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

Funding/Support: This study was supported by funding from the NHS Grampian Endowment Fund (Mr Masannat).Peer reviewedPublisher PD

Skin and Soft Tissue Infections in Patients with Solid Tumours

Background. Skin and soft tissue infections (SSTIs) in cancer patients represent a diagnostic challenge, as etiologic diagnosis is often missing, and clinical assessment of severity is difficult. Few studies have described (SSTIs) in patients with solid tumours (STs). Patients and Methods. Records of patients with ST and SSTI, cared for at the University Hospital of Heraklion, from 2002 to 2006 were retrospectively studied. Results. A total of 81 episodes of SSTIs, occurring in 71 patients with ST, have been evaluated. Their median age was 65 years (34–82). The most common underlying malignancy was breast cancer in 17 patients (24%). Most episodes (89%) occurred in nonneutropenics. Cellulitis/erysipelas was the most common clinical presentation (56; 69%). Bacterial cultures were possible in 29 (36%) patients. All patients received antimicrobial therapy, while in 17 episodes (21%) an incision and drainage was required. Treatment failure occurred in 20 episodes (25%). Five patients (7%) died due to sepsis. None was neutropenic. Severe sepsis on admission (=0.002) and prior blood transfusion (=0.043) were independent predictors of treatment failure. Conclusion. SSTIs can be life threatening among patients with ST. Early diagnosis and appropriate treatment are of the utmost importance, since sepsis was proven a significant factor of unfavourable outcome

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

COVID-19 vaccinations: summary guidance for Cancer patients in 28Languages: 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.info:eu-repo/semantics/publishedVersio

Μετα-ανάλυση τυχαιοποιημένων κλινικών μελετών χημειοθεραπείας, ακτινοθεραπείας και ορμονοθεραπείας στον καρκίνο του μαστού

Background: Breast cancer is the most frequently diagnosed cancer and the leading cause of cancer death in females worldwide. Despite the growing body of randomized controlled trials (RCTs) regarding the use of various treatment strategies (chemotherapy, endocrine therapy, radiotherapy) in breast cancer, the efficacy of some strategies remains unclear and questionable. A meta-analysis, by combining the results of all available trials that studied the same question, could help to reduce the level of uncertainty and provide reliable conclusions about the role of various therapeutic choices for breast cancer patients.Objective: The purpose of this thesis was to identify controversial therapeutic strategies in the treatment of breast cancer and to perform, when possible, meta-analyses to find out which of these strategies are valuable in breast cancer therapy. We conducted 7 separate meta-analyses in order to answer to 7 different clinical questions. We choose 7 topics with controversial results in the therapeutic strategy of breast cancer patients, namely the role of bisphosphonates as antitumor therapy and as preventive agents against fractures in adjuvant setting, the risk of osteonecrosis of the jaw (ONJ) with the use of bisphosphonates in adjuvant setting, the use of fulvestrant in advanced breast cancer, the safety of partial breast irradiation (PBI) compared with whole-breast radiotherapy (WBRT), the role of bevacizumab in advanced breast cancer and finally the value of trastuzumab as neoadjuvant therapy in Her2-positive breast cancer patients.Materials and Methods: In all 7 meta-analyses we used the same basic principles of meta-analysis, with some minor but necessary changes in order to fit our methodology to specific aims of each trial. In general, we conducted systematic reviews of all English and non-English medical literature using MEDLINE, the Cochrane Controlled Trials Register and ISI Web of Knowledge. We set no year restriction. The references of all eligible trials were also searched in order to find any potentially eligible trial that it was not identified by our searching algorithm. Abstracts of major meetings were also searched. Eligible studies were identified according to prespecified criteria for each meta-analysis. Data extraction was conducted independently by two investigators. In case of discrepancy, consensus was reached by involvement of a third investigator. When data on the outcome were not available from trials, we contacted the primary investigators of the eligible trials. Data synthesis was perfomed by choosing the appropriate effect size measure (Odds Ratio, Risk Ratio or Hazard Ratio) for each outcome and by combining the results using fixed- or random-effects models.Results: Regarding bisphosphonates in adjuvant setting, pooled results showed no statistical significant differences with the use of bisphosphonates in early breast cancer versus non-use for the overall number of deaths (summary OR, 0.708; 95% CI, 0.482–1.041; p-value =0.079), disease recurrences(summary OR, 0.843; 95% CI, 0.602–1.181; p-value =0.321), and bone metastases (summary OR, 0.925; 95% CI, 0.768–1.114; p-value =0.413). Subgroup analyses for disease recurrences according to the type of bisphosphonate used showed a statistically significant lower risk for disease recurrences with zoledronic acid (6 trials, OR, 0.675; 95% CI, 0.479–0.952; p-value = 0.025). In addition, bisphosphonates did not reduce fracture rate (OR=0.99, 95% CI=0.73–1.34) neither in postmenopausal women (OR=0.82, 95% CI=0.55–1.20) nor in women with breast cancer receiving aromatase inhibitors (OR=0.79, 95% CI=0.53–1.17). Overall, treatment with bisphosphonates was significantly associated with the occurrence of osteonecrosis of the jaw (ONJ) (OR = 3.23, 95% CI = 1.7–8) compared with no use but it was a rare event, occurring in 13 (0.24%) of the 5,312 patients receiving bisphosphonates.Considering fulvestrant, we found no difference between fulvestrant versus other hormonal agents regarding overall survival (HR: 1.047, 95% CI: 0.688–1.592; p-value = 0.830) and time to tumor progression (HR: 0.994, 95% CI: 0.691–1.431; p-value = 0.975).Partial breast irradiation (PBI) did not influence survival (OR 0.912, 95% CI, 0.674–1.234, p-value = 0.550) compared with WBRT but it was found to lead to statistically significant higher risk for developing local recurrences (pooled OR 2.150, 95% CI, 1.396–3.312; p-value = 0.001) and axillary recurrences (pooled OR 3.430, 95% CI, 2.058–5.715; p-value < 0.0001).The combination of bevacizumab and chemotherapy resulted in a statistically significant improvement in progression-free survival compared with chemotherapy alone (HR = 0.70, 95% CI = 0.60–0.82, p-value = 9.3x10-6), especially when bevacizumab was combined with taxanes. However, the pooled HR for overall survival did not show significant advantage for the use of bevacizumab compared to placebo arm (pooled HR = 0.90, 95% CI 0.80–1.03, p-value = 0.119).Finally, the use of trastuzumab as neoadjuvant therapy lead to higher absolute pathologic complete response (pCR) rate (38% in trastuzumab arm in comparison with 21% in no trastuzumab arm) (RR 1.85, 95% CI: 1.39-2.46; p-value < 0.001). Two out of 217 (0.9%) patients in the trastuzumab arms presented congestive heart failure compared with none in the chemotherapy alone arms.Conclusions: The meta-analysis of bisphosphonates in adjuvant breast cancer therapy showed that currently available randomized evidence does not support the hypothesis that using bisphosphonates in adjuvant treatment of early breast cancer alters the natural course of the disease. In addition bisphosphonates do not seem to prevent bone fractures. However, ONJ is a rare event in breast cancer patients treated with adjuvant use of bisphosphonates.Our meta-analysis of fulvestrant suggests that fulvestrant 250 mg is similar to other hormonal agents with respect to efficacy measures with equal or even better tolerability profile compared with other hormonal agents.Our meta-analysis of PBI, despite the fact that it is based on limited randomized evidence, suggests that PBI is a safe treatment modality as it does not seem to jeopardize survival compared with standard WBRT. Nevertheless, the issue of locoregional recurrence needs to be further addressed.The results of the meta-analysis of bevacizumab show that the addition of bevacizumab to chemotherapy offers a statistically significant improvement in progression free survival in patients with metastatic breast cancer but does not benefit overall survival. In addition, clinical significance of this improvement is questionable. As a result, bevacizumab treatment cannot be suggested for treatment of 1st line metastatic breast cancer,Finally, the meta-analysis of trastuzumab as neoadjuvant treatment underscores the beneficial effects of trastuzumab treatment in neoadjuvant regimens among HER2-positive breast cancer patients in terms of pCR. Of interest, no additional cardiotoxicity was documented in the trastuzumab armsΕισαγωγή: Ο καρκίνος του μαστού είναι ο πιο συχνός τύπος καρκίνου και η κύρια αιτία θανάτου από καρκίνο παγκοσμίως. Παρά το γεγονός οτι ο αριθμός των τυχαιοποιημένων κλινικών μελετών που αφορούν τη χρήση διαφόρων θεραπευτικών μεθόδων (χημειοθεραπεία, ακτινοθεραπεία, ορμονοθεραπεία) στον καρκίνο του μαστού αυξάνεται συνεχώς, η αξία ορισμένων θεραπειών παραμένει υπό αμφισβήτηση. Η μετα-ανάλυση, συνδυάζοντας με στατιστικές μεθόδους τα αποτελέσματα κλινικών μελετών που έχουν μελετήσει το ίδιο κλινικό ερώτημα, μπορούν να βοηθήσουν στη μείωση της αβεβαιότητας και να παρέχουν αξιόπιστα συμπεράσματα για την αξία διαφόρων θεραπευτικών επιλογών στον καρκίνο του μαστού.Σκοπός: Σκοπός της διατριβής ήταν η διαπίστωση αμφιλεγόμενες θεραπευτικές στρατηγικές στον καρκίνο του μαστού και κατόπιν η εφαρμογή μετα-αναλύσεων ώστε να αξιολογηθεί ποιές από αυτές τις στρατηγικές είναι χρήσιμες στον καρκίνο του μαστού. Προχωρήσαμε σε 7 διαφορετικές μετα-αναλύσεις ώστε να απαντηθούν 7 διαφορετικά κλινικά ερωτήματα. Επιλέξαμε 7 θέματα με αμφιλεγόμενα αποτελέσματα, που περιλαμβάνουν το ρόλο των διφωσφονικών ως αντικαρκινική θεραπεία αλλά και ως θεραπεία προστασίας καταγμάτων όταν χρησιμοποιούνται σαν μεταγχειρητική/προφυλακτική θεραπεία, τον κίνδυνο οστεονέκρωσης κάτων γνάθου με την χρήση διφψσφονικών, τη χρήση του fulvestrant στον προχωρημένο καρκίνο του μαστού, την ασφάλεια της χρήσης μερικής ακτινοβόλησης του μαστού μετά από τμηματεκτομή ή μερική μαστεκτομή αντί της θεραπείας επιλογής που είναι η ολική ακτινοβόληση του μαστού, το ρόλο του bevacizumab σε συνδυασμό με χημειοθεραπεία στον προχωρημένο καρκίνο του μαστου και τέλος την αξία του trastuzumab ως προεγχειρητική θεραπεία σε ασθενείς με Her2-θετική νόσο.Υλικό και Μέθοδος: Σε όλες τις 7 μετα-αναλύσεις χρησιμοποιήσαμε τις ίδες βασικές αρχές, με κάποιες μικρές διαφοροποιήσεις που ήταν απαραίτητες ώστε να ταιριάζει η μεθοδολογία μας στον ειδικό σκοπό της κάθε μετα-ανάλυσης. Γενικά, προχωρήσαμε σε συστηματική ανασκόπηση της βιβλιογραφίας, χρησιμοποιώντας 3 βάσεις δεδομένων (MEDLINE, the Cochrane Controlled Trials Register, και ISI Web of Knowledge) χωρίς χρονικό ή γλωσσικό περιορισμό. Αναζητήσαμε τυχόν επιπλέον μελέτες μέσω του ελέγχου των βιβλιογραφικών αναφορών των επιλεγμένων μελετών και των περιλήψεων των κύριων διεθνών συνεδρίων Ογκολογίας. Οι μελέτες που ήταν κατάλληλες για τις μετα-αναλύσεις επιλέχθηκαν με βάση προ-αποφασισμένων κριτηρίων. Η εξαγωγή δεδομένων έγινε από 2 ανεξάρτητος ερευνητές, ενώ ένας τρίτος ερευνητής συμμετείχε στη διαδικασία για την επίλυση τυχών ασυμφωνιών. Σε περίπτωση μη διαθέσιμων δεδομένων, επικοικωνούσαμε με τους ερευνητές των πρωτογενών μελετών ώστε να μας τα παρέχουν. Η στατιστική σύνθεση των δεδομένων λάμβανε χώρο μετά από επιλογή του κατάλληλου στατιστικού μέτρου (Odds Ratio, Risk Ratio ή Hazard Ratio) για το κάθε αποτέλεσμα και εφαρμογή του κατάλληλου μετα-αναλυτικού μοντέλου (fixed- ή random-effects models).Αποτελέσματα: Αναφορικά με τα διφωσφονικά ως προφυλακτική θεραπεία, τα αποτελέσματα των μετα-αναλύσεων δε δείχνουν κάποια στατιστικά σημαντική διαφορά με τη χρήση τους στον αριθμό των θανάτων (OR, 0.708; 95% CI, 0.482–1.041; p-value =0.079), των συνολικών υποτροπών (OR, 0.843; 95% CI, 0.602–1.181; p-value =0.321), και των σκελετικών μεταστάσεων (OR, 0.925; 95% CI, 0.768–1.114; p-value =0.413). Σε ανάλυση υπο-ομάδων με βάση τον τύπο των διφωσφονικών διαπιστώθηκε οτι το zoledronic acid μειώνει τον κίνδυνο για υποτροπή (6 μελέτες, OR, 0.675; 95% CI, 0.479–0.952; p-value = 0.025). Επιπλέον, τα διφωσφονικά δεν μειώνουν τον κίνδυνο για κάταγμα (OR=0.99, 95% CI=0.73–1.34) τόσο στις μετεμμηνοπαυσιακές ασθενείς (OR=0.82, 95% CI=0.55–1.20) όσο και στις ασθενείς που λαμβάνουν αναστολείς της αροματάσης (OR=0.79, 95% CI=0.53–1.17). Συνολικά, η θεραπεία με διφωσφονικά σχετίζεται σε σημαντικό βαθμό με την εμφάνιση οστεονέκρωσης της γνάθου (OR = 3.23, 95% CI = 1.7–8) αλλά η συγκεκριμένη παρενέργεια είναι ένα σπάνιο συμβάν που συνέβη σε 13 (0.24%) από τις 5,312 ασθενείς που έλαβαν διφωσφονικά.Σχετικά με το fulvestrant, δε διαπιστώθηκαν διαφορές με τη χρήση του εν συγκρίσει με άλλες ορμονοθεραπείες σε σχέση με την ολική επιβίωση (HR: 1.047, 95% CI: 0.688–1.592; p-value = 0.830) και το χρόνο ως την υποτροπή (HR: 0.994, 95% CI: 0.691–1.431; p-value = 0.975).Η μερική ακτινοβόληση του μαστού δεν επηρεάζει την επιβίωση των ασθενών με καρκίνο του μαστου (OR 0.912, 95% CI, 0.674–1.234, p-value = 0.550) όταν συγκριθεί με την ολική ακτινοβόληση αλλά οδηγεί σε στατιστικώς σημαντικά μεγαλύτερο κίνδυνο για τοπικές (OR 2.150, 95% CI, 1.396–3.312; p-value = 0.001) και περιοχικές υποτροπες (OR 3.430, 95% CI, 2.058–5.715; p-value < 0.0001).Ο συνδυασμός bevacizumab και χημειοθεραπείας οδηγεί σε σημαντική βελτίωση του χρόνου ως την υποτροπή σε σύγκριση με μόνο χημειοθεραπεία (HR = 0.70, 95% CI = 0.60–0.82, p-value = 9.3x10-6), ειδικά όταν συνδιάζεται με ταξάνες. Αντιθέτως, δε διαπιστώθηκε καμία βελτίωση στην επιβίωση με την προσθήκη bevacizumab (HR = 0.90, 95% CI 0.80–1.03, p-value = 0.119).Τέλος, η χρήση trastuzumab ως προεγχηρητική θεραπεία οδηγεί σε αύξηση του αριθμού των παθολογοανατομικών πλώρων υφέσεων (38% στο σκέλος με trastuzumab, 21% στο σκέλος χωρίς trastuzumab) (RR 1.85, 95% CI: 1.39-2.46; p-value < 0.001). Δύο από τους 217 (0.9%) ασθενείς που έλαβαν trastuzumab ανέπτυξαν καρδιακή ανεπάρκεια.Συμπεράσματα: Η μετα-ανάλυση των διφωσφονικών ως προφυλακτική θεραπεία στον καρκίνο του μαστού έδειξε οτι, με βάση τα υπάρχοντα τυχαιοποιημένα δεδομένα, η υπόθεση οτι τα διφωσφονικά μπορούν να επηρεάσουν τη φυσική ιστορία του καρκίνου του μαστού δεν επιβεβαιώνεται. Επιπλέον, τα διφωσφονικά δε φαίνεται να προλαμβάνουν τα κατάγματα σε αυτούς τους ασθενείς. Σχετικά με τον κίνδυνο οστεονέκρωσης της γνάθου,φαίνεται να είναι ένα σπάνιο γεγονός σε αυτόν τον τρόπο χρήσης διφωσφονικών.Η μετα-ανάλυση του fulvestrant προτείνει οτι το fulvestrant σε δόση 250 mg έχει ίδια δραστικότητα με τις υπόλοιπες ορμονοθεραπείες, με παρόμοιο προφίλ παρενεργειών.Η μετα-ανάλυση της μερικής ακτινοβόλησης του μαστού, παρόλο το γεγονός οτι στηρίζεται σε περιορισμένα τυχαιοποιημένα δεδομένα, προτείνει ότι η μερική ακτινοβόληση είναι μια ασφαλής θεραπευτική επιλογή σε επιλεγμένους ασθενείς καθώς δε φαίνεται να επηρεάζει την επιβίωση σε σύγκριση με την ολική ακτινοβόληση του μαστού, που παραμένει πάντως θεραπεία επιλογής. Όμως. το θέμα των τοπικοπεριοχικών υποτροπών απαιτεί περαιτέρω διερεύνηση.Τα αποτελέσματα της μετα-ανάλυσης για το bevacizumab δείχνουν οτι η προσθήκη του συγκεκριμένου φαρμάκου στην χημειοθεραπεία σε ασθενείς με προχωρημένο καρκίνο του μαστού προσφέρει μια βελτίωση στον χρόνο ως την υποτροπή αλλά δεν επηρεάζει τη συνολική επιβίωση. Η κλινική αξία της βελτίωσης αυτής είναι αμφιλεγόμενη. Ως εκ τούτου, η θεραπεία με bevacizumab σε αυτούς του ασθενείς δε συνίσταται.Τέλος, η μετα-ανάλυση του trastuzumab ως προεγχειρητική θεραπεία υπογραμμίζει τη θετική επίδραση του φαρμάκου, σε συνδυασμό με τη χημειοθεραπεία, σε ασθενέις με Her2-θετική νόσο, προσφέροντας σημαντικό όφελος στην πλήρη ύφεση. Είναι άξιο λόγου το γεγονός οτι η προσθήκη του trastuzumab δεν προσθέτει επιπλέον καρδιοτοξικότητα για τους ασθενείς

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

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

Predictive role of HER2-status on the effectiveness of endocrine adjuvant treatment in postmenopausal breast cancer patients : a population-based cohort study

Purpose: There are conflicting results on the potential role of HER2-status on the efficacy of aromatase inhibitors (AIs) and tamoxifen (TAM) in patients with hormone receptor (HR)-positive breast cancer (BC). The purpose of this population-based cohort study was to investigate the potential benefit of AIs compared to TAM as adjuvant therapy in postmenopausal BC patients by HER2-status in the era of modern therapy with HER2-blockade. Methods: A population-based cohort study was performed including all postmenopausal women diagnosed with HR-positive BC without distant metastasis between 2007 and 2012 in three healthcare regions in Sweden. We analyzed the breast cancer-specific survival (BCSS) and overall survival (OS) in two distinct cohorts (HER2-negative, HER2-positive) based on the type of endocrine therapy (ET) used. A propensity score matching was performed separately in the HER2-negative and HER2-positive cohorts, respectively. Results: After propensity score matching, 4368 patients with HER2-negative and 214 patients with HER2-positive BC were available for analysis. In the HER2-negative cohort, an improved BCSS [Hazard Ratio (HR): 0.51; 95% confidence interval (CI): 0.34–0.77, p value &lt; 0.001] and a trend toward improved OS (HR: 0.66; 95% CI: 0.41–1.08, p value = 0.093) in favor of AI-based therapy was observed. In the HER2-positive cohort, no statistically significant difference between AI-based ET and TAM was found in terms of either BCSS or OS, although the direction of HR was similar as in the HER2-negative cohort (HR for BCSS: 0.84; 95% CI: 0.14–5.04, p = 0.849; HR for OS: 0.62; 95% CI: 0.10–3.38, p = 0.345). Conclusion: Our study results, based on propensity-matched cohorts, did not support any predictive value of HER2-status on endocrine therapy in postmenopausal BC patients. AI-based ET remains the treatment of choice for postmenopausal BC patients with HR-positive disease in the modern era of HER2-directed therapy irrespective of HER2-status

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