI, 68%-90%) and 26 of 27 patients (96%; 95% CI; 81%-100%), respectively (P = .12). No grade 3 or 4 toxicity was observed in either arm. CONCLUSIONS: SBRT did not significantly improve pain response in patients with painful bone metastases. One in 4 patients preferred to undergo cRT over SBRT, and 1 in 5 patients starting SBRT was unable to complete this treatment. Because of this selective dropout, which can be attributed to the character of the intervention, the trial was underpowered to detect the prespecified difference in pain response.

Microscopic resection margin status in pancreatic ductal adenocarcinoma - A nationwide analysis.

INTRODUCTION: First, this study aimed to assess the prognostic value of different definitions for resection margin status on disease-free survival (DFS) and overall survival (OS) in pancreatic ductal adenocarcinoma (PDAC). Second, preoperative predictors of direct margin involvement were identified. MATERIALS AND METHODS: This nationwide observational cohort study included all patients who underwent upfront PDAC resection (2014-2016), as registered in the prospective Dutch Pancreatic Cancer Audit. Patients were subdivided into three groups: R0 (≥1 mm margin clearance), R1 (<1 mm margin clearance) or R1 (direct margin involvement). Survival was compared using multivariable Cox regression analysis. Logistic regression with baseline variables was performed to identify preoperative predictors of R1 (direct). RESULTS: 595 patients with a median OS of 18 months (IQR 10-32 months) months were analysed. R0 (≥1 mm) was achieved in 277 patients (47%), R1 (<1 mm) in 146 patients (24%) and R1 (direct) in 172 patients (29%). R1 (direct) was associated with a worse OS, as compared with both R0 (≥1 mm) (hazard ratio (HR) 1.35 [95% and confidence interval (CI) 1.08-1.70); P < 0.01) and R1 (<1 mm) (HR 1.29 [95%CI 1.01-1.67]; P < 0.05). No OS difference was found between R0 (≥1 mm) and R1 (<1 mm) (HR 1.05 [95% CI 0.82-1.34]; P = 0.71). Preoperative predictors associated with an increased risk of R1 (direct) included age, male sex, performance score 2-4, and venous or arterial tumour involvement. CONCLUSION: Resection margin clearance of <1 mm, but without direct margin involvement, does not affect survival, as compared with a margin clearance of ≥1 mm. Given that any vascular tumour involvement on preoperative imaging was associated with an increased risk of R1 (direct) resection with upfront surgery, neoadjuvant therapy might be considered in these patients.

Pre-treatment expectations of patients with spinal metastases: what do we know and what can we learn from other disciplines? A systematic review of qualitative studies.

BACKGROUND: Little is known about treatment expectations of patients with spinal metastases undergoing radiotherapy and/or surgery. Assuming that patients with spinal metastases share characteristics with patients who had spinal surgery for non-cancer related conditions and with advanced cancer patients, we performed a systematic review to summarize the literature on patient expectations regarding treatment outcomes of spinal surgery and advanced cancer care. METHODS: A comprehensive search was performed in MEDLINE, EMBASE and PsycINFO for studies between 2000 and sep-2019. Studies including adult patients (> 18 years), undergoing spinal surgery or receiving advanced cancer care, investigating patients' pre-treatment expectations regarding treatment outcomes were included. Two independent reviewers screened titles, abstracts and full-texts, extracted data and assessed methodological quality. RESULTS: The search identified 7343 articles, of which 92 were selected for full-text review. For this review, 31 articles were included. Patients undergoing spinal surgery had overly optimistic expectations regarding pain and symptom relief, they underestimated the probability of functional disability, and overestimated the probability of (complete) recovery and return to work. Studies highlighted that patients feel not adequately prepared for surgery in terms of post-treatment expectations. Similarly, advanced cancer patients receiving palliative treatment often had overly optimistic expectations regarding their survival probability and cure rates. CONCLUSIONS: Patients tend to have overly optimistic expectations regarding pain and symptom relief, recovery and prognosis following spinal surgery or advanced cancer care. Pretreatment consultation about the expected pain and symptom relief, recovery and prognosis may improve understanding of prognosis, and promote and manage expectations, which, in turn, may lead to better perceived outcomes. TRIAL REGISTRATION: PROSPERO registration number: CRD42020145151 .

Assessing the effect of hyperbaric oxygen therapy in breast cancer patients with late radiation toxicity (HONEY trial): a trial protocol using a trial within a cohort design.

BACKGROUND: Breast cancer treatment with radiotherapy can induce late radiation toxicity, characterized by pain, fibrosis, edema, impaired arm mobility, and poor cosmetic outcome. Hyperbaric oxygen therapy (HBOT) has been proposed as treatment for late radiation toxicity; however, high-level evidence of effectiveness is lacking. As HBOT is standard treatment and reimbursed by insurers, performing classic randomized controlled trials is difficult. The "Hyperbaric OxygeN therapy on brEast cancer patients with late radiation toxicity" (HONEY) trial aims to evaluate the effectiveness of HBOT on late radiation toxicity in breast cancer patients using the trial within cohorts (TwiCs) design. METHODS: The HONEY trial will be conducted within the Utrecht cohort for Multiple BREast cancer intervention studies and Long-term evaluation (UMBRELLA). Within UMBRELLA, breast cancer patients referred for radiotherapy to the University Medical Centre Utrecht are eligible for inclusion. Patients consent to collection of clinical data and patient-reported outcomes and provide broad consent for randomization into future intervention studies. Patients who meet the HONEY in- and exclusion criteria (participation ≥ 12 months in UMBRELLA, moderate/severe breast or chest wall pain, completed primary breast cancer treatment except hormonal treatment, no prior treatment with HBOT, no contraindications for HBOT, no clinical signs of metastatic or recurrent disease) will be randomized to HBOT or control group on a 2:1 ratio (n = 120). Patients in the control group will not be informed about participation in the trial. Patients in the intervention arm will undergo 30-40 HBOT treatment sessions in a high pressure chamber (2.4 atmospheres absolute) where they inhale 100% oxygen through a mask. Cohort outcome measures (i.e., physical outcomes, quality of life, fatigue, and cosmetic satisfaction) of the HBOT group will be compared to the control group at 3 months follow-up. DISCUSSION: This pragmatic trial within the UMBELLA cohort was designed to evaluate the effectiveness of HBOT on late radiation toxicity in breast cancer patients using the TwiCs design. Use of the TwiCs design is expected to address issues encountered in classic randomized controlled trials, such as contamination (i.e., HBOT in the control group) and disappointment bias, and generate information about acceptability of HBOT. TRIAL REGISTRATION: ClinicalTrials.gov. NCT04193722 . Registered on 10 December 2019.