Incidence and risk factors of hypothyroidism after treatment for early breast cancer: a population-based cohort study.

PURPOSE: An increased incidence of hypothyroidism among breast cancer survivors has been observed in earlier studies. The impact of the postoperative treatment modalities and their potential interplay on hypothyroidism development needs to be studied. METHODS: We conducted a population- and registry-based study using the Breast Cancer Data Base Sweden (BCBaSe) including females diagnosed with breast cancer between 2006 and 2012. In total, 21,268 female patients diagnosed with early breast cancer between 2006 and 2012, with no previous prescription of thyroid hormones and no malignant diagnosis during the last ten years before breast cancer diagnosis, were included in the final analysis. RESULTS: During the follow-up (median follow-up time 7.9 years), 1212 patients (5.7%) developed hypothyroidism at a median time of 3.45 years from the index date. No association of the systemic oncological treatment in terms of either chemotherapy or endocrine therapy and hypothyroidism development could be identified. A higher risk (HR 1.68;95% CI 1.42-1.99) of hypothyroidism identified among patients treated with radiation treatment of the regional lymph nodes whereas no increased risk in patients treated only with radiation therapy to the breast/chest wall was found (HR 1.01; 95% CI 0.86-1.19). The risk of hypothyroidism in the cohort treated with radiotherapy of the regional lymph nodes was present irrespective of the use of adjuvant chemotherapy treatment. CONCLUSIONS: Based on the results of our study, the implementation of hypothyroidism surveillance among the breast cancer survivors treated with radiotherapy of the regional lymph nodes can be considered as reasonable in the follow-up program.

Treatment utilization and effectiveness of neoadjuvant chemotherapy comparing men and women diagnosed with breast cancer: a Swedish retrospective cohort study.

PURPOSE: Evidence supporting the use of neoadjuvant chemotherapy (NAC) in early breast cancer is based on studies mainly including women, whereas the utilization and effectiveness of NAC in men is less studied. The present study aimed to investigate the utilization and effectiveness of NAC in men and women with early breast cancer. METHODS: Eligible patients were identified through the Swedish National Breast Cancer Quality Register, that includes all newly diagnosed breast cancer cases in Sweden from 2008 and onwards. For the treatment utilization analysis, all patients with stage I-III between 2008 and 2020 were included (n = 82,888), whereas for the effectiveness analysis the cohort was restricted to patients receiving NAC (n = 6487). For both analyses, multivariate logistic regression models were applied to investigate potential sex disparities in NAC utilization and effectiveness, adjusted for patient- and tumor characteristics. RESULTS: In the NAC utilization analysis, 487 men and 82,401 women with stage I-III were included. No statistically significant difference between sexes in terms of NAC utilization was observed (adjusted Odds Ratio (adjOR): 1.135; 95% Confidence Interval (CI) 0.606-2.128) with an overall utilization rate of 4.9% in men compared to 7.8% in women. Among the 24 men and 6463 women who received NAC, the pathologic complete response (pCR) rates were 16.7% and 21.2%, respectively (adjOR: 1.141; 95% CI 0.141-9.238). CONCLUSION: The present study did not find any sex disparities in NAC utilization or effectiveness in terms of pCR. This supports the current recommendations of treating men with breast cancer with the same indications for NAC as women.

The role of dacarbazine and temozolomide therapy after treatment with immune checkpoint inhibitors in malignant melanoma patients: A case series and meta-analysis.

Dacarbazine (DTIC) and its oral counterpart temozolomide (TMZ) have been the most used agents in advanced malignant melanoma (MM) patients and they are still used routinely. The preferred first line treatment, immune checkpoint inhibitors (CPIs) might shape the tumor and the tumor microenvironment, possibly affecting the response to subsequent therapies. The aim of this study was to investigate the treatment effect of DTIC/TMZ in MM patients after CPI therapy in a consecutive patient cohort and through systematic literature review and meta-analysis. Thirty-five patients with advanced MM treated with DTIC/TMZ after previous CPI therapy in three Swedish regions between 2017 and 2021 were recognized and seven case series studies were identified through systematic database review. Pooled data from all 345 patients showed a median real-world progression-free survival (rwPFS) of 1.9 months and overall survival (OS) of 6.0 months. Three of these studies were included in a meta-analysis comparing DTIC/TMZ after CPI treatment, versus no previous immunotherapy, showing no statistically significant differences in rwPFS or OS but higher real-world response rate to chemotherapy for the prior-CPI treated group (Odds Ratio: 2.24; 95% Confidence Interval: 1.04-4.86). The current study supports consideration of DTIC/TMZ in later line of treatment in the immunotherapy era.

Discordance of PIK3CA mutational status between primary and metastatic breast cancer: a systematic review and meta-analysis.

INTRODUCTION: In light of the clinically meaningful results of the PI3K inhibitors in PIK3CA-mutated metastatic breast cancer (BC) patients, the reliable identification of PIK3CA mutations is of outmost importance. However, lack of evidence on the optimal site and timing of assessment, presence of temporal heterogeneity and analytical factors pose several challenges in clinical routine. We aimed to study the discordance rates of PIK3CA mutational status between primary and matched metastatic tumors. METHODS: A systematic literature search was performed in three different databases (Embase, Pubmed, Web of Science) and-upon screening-a total of 25 studies reporting PIK3CA mutational status both on primary breast tumors and their matched metastases were included in this meta-analysis. The random-effects model was used for pooled analyses of discordance of PIK3CA mutational status. RESULTS: The overall discordance rate of PIK3CA mutational status was 9.8% (95% CI, 7.0-13.0; n = 1425) and did not significantly differ within BC subtypes or metastatic sites. The change was bi-directional, more commonly observed from PIK3CA mutated to wild-type status (14.9%, 95% CI 11.8-18.2; n tumor pairs = 453) rather than the opposite direction (8.9%, 95% CI 6.1-12.1; n tumor pairs = 943). CONCLUSIONS: Our results indicate the need of obtaining metastatic biopsies for PIK3CA-mutation analysis and the possibility of testing of the primary tumor, in case a re-biopsy deemed non-feasible.

De novo metastatic breast cancer in men vs women: a Swedish population-based cohort study.

Current evidence on de novo metastatic breast cancer is based on data from women. This Swedish population-based cohort study compared the incidence over time and prognosis of de novo metastatic breast cancer between sexes using data from the Swedish National Quality Register for Breast Cancer. Joinpoint regression analysis was used to compare incidence trends in all stages (104 733 women, 648 men) and multivariate Cox regression analysis to investigate potential sex disparities in de novo metastatic breast cancer prognosis (6005 women, 41 men). For both sexes, increased trends were evident for cancer stages I and II, with a stabilizing trend at the later years for women, while stage III incidence remained stable. An increased trend for de novo metastatic breast cancer in women, and to a lesser extent in men, was observed. No difference in de novo metastatic breast cancer overall survival between sexes was observed (hazard ratio = 1.24; 95% confidence interval = 0.85 to 1.81). The comparable features in terms of incidence and prognosis of de novo metastatic breast cancer between sexes imply similarities, supporting the adoption of common treatment strategies.

Outcomes of Different Quality of Life Assessment Modalities After Breast Cancer Therapy: A Network Meta-analysis.

Importance: Improvement in clinical understanding of the priorities of patients with breast cancer (BC) regarding postoperative aesthetic outcomes (AOs) is needed. Objective: To assess expert panel and computerized evaluation modalities against patient-reported outcome measures (PROMs), the gold standard of AO assessment, in patients after surgical management of BC. Data Sources: Embase, MEDLINE, PsycINFO, PubMed, the Cochrane Central Register of Controlled Trials, the World Health Organization International Clinical Trials Registry Platform, and ClinicalTrials.gov were interrogated from inception through August 5, 2022. Search terms included breast conserving AND aesthetic outcome AND breast cancer. Ten observational studies were eligible for inclusion, with the earliest date of database collection on December 15, 2022. Study Selection: Studies with at least 1 pairwise comparison (PROM vs expert panel or PROM vs computerized evaluation with Breast Cancer Conservation Treatment cosmetic results [BCCT.core] software) were considered eligible if they included patients who received BC treatment with curative intent. Studies reporting solely on risk reduction or benign surgical procedures were excluded to ensure transitivity. Data Extraction and Synthesis: Two independent reviewers extracted study data with an independent cross-check from a third reviewer. The quality of included observational studies was assessed using the Newcastle-Ottawa Scale, and the level of evidence quality was assessed using the Grading of Recommendations Assessment, Development and Evaluation tool. Confidence in network meta-analysis results was analyzed with the Confidence in Network Meta-analysis semiautomated tool. Effect size was reported using random-effects odds ratios (ORs) and cumulative ratios of ORs with 95% credibility intervals (CrIs). Main Outcomes and Measures: The primary outcome of this network meta-analysis was modality (expert panel or computer software) discordance from PROMs. Four-point Likert responses across PROMs, expert panel assessment, and BCCT.core evaluation of AOs were assessed. Results: A total of 10 observational studies including 3083 patients (median [IQR] age, 59 [50-60] years; median [range] follow-up, 39.0 [22.5-80.5] months) with reported AOs were assessed and homogenized in 4 distinct Likert response groups (excellent, very good, satisfactory, and bad). Overall network incoherence was low (χ22 = 0.35; P = .83). Overall, panel and software modalities graded AO outcomes worse than PROMs. Specifically, for excellent vs all other responses, the panel to PROM ratio of ORs was 0.30 (95% CrI, 0.17-0.53; I2 = 86%) and the BCCT.core to PROM ratio of ORs was 0.28 (95% CrI, 0.13-0.59; I2 = 95%), while the BCCT.core to panel ratio of ORs was 0.93 (95% CrI, 0.46-1.88; I2 = 88%). Conclusions and Relevance: In this study, patients scored AOs higher than both expert panels and computer software. Standardization and supplementation of expert panel and software AO tools with racially, ethnically, and culturally inclusive PROMs is needed to improve clinical evaluation of the journey of patients with BC and to prioritize components of therapeutic outcomes.

Predicting immune-related adverse events using a simplified frailty score in cancer patients treated with checkpoint inhibitors: A retrospective cohort study.

OBJECTIVE: Checkpoint inhibitors (CPIs) are in widespread clinical use. Little is known about which patients are at risk for developing toxicity. It is essential being able to identify patients with higher risk of experiencing immune-related adverse events (IRAEs) before initiation of CPI treatment to optimize treatment decisions and follow-up strategy. The aim of this study was to investigate whether a simplified frailty score based on performance status (PS), age, and comorbidity expressed as Charlson comorbidity index (CCI) could predict development of IRAEs. METHODS: We performed a retrospective cohort study at three Swedish centers. All patients (n = 596) treated with PD-L1 or PD-1 inhibitor for advanced cancer between January 2017 and December 2021 were included. RESULTS: In total, 361 patients (60.6%) were classified as nonfrail and 235 (39.4%) as frail. The most common cancer type was non-small cell lung cancer (n = 203; 34.1%) followed by malignant melanoma (n = 195; 32.7%). Any grade of IRAE occurred in 138 (58.7%) frail and in 155 (42.9%) non-frail patients (OR: 1.58; 95% CI: 1.09-2.28). Age, CCI, and PS did not independently predict the occurrence of IRAEs. Multiple IRAEs occurred in 53 (22.6%) frail and in 45 (12.5%) nonfrail patients (OR: 1.62; 95% CI: 1.00-2.64). DISCUSSION: In conclusion, the simplified frailty score predicted all grade IRAEs and multiple IRAEs in multivariate analyses whereas age, CCI, or PS did not separately predict development of IRAEs suggesting that this easy-to-use score may be of value in clinical decision making but a large prospective study is needed to assess its true value.

Evolution and refinement of magnetically guided sentinel lymph node detection in breast cancer: meta-analysis.

BACKGROUND: Superparamagnetic iron oxide nanoparticles (SPIO) have been used as a tracer for sentinel lymph node (SLN) localization in breast cancer, demonstrating comparable performance to the combination of radioisotope (RI) and blue dye (BD). METHODS: A systematic literature search and meta-analysis with subgroup and meta-regression analysis were undertaken to update the available evidence, assess technique evolution, and define knowledge gaps. Recommendations were made using the GRADE approach. RESULTS: In 20 comparative studies, the detection rate was 97.5 per cent for SPIO and 96.5 per cent for RI ± BD (risk ratio 1.006, 95 per cent c.i. 0.992 to 1.019; P = 0.376, high-certainty evidence). Neoadjuvant therapy, injection site, injection volume or nodal metastasis burden did not affect the detection rate, but injection over 24 h before surgery increased the detection rate on meta-regression. Concordance was 99.0 per cent and reverse concordance 97.1 per cent (rate difference 0.003, 95 per cent c.i. -0.009 to 0.015; P = 0.656, high-certainty evidence). Use of SPIO led to retrieval of slightly more SLNs (pooled mean 1.96 versus 1.89) with a higher nodal detection rate (94.1 versus 83.5 per cent; RR 1.098, 1.058 to 1.140; P < 0.001; low-certainty evidence). In meta-regression, injection over 24 h before surgery increased the SPIO nodal yield over that of RI ± BD. The skin-staining rate was 30.8 per cent (very low-certainty evidence), and possibly prevented with use of smaller doses and peritumoral injection. CONCLUSION: The performance of SPIO is comparable to that of RI ± BD. Preoperative injection increases the detection rate and nodal yield, without affecting concordance. Whether skin staining and MRI artefacts are reduced by lower dose and peritumoral injection needs to be investigated.

Expression patterns and prognostic implications of tumor-infiltrating lymphocytes dynamics in early breast cancer patients receiving neoadjuvant therapy: A systematic review and meta-analysis.

Purpose: High levels of tumor-infiltrating lymphocytes (TILs) are associated with better outcomes in early breast cancer and higher pathological response rates to neoadjuvant chemotherapy especially in the triple-negative (TNBC) and HER2+ subtypes. However, the dynamic changes in TILs levels after neoadjuvant treatment (NAT) are less studied. This systematic review and meta-analysis aimed to investigate the patterns and role of TILs dynamics change in early breast cancer patients receiving NAT. Methods: Medline, Embase, Web of Science Core Collection and PubMed Central databases were searched for eligible studies. Data were extracted independently by two researchers and discordances were resolved by a third. Pooled TILs rates pre- & post-treatment (overall and per subtype), pooled rates of ΔTILs and direction of change after NAT as well as correlation of ΔTILs with survival outcomes were generated in the outcome analysis. Results: Of 2116 identified entries, 34 studies fulfilled the criteria and provided adequate data for the outcomes of interest. A decreased level of TILs was observed after NAT in paired samples across all subtypes. The effect of NAT on TILs was most prominent in TNBC subtype with a substantial change, either increase or decrease, in 79.3% (95% CI 61.7-92.6%) of the patients as well as in HER2+ disease (14.4% increased vs 46.2% decreased). An increase in ΔTILs in TNBC was associated with better disease-free/relapse-free survival in pooled analysis (univariate HR = 0.59, 95% CI: 0.37-0.95, p = 0.03). Conclusion: This meta-analysis illustrates the TILs dynamics during NAT for breast cancer and indicates prognostic implications of ΔTILs in TNBC. The potential clinical utility of the longitudinal assessment of TILs during neoadjuvant therapy warrants further validation.

Digitally distributed Yoga Intervention in Breast Cancer Rehabilitation (DigiYoga CaRe): protocol for a randomised controlled trial.

INTRODUCTION: Breast cancer is the most prevalent cancer among women. The treatment is extensive; in addition to surgery, various combinations of radiation therapy, chemotherapy and antibody and endocrine treatment can be applied. Cancer-related fatigue (CRF) is high in patients with breast cancer, peaking during chemotherapy, but may persist for several years. Physical activity has proven to be effective in reducing CRF in breast cancer rehabilitation, but many patients tend to be less active after the diagnosis. Yoga has a previously demonstrated effect on energy levels and digitally distributed yoga intervention can potentially increase accessibility in pandemic times and facilitate participation for patients susceptible to infection and those living far from organised rehabilitation opportunities. The purpose of this study, Digital Yoga Intervention in Cancer Rehabilitation (DigiYoga CaRe) is to investigate whether a 12-week digitally distributed yoga intervention can reduce CRF and stress, improve health-related quality of life (HRQL) and affect pro-inflammatory and metabolic markers in patients with breast cancer. METHODS AND ANALYSIS: This multicentre study will adopt a randomised controlled design including 240 persons after their breast cancer surgery. They will be randomised to a 12-week digitally distributed yoga intervention or to a control group. The intervention group practice yoga two times a week, one yoga class live-streamed to the patient's computer or mobile device and one prerecorded video class for self-training. The controls receive standardised care, gift cards for flowers and access to yoga video links after the data collection has ended. The primary analysis will be performed following the principle of intention to treat. Data will be collected by questionnaires, blood samples, accelerometers and interviews. ETHICS AND DISSEMINATION: The DigiYoga CaRe study was approved by the Regional Ethical Review Board in Lund. The final results of this study will be disseminated to conference, patient and public involvements and peer-reviewed publications. TRIAL REGISTRATION NUMBER: NCT04812652.

Risk for morbidity and mortality after neurosurgery in older patients with high grade gliomas - a retrospective population based study.

BACKGROUND: Although high grade gliomas largely affect older patients, current evidence on neurosurgical complications is mostly based on studies including younger study populations. We aimed to investigate the risk for postoperative complications after neurosurgery in a population-based cohort of older patients with high grade gliomas, and explore changes over time. METHODS: In this retrospective study we have used data from the Swedish Brain Tumour Registry and included patients in Sweden age 65 years or older, with surgery 1999-2017 for high grade gliomas. We analysed number of surgical procedures per year and which factors contribute to postoperative morbidity and mortality. RESULTS: The study included 1998 surgical interventions from an area representing 60% of the Swedish population. Over time, there was an increase in surgical interventions in relation to the age specific population (p < 0.001). Postoperative morbidity for 2006-2017 was 24%. Resection and not having a multifocal tumour were associated with higher risk for postoperative morbidity. Postoperative mortality for the same period was 5%. Increased age, biopsy, and poor performance status was associated with higher risk for postoperative mortality. CONCLUSIONS: This study shows an increase in surgical interventions over time, probably representing a more active treatment approach. The relatively low postoperative morbidity- and mortality-rates suggests that surgery in older patients with suspected high grade gliomas can be a feasible option. However, caution is advised in patients with poor performance status where the possible surgical intervention would be a biopsy only. Further, this study underlines the need for more standardised methods of reporting neurosurgical complications.

Effect of Smoking on Treatment Efficacy and Toxicity in Patients with Cancer: A Systematic Review and Meta-Analysis.

AIM: The aim of the present systematic review and meta-analysis was to summarize the current evidence on the potential impact of smoking during cancer treatment on treatment efficacy and toxicity irrespective of cancer type. METHODS: A systematic literature search was performed using two electronic databases for potentially eligible studies. Only studies based on multivariable analysis for the association between smoking, compared to non-smokers (never or former), and treatment efficacy or toxicity were included. Pooled Hazard Ratios (HRs) or Odds Ratios (ORs) and corresponding 95% Confidence Intervals (CIs) were estimated through random-effects meta-analyses. RESULTS: In total, 97 eligible studies were identified, of which 79 were eligible for the pooled analyses. Smoking during radiation therapy, with or without chemotherapy, was associated with an increased risk of locoregional recurrence (pooled HR: 1.56; 95% CI: 1.28-1.91 for radiation therapy; pooled HR: 4.28; 95% CI: 2.06-8.90 for chemoradiotherapy) and worse disease-free survival (pooled HR: 1.88; 95% CI: 1.21-2.90 for radiation therapy; pooled HR: 1.92; 95% CI: 1.41-2.62 for chemoradiotherapy) as well as a higher risk for radiation-induced toxicity (pooled OR: 1.84; 95% CI: 1.32-2.56 for radiation therapy; pooled OR: 2.43; 95% CI: 1.43-4.07 for chemoradiotherapy) with low-to-moderate certainty of evidence. Smoking during treatment with EGFR tyrosine kinase inhibitors (EGFR-TKIs) in patients with lung cancer was associated with worse progression-free survival compared to non-smokers (pooled HR: 1.43; 95% CI: 1.14-1.80; moderate certainty of evidence), whereas smoking was associated with improved progression-free survival in patients treated with checkpoint inhibitors (HR: 0.70; 95% CI: 0.58-0.84; moderate certainty of evidence). No statistically significant associations were observed between smoking and treatment efficacy or toxicity to chemotherapy. CONCLUSION: The present meta-analysis confirms earlier evidence of the negative impact of smoking during radiation therapy, with or without chemotherapy, on treatment efficacy and radiation-induced toxicity as well as a negative impact of smoking on the efficacy of EGFR-TKIs and a positive impact on the efficacy of checkpoint inhibitors. The evidence is too weak to draw firm conclusions on the potential association between smoking and chemotherapy, whereas there is no evidence for pooled analyses regarding other types of systemic oncological therapy.

Older meningioma patients: a retrospective population-based study of risk factors for morbidity and mortality after neurosurgery.

BACKGROUND: Meningioma is the most common primary CNS tumour. Most meningiomas are benign, and most patients are 65 years or older. Surgery is usually the primary treatment option. Most prior studies on early surgical outcomes in older patients with meningioma are small, and there is a lack of larger population-based studies to guide clinical decision-making. We aimed to explore the risks for perioperative mortality and morbidity in older patients with meningioma and to investigate changes in surgical incidence over time. METHODS: In this retrospective population-based study on patients in Sweden, 65 years or older with surgery 1999-2017 for meningioma, we used data from the Swedish Brain Tumour Registry. We analysed factors contributing to perioperative mortality and morbidity and used official demographic data to calculate yearly incidence of surgical procedures for meningioma. RESULTS: The final study cohort included 1676 patients with a 3.1% perioperative mortality and a 37.6% perioperative morbidity. In multivariate analysis, higher age showed a statistically significant association with higher perioperative mortality, whereas larger tumour size and having preoperative symptoms were associated with higher perioperative morbidity. A numerical increased rate of surgical interventions after 2012 was observed, without evidence of worsening short-term surgical outcomes. CONCLUSIONS: Higher mortality with increased age and higher morbidity risk in larger and/or symptomatic tumours imply a possible benefit from considering surgery in selected older patients with a growing meningioma before the development of tumour-related symptoms. This study further underlines the need for a standardized method of reporting and classifying complications from neurosurgery.

A Systematic Review and Meta-Analysis on the Role of Repeat Breast-Conserving Surgery for the Management of Ipsilateral Breast Cancer Recurrence.

INTRODUCTION: The standard surgical management of ipsilateral breast cancer recurrence (IBCR) in patients previously treated with breast-conserving surgery (BCS) and radiotherapy (RT) is mastectomy. Recent international guidelines provide conflicting recommendations. The aim of this study was to perform a systematic literature review and meta-analysis of the oncological outcomes in patients with IBCR treated with repeat BCS (rBCS). METHODS: The MEDLINE and EMBASE databases were searched for relevant English-language publications, with no date restrictions. All relevant studies providing sufficient data to assess oncological outcomes (second local recurrence [LR] and overall survival [OS]) of rBCS for the management of IBCR after previous BCS and RT were included (PROSPERO registration CRD42021286123). RESULTS: Forty-two observational studies met the criteria and were included in the analysis. The pooled second LR rate after rBCS was 15.7% (95% confidence interval [CI] 12.1-19.7), and 10.3% (95% CI 6.9-14.3) after salvage mastectomy. On meta-analysis of comparative studies (n = 17), the risk ratio (RR) for second LR following rBCS compared with mastectomy was 2.103 (95% CI 1.535-2.883; p < 0.001, I2 = 55.1%). Repeat RT had a protective effect (coefficient: - 0.317, 95% CI - 0.596 to - 0.038; p = 0.026, I2 = 40.4%) for second LR. Pooled 5-year OS was 86.8% (95% CI 83.4-90.0) and 79.8% (95% CI 74.7-84.5) for rBCS and salvage mastectomy, respectively. Meta-analysis of comparative studies (n = 20) showed a small OS benefit in favor of rBCS (RR 1.040, 95% CI 1.003-1.079; p = 0.032, I2 = 70.8%). Overall evidence certainty was very low. CONCLUSIONS: This meta-analysis suggests rBCS could be considered as an option for the management of IBCR in patients previously treated with BCS and RT. Shared decision making, appropriate patient selection, and individualized approach are important for optimal outcomes.

Predicting toxicity caused by high-dose-rate brachytherapy single boost for prostate cancer.

PURPOSE: Treating localized prostate cancer (PC) with combination radiotherapy consisting of external beam radiotherapy (EBRT) and high-dose-rate brachytherapy (HDR-BT) has been proven to result in better disease outcome than EBRT only. We aimed to evaluate the incidence of toxicities due to combination therapy and identify parameters correlated to acute or late urinary, rectal, and erectile toxicities. MATERIAL AND METHODS: Data on symptoms and tumor/treatment parameters were collected from 359 patients treated between 2008 and 2018 with EBRT (42 Gy in 14 fractions) and HDR-BT (14.5 Gy in one fraction) for localized PC, at the Örebro University Hospital. Urinary, rectal, and erectile symptoms were presented descriptively, and bivariate analyses for correlation between grade ≥ 2 toxicity and potential predictors were performed. To evaluate prognostic models, multivariable analyses were applied. RESULTS: Urinary toxicity grade ≥ 2 was observed in 154 patients (47% of patients without pre-existing symptoms grade ≥ 2), of which 15 were grade 3. Rectal toxicity grade 2 was observed in 22 (6%) patients. Any grade erectile dysfunction was evident in all patients without pre-existing dysfunction (n = 103), whereas only 7 recovered completely. In bivariate analyses age was correlated with higher risk of acute urinary toxicity, and irradiated volume was associated with both urinary and rectal toxicities. However, we found no multivariable model of clinical and statistical significance to predict the risk of urinary or rectal toxicities. CONCLUSIONS: In our study cohort, the severity of toxicities was in general mild or moderate and temporary, whereas the incidence of severe toxicity was considerably low. Although we found no predictive models for toxicities, our findings are reassuring that this treatment approach as curative therapy for localized PC is well-tolerated.

Quality of Life in the First Year of Follow-Up in a Randomized Multicenter Trial Assessing the Role of Imaging after Radical Surgery of Stage IIB-C and III Cutaneous Melanoma (TRIM Study).

The benefit of imaging in the follow-up setting for high-risk melanoma patients is uncertain, and even less is known about the impact of intensive follow-up on the patient´s quality of life. In 2017, a Swedish prospective randomized multicenter study started, in which high-risk melanoma patients are randomly assigned 1:1 to follow-up by physical examinations +/- whole-body imaging. The first-year examinations are scheduled at 0, 6 and 12 months. The aim of this study was to investigate whether the patients´ health-related quality of life (HRQoL) and levels of anxiety and depression were affected at 1 year by imaging. Anxiety/depression and HRQoL were assessed at 0 and 12 months by the questionnaires Hospital Anxiety and Depression (HAD) scale and EORTC QLQ-C30 version 3. Expected baseline QLQ-C30 values for the patients were calculated using data from the general population. In total, 204 patients were analyzed. Mean differences in subscale scores at 1 year were not statistically significant either for HRQoL or for anxiety/depression. Baseline HRQoL did not differ from expected values in the general Swedish population. In conclusion, the patients in general coped well with the situation, and adding whole-body imaging to physical examinations did not affect the melanoma patients' HRQoL or levels of anxiety or depression.

Next-Generation Sequencing of Circulating Tumor DNA Can Optimize Second-Line Treatment in RAS Wild-Type Metastatic Colorectal Cancer after Progression on anti-EGFR Therapy: Time to Rethink Our Approach.

BACKGROUND: Management of Ras wild-type colorectal cancer (CRC) patients upon disease progression after the successful use of targeted treatment with anti-EGFR monoclonal antibodies and backbone chemotherapy remains a clinical challenge. SUMMARY: Development of treatment resistance with prevalence of preexisting RAS mutated clones, RAS mutation conversion, truncation of extracellular receptor domains as well as HER2 and MET amplification are molecular events that can be difficult to follow without the use of sophisticated laboratory techniques. The clinical hurdle of re-biopsy and tumor heterogeneity can be overcome by the implementation of next-generation sequencing (NGS) to analyze circulating tumor DNA (ctDNA) and identify druggable mutations or recovery of RAS-wildness. In this opinion paper, we summarize with critical thinking the clinical approach to be followed after the failure of first-line treatment in Ras wild-type CRC tumors with the use of NGS. Rechallenge with anti-EGFR inhibitors, in case of persistent or recovery of RAS-wildness, and targeted approach of specific mutations (BRAF inhibitors), amplifications (anti-Her2 treatment), or fusion proteins (NTRK inhibitors) can by guided by the use of NGS. The use of NGS platforms for serial analysis of ctDNA is an important step to better understand the molecular landscape of metastatic CRC and guide clinical decisions. KEY MESSAGES: NGS should be considered a mainstay in clinical practice for the management of CRC patients and health authorities should consider reimbursing its use in the appropriate clinical settings.

COVID-19 Vaccinations: Summary Guidance for Cancer Patients in 28 Languages: Breaking Barriers to Cancer Patient Information.

BACKGROUND: Covid-19 vaccination has started in the majority of the countries at the global level. Cancer patients are at high risk for infection, serious illness, and death from COVID-19 and need vaccination guidance and support. Guidance availability in the English language only is a major limit for recommendations' delivery and their application in the world's population and generates information inequalities across the different populations. METHODS: Most of the available COVID-19 vaccination guidance for cancer patients was screened and scrutinized by the European Cancer Patients Coalition (ECPC) and an international oncology panel of 52 physicians from 33 countries. RESULTS: A summary guidance was developed and provided in 28 languages in order to reach more than 70 percent of the global population. CONCLUSION: Language barrier and e-guidance availability in the native language are the most important barriers when communicating with patients. E-guidance availability in various native languages should be considered a major priority by international medical and health organizations that are communicating with patients at the global level.

Discordance of PD-L1 status between primary and metastatic breast cancer: A systematic review and meta-analysis.

INTRODUCTION: Programmed cell death ligand 1 (PD-L1) expression is predictive for benefit from immunotherapy in several human malignancies including triple negative breast cancer. Lower positivity rates but a larger relative benefit from atezolizumab has been implied when PD-L1 status is assessed at metastatic sites. We aimed to study the discordance of PD-L1 expression between primary tumor and metastasis in breast cancer due to its potential clinical utility. METHODS: Cochrane Library, Embase, Medline and Web of science were searched for studies reporting on PD-L1 expression in primary and metastatic breast cancer, followed by data extraction. Outcomes included pooled PD-L1 positivity rates in tumor cells, immune cells or both in primary tumor and metastasis, PD-L1 discordance between matched primary tumors and metastasis and direction of discordance. RESULTS: Of 2552 identified entries following de-duplication, 20 studies fulfilled the predefined inclusion criteria. Pooled PD-L1 positivity rate was higher in primary tumors compared to metastasis when assessed in immune cells (51.2% vs 37.1% p < 0.001) and tumor/immune cells (30.1% vs 14.6% p < 0.001), but not in tumor cells (18.7% vs 17.8% p = 0.65). PD-L1 positivity was lowest when assessed in bone metastases (12%) and highest in lymph nodes (60%). Discordance between primary tumors and metastasis was bidirectional, with higher pooled discordance rates when PD-L1 expression was assessed in immune compared to tumor cells (39.5% vs 13.6%, p < 0.001). CONCLUSION: The observed considerable discordance between PD-L1 status in primary and metastatic breast cancer emphasizes the importance of appropriate tissue sampling when selecting patients for immunotherapy.