Effects of locoregional radiotherapy in patients with metastatic breast cancer

ObjectivesThis study aims to assess the clinical outcomes of patients with metastatic breast cancer (MBC) who underwent local radiation therapy (RT) for the primary site.Material and methodsBetween 2005 and 2013, we retrospectively evaluated patients with MBC who received breast or chest wall RT with or without regional lymph node irradiation.Results2761 patients with breast cancer were treated with RT. Of them, 125 women with stage IV breast carcinoma were included. The median follow-up was 15 months (ranging from 3.8 to 168 months), when 54.7% of the patients had died; local progression was observed in 22.8% of the patients. The mean overall survival (OS) and local progression free survival (LoPFS) were 23.4 ± 2.4 months and 45.1 ± 2.9 months, respectively. Three- and five-year overall survival rates were, respectively, 21.2% and 13.3%. Local progression free survival was the same, 67.3%, at three and five years, respectively. Karnofsky Performance Status (KPS) (p = 0.015), number of metastatic sites (p = 0.031), RT dose (p = 0.0001) and hormone therapy (p = 0.0001) were confirmed as independent significant variables correlated with OS. The variables that were independently correlated with LoPFS were the number of previous chemotherapy lines (p = 0.038) and RT dose (p = 0.0001).ConclusionRT of the primary site in patients with MBC is well tolerated. The factors that presented positive impact on survival were good KPS, low disease burden (1–3 metastatic sites), and the use of hormone therapy.     

Internal mammary node irradiation in node-positive breast cancer treated with mastectomy and taxane-based chemotherapy

BackgroundIt is important to continually reevaluate the risk/benefit calculus of internal mammary node irradiation (IMNI) in the era of modern systemic therapy. We aimed to investigate the effect of IMNI on survival in node-positive breast cancer treated with mastectomy and anthracycline plus taxane-based chemotherapy.MethodsWe analyzed 348 patients who underwent mastectomy and anthracycline plus taxane-based chemotherapy for node-positive breast cancer between January 2006 and December 2011. All patients received postoperative radiation therapy (RT) with IMNI (n = 105, 30.2%) or without IMNI (n = 243, 69.8%). The benefit of IMNI for disease-free survival (DFS) and overall survival (OS) was evaluated using multivariate analysis and inverse probability of treatment weighting (IPTW) to adjust for unbalanced covariates between the groups.ResultsAfter a median follow-up of 95 months, the 10-year locoregional recurrence-free survival rate, DFS, and OS in all patients were 94.8%, 77.4%, and 86.2%, respectively. The IPTW-adjusted hazard ratio (HR) for the association of IMNI (vs. no IMNI) with DFS and OS was 0.208 (95% confidence intervals (CI) 0.045–0.966) and 0.460 (95% CI, 0.220–0.962), respectively. In multivariate analysis, IMNI was a favorable factor for DFS (HR, 0.458; P = 0.021) and OS (HR 0.233, P = 0.018).ConclusionsIMNI was associated with improved DFS and OS in node-positive patients treated with mastectomy, post-mastectomy RT, and taxane-based chemotherapy, although the rate of locoregional recurrence was low.     

Locoregional therapy in de novo metastatic breast cancer: Systemic review and meta-analysis

BackgroundLocoregional therapy (LRT) in de novo metastatic disease is controversial with inconsistent results from randomized control trials (RCTs).MethodsRCTs comparing LRT and systemic therapy to standard therapy alone in de novo metastatic breast cancer were identified. Hazard ratios (HRs) and their associated 95% confidence intervals (CIs) were computed and pooled in a meta-analysis using generic inverse variance. Overall survival (OS) and time to locoregional progression data were extracted for the intention to treat (ITT) population. Data on OS for pre-specified subgroups defined by tumor subtype and by site of metastases were also extracted.ResultsAnalyses included 4 trials comprising 970 patients. LRT included standard surgery to the primary breast tumor in all studies, and adjuvant radiation per standard of care was required in 3 studies. Compared to standard treatment, LRT was not associated with improved OS in the ITT population (HR 0.97, 95% CI 0.72–1.29, p = 0.81). However, LRT was associated with improved time to locoregional progression (HR 0.36, 95% CI 0.14–0.95, p = 0.04). LRT was not associated with improved OS in any tumor subtypes, including hormone receptor positive (HR 0.96, 95% CI 0.65–1.43), triple negative (HR 1.4, 95% CI 0.50–3.91) and human epidermal growth factor receptor 2 positive disease (HR 0.93, 95% CI 0.68–1.28). Additionally, LRT did not improve OS in bone only disease (HR 0.97, 95% CI 0.58–1.62) and in visceral disease (HR = 1.02, 95% CI 0.77–1.35). Our critical appraisal has identified some methodological problems in the design and conduct of the studies included that could affect the meta-analysis result.ConclusionsLRT in de novo metastatic breast cancer is not associated with improved OS. Results are consistent among different breast cancer subgroups. However, this conclusion should be interpreted with caution in view of the limitations identified in meta-analysis.     

Clinical outcome in women with HER2-positive de novo or recurring stage IV breast cancer receiving trastuzumab-based therapy

BackgroundFive to 10% of women with newly diagnosed breast cancer have synchronous metastases (de novo stage IV). A further 20% will develop metastases during follow-up (recurring stage IV). We compared the clinical outcomes of women with HER2-positive metastatic breast cancer (MBC) receiving first-line trastuzumab-based therapy according to type of metastatic presentation.Patients and methodsRetrospective analysis of 331 MBC patients receiving first-line trastuzumab-based treatment. Response rates (RR) were compared by the chi-square test. Time-to progression (TTP) and overall survival (OS) curves were compared by the log-rank test. Cox-proportional hazards models were used to study predictors of PFS and OS, including the type of metastatic presentation.ResultsSeventy-seven patients (23%) had de novo stage IV disease. Forty-six of these patients underwent surgery of the primary (“de novo/surgery”). Response rates to first-line trastuzumab-based therapy and median progression-free survival did not differ in patients with “recurring”, “de novo/surgery” and “de novo” without surgery (“de novo/no surgery) stage IV breast cancer. However, women with “de novo/surgery” stage IV breast cancer had the longest median OS (60 months), and those with “de novo/no surgery” stage IV breast cancer the shortest (26 months). For women with recurring metastatic breast cancer median OS was 40 months (overall log-rank test, p < 0.01). Multivariate analysis confirmed these findings.ConclusionOur analysis shows that response rates and PFS to first-line trastuzumab-based therapy do not differ significantly between de novo and recurring stage IV, HER2 positive breast cancer. The observed difference in OS favoring women with de novo stage IV disease submitted to surgery of the primary tumor could be the result of a selection bias.     

Outcome beyond third-line chemotherapy for metastatic triple-negative breast cancer in the French ESME program

PurposeAmong metastatic breast cancer (MBC) patients, those with a triple-negative breast cancer phenotype (mTNBC) have the worst prognosis, but the benefit of chemotherapy beyond second line on outcome remains uncertain. The purpose of this study was to identify predictive factors of outcome after third- or fourth-line chemotherapy.MethodsThe ESME-MBC database is a French prospective real-life cohort with homogeneous data collection, including patients who initiated first-line treatment for MBC (2008–2016) in 18 cancer centers. After selection of mTNBC cases, we searched for independent predictive factors (Cox proportional-hazards regression models) for overall survival (OS) on third- and fourth-line chemotherapy (OS3, OS4). We built prognostic nomograms based on the main prognostic factors identified.ResultsOf the 22,266 MBC cases in the ESME cohort, 2903 were mTNBC, 1074 (37%) and 598 (20%) of which had received at least 3 or 4 lines of chemotherapy. PFS after first- and second-line chemotherapy (PFS1, PFS2) and number of metastatic sites ≥3 at baseline were identified by multivariate analysis as prognostic factors for both OS3 (HR = 0.76 95%CI[0.66–0.88], HR = 0.55 95%CI[0.46–0.65], HR = 1.36 95%CI[1.14–1.62], respectively), and OS4 (HR = 0.76 95%CI[0.63–0.91], HR = 0.56 95%CI[0.45–0.7], HR = 1.37 95%CI[1.07–1.74]), respectively. In addition, metastasis-free interval was identified as a prognostic factor for OS3 (p = 0.01), while PFS3 influenced OS4 (HR = 0.75 95%CI[0.57–0.98]). Nomograms predicting OS3 and OS4 achieved a C-index of 0.62 and 0.61, respectively.ConclusionThe duration of each previous PFS is a major prognostic factor for OS in mTNBC patients receiving third- or fourth-line chemotherapy. The clinical utility of nomograms including this information was not demonstrated.     

Efficacy of taxanes rechallenge in first-line treatment of early metastatic relapse of patients with HER2-negative breast cancer previously treated with a (neo)adjuvant taxanes regimen: A multicentre retrospective observational study

BackgroundTaxanes are one of the most effective chemotherapies (CT) in breast cancer (BC), but the efficacy of taxanes rechallenge in early metastatic relapse has been poorly studied in patients previously treated by taxanes in the (neo)adjuvant setting. Our study aimed to analyse the efficacy of taxane rechallenge in case of early metastatic relapse in a multicentre retrospective observational study compared with other chemotherapies.MethodsWe analysed the French national ESME metastatic BC (MBC) database and selected HER2- MBC patients who received CT in first-line treatment for a metastatic relapse occurring 3–24 months after previous (neo)adjuvant taxanes treatment.ResultsOf 23,501 female patients with MBC in ESME, 1057 met the selection criteria. 58.4% received a taxane-based regimen (75.4% concomitant bevacizumab) and 41.6% received other CT.In hormone-receptor positive (HR+)/HER2- MBC, multivariate analysis showed no difference in OS between taxanes without bevacizumab compared to other CT (HZR = 1.3 [0.97; 1.74], but taxanes was significantly associated with worse PFS (HZR = 1.48 [1.14; 1.93]).In TNBC, taxanes without bevacizumab and carboplatin/gemcitabine were not superior to other CT for OS (HZR = 1.07 [0.79; 1.44] and HZR = 0.81 [0.58; 1.13], respectively), while for PFS, taxanes was inferior (HZR = 1.33 [1.06–1.67]) and carboplatin plus gemcitabine was superior to other CT (HZR = 0.63 [0.46; 0.87]).For both subtypes, the worse outcome observed with paclitaxel was no longer observed with the addition of bevacizumab.ConclusionsWith the limitation of retrospective design, taxanes rechallenge in early metastatic relapse of BC may result in a worse PFS in TNBC and HR+/HER2- MBC, which was not observed with the addition of bevacizumab.     

First-line vs second-line fulvestrant for hormone receptor-positive advanced breast cancer: A post-hoc analysis of the CONFIRM study

ObjectivesThe double-blind, phase III CONFIRM study (NCT00099437) evaluated fulvestrant 500 mg vs fulvestrant 250 mg in postmenopausal women with hormone receptor-positive locally advanced/metastatic breast cancer (LA/MBC). This post-hoc analysis investigated the efficacy and safety of fulvestrant given either first-line or second-line for advanced disease.Materials & methodsProgression-free survival (PFS) and overall survival (OS) with fulvestrant 500 mg vs fulvestrant 250 mg was evaluated using unadjusted log-rank tests in patients treated in the first- (progression during or within 12 months after completing adjuvant endocrine therapy; n = 387) and second-line (following endocrine therapy for LA/MBC; n = 343) settings.ResultsFirst-line fulvestrant 500 mg significantly prolonged PFS vs fulvestrant 250 mg (median PFS 5.6 vs 4.2 months; hazard ratio [HR] 0.80; 95% confidence interval [CI] 0.64–1.00; p = .047). Median PFS was numerically greater with second-line fulvestrant 500 mg vs fulvestrant 250 mg (7.9 vs 6.3 months; HR 0.80; 95% CI 0.64–1.02; p = .068). At data cut-off (75.5% maturity), median OS with first-line fulvestrant 500 mg was 23.2 vs 22.1 months with fulvestrant 250 mg (HR 0.87; 95% CI 0.70–1.10; p = .251), and 29.2 vs 22.8 months, respectively, in the second-line (HR 0.75; 95% CI 0.58–0.96; p = .020). The safety profile was broadly comparable between dose groups and across treatment lines, and consistent with the overall patient population.ConclusionThe superiority of fulvestrant 500 mg over fulvestrant 250 mg in patients with LA/MBC in CONFIRM was consistent in both the first- and second-line settings for PFS, and numerically greater in both settings for OS.     

Real world initial palliative treatment patterns and clinical outcomes in premenopausal patients with hormone receptor-positive,HER2-negative metastatic breast cancer: A study of the National Cancer Center,China

BackgroundTo observe whether guideline non-adherence in initial palliative treatment choices for premenopausal hormone receptor-positive (HR+), HER2-negative metastatic breast cancer (MBC) patients result in worse clinical outcomes in the Chinese population.MethodsThe China National Cancer Center database was used to identify 2194 patients diagnosed between 2004 and 2015. A total of 451 premenopausal patients with HR + HER2- MBC were included. Clinicopathological features and survival information were extracted. Progression-free survival (PFS) and overall survival (OS) were estimated using the Kaplan–Meier method and compared using log-rank test.ResultsThe number of patients receiving initial chemotherapy, endocrine therapy and chemo-endocrine therapy were 222 (49.2%), 80 (17.7%), and 149 (33.0%), respectively. Patients receiving initial chemotherapy were more likely to be luminal B subtype, had more de novo stage IV disease and more liver metastasis, compared with patients receiving initial endocrine therapy. Both PFS and OS were significantly longer for chemo-endocrine therapy group (median PFS 18.9 months and OS 75.0 months), than for endocrine therapy group (median PFS 11.7 months and OS 53.5 months), and chemotherapy group (median PFS 7.1 months and OS 43.9 months). In multivariate analysis, none of the three treatment strategies were independently associated with PFS or OS.ConclusionIn real world, a high percentage of premenopausal patients with HR + HER2- disease received chemotherapy as initial palliative treatment in China, which was not associated with worsened survival. Further studies with larger sample size across China are needed to explore the relationship between this guideline non-adherence and clinical outcomes.     

Limb salvage surgery has a higher complication rate than amputation but is still beneficial for patients younger than 10 years old with osteosarcoma of an extremity

Background/PurposeLimb preserving surgery for the treatment of patients with osteosarcoma younger than 10 years old is challenging and some authors have advocated amputation to reduce the risk of complications. The aim of this study was to compare the clinical outcomes and surgical complications of patients with osteosarcoma of the extremity aged <10 years old who were treated with limb salvage and amputation.Patients and methodsRetrospective review of patients aged <10 years old who were treated for primary osteosarcoma of bone between 2000 and 2018.ResultsWe analyzed 82 consecutive patients (32 males, 50 females; median age 8, range 3–9 yrs). Limb-salvage surgery (LSS; n = 65, 79%) and amputation (n = 17, 21%) were performed. Fourteen patients had metastasis at surgery. In patients without metastasis at surgery, the metastasis-free and overall survival rates at 5 years following LSS vs. amputation were 75% vs. 58% (p = 0.162) and 71% vs. 55% (p = 0.516), respectively. The 2-year and 5-year OS rates of the LSS and amputation groups of patients with metastasis at surgery were 88% versus 83% and 50% versus 0%, respectively (p = 0.180). The overall complication rates were 46% post-LSS with 31% requiring re-operation versus 12% post-amputation, with 6% requiring re-operation (p = 0.010).ConclusionThe prognosis of patients with localized osteosarcoma aged <10 years undergoing LSS is similar to those treated with amputation, but LSS is associated with a higher risk of complications and subsequent re-operation.Level of evidenceLevel III     

Concept: A randomised multicentre trial of first line chemotherapy comparing three weekly cabazitaxel versus weekly paclitaxel in HER2 negative metastatic breast cancer

BackgroundPaclitaxel is commonly used as first-line chemotherapy for HER2-negative metastatic breast cancer (MBC) patients. However, with response rates of 21.5–53.7% and significant risk of peripheral neuropathy, there is need for better chemotherapy.Patients and methodsThis open-label phase II/III trial randomised HER2-negative MBC patients 1:1 to either 6 cycles of three-weekly cabazitaxel (25 mg/m²), or, weekly paclitaxel (80 mg/m²) over 18 weeks.The primary endpoint was progression free survival (PFS). Secondary endpoints included objective response rate (ORR), time to response (TTR), overall survival (OS), safety and tolerability and quality of life (QoL).Results158 patients were recruited. Comparing cabazitaxel to paclitaxel, median PFS was 6.7 vs 5.8 months (HR 0.87; 80%CI 0.70–1.08, P = 0.4). There was no difference in median OS (20.6 vs 18.2 months, HR 1.00; 95%CI 0.69–1.45, P = 0.99), ORR (41.8% vs 36.7%) or TTR (HR 1.09; 95%CI 0.68–1.75, P = 0.7).Grade ≥3 adverse events occurred in 41.8% on cabazitaxel and 46.8% on paclitaxel; the most common being neutropenia (16.5%) and febrile neutropenia (12.7%) cabazitaxel and neutropenia (8.9%) and lung infection (7.6%) paclitaxel. Peripheral neuropathy of any grade occurred in 54.5% paclitaxel vs 16.5% cabazitaxel.Mean EQ-5D-5L single index utility score (+0.05; 95%CI 0.004–0.09, P = 0.03) and visual analogue scale score (+7.7; 95%CI 3.1–12.3, P = 0.001) were higher in cabazitaxel vs paclitaxel.ConclusionsThree-weekly cabazitaxel in HER2-negative MBC does not significantly improve PFS compared to weekly paclitaxel, although it has a lower risk of peripheral neuropathy with better patient reported QoL outcomes. It is well tolerated and requires fewer hospital visits.     

Objective Response to First-Line Treatment as a Predictor of Overall Survival in Metastatic Breast Cancer: A Retrospective Analysis from Two Centers over a 25-Year Period

IntroductionThe purpose of this study was to study the efficacy of subsequent treatment lines for metastatic breast cancer (MBC), as well as the association between radiologic objective response rate (ORR) and overall survival (OS).MethodsIn this retrospective study, consecutive patients treated for MBC in two centers in Greece from January 1, 1992, to December 31, 2016, were identified and clinicopathologic data regarding tumor characteristics and administered treatments were collected. The efficacy per treatment line in terms of ORR, progression-free survival (PFS) and OS, as well as the prognostic value of ORR at first line were investigated.ResultsA total of 977 patients with MBC were identified; 950 received any treatment. At first line, ORR was 43.5%, PFS 11.4 months (95% CI 10.4–12.4), and median OS 52.4 months (95% CI 47.7–57.1). Lower ORR and shorter PFS were observed with each subsequent line. Median OS was significantly longer for patients that had an objective response at first line, 61.9 months (95% CI 51.1–69.7) for responders versus 41.3 months (95% CI 44.1–63.3) for nonresponders (p < 0.001). In multivariable analysis, failure to achieve an objective response was an independent predictor of poor survival (hazard ratio 1.70, 95% CI 1.34–2.15, p < 0.001).ConclusionLate treatment lines for MBC seem to have limited efficacy, while response to first-line therapy is associated with long-term survival. The latter should be considered in the treatment strategy of patients with MBC.     

Survival outcomes after breast-conserving therapy compared with mastectomy for patients with early-stage metaplastic breast cancer: a population-based study of 2412 patients

BackgroundPrevious studies revealed that patients with early-stage metaplastic breast cancer (MBC) underwent mastectomy more often than breast-conserving therapy (BCT) mainly due to the larger tumor size. This study was performed to compare the survival outcomes following BCT versus mastectomy for patients with early-stage MBC.MethodsSurveillance, Epidemiology, and End Results (SEER) database was used to identify women diagnosed with early-stage MBC (T1-3N0-3M0) between 2001 and 2016, who were treated with either BCT or mastectomy. We assessed overall survival (OS) and breast cancer-specific survival (BCSS) using the Kaplan-Meier method and hazard ratios using Cox proportional hazards models.ResultsA total of 2412 MBC patients were identified, 881 (36.5%) of whom underwent BCT and 1531(63.5%) underwent mastectomy. The median follow-up time was 73 months. Most of patients had older age (≥50 years old), larger tumor size, higher American Joint Committee on Cancer (AJCC) stage and hormone receptor negativity. After adjustment for confounding variables, patients who underwent BCT had significantly improved OS (5-year OS: 84.3% vs 62.5%; 10-year OS: 73.0% vs 52.1%; adjusted HR = 0.76, 95%CI: 0.59–0.97, p = 0.028) and BCSS (5-year BCSS: 89.1% vs 70.8%; 10-year BCSS: 83.9% vs 67.5%; adjusted HR = 0.72, 95%CI: 0.53–0.96, p = 0.026) than those who underwent mastectomy, and this improvement remained significant for all T and N stages of MBC except for N2-3 stage.ConclusionBCT conferred improved OS and BCSS compared with mastectomy for patients with early-stage MBC, and the improvement persisted in almost all of the subgroups of different T and N stages.     

Treatment and Outcome of Patients with Skull Base Chordoma: A Meta-analysis

Objective Chordoma is a locally aggressive tumor. The aim of this study was to assess the efficacy of different surgical approaches and adjuvant radiation modalities used to treat these patients. Design Meta-analysis. Main Outcome Measures Overall survival (OS), disease-specific survival (DSS), and progression-free survival (PFS). Results The 5-year OS and PFS rates of the whole cohort (n = 467) were 86% and 65.7%, respectively. The 5-year DSS for patients who underwent open surgery and endoscopic surgery was 45% and 49%, respectively (p = 0.8); PFS was 94% and 79%, respectively (p = 0.11). The 5-year OS of patients treated with surgery followed by adjuvant radiotherapy was 90% compared with 70% of those treated by surgery alone (p = 0.24). Patients undergoing partial resection without adjuvant radiotherapy had a 5-year OS of 41% and a DSS of 45%, significantly lower than in the total-resection group (p = 0.0002 and p = 0.01, respectively). The complication rates were similar in the open and endoscopic groups. Conclusions Patients undergoing total resection have the best outcome; adjuvant radiation therapy improves the survival of patients undergoing partial resection. In view of the advantages of minimally invasive techniques, endoscopic surgery appears an appropriate surgical approach for this disease.     

Prolonged clinical benefit from the maintenance hormone therapy in patients with metastatic breast cancer

ObjectiveWe investigated the efficacy of maintenance hormone therapy (MHT), which was given to hormone positive metastatic breast cancer (MBC) patients in non-progression status to the previous chemotherapy.MethodsThis study retrospectively analyzed 76 MBC patients who had been treated with MHT from 2006 to 2010 at a single institute.ResultsFor the 76 patients reviewed, the median progression free survival (PFS) to MHT was 14.4 months (95% CI, 11.6–17.3). Prolonged PFS was associated with less previous palliative chemotherapy, fewer metastatic sites, and the absence of visceral metastasis in univariate analysis. Multivariate analysis showed that only the number of previous palliative chemotherapy (HR 1.73, 95% CI, 1.00–2.98; P = 0.04) remained as a significant variable. MHT was generally well tolerated.ConclusionsMHT showed considerable efficacy and tolerability in this study. Further randomized prospective study is warranted.     

The continuing conundrum in oligometastatic breast carcinoma: A real-world data

The optimal management in Oligometastatic (OM) breast carcinoma is not defined.ObjectivesTo identify the prognostic factors influencing OM and the effect of Locoregional treatment (LRT) on survival in OM.MethodologyPatients with ≤5 metastases and each with ≤ 5 cm size were defined as OM. Data of OM were extracted from the Institute Registry between 2012 and 2018. The impact of prognostic factors on survival was analysed by univariate and multivariate Cox regression. The Kaplan Meier survival curves were used to plot PFS and OS.ResultsThere were 170 patients with OM. The median follow-up was 61 months. Median OS was 43.3 months. The median OS was 74 months in OMD vs 22.7 months in Oligorecurrent disease (ORD) with 5year OS rate of 55.3% vs 16.5% respectively. In the multivariate analyses of OMD both Ki67 ≤ 50% and hormone therapy (HT) showed significant favourable survival outcome. While premenopausal status and HT showed significant survival benefits in ORD. The worse survival outcome in ORD could be because of their aggressive biology and deficit in LRT compared to literature review. The prognostic factors were swayed by the uneven distribution of HR status, grade and Ki67.ConclusionThe survival of OM was influenced by OMD, Ki67 ≤ 50%, premenopausal status and HT. The lesser survival rates of OM in the long term suggest the need for curative LRT to metastatic sites and primary tumor. The potential role of HT and targeted therapy with or without LRT need to be assessed in future randomised trials.     

Outcomes of Busulfan,Fludarabine, and 400 cGy Total Body Irradiation Compared With Busulfan and Fludarabine Reduced-Intensity Conditioning Regimens for Allogeneic Stem Cell Transplantation in Adult Patients With Hematologic Diseases: A Single-Center Experience

BackgroundReduced intensity conditioning (RIC) regimens decrease the risk for nonrelapse mortality (NRM) in adult patients undergoing allogeneic hematopoietic stem cell transplantation for hematologic malignancies but increase the risk for relapse. The aim of this study was to compare the outcomes of fludarabine–total body irradiation (TBI) with fludarabine among patients with hematologic diseases.Patients and MethodsThis retrospective study of 137 patients with different hematologic malignancies compared the outcomes of 63 patients who received a conventional RIC regimen with 2 days of IV busulfan (3.2 mg/kg/d × 2 days) and fludarabine with 74 patients who received the same regimen plus 400 cGy of fludarabine and busulfan (FB)-TBI divided in 2 doses over 1 day (200 cGy BID). Median follow-up was 4.62 years.ResultsThe donors were either HLA-matched siblings (36%) or HLA-matched unrelated donors (64%). The FB-TBI showed trends toward improvement in progression-free survival (PFS) and overall survival (OS) over FB (5-year PFS rates 50% vs 34%, P = .06, and 5-year OS rate 53% vs 39%, P = .13). Acute graft-vs-host disease (aGVHD), relapse, and NRM were similar between the 2 groups. The 5-year cumulative incidence of chronic GVHD (cGVHD) was lower in the FB-TBI group compared with the FB group (29% vs 52%, P = .003). Multivariable analysis revealed that grade III-IV aGVHD was the only independent risk factor for worse OS (P = .001) in both groups. A high disease risk index was possibly associated with inferior OS (P = .07) in both groups.ConclusionsThe FB-TBI is a safe and effective intensified RIC regimen for adult patients with hematologic malignancies. It predicted a lower risk for cGVHD and showed possibly improved PFS and OS compared with FB.     

Comparison between doublet agents versus single agent in metastatic breast cancer patients previously treated with an anthracycline and a taxane: A meta-analysis of four phase III trials

AimTo compare doublet agents with single agent as salvage treatment in metastatic breast cancer (MBC) patients pre-treated with an anthracycline and a taxane.MethodsWe systematically searched for randomised clinical trials that compared doublet agents with single agent in MBC patients pre-treated with an anthracycline and a taxane. The primary end point was overall survival (OS). Secondary end points were progression-free survival, overall response rate and grade 3 or 4 toxicity. Data were extracted from the studies by two independent reviewers. The meta-analysis was performed by Stata version 10.0 software (Stata Corporation, College Station, TX, USA).ResultsFour trials comprising 2373 patients were eligible for inclusion. Meta-analysis showed that there was significant improvement in progression-free survival (PFS) (hazard ratio (HR) 0.79, 95% confidence interval (CI) 0.72–0.86, P = 0.000) and overall response rate (risk ratio (RR) 1.47, 95%CI 1.13–1.91; p = 0.004) in doublet agents group, though the pooled HR for OS (HR 0.96, 95%CI 0.87–1.05; p = 0.356) showed no significant difference. Subgroup analysis also favoured capecitabine-based doublet agents therapy in terms of PFS (HR 0.77, 95%CI 0.70–0.86; p = 0.000) and overall response rate (ORR) (RR 1.65, 95%CI 1.06–2.56; p = 0.026), but gemcitabine-based doublet agents therapy gained no clinical benefits. There were more incidences of grade 3 or 4 anaemia (RR 1.610, 1.212–2.314, p = 0.01), neutropenia (RR 2.239, 1.231–4.071, p = 0.008), thrombocytopaenia (RR 2.401, 1.595–3.615, p = 0.000), fatigue (RR 2.333, 1.338–4.006, p = 0.000) and nausea and vomiting (RR 2.233, 1.558–3.199, p = 0.000) in the combination group. With regard to the risk of grade 3 or 4 stomatitis (RR 1.666, 0.818–3.392, p = 0.160), diarrhoea (RR 0.739, 0.542–1.008, p = 0.056) and hand–foot syndrome (RR 1.002, 0.835–1.203, p = 0.983), equivalent frequencies were found between the two groups.ConclusionCombination chemotherapy offered a significant improvement in PFS and ORR in patients with MBC pre-treated with an anthracycline and a taxane but did not benefit OS. With present available data from randomised clinical trials, we were still unable to clearly set the role of combination therapy in the treatment of MBC in this setting.     

Phyllodes tumors of the breast: Adjuvant radiation therapy revisited

BackgroundPhyllodes tumors (PT) are rare entity and surgical resection is the cornerstone of treatment. No standard of care exists regarding adjuvant treatment especially radiation therapy (RT).Patients and methodsWe analyzed all patients with non-metastatic, resected phyllodes tumors who presented to our institution from January 2005 through December 2019. Primary study endpoints included local recurrence free survival (LRFS) and overall survival (OS).ResultsOne hundred and eight patients were analyzed (patients with incomplete treatment and follow up data were excluded). Fifty patients had benign phyllodes, 26 patients had borderline and 32 patients had malignant phyllodes. In the benign group, no significant difference in LRFS was observed between patients who received adjuvant RT (n = 3) and those who did not (5-year LRFS 100% vs. 85% respectively, p = 0.49). The 5 year OS for patients who received RT was 60% vs. 89% for those who did not (p 0.40). In the borderline/malignant group, adjuvant RT significantly improved five year LRFS (90% in the RT group vs. 42% in the no RT group, p = 0.005). The 5 year LRFS in patients treated with margin negative breast conserving surgery and RT was 100% vs. 34.3% in patients who did not receive RT (p 0.022). Patients treated with mastectomy and RT had a 5 year LRFS of 100% vs. 83% for patients who did not receive RT (p 0.24). On multivariate analysis, radiation therapy was independently associated with decreased hazard of local failure (HR 0.21, CI 0.05–0.89, p = 0.03). No difference in OS was found between the RT and no RT groups (5-year OS was 52% vs. 45% respectively, p 0.54).ConclusionThe results of the current study confirm the excellent prognosis of benign phyllodes tumors; warranting no further adjuvant treatment after margin-negative surgical resection. For patients with borderline/malignant phyllodes tumors, adjuvant radiation therapy significantly improved LRFS after margin negative wide local excision; however, patients treated with mastectomy did not attain the same benefit from adjuvant irradiation.     

Is early mobilization after volar locking plate fixation in distal radius fractures really beneficial? A meta-analysis of prospective randomized studies

Study designThis was a systematic review with a meta-analysis.IntroductionDespite rising trends toward surgical treatment of distal radius fractures (DRF) with volar locking plate (VLP) fixation, there is a lack of consensus on when to start vigorous wrist range of motion (ROM) exercises after surgery.PurposeWe performed a meta-analysis to compare early and late mobilization after VLP fixation in patients with DRF.MethodsFour prospective randomized controlled trials with a minimum of 6 months of follow-up were retrieved through MEDLINE (PubMed), EMBASE, Web of Science, the Cochrane Library, and the KoreaMed databases in March 2021. We divided patients into an early group (patients who started ROM exercises of the wrist within 2 weeks after surgery), and a late group (patients who started ROM exercises 5 or 6 weeks after surgery). The primary outcome was treatment efficacy which was measured through improvement in pain score, function score, ROM, and grip power. The secondary outcome was the incidence of postoperative complications.ResultsThis meta-analysis included 127 patients in the early group and 131 patients in the late group. The outcomes were compared at 6 weeks, 3 months, and 6 months postoperatively. There was no significant difference in pain score, though the early group had a lower average visual analog scale score. The early group had a lower arm, shoulder, and hand disability score than the late group (95 % CI, -16.25 to -8.35 points; P < .001) at 6 weeks postoperatively, suggesting significantly superior outcomes. A similar trend persisted at 3 (n = 74 in the early group and n = 77 in the late group; 95% CI, -5.45 to -0.30; P = .029) and 6 months (n = 102 in the early group and n = 100 in the late group; 95% CI, -4.81 to 0.21; P = .073), but the differences were smaller. The early group had a higher grip power at all follow-up periods, but the difference was only significant at 6 months postoperatively (n = 88 in the early group and n = 83 in the late group; 95% CI, 0.50 to 6.99; P = 0.024). The early group also had more favorable ROM in all directions at 6 weeks, but only in supination at 6 months. The complication rate was not significantly different between the 2 groups. There were no differences in the rates of secondary operation and reduction loss.ConclusionEarly ROM exercise after VLP in DRF resulted in superior functional scores and grip power until 6 months postoperatively. The dominance of the joint ROM, which was seen at 6 weeks after surgery in the early exercise group, decreased with time and ultimately showed little difference at 6 months. Early exercise is safe and did not increase complication rates.