Survival outcomes of breast cancer patients with brain metastases: A multicenter retrospective study in Korea (KROG 16–12)

PurposeThis study evaluated the influence of prognostic factors and whole brain radiotherapy (WBRT) on overall survival (OS) of breast cancer (BC) patients with brain metastases (BM).Methods and materialsMedical records of 730 BC patients diagnosed with BM from 2000 to 2014 at 17 institutions were retrospectively reviewed. OS was calculated from BM diagnosis. Median follow-up duration was 11.9 months (range, 0.1–126.2).ResultsMedian OS was 15.0 months (95% CI: 14.0–16.9). Patients with different BC-specific graded prognostic assessment (GPA) scores showed significant differences (p < 0.001) in OS. In multivariate analysis, histologic grade 3 (p = 0.014), presence of extracranial metastasis (p < 0.001), the number of BM (>4; p = 0.002), hormone receptor negativity (p = 0.005), HER2-negativity (p = 0.003), and shorter time interval (<30 months) between BC and BM diagnosis (p = 0.007) were associated with inferior OS. By summing the β-coefficients of variables that were prognostic in multivariate analyses, we developed a prognostic model that stratified patients into low-risk (≤0.673) and high-risk (>0.673) subgroups; the high-risk subgroup had poorer median OS (10.1 months, 95% CI: 7.9–11.9 vs. 21.9 months, 95% CI: 19.5–27.1, p < 0.001). Univariate and multivariate analyses of propensity score-matched patients diagnosed with BM ≥ 30 months after BC diagnosis (n = 389, “late BM”) revealed that WBRT-treated patients showed superior OS compared to non-WBRT-treated patients (p = 0.070 and 0.030, respectively).ConclusionOur prognostic model identified high-risk BC patients with BM who might benefit from increased surveillance; if validated, our model could guide treatment selection for such patients. Patients with late BM might benefit from WBRT as initial local treatment.     

Upfront brain radiotherapy may improve survival for unfavorable prognostic breast cancer brain metastasis patients with Breast‐GPA 0‐2.0

In this study, we attempted to assess the efficacy of upfront brain radiotherapy (RT) in breast cancer (BC) patients with brain metastases (BM). Medical records of 111 consecutive BC patients treated with WBRT or SRS between August 2009 and November 2017 in single center were retrospectively reviewed. Eighty patients received upfront brain RT after BM diagnosis and 31 had delayed RT. The median age at BM was 54 years (22‐77), with median KPS 80 (50‐90). The molecular BC subtypes of Luminal A, Luminal B, triple‐negative and HER2 overexpression were 16, 47, 27, and 19, respectively, with 2 unknown. Of them, 83 received WBRT after BM and 28 SRS. Median overall survival (OS) was significantly related to Breast‐GPA, as following: 6.5, 9.9, 14.4, and 24.5 months in 0‐1.0, 1.5‐2.0, 2.5‐3.0, and 3.5‐4.0 subgroups, respectively (P = 0.007). Univariate and multivariate analysis showed that KPS ≤70, infratentorial involvement, extracranial metastases, and no continuing systemic therapy were independent risk factors for OS. In the whole group, no significant difference in OS was found between upfront or delayed RT. For Breast‐GPA 0‐2.0 subgroup, upfront RT was associated with increased median OS (3.3 vs 9.8 months, P = 0.04). In GPA 2.5‐4.0 subgroup, the median OS for upfront and delayed RT was 13.8 and 16.5 months, respectively (P = 0.58). In conclusion, BCBM patients with better KPS, systemic therapy, without infratentorial involvement and extracranial metastases are associated with better OS. Patients with Breast‐GPA 0‐2.0 might benefit from upfront brain RT.     

Prognostic factors of brain metastases from breast cancer: Impact of targeted therapies

IntroductionBrain metastases (BM) from breast cancer are associated with poor prognosis. This study was made to determine the prognostic influence of breast cancer biological subtypes, and to define the best therapeutic options in this setting, with a special focus on the HER2-positive population.Patients and methodsBreast cancer patients with known hormone receptors (HR) and HER2 status presenting with BM treated between 1995 and 2010 in our two institutions were considered for this retrospective study.Results250 patients were included. The study population consisted of 25.6% patients categorized as triple-negative (HR?/HER2?), 30.8% as HR+/HER2? and 43.6% as HER2+ breast cancer. Median overall survival (OS) was 8.9 months (95% CI, 6.9–10.3 months). Cerebral progression remained the most frequent cause of death (57.1%). On multivariate analysis, HER2 positivity and the RPA score were the two most important prognostic factors. Local treatment (surgery or stereotactic radiotherapy) and chemotherapy were significantly associated with an increased survival. On multivariate analysis of the RPA1-2 population, local treatment and chemotherapy were independent prognostic factors in addition to biological subtypes, RPA class, liver metastases and clinical signs of intra-cranial hypertension. Anti-HER2 therapies administered after BM diagnosis significantly and independently increased OS. Median OS in patients receiving both trastuzumab and lapatinib after BM diagnosis was significantly better than that the one of patients receiving only one of the 2 targeted therapies (25.7 vs. 9.6 months, p < 0.001).ConclusionsBiological subtypes are independent prognostic determinants. Chemotherapy and targeted therapies positively affect the prognosis after first BM.     

Breast cancer patients with brain metastases or leptomeningeal disease: 10‐year results of a national cohort with validation of prognostic indexes

Development of brain metastasis (BM) and leptomeningeal (LM) disease in breast cancer (BC) patients indicates poor prognosis and impairs patients’ quality of life. Prognostic survival scores for BM can help predict expected survival in order to choose the most appropriate treatment. The aim of our study was to analyze national data for BC patients treated with radiation therapy for BM/LM disease and validate the applicability of different survival prognostic scores. We retrospectively evaluated medical records of 423 BC patients with BM/LM disease receiving radiation therapy between April 2005 and December 2015. Patients were classified by BC Recursive Partitioning Analysis (B‐RPA), Breast Graded Prognostic Assessment (Breast‐GPA), Modified Breast Graded Prognostic Assessment (MB‐GPA), and Simple Survival score for patients with BM from BC (SS‐BM). Overall survival (OS) was calculated from the development of BM/LM disease to death or last follow‐up date. After a median follow‐up of 7.5 years, the median OS was 6.9 months (95% CI 5.5‐7.8, range 0‐146.4) and 1‐ and 2‐year survival rates were 35% and 17%, respectively. Survival analysis showed significant differences in median OS regarding biologic subtypes (P < 0.0001), as follows: 3.2 (95% Confidence Interval (CI) 2.5‐3.9), 3.9 (95% CI 2.3‐5.6), 7.1 (95% CI 4.3‐9.8), 12.1 (95% CI 8.3‐15.9), and 15.4 (95% CI 8.8‐22.1) months for primary triple‐negative BC (TNBC), Luminal B HER2‐negative, Luminal A, HER2‐enriched, and Luminal B HER2‐positive tumors, respectively. Good Karnofsky Performance Status (KPS), single metastasis, and absence of LM or extracranial disease all demonstrated better OS in univariate and multivariate analysis. All four employed prognostic indexes provided good prognostic value in predicting survival. SS‐BM and MB‐GPA showed the best discriminating ability (Concordance indexes C were 0.768 and 0.738, respectively). This study presents one of the largest single‐institution series validating prognostic scores for BC patients with BM/LM. SS‐BM and MB‐GPA proved to be useful tools in the clinical decision‐making process.     

Posterior fossa metastases: aggressive treatment improves survival

BACKGROUND: Brain metastases are a leading cause of mortality and morbidity in patients with malignancies. Infratentorial location has been considered a negative prognostic factor. METHODS: This retrospective study evaluated patients with cerebellar metastasis. Statistical analysis assessed age, extracranial disease, performance status and treatment. Patients were categorized by Radiation Therapy Oncology Group recursive partitioning analysis (RPA). Treatment included surgery, stereotactic radiosurgery (SRS) and whole brain radiotherapy (WBRT) alone or in combination. RESULTS: Of 93 patients, the median survival was 12.9 months for RPA class I, 11 months for class II and 8 months for class III. On multivariate analysis, RPA class was an important predictor for overall survival. However, SRS with WBRT or surgery with WBRT or a combination of SRS, surgery and WBRT, was more favorable than surgery or SRS alone within RPA class II patients. CONCLUSIONS: Survival of patients with cerebellar brain metastasis is comparable to that of patients with supratentorial brain metastasis using RPA classification. Aggressive multimodality therapy has a favorable impact on survival.     

Prognostic factors in patients treated with stereotactic image-guided robotic radiosurgery for brain metastases: a single-center retrospective analysis of 223 patients

In this retrospective study, we evaluated the overall survival (OS) and local control (LC) of brain metastases (BM) in patients treated with stereotactic radiosurgery (SRS). The scope was to identify host, tumor, and treatment factors predictive of LC and survival and define implications for clinical decisions. A total of 223 patients with 360 BM from various histologies treated with SRS alone or associated with whole brain radiotherapy (WBRT) in our institution between July 1, 2008 and August 31, 2013 were retrospectively reviewed. Among other prognostic factors, we had also evaluated retrospectively Karnofsky performance status scores (KPS) and graded prognostic assessment (GPA). Overall survival (OS) and local control (LC) were the primary endpoints. Kaplan-Meier and Cox proportional hazards models were used to estimate OS and LC and identify factors predictive of survival and local control. The median duration of follow-up time was 9 months (range 0.4–51 months). Median overall survival of all patients was 11 months. The median local control was 38 months. No statistical difference in terms of survival or LC between patients treated with SRS alone or associated with WBRT was found. On multivariate analysis, KPS was the only statistically significant predictor of OS (hazard ratio [HR] 2.53, p?=?0.006). On univariate analysis, KPS and GPA were significantly prognostic for survival. None of the host, tumor, or treatment factors analyzed in the univariate model factors were significantly associated with local failure.     

Efficacy and limitations of salvage gamma knife radiosurgery for brain metastases of small-cell lung cancer after whole-brain radiotherapy

Background

The efficacy and limitations of salvage gamma knife surgery (GKS) have not been thoroughly described. This study evaluated the efficacy of GKS for treating brain metastases associated with small-cell lung cancer (SCLC) after whole-brain radiotherapy (WBRT) as the first-line radiation therapy.

Methods

Forty-four patients with recurrent or new SCLC-associated brain metastases underwent GKS after receiving WBRT (median age, 62 years; median duration between WBRT and first GKS, 8.8 months). The median Karnofsky performance status (KPS) score was 100 (range, 40–100), and the median number of brain metastases at the first GKS was five. Ten patients who partially or completely responded to chemotherapy received prophylactic cranial irradiation (PCI) for limited disease.

Results

The median prescribed dose and number of lesions treated with the initial GKS were 20.0 Gy and 3.5, respectively, and the tumor control rate was 95.8 % (median follow-up period, 4.0 months). The 6-month new lesion-free survival, functional preservation rates, and overall survival were 50.0 %, 94.7 %, and 5.8 months, respectively. Neurological death occurred in 17.9 % of cases. The poor prognostic factors for new lesion-free survival time and functional preservation were >5 brain metastases and carcinomatous meningitis, respectively. Poor prognostic factors for survival time were KPS <70, >10 brain metastases, diameter of the largest tumor >20 mm, and carcinomatous meningitis. Median overall survival time from brain metastasis diagnosis was 16.9 months.

Conclusions

GKS may be an effective option for controlling SCLC-associated brain metastases after WBRT and for preventing neurological death in patients without carcinomatous meningitis.     

Clinical outcome of patients with brain metastases from breast cancer - A population based study over 21 years

BackgroundBrain metastases (BM) are a feared progression of breast cancer (BC) with impact on quality of life and survival. Despite improved treatments, it is believed patients suffering from BM are increasing.AimsTo study potential changes in the number of BM, the possible links between BC subgroup and extent of BM with prognosis. To investigate the interval between primary BC/extra cranial recurrence, and diagnosis of BM in the years 1994–2014.Patients and methodsClinical data from 191 patients with BM diagnosed 1994–2014, was retrieved from charts. Primary tumours where re-evaluated histologically.ResultsThere was an increase of BM in 5 years cohorts (1994-99 (n = 9); 2000-04 (n = 36); 2005-09 (n = 60); 2010-14 (n = 86)). We found no difference in the time interval from primary BC to BM but an insignificant increase in time from extra cranial relapse to development of BM in the time periods 1994–2004 and 2005–2014 of 15.5 and 25.0 months (p = 0.0612). Survival after BM was 7 months (95% CI 6–10) with a statistically significant difference between HER2 positive and TNBC with an inferior outcome for the latter (p = 0.018) whilst no differences were present when Luminal BC were compared with HER2 positive BC (p = 0.073).ConclusionsWe show an increase of BM over time whilst the time span from primary BC to BM is unchanged supports earlier findings that adjuvant treatments have little preventive function. Time from extra cranial recurrence to BM was prolonged with one year. Patients with TNBC or more advance extent of BM had the shortest survival with BM.     

Gamma knife surgery for brain metastases: indications for and limitations of a local treatment protocol

Summary Objective. The purpose of this retrospective study was to evaluate results of a local treatment protocol using gamma knife surgery (GKS) for brain metastases without upfront whole brain radiation therapy (WBRT).Methods. Results for 521 consecutive patients satisfying the following 3 criteria were analysed: 1) a maximum of 3 tumours with a diameter of 25 mm or more; 2) no prior WBRT; 3) no surgically in accessible large (>30 mm) tumours. Large tumours were surgically removed and all smaller lesions were treated by GKS without up front WBRT. New lesions, detected with follow-up MRI, were appropriately treated with repeat GKS. Overall survival (OS), neurological survival (NS), qualitative survival (QS) and new lesion-free survival (NLFS) curves were calculated and the prognostic values of covariates were obtained. OS and NS were compared according to tumour number.Results. In total, 1023 separate sessions were required to treat 4562 lesions. The primary organs were lung in 369 patients, gastro-intestinal tract in 70, breast in 33, urinary tract in 24, and others/unknown in 25. The median OS period was 9.0 months. On multivariate analysis, the significant prognostic factors for OS were found to be extracranial disease (risk factor: active), Karnofsky performance status (KPS) score (<70) and gender (male). NS and QS at one year were 85.6% and 73.0%, respectively. The only significantly poor prognostic factor for NS was carcinomatous meningitis. NLFS at 6 months was 68.9%. For both OS and NS, the differences between a few (≤3) and many (4–10) brain lesions were not significant (OS: p=0.3128, NS: p=0.5509). Patients with numerous (>10) tumours had a significantly poorer prognosis than those with ≤10.Conclusion. Our protocol, aggressively applying GKS, provides excellent results in selected patients with ≤10 brain lesions and no carcinomatous meningitis.     

Clinical outcomes of platinum-based chemotherapy in patients with advanced breast cancer: An 11-year single institutional experience

Background/methods: Although the prognosis of metastatic breast cancer (BC) has improved, some patients still develop high burden metastases or visceral crisis (VC) and polychemotherapy is commonly used in these cases. Data reporting the real effectiveness of this strategy are scanty. Therefore, the outcomes of patients with metastatic BC treated with platinum-based chemotherapy (P-ChT) at the Jules Bordet Institute during the period of January 2008 and December 2018 were retrospectively reviewed. The presence of VC was defined according to ABC 4 criteria.Results441 patients were identified: visceral metastases were observed in 430 (97.5%) while 261 (59.2%) presented VC. As for metastatic BC subtype, 255 (57.8%) had ER-positive/HER2-negative, 41 (9.3%) ER-positive/HER2-positive, 34 (7.7%) ER-negative/HER2-positive and 111 (25.1%) triple-negative BC. Median number of prior treatment lines was 3.8 (0–12). Median OS with P-ChT in the entire cohort was 6.13 months. Patients with VC had lower OS than patients without VC (8.6 vs 3.7 months; p < 0.001). On multivariate analysis, the variables correlated with worse OS were hyperbilirubinemia (HR 1.90; 95% CI 1.34–2.75), ECOG ≥2 (HR 1.77; 95% CI 1.13–2.78) and ECOG ≥3 (HR 2.52; 95% CI 1.48–4.28), and >3 previous treatment lines (HR 2.27; 95% CI 1.53–3.21). Of the 261 patients with VC, 106 (40.5%) presented a resolution of the VC which correlated with better OS (9.3 vs 2.0 months, HR 0.27; 95% CI 0.21–0.36).ConclusionPatients who overcome VC benefit from P-ChT with OS similar to patients without VC. In this analysis, hyperbilirubinemia, poor ECOG and >3 previous treatment lines were significant prognostic factors in the overall study population.     

Retrospective study of 127 surgically treated patients with multiple brain metastases: indication, prognostic factors, and outcome

Background

Metastases are the most frequent tumours in the brain. At the time of diagnosis, more than 50% of patients present with multiple lesions. The goal of our retrospective investigation was to evaluate the outcome of patients who undergo surgery for multiple cerebral metastases and to determine prognostic factors.

Methods

We included 127 patients with multiple brain metastases in the study. The median number of metastases was three. All patients were operated on for at least one lesion. The indications for surgery were: large tumours ≥27 cm³, metastases of unknown primaries at the time of diagnosis, and space-occupying cerebellar lesions. If possible, adjuvant WBRT was applied.

Results

The median MST of the whole group was 6.5 months; for patients with complete resection, 10.6 months. According to the RPA classification the MST ranged between 19.4 (class I), 7.8 (class II), and 3.4 months (class III) (p < 0.001). KPS?>?70 had a significant influence on MST (9.1 months vs. 3.4 months, p?<?0.001), the number of lesions: 2–4 vs. >4 (p?=?0.046), and postoperative WBRT in multivariate analysis (p?=?0.026). Age was not a significant factor. The 2-year survival rate was 15% and the 3-year survival rate 10%.

Conclusions

Favourable factors for prolonged survival were complete resection of all lesions, no more than four metastases, RPA-class I and adjuvant WBRT. The resection of large lesions, while leaving smaller residual ones, did not result in increased survival.     

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.     

Stereotactic radiosurgery for patients with "radioresistant" brain metastases

OBJECTIVE: Our aim was to evaluate the efficacy of stereotactic radiosurgery (SRS) for the treatment of patients with brain metastases that have been determined to be "radioresistant" on the basis of histological examination. METHODS: We reviewed the medical records of 41 consecutive patients who presented with 83 brain metastases from radioresistant primaries and subsequently underwent SRS. All patients were followed until death or for a median of 31 months after SRS. Tumor histologies included renal cell carcinoma (16 patients), melanoma (23 patients), and sarcoma (2 patients). Eighteen patients (44%) had a solitary metastasis, and 23 patients (56%) had multiple metastases. RESULTS: The median overall survival time was 14.2 months after SRS. On the basis of univariate analysis, systemic disease status (P = 0.006) and Radiation Therapy Oncology Group recursive partitioning analysis (RPA) class (P = 0.005) were associated with survival. The median survival time was 23.5 months for patients in RPA Class I status and 10.5 months for patients in RPA Class II or III status. There was a trend (P = 0.12) toward improved median survival for patients with renal cell carcinoma (17.8 mo) as compared with patients with melanoma (9.7 mo). Multivariate analysis showed RPA class (P = 0.038) and histological diagnosis of primary tumor (P < 0.001) to be independent predictors for overall survival. In the 35 patients who underwent follow-up imaging, 9 (12%) of 73 tumors recurred locally. In 54% of the patients, distant brain failure (DBF) developed. Whole brain radiotherapy (WBRT) improved local control and decreased DBF, according to the univariate and multivariate analyses. Patients who received adjuvant WBRT in addition to SRS had 6-month actuarial local control of 100% as compared with 85% among those who did not receive WBRT (P = 0.018). Patients who received adjuvant WBRT with SRS had a 6-month actuarial DBF rate of 17%, as compared with a rate of 64% among patients who had SRS alone (P = 0.0027). CONCLUSION: Well-selected patients with brain metastases from radioresistant primary tumors who undergo SRS survive longer than historical controls. RPA Class I status and primary renal cell carcinoma predict longer survival. Adjuvant WBRT improves local control and decreases DBF but does not affect overall survival. Further studies are needed to determine which patients should receive WBRT.     

Brain metastasis from renal cell carcinoma

BackgroundPatients with brain metastasis (BM) from renal cell carcinoma (RCC) have a poorly known prognosis due to the rarity of this disease. The aim of our study was to assess the outcome of patients with a BM due to RCC, and to determine the predictive factors for survival.MethodsConsecutive patients who underwent treatment between 1997 and 2012 were identified retrospectively from a database (n = 28, median age of 57.8 years, sex ratio M/F: 3.7). Main criteria collected concerned survival time. Other data collected were relative to initial histology, clinical findings at the time of BM diagnosis (diagnosis circumstances, KPS), radiological findings and BM characteristics (number, size and localization), treatment of BM (including surgery, stereotactic radiosurgery [SRS], systemic treatments, whole brain radiotherapy [WBRT]) and the outcome of surgery if performed. Statistical analysis of survival was performed using the Kaplan-Meier method.ResultsMedian survival was 13.3 months, 1-year survival was 60.2%, 2-year survival was 16.4%. Univariate analysis showed the existence of intracranial hypertension (P = 0.01), other systemic metastasis (P = 0.049), the absence of deep metastasis (P = 0.03) which are all linked to shorter survival. Age, KPS, initial histology of RCC, number, size, localization, and hemorrhage in BM were not correlated to survival. The median survival in the surgical resection group was 25.3 months versus 8.6 months (P = 0.02). The main criteria for the selection of the surgical group were a single BM (P = 0.04), and superficial metastasis (P = 0.02).ConclusionsThree predictive factors for longer survival in BMRCC were the absence of intracranial hypertension, the absence of acute metastasis and the absence of extracranial metastasis. Surgical removal, when possible, seems to benefit patient survival.     

Prognostic Value of Disseminated Tumor Cells in the Bone Marrow of Patients with Operable Primary Breast Cancer: A Long-term Follow-up Study

Background

Detection of disseminated tumor cells (DTC) in primary breast cancer (BC) patients’ bone marrow (BM) seems to be a surrogate marker of tumor spread and an independent prognostic factor for disease-free and overall survival.

Methods

Here we present the largest single-center cohort of patients (n = 1378) with the longest observation time (median 82.0 months). Immunocytochemical staining was performed using murine monoclonal antibody 2E11 with the avidin–biotin complex technique.

Results

At primary surgery, 49 % of patients showed MUC-1 positive cells inside their BM. Patients without BM DTC had significantly more often T1-tumors (P = 0.007) with less often affected axillary lymph nodes (P < 0.001). We observed a significantly higher incidence of distant metastases in DTC positive patients (P < 0.001). This leads to a reduced disease-free survival (P < 0.0001). Furthermore, in DTC positive patients there was a higher mortality rate and, accordingly, a reduced overall survival (P < 0.0001).

Conclusions

Due to the presence of BM DTC, patients with a clinically poorer outcome can be identified at primary surgery. We therefore suggest that DTC analysis can be used as a prognostic factor and monitoring tool in clinical trials. Future study concepts relating to DTC should aim at identification of BC patients who may profit from adjuvant systemic therapy.     

Is [18F] fluorodeoxyglucose uptake by the primary tumor a prognostic factor in breast cancer?

BackgroundWe retrospectively investigated ¹⁸F-FDG uptake by the primary breast tumor as a predictor for relapse and survival.Patients and methodsWe studied 203 patients with cT1-T3N0 breast cancer. Standardized uptake value (SUVmax), was measured on the primary tumor. After a median follow-up of 68 months (range 22–80), the relation between SUVmax and tumor factors, disease free-survival (DFS) and overall survival (OS) was investigated.ResultsIn the PET-positive patients, the median FDG uptake by the tumor was 4.7. FDG uptake was significantly related to tumor size, number of involved axillary nodes, grade, negative ER, high Ki-67 and HER2 overexpression. No distant metastases or deaths occurred in the PET-negative group. Five-year DFS was 97% and 83%, respectively in the PET-negative and PET-positive groups (P = 0.096). At univariate analysis, DFS was significantly lower in patients with SUVmax >4.7 compared to the patients with negative PET (P = 0.042), but not to the patients with SUVmax ≤4.7 (P = 0.106). At multivariable analysis, among PET-positive patients, SUVmax was not an independent prognostic factor for DFS (HR_{>4.7 vs ≤4.7}: 1.02 (95% CI 0.45–2.31)). Five-year OS was 100% and 93%, respectively, in the PET-negative and PET-positive groups (P = 0.126).ConclusionFDG uptake by the primary lesion was significantly associated with several prognostic variables, but it was not an independent prognostic factor.     

Implication of breast cancer phenotype for patients with leptomeningeal carcinomatosis

BackgroundWe aimed to study the implications of breast cancer (BC) subtypes for the development and prognosis of leptomeningeal carcinomatosis (LC).Patients and methodsData from the breast cancer patients diagnosed with LC between 2005 and 2010 were retrieved. Patients were classified in luminal A, B, HER2 positive and triple negative (TN) and their BC diagnosis, treatment, and outcome were analyzed according to each subtype. Pearson's chi-square and Fisher's exact test were used for categorical variables. Survival analyses were performed by Kaplan–Meier method and compared with the log-rank test.ResultsA total of 38 BC patients were identified, with a median age of 54.8 years (range 36–79). The proportion of luminal A, B, HER2 positive and TN was 18.4%, 31.6%, 26.3% and 23.7%, respectively. LC was the first evidence of metastatic disease in 5 BC patients. Twenty patients received the systemic chemotherapy, with 16 (80%) whole brain radiotherapy (WBRT). Nine patients received only WBRT. TN patients had the shorter interval between metastatic breast cancer diagnosis and the development of LC. Median survival after the diagnosis of LC (OSLC) was 2.6 months (range 1.2–6.4), and did not differ across breast cancer subtypes. In univariate analysis, performance status (ECOG = 0–2) and chemotherapy were prognostic for OSLC, but only the treatment stood as an independent prognostic factor in multivariate analysis.ConclusionsBreast cancer subtype influences the timing of LC appearance, but not OSLC. Patients with LC from breast cancer should be offered systemic treatment, as it appears to associate with the improved outcome. New therapeutic strategy, including, targeted and intrathecal therapy are deserved for BC patients with LC.     

Radioterapia intraoperatoria en cáncer de mama precoz: análisis observacional frente a radioterapia externa

IntroductionIn early breast cancer (EBC), a single dose of intraoperative radiotherapy (IORT) might be an option to standard whole breast radiotherapy (WBRT). However, there is no consensus about its use and clinical results.Aimto analyse the morbidity and oncological outcomes of IORT as monotherapy in EBC.MethodsA single centre observational analytic study was performed. A prospective IORT cohort (2015-17) and a retrospective WBRT cohort (2012-17) were selected following the same criteria: ≥ 45 y.o., invasive ductal carcinoma or variants, radiological tumour size ≤ 3 cm, positive oestrogenic receptors, negative HER2, cN0; exclusion criteria: lymphovascular invasion, multicentricity/multifocality, BRCA mutation and neoadjuvant therapy. Clinical, histological, surgical, oncological characteristics and complications were collected.ResultsA total of 425 cases were selected: 217 in IORT cohort and 208 in WBRT cohort. Average age in IORT and WBRT groups was 67±9.5 and 64.8 ± 9.9 y.o. respectively (p = 0.01). ASA 3 risk score patients were 17.7% in IORT and 24 cases in WBRT (p = 0.027). There were no differences in histological results or tumoral stage. Average follow up was 24.4 ± 8 months in IORT and 50.5 ± 18 months in WBRT (p < 0.001). No differences were detected in local recurrence, metastases or mortality. Complications that required reintervention or hospitalization were similar in both groups. A total of 3 and 14 cases developed early severe dermatitis in IORT and WBRT groups respectively (p = 0.01).ConclusionIORT as monotherapy in selected patients with EBC stands for an alternative option versus WBRT. It seems especially useful in advanced-age patients with severe comorbidities. IORT associates lesser early severe dermatitis.     

Benefits of neoadjuvant therapy compared with adjuvant chemotherapy for the survival of patients with HER2-positive breast cancer: A retrospective cohort study at FUSCC

PurposeNeoadjuvant therapy (NAT) is considered the standard of care for patients with HER2-positive breast cancer (BC). However, there is no proven survival benefit of NAT compared to adjuvant therapy for the survival of patients with early-stage HER2-positive BC. This study aimed to compare the prognosis of HER2-positive BC patients treated with NAT to that of patients treated with adjuvant therapy.MethodsThis was a single-center real-world retrospective study. This study analyzed the disease-free survival (DFS) and overall survival (OS) of 538 HER2-positive BC patients treated with neoadjuvant therapy and 2684 patients treated with adjuvant therapy at Fudan University Shanghai Cancer Center (FUSCC) between 2012 and 2016. Patients with a clinical tumor size (cT) ≤5 cm or >5 cm were matched using the propensity score matching (PSM) method to prevent selection bias.ResultsAfter PSM, among patients with cT ≤ 5 cm, there was no significant difference in DFS (P = 0.08) or OS (P = 0.11) between the two groups. The analysis of survival outcomes of patients treated with neoadjuvant and adjuvant therapy in the different chemotherapy subgroups yielded consistent results. According to multivariate analysis, lymph node status and response to NAT showed independent prognostic value for OS and DFS. Among patients with cT > 5 cm, the DFS (P = 0.25) and OS (P = 0.57) of patients treated with NAT were similar to those of patients treated with adjuvant therapy after PSM.ConclusionWe confirmed the equivalent effects of adjuvant therapy and NAT in HER2-positive BC patients. Neoadjuvant therapy should be used for patients with HER2-positive BC.     

Bone metastasis is associated with poor prognosis in metastatic papillary renal cell carcinoma patients treated with first agent angiogenesis inhibitors

ObjectivePapillary renal cell carcinoma (papRCC) is a rare (10%–15%) subtype of renal cancer. Few prognostic biomarkers have been described in metastatic papRCC (m-papRCC) patients treated with vascular endothelial growth factor receptor tyrosine kinase inhibitors (VEGFR-TKIs). We aimed to study the prognostic impact of bone metastases (BM) on response rate, progression-free and overall survival (PFS and OS) in patients with m-papRCC treated with first agent VEGFR-TKIs.Patients and methodsA multicentric, retrospective analysis of patient records was conducted. BM were detected by computed tomography and/or bone scintigraphy. The International Metastatic RCC Database Consortium (IMDC) score was calculated at start of first agent VEGFR-TKI treatment.ResultsForty-nine patients were included. Best objective response was partial response in 20%, stable disease in 60% and early progressive disease in 20% of patients. Median PFS (mPFS) was 6.0 months and median OS (mOS) 14.0 months after start of first agent VEGFR-TKI. The IMDC score correlated with mOS: 77.5 months in good, 17.0 months in intermediate and 8.0 months in poor risk patients (P = 0.002). Patients with BM had a poorer outcome compared to patients without BM: mPFS was 4.0 vs. 7.0 months (P = 0.006) and mOS 7.5 vs. 19.0 months (P = 0.002). On bivariate analysis, the presence of BM was independently associated with PFS (P = 0.02) and OS (P = 0.049), independent of the IMDC risk groups.ConclusionIn m-papRCC patients treated with first agent VEGFR-TKIs, the presence of BM is an unfavorable prognostic factor, associated with shorter PFS and OS.