Mapping the Evidence on the Impact of mHealth Interventions on Patient-Reported Outcomes in Patients With Breast Cancer: A Systematic Review.

PURPOSE: To comprehensively synthesize the existing evidence concerning mHealth interventions for patients with breast cancer (BC). DESIGN: On July 30, 2023, we searched PubMed, PsycINFO, and Google Scholar for articles using the following inclusion criteria: evaluation of mHealth interventions in patients with cancer, at least 30 participants with BC, randomized control trials or prospective pre-post studies, determinants of health (patient-reported outcomes [PROs] and quality of life [QoL]) as primary outcomes, interventions lasting at least 8 weeks, publication after January 2015. Publications were excluded if they evaluated telehealth or used web-based software for desktop devices only. The quality of the included studies was analyzed with the Cochrane Collaboration Risk of Bias Tool and the Methodological Index for Non-Randomized Studies. RESULTS: We included 30 studies (20 focused on BC), encompassing 5,691 patients with cancer (median 113, IQR, 135.5). Among these, 3,606 had BC (median 99, IQR, 75). All studies contained multiple interventions, including physical activity, tailored information for self-management of the disease, and symptom tracker. Interventions showed better results on self-efficacy (3/3), QoL (10/14), and physical activity (5/7). Lifestyle programs (3/3), expert consulting (4/4), and tailored information (10/11) yielded the best results. Apps with interactive support had a higher rate of positive findings, while interventions targeted to survivors showed worse results. mHealth tools were not available to the public in most of the studies (17/30). CONCLUSION: mHealth interventions yielded heterogeneous results on different outcomes. Identifying lack of evidence on clinical scenarios (eg, patients undergoing systemic therapy other than chemotherapy) could aid in refining strategic planning for forthcoming research endeavors within this field.

Postmastectomy radiation therapy in breast cancer patients with micrometastatic disease in sentinel node dissection: A cohort study and meta-analysis.

Aim: The potential role of postmastectomy radiation therapy (PMRT) on prognosis in patients with T1-2 breast cancer and micrometastatic disease in sentinel lymph node dissection (SLND) has not yet been established. The aim of this study was to investigate the impact of PMRT on prognosis in patients with T1-2 breast cancer and micrometastatic in SLND. Method: A register- and population-based cohort was utilized by identifying eligible patients on the research database BcBase 3.0. Multivariate Cox regression models were applied for survival outcomes. In addition, a systematic literature review and meta-analysis including all relevant studies on this topic was performed. Results: In total, 956 patients fulfilling the inclusion criteria were found through the BcBaSe 3.0 with 237 (25.0 %) receiving PMRT and 719 (75.0 %) not receiving PMRT. No statistically significant differences between the two patient groups in terms of neither breast cancer-specific (adjusted Hazard Ratio (HR): 0.49; 95 % Confidence Interval (CI): 0.14 - 1.73) nor overall survival (adjusted HR: 0.63; 95 % CI: 0.29 - 1.35) was found. In the pooled analyses after literature review, PMRT did not result in better breast cancer-specific (5 studies; pooled HR: 1.06; 95 % CI: 0.88-1.27; I2 = 1 %; low certainty of evidence) or overall survival (6 studies; pooled HR: 1.01; 95 % CI: 0.91-1.13; I2 = 10 %; low certainty of evidence). Conclusion: PMRT does not seem to impact survival in patients with T1 or T2 breast cancer with micrometastatic disease in SLND. Considering the low level of evidence and the relatively short follow-up of included studies, caution in interpreting the results into clinical practice is suggested.

Intraoperative Radiation Therapy Delivered by Brachytherapy in Breast Cancer: An Interim Analysis of a Phase 2 Trial.

PURPOSE: Intraoperative breast cancer radiotherapy (IORT) offers an alternative to external beam radiotherapy (EBRT) after breast-conserving surgery (BCS). The Intraoperative brachytherapy (IOBT) trial applies high dose rate (HDR) brachytherapy with a new applicator prototype as IORT after BCS. In this interim analysis of the IOBT trial, we present the oncological safety and toxicity of the method METHODS: Eligible patients were women, ≥ 50 years old with an unifocal nonlobular, estrogen-receptor-positive, HER2-negative breast cancer, cN0, ≤ 3 cm, treated with BCS and sentinel node biopsy (SNB). Toxicity was registered according to the LENT-SOMA scale. Cumulative incidence of local (LR) and regional recurrence (RR) were calculated through cumulative incidence function whereas overall survival (OS) was illustrated through Kaplan-Meier curve. RESULTS: Until February 2023, 155 women (median age 68 years) were included in the trial. Twenty-nine women (18.7%) received supplemental EBRT, mostly due to positive SNB. Three-year cumulative incidence of LR and RR were 1.0% (CI 95 % 0.1%-2.3%) and 2.1% (CI 95% 0.8%-4.2%) respectively. Five- year cumulative incidence of LR and RR were 3.9% (CI 95% 1.8%-6.4%) and 2.1% (CI 95% 0.8%-4.2%) respectively. Five-year OS was 96.3% (CI 95% 93.6%-98.4%). Side effects were limited, low grade, and transient. CONCLUSION: Acknowledging the short median follow-up time at interim analysis, our initial results indicate that delivering IORT through HDR brachytherapy in carefully selected breast cancer patients is feasible and oncological safe so far. A long-term follow-up is essential to confirm the initial results.

ProFertil study protocol for the investigation of gonadotropin-releasing hormone agonists (GnRHa) during chemotherapy aiming at fertility protection of young women and teenagers with cancer in Sweden-a phase III randomised double-blinded placebo-controlled study.

BACKGROUND: Gonadotropin-releasing hormone agonists (GnRHa) cotreatment used to transiently suppress ovarian function during chemotherapy to prevent ovarian damage and preserve female fertility is used globally but efficacy is debated. Most clinical studies investigating a beneficial effect of GnRHa cotreatment on ovarian function have been small, retrospective and uncontrolled. Unblinded randomised studies on women with breast cancer have suggested a beneficial effect, but results are mixed with lack of evidence of improvement in markers of ovarian reserve. Unblinded randomised studies of women with lymphoma have not shown any benefit regarding fertility markers after long-term follow-up and no placebo-controlled study has been conducted so far. The aim of this study is to investigate if administration of GnRHa during cancer treatment can preserve fertility in young female cancer patients in a double-blind, placebo-controlled clinical trial. METHODS AND ANALYSIS: A prospective, randomised, double-blinded, placebo-controlled, phase III study including 300 subjects with breast cancer. In addition, 200 subjects with lymphoma, acute leukemias and sarcomas will be recruited. Women aged 14-42 will be randomised 1:1 to treatment with GnRHa (triptorelin) or placebo for the duration of their gonadotoxic chemotherapy. Follow-up until 5 years from end of treatment (EoT). The primary endpoint will be change in anti-Müllerian hormone (AMH) recovery at follow-up 12 months after EoT, relative to AMH levels at EoT, comparing the GnRHa group and the placebo group in women with breast cancer. ETHICS AND DISSEMINATION: This study is designed in accordance with the principles of Good Clinical Practice (ICH-GCP E6 (R2)), local regulations (ie, European Directive 2001/20/EC) and the ethical principles of the Declaration of Helsinki. Within 6 months of study completion, the results will be analysed and the study results shall be reported in the EudraCT database. STUDY REGISTRATION: The National Institutional review board in Sweden dnr:2021-03379, approval date 12 October 2021 (approved amendments 12 June 2022, dnr:2022-02924-02 and 13 December 2022, dnr:2022-05565-02). The Swedish Medical Product Agency 19 January 2022, Dnr:5.1-2021-98927 (approved amendment 4 February 2022). Manufacturing authorisation for authorised medicinal products approved 6 December 2021, Dnr:6.2.1-2020-079580. Stockholm Medical Biobank approved 22 June 2022, RBC dnr:202 253. TRIAL REGISTRATION NUMBER: NCT05328258; EudraCT number:2020-004780-71.

Current treatment landscape of HR+/HER2- advanced breast cancer in the Nordics: a modified Delphi study.

BACKGROUND: This Delphi study aimed to assess current perspectives on hormone receptor-positive/human epidermal growth factor receptor 2-negative(HR+/HER2-) advanced breast cancer (aBC) treatment strategies across the Nordics, and to establish where consensus exists across the Nordics on HR+/HER2- aBC treatment. MATERIAL AND METHODS: A modified, three-round Delphi method was followed. A steering committee was appointed for study coordination, panellist selection, and questionnaire development. The questionnaires covered relevant topics on HR+/HER2- aBC treatment: treatment patterns in different lines of therapy (first [1L], second [2L], and third [3L]), oligometastatic disease, de novo aBC, brain metastases, age as influential factor, visceral crisis, radiotherapy, diagnostics, and clinical guidelines. Both open and closed-ended questions were included. Consensus was defined as at least 70% agreement. RESULTS: In total, 28 experienced BC oncologists participated in the study from all five Nordic countries. Overall, topics reaching consensus included: preferred treatment approach in 1L and 2L therapy, treatment of oligometastatic disease, visceral crisis, brain metastases, and age-related treatment considerations. No consensus was reached for 3L therapy and local treatment for primary tumour in de novo aBC. Endocrine therapy (ET) combined with a cyclin-dependent kinase (CDK)4/6 inhibitor was the treatment of choice for 1L and 2L therapy. Treatment patterns in clinical practice did not always follow recommendations in current Nordic guidelines, as seen in the case of recently approved treatments. DISCUSSION: ET in combination with a CDK4/6 inhibitor is the preferred frontline treatment for HR+/HER2- aBC in the Nordics. The observed discrepancy between current guidelines and clinical practice could be due to differences in the reimbursement of novel treatments in the Nordics. Collaborative research efforts are warranted for topics that lack consensus.

Estrogen therapy after breast cancer diagnosis and breast cancer mortality risk.

PURPOSE: The safety of local estrogen therapy in patients on adjuvant endocrine treatment is questioned, but evidence on the issue is scarce. This nested case-control registry-based study aimed to investigate whether estrogen therapy affects breast cancer mortality risk in women on adjuvant endocrine treatment. METHODS: In a cohort of 15,198 women diagnosed with early hormone receptor (HR)-positive breast cancer and adjuvant endocrine treatment, 1262 women died due to breast cancer and were identified as cases. Each case was matched with 10 controls. Exposure to estrogen therapy with concurrent use of aromatase inhibitors (AIs), tamoxifen, or both sequentially, was compared between cases and controls. RESULTS: No statistically significant difference in breast cancer mortality risk was seen in patients with exposure to estrogen therapy concurrent to endocrine treatment, neither in short-term or in long-term estrogen therapy use. CONCLUSIONS: The study strengthens current evidence on local estrogen therapy use in breast cancer survivors, showing no increased risk for breast cancer mortality in patients on adjuvant AIs or tamoxifen.

Yield of Surveillance Imaging After Mastectomy With or Without Reconstruction for Patients With Prior Breast Cancer: A Systematic Review and Meta-analysis.

Importance: A discrepancy on current guidelines and clinical practice exists regarding routine imaging surveillance after mastectomy, mainly regarding the lack of adequate evidence for imaging in this setting. Objective: To investigate the usefulness of imaging surveillance in terms of cancer detection and interval cancer rates after mastectomy with or without reconstruction for patients with prior breast cancer. Data Sources: A comprehensive literature search was conducted in 3 electronic databases-PubMed, ISI Web of Science, and Scopus-without year restriction. References from relevant reviews and eligible studies were also manually searched. Study Selection: Eligible studies were defined as those conducting surveillance imaging (mammography, ultrasonography, or magnetic resonance imaging [MRI]) of patients with prior breast cancer after mastectomy with or without reconstruction that presented adequate data to calculate cancer detection rates for each surveillance method. Data Extraction and Synthesis: Independent data extraction by 2 investigators with consensus on discrepant results was performed. A quality assessment of studies was performed using the QUADAS-2 (Quality Assessment of Diagnostic Accuracy Studies-2) template. The generalized linear mixed model framework with both fixed-effects and random-effects models was used to meta-analyze the proportion of cases across studies including 3 variables: surveillance method, reconstruction after mastectomy, and surveillance measure. Main Outcomes and Measures: Three outcome measures were calculated for each eligible study and each surveillance imaging method within studies: overall cancer detection (defined as ipsilateral cancer, both palpable and nonpalpable) rate per 1000 examinations, clinically occult (nonpalpable) cancer detection rate per 1000 examinations, and interval cancer rate per 1000 examinations. Results: In total, 16 studies were eligible for the meta-analysis. The pooled overall cancer detection rates per 1000 examinations were 1.86 (95% CI, 1.05-3.30) for mammography, 2.66 (95% CI, 1.48-4.76) for ultrasonography, and 5.17 (95% CI, 1.49-17.75) for MRI. For mastectomy without reconstruction, the rate of clinically occult (nonpalpable) cancer per 1000 examinations (2.96; 95% CI, 1.38-6.32) and the interval cancer rate per 1000 examinations (3.73; 95% CI, 0.84-3.98) were lower than the overall cancer detection rate (including both palpable and nonpalpable lesions) per 1000 examinations (6.41; 95% CI, 3.09-13.25) across all imaging modalities. The interval cancer rate per 1000 examinations for mastectomy with reconstruction (3.73; 95% CI, 0.41-2.73) was comparable to the pooled cancer detection rate per 1000 examinations (4.73; 95% CI, 2.32-9.63) across all imaging modalities. In all clinical scenarios and imaging modalities, lower rates of clinically occult cancer compared with cancer detection rates were observed. Conclusions and Relevance: Lower detection rates of clinically occult-compared with overall-cancer across all 3 imaging modalities challenge the use of imaging surveillance after mastectomy, with or without reconstruction. Findings suggest that imaging surveillance in this context is unnecessary in clinical practice, at least until further studies demonstrate otherwise. Future studies should consider using the clinically occult cancer detection rate as a more clinically relevant measure in this setting.

Randomized Versus Real-World Evidence on the Efficacy and Toxicity of Checkpoint Inhibitors in Cancer in Patients with Advanced Non-small Cell Lung Cancer or Melanoma: A Meta-analysis.

BACKGROUND: Both randomized controlled trials (RCTs) and real-world evidence (RWE) studies provide results regarding the efficacy and toxicity of checkpoint inhibitors in cancer patients. The results from these two sources are considered complementary but whether they are comparable remains unknown. OBJECTIVE: The aim of this study was to compare the efficacy and toxicity of checkpoint inhibitors between RCTs and RWE studies in patients with advanced non-small cell lung cancer (NSCLC) or melanoma. PATIENTS AND METHODS: Two electronic databases were searched to identify eligible studies, either RCTs or RWE studies, investigating the efficacy or toxicity of checkpoint inhibitors given for indications that were approved by the European Medicines Agency (EMA) at the date of the last search. A meta-analysis was performed and the pooled estimates of objective response rates (ORR), progression-free survival (PFS), overall survival (OS), and toxicity and treatment discontinuation between RCTs and RWE studies were compared. RESULTS: In total, 43 RWE studies and 15 RCTs were eligible, with adequate data for pooled estimates for immunotherapy indications regarding NSCLC and melanoma. No statistically significant or clinically meaningful differences in terms of pooled PFS, OS, or rates of treatment discontinuation due to toxicity between RCTs and RWE studies were observed. In some indications, a higher rate of response rates and lower rate of toxicity in favor of RWE was observed. CONCLUSION: In patients with melanoma or NSCLC, the clinical value of checkpoint inhibitors is evident in both RCTs and real-world settings. Some differences in response or toxicity rates in favor of RWE mainly reflects the inherent difficulties in evaluating these outcomes in RWE studies.

Overall survival of patients with metastatic breast cancer in Sweden: a nationwide study.

BACKGROUND: Breast cancer is the most common cancer among women in Sweden. Whereas survival for the overall breast cancer population is well-documented, survival of patients with metastatic breast cancer (MBC) is harder to quantify due to the lack of reliable data on disease recurrence in national cancer registers. METHODS: This study used machine learning to classify the total MBC population in Sweden diagnosed between 2009 and 2016 using national registers, with the aim to estimate overall survival (OS). RESULTS: The total population consisted of 13,832 patients-2528 (18.3%) had de novo MBC whereas 11,304 (81.7%) were classed as having a recurrent MBC. Median OS for patients with MBC was found to be 29.8 months 95% confidence interval (CI) [28.9, 30.6]. Hormone-receptor (HR)-positive MBC had a median OS of 37.0 months 95% CI [35.9, 38.3] compared to 9.9 months 95% CI [9.1, 11.0] for patients with HR-negative MBC. CONCLUSION: This study covered the entire MBC population in Sweden during the study time and may serve as a baseline for assessing the effect of new treatment strategies in MBC introduced after the study period.

Artificial intelligence supporting cancer patients across Europe-The ASCAPE project.

INTRODUCTION: Breast and prostate cancer survivors can experience impaired quality of life (QoL) in several QoL domains. The current strategy to support cancer survivors with impaired QoL is suboptimal, leading to unmet patient needs. ASCAPE aims to provide personalized- and artificial intelligence (AI)-based predictions for QoL issues in breast- and prostate cancer patients as well as to suggest potential interventions to their physicians to offer a more modern and holistic approach on cancer rehabilitation. METHODS AND ANALYSES: An AI-based platform aiming to predict QoL issues and suggest appropriate interventions to clinicians will be built based on patient data gathered through medical records, questionnaires, apps, and wearables. This platform will be prospectively evaluated through a longitudinal study where breast and prostate cancer survivors from four different study sites across the Europe will be enrolled. The evaluation of the AI-based follow-up strategy through the ASCAPE platform will be based on patients' experience, engagement, and potential improvement in QoL during the study as well as on clinicians' view on how ASCAPE platform impacts their clinical practice and doctor-patient relationship, and their experience in using the platform. ETHICS AND DISSEMINATION: ASCAPE is the first research project that will prospectively investigate an AI-based approach for an individualized follow-up strategy for patients with breast- or prostate cancer focusing on patients' QoL issues. ASCAPE represents a paradigm shift both in terms of a more individualized approach for follow-up based on QoL issues, which is an unmet need for cancer survivors, and in terms of how to use Big Data in cancer care through democratizing the knowledge and the access to AI and Big Data related innovations. TRIAL REGISTRATION: Trial Registration on clinicaltrials.gov: NCT04879563.

Adjuvant locoregional radiation therapy in breast cancer patients with pathologic complete response after neoadjuvant chemotherapy: A systematic review and meta-analysis.

PURPOSE: The aim of the present meta-analysis was to investigate the impact of adjuvant locoregional radiation therapy (LRRT) in breast cancer patients with clinical lymph node metastatic disease achieving ypN0 after neoadjuvant chemotherapy (NACT). MATERIALS AND METHODS: A systematic review of studies on PubMed was performed. A meta-analysis was conducted by computing extracted hazard ratios (HRs) and 95% confidence intervals (CIs) into a fixed-effects model. RESULTS: Thirteen studies were included in the meta-analysis. Adjuvant LRRT significantly reduced the risk of locoregional recurrence (LRR) in patients with N+ at diagnosis and ypN0 (HR 0.59; 95% CI 0.42-0.81). However, no statistically significant difference on disease-free survival (DFS) or overall survival (OS) was found. CONCLUSIONS: LRRT significantly reduced the risk of LRR in patients with ypN0 after NACT whereas no impact on DFS or OS was observed. The low level of evidence should be considered when interpreting the results in clinical practice.

Mammographic Density Changes over Time and Breast Cancer Risk: A Systematic Review and Meta-Analysis.

The aim of this meta-analysis was to evaluate the association between mammographic density changes over time and the risk of breast cancer. We performed a systematic literature review based on the PubMed and ISI Web of Knowledge databases. A meta-analysis was conducted by computing extracted hazard ratios (HRs) and 95% confidence intervals (CIs) for cohort studies or odds ratios (ORs) and 95% confidence interval using inverse variance method. Of the nine studies included, five were cohort studies that used HR as a measurement type for their statistical analysis and four were case-control or cohort studies that used OR as a measurement type. Increased breast density over time in cohort studies was associated with higher breast cancer risk (HR: 1.61; 95% CI: 1.33-1.96) whereas decreased breast density over time was associated with lower breast cancer risk (HR: 0.78; 95% CI: 0.71-0.87). Similarly, increased breast density over time was associated with higher breast cancer risk in studies presented ORs (pooled OR: 1.85; 95% CI: 1.29-2.65). Our findings imply that an increase in breast density over time seems to be linked to an increased risk of breast cancer, whereas a decrease in breast density over time seems to be linked to a lower risk of breast cancer.

Use of classifiers to optimise the identification and characterisation of metastatic breast cancer in a nationwide administrative registry.

BAKGROUND: The prognosis for patients with metastatic breast cancer (MBC) is substantially worse when compared with patients with earlier stage disease. Therefore, understanding the differences in epidemiology between these two patient groups is important. Studies using population-based cancer registries to identify MBC are hampered by the quality of reporting. Patients are registered once (at time of initial diagnosis); hence only data for patients with de novo MBC are identifiable, whereas data for patients with recurrent MBC are not. This makes accurate estimation of the epidemiology and healthcare utilisation of MBC challenging. This study aimed to investigate whether machine-learning could improve identification of MBC in national health registries. MATERIAL AND METHODS: Data for patients with confirmed MBC from a regional breast cancer registry were used to train machine-learning algorithms (or 'classifiers'). The best performing classifier (accuracy 97.3%, positive predictive value 85.1%) was applied to Swedish national registries for 2008 to 2016. RESULTS: Mean yearly MBC incidence was estimated at 14 per 100,000 person-years (with 18% diagnosed de novo and 76% of the total with HR-positive MBC). CONCLUSION: To our knowledge, this is the first study to use machine learning to identify MBC regardless of stage at diagnosis in health registries covering the entire population of Sweden.

Aromatase inhibitors use and risk for cardiovascular disease in breast cancer patients: A population-based cohort study.

BACKGROUND: Prior studies regarding use of Aromatase inhibitors (AIs) and risk for cardiovascular disease (CVD) have shown conflicting results. This retrospective cohort study aimed to investigate whether AIs use affects risk for CVD events in postmenopausal breast cancer survivors. METHODS: Using a retrospective cohort study design, four CVD outcomes; heart failure or cardiomyopathy, arrhythmia, acute ischemic heart disease and ischemic stroke or Transient Ischemic Attack were compared with uni- and multivariate Cox regression analyses according to exposure to endocrine therapy (use of AI, tamoxifen or AI/tamoxifen sequentially) or no endocrine therapy. RESULTS: In total 15815 postmenopausal women, surgically treated to early breast cancer during 2006-2012, were included. No significantly increased risk for CVD events was observed in patients with AI use in the whole cohort. However, two subgroup analyses showed increased risk for CVD events in the AI/tamoxifen sequential group; heart failure in patients older than 75 years (Hazard Ratio (HR) 2.44; 95% Confidence Interval (CI): 1.32-4.54) and arrhythmia in patients without prior CVD (HR 1.45; 95% CI: 1.01-2.10). An increased risk for arrhythmia and acute ischemic heart disease in patients with at least four years of AI treatment compared with no or short-time exposure was observed (HR 2.12; 95% CI: 1.40-3.25 for arrhythmia; HR 2.03; 95% CI: 1.15-3.58 for ischemic heart disease). CONCLUSION: Our results indicate an increased risk for ischemic heart disease and arrhythmia in patients treated for more than four years with AIs. This should be considered in the risk-benefit assessment concerning endocrine therapy.

Treatment patterns, risk for hospitalization and mortality in older patients with triple negative breast cancer.

OBJECTIVES: To study the treatment patterns, potential risk factors for hospitalization within one year from diagnosis, and causes of death in older patients with triple negative breast cancer (TNBC). MATERIALS AND METHODS: We performed a registry-based cohort study using the BCBaSe database which links cases of breast cancer from three Swedish healthcare regions with socioeconomic factors, hospitalizations and causes of death. Women ≥70 years old with non-metastatic TNBC, between 1/12007 and 31/122012 were included (n = 413). RESULTS: In total, 168 patients (40.7%) received chemotherapy after surgery and 123 patients (30.0%) in the whole cohort had at least one hospitalization within one year from diagnosis. The risk of hospitalization overall was increased in the group receiving chemotherapy (Odds Ratio 2.35, 95% Confidence Intervall: 1.30-4.26) mainly due to toxicities. Cumulative incidence of breast cancer mortality was comparable among different age groups (70-74 vs. 75-79 vs. ≥ 80 years old) whereas non-breast cancer mortality was higher in patients ≥80 years old. Stage at diagnosis and comorbidities were independently associated with both breast cancer-specific- and overall mortality whereas age was only associated with overall mortality. CONCLUSIONS: The use of chemotherapy in older patients with TNBC was associated with age, tumor stage, and comorbidities. Chemotherapy use was also associated with increased risk for hospitalization within one year from diagnosis. Although the impact of chemotherapy on mortality was analyzed in a multivariate manner showing neither increased or decreased mortality, no firm conclusion can be drawn due to unmeasured confounders.

Synthesis of Recommendations From 25 Countries and 31 Oncology Societies: How to Navigate Through Covid-19 Labyrinth.

INTRODUCTION: Pandemic COVID-19 is an unexpected challenge for the oncological community, indicating potential detrimental effects on cancer patients. Our aim was to summarize the converging key points providing a general guidance in order to support decision making, pertaining to the oncologic care in the middle of a global outbreak. METHODS: We did an international online search in twenty five countries that have managed a surge in cancer patient numbers. We collected the recommendations from thirty one medical oncology societies. RESULTS: By synthesizing guidelines for a) oncology service delivery adjustments, b) general and specific treatment adaptations, and c) discrepancies from guidelines comparison, we present a clinical synopsis with the forty more crucial statements. A Covid-19 risk stratification base was also created in order to obtain a quick, objective patient assessment and a risk-benefit evaluation on a case-by-case basis. CONCLUSIONS: In an attempt to face these complex needs and due to limited understanding of COVID-19, a variability of recommendations based on general epidemiological and infectious disease principles rather than definite cancer-related evidence has evolved. Additionally, the absence of an effective treatment or vaccine requires the development of cancer management guidance, capitalizing on comprehensive COVID-19 oncology experience globally.

TRIM study protocol - a prospective randomized multicenter Trial to assess the Role of Imaging during follow-up after radical surgery of stage IIB-C and III cutaneous malignant Melanoma.

BACKGROUND: The incidence of cutaneous malignant melanoma (CMM) is increasing worldwide. In Sweden, over 4600 cases were diagnosed in 2018. The prognosis after radical surgery varies considerably with tumor stage. In recent years, new treatment options have become available for metastatic CMM. Early onset of treatment seems to improve outcome, which suggests that early detection of recurrent disease should be beneficial. Consequently, in several countries imaging is a part of the routine follow-up program after surgery of high risk CMM. However, imaging has drawbacks, including resources required (costs, personnel, equipment) and the radiation exposure. Furthermore, many patients experience anxiety in waiting for the imaging results and investigations of irrelevant findings is another factor that also could cause worry and lead to decreased quality of life. Hence, the impact of imaging in this setting is important to address and no randomized study has previously been conducted. The Swedish national guidelines stipulate follow-up for 3 years by clinical examinations only. METHODS: The TRIM study is a prospective randomized multicenter trial evaluating the potential benefit of imaging and blood tests during follow-up after radical surgery for high-risk CMM, compared to clinical examinations only. Primary endpoint is overall survival (OS) at 5 years. Secondary endpoints are survival from diagnosis of relapse and health-related quality of life (HRQoL). Eligible for inclusion are patients radically operated for CMM stage IIB-C or III with sufficient renal function for iv contrast-enhanced CT and who are expected to be fit for treatment in case of recurrence. The planned number of patients is > 1300. Patients are randomized to clinical examinations for 3 years +/- whole-body imaging with CT or FDG-PET/CT and laboratory tests including S100B protein and LDH. This academic study is supported by the Swedish Melanoma Study Group. DISCUSSION: This is the first randomized prospective trial on the potential benefit of imaging as a part of the follow-up scheme after radical surgery for high-risk CMM. RESULTS: The first patient was recruited in June 2017 and as of April 2020, almost 500 patients had been included at 19 centers in Sweden. TRIAL REGISTRATION: ClinicalTrials.gov , NCT03116412 . Registered 17 April 2017, https://clinicaltrials.gov/ct2/show/study/NCT03116412.

PD-1 protein and gene expression as prognostic factors in early breast cancer.

BACKGROUND: There is a paucity of data on the prognostic value of programmed cell death protein 1 (PD-1) protein and gene expression in early breast cancer (BC) and the present study's aim was to comprehensively investigate it. METHODS: The study consisted of three parts: a correlative analysis of PD-1 protein and gene expression from an original patient cohort of 564 patients with early BC; a systematic review and trial-level meta-analysis on the association between PD-1 protein expression and disease-free survival/overall survival (OS) in early BC; and a pooled gene expression analysis from publicly available transcriptomic datasets regarding PDCD1 expression. RESULTS: In the study cohort, PD-1 protein, but not gene expression, was associated with improved OS (HRadj=0.73, 95% CI 0.55 to 0.97, p=0.027 and HRadj=0.88, 95% CI 0.68 to 1.13, p=0.312, respectively). In the trial-level meta-analysis, PD-1 protein expression was not found to be statistically significantly associated with outcomes in the overall population. Finally, in the pooled gene expression analysis, higher PDCD1 expression was associated with better OS in multivariable analysis in the entire population (HRadj=0.89, 95% CI 0.80 to 0.99, p=0.025) and in basal-like tumours. CONCLUSIONS: PD-1 protein and gene expression seem to be promising prognostic factors in early BC. Standardisation of detection and assessment methods is of utmost importance.

Upfront Radiotherapy in Patients With Asymptomatic Incurable Rectal Cancer: A Retrospective Cohort Study.

BACKGROUND/AIM: The optimal treatment sequencing for asymptomatic de novo metastatic rectal cancer is unclear. The aim of this study was to investigate the role of upfront radiotherapy, with or without chemotherapy on risk for local complications, in patients with asymptomatic advanced metastatic rectal cancer treated with palliative intention. PATIENTS AND METHODS: All patients with de novo metastatic rectal cancer diagnosed between January 2008 and December 2017 in two healthcare regions in Sweden (Örebro län, Sörmland) were identified and data were extracted from electronic medical records. Patients were divided into 3 groups based on treatment sequence: upfront radiotherapy, upfront chemotherapy, and only palliative surgery. RESULTS: In total, 102 patients were included in the study cohort, 30 patients in upfront radiotherapy group, 54 in upfront chemotherapy, and 18 in only palliative surgery group. Patients with only upfront CT [odds ratio (OR)= 5.10; 95% confidence interval (CI)=1.24-20.91, p=0.024] had a higher risk to suffer from a local complication compared to those who received upfront radiotherapy. Cause-specific Cox regression analysis among patients who received oncological therapy revealed that female patients [cause-specific hazard ratio (csHR)=3.61; 95% confidence interval (CI)=1.67-7.81] and upfront chemotherapy [csHR=1.85; 95% CI=1.11-3.77] were associated with increased cumulative incidence of local complication over time, whereas primary surgery with ostomy or stent with lower risk [csHR=0.45; 95% CI=0.21-0.99]. CONCLUSION: Patients who received upfront radiotherapy, with or without chemotherapy, had fewer local complications due to primary tumor compared to patients who only received chemotherapy. This could indicate that radiotherapy to the primary tumor could be discussed with the patients as a first treatment option for asymptomatic metastatic rectal cancer to prevent local complications later during the disease.

Behind the numbers and the panic of a viral pandemic: fixed restrictive oncology guidance may jeopardize patients' survival.

To protect cancer patients from COVID-19 exposure, prioritization strategies are being implemented at global level. Measures include use of tele-health services, deferring elective surgeries, delaying non life-saving therapies, interrupting maintenance and supportive care regimens and suspending screening and regular follow-up visits. Nonetheless, the risk of infection may not always outweigh oncology treatment benefit. Lives of most oncology patients depend on their ability to receive medical, surgical and radiotherapy care. Postponing screening, follow-up and radical surgeries increase patients' risk of developing metastatic disease. A viral pandemic lasts long time and exhibits seasonal and geographical variations. Though vaccines will be available only in the 2021, a global, aggressive, all-embracing and protracted slowdown of oncologic activities will severely jeopardize patients' outcomes. A present international oncologists' panel, ECPC and FAVO, strongly suggest that Hospital measures in a specific geographical area/Nation should be in line with the local epidemic, and restrictions adopted should be adapted and stratified over time.