A nested case-control study on radiation dose-response for cardiac events in breast cancer patients in Germany

BackgroundPrevious studies with the majority of breast cancer (BC) patients treated up to 2000 provided evidence that radiation dose to the heart from radiotherapy (RT) was linearly associated with increasing risk for long-term cardiac disease. RT techniques changed substantially over time. This study aimed to investigate the dose-dependent cardiac risk in German BC patients treated with more contemporary RT.MethodsIn a cohort of 11,982 BC patients diagnosed in 1998–2008, we identified 494 women treated with 3D-conformal RT who subsequently developed a cardiac event. Within a nested case-control approach, these cases were matched to 988 controls. Controls were patients without a cardiac event after RT until the index date of the corresponding case. Separate multivariable conditional logistic regression models were used to assess the association of radiation to the complete heart and to the left anterior heart wall (LAHW) with cardiac events.ResultsMean dose to the heart for cases with left-sided BC was 4.27 Gy and 1.64 Gy for cases with right-sided BC. For controls, corresponding values were 4.31 Gy and 1.66 Gy, respectively. The odds ratio (OR) per 1 Gy increase in dose to the complete heart was 0.99 (95% confidence interval (CI): 0.94–1.05, P = .72). The OR per 1 Gy increase in LAHW dose was 1.00 (95% CI: 0.98–1.01, P = .68).ConclusionsContrary to previous studies, our study provided no evidence that radiation dose to the heart from 3D-conformal RT for BC patients treated between 1998 and 2008 was associated with risk of cardiac events.     

A case-control study of the joint effect of reproductive factors and radiation treatment for first breast cancer and risk of contralateral breast cancer in the WECARE study

ObjectiveTo examined the impact of reproductive factors on the relationship between radiation treatment (RT) for a first breast cancer and risk of contralateral breast cancer (CBC).MethodsThe Women’s Environmental Cancer and Radiation Epidemiology (WECARE) Study is a multi-center, population-based case-control study where cases are women with asynchronous CBC (N = 1521) and controls are women with unilateral breast cancer (N = 2211). Rate ratios (RR) and 95% confidence intervals (CI) were estimated using conditional logistic regression to assess the independent and joint effects of RT (ever/never and location-specific stray radiation dose to the contralateral breast [0, >0-<1Gy, ≥1Gy]) and reproductive factors (e.g., parity).ResultsNulliparous women treated with RT (≥1Gy dose) were at increased risk of CBC compared with nulliparous women not treated with RT, although this relationship did not reach statistical significance (RR = 1.34, 95% CI 0.87, 2.07). Women treated with RT who had an interval pregnancy (i.e., pregnancy after first diagnosis and before second diagnosis [in cases]/reference date [in controls]) had an increased risk of CBC compared with those who had an interval pregnancy with no RT (RR = 4.60, 95% CI 1.16, 18.28). This was most apparent for women with higher radiation doses to the contralateral breast.ConclusionAmong young female survivors of breast cancer, we found some evidence suggesting that having an interval pregnancy could increase a woman’s risk of CBC following RT for a first breast cancer. While sampling variability precludes strong interpretations, these findings suggest a role for pregnancy and hormonal factors in radiation-associated CBC.     

Brain natriuretic peptide as a cardiac marker of transient radiotherapy-related damage in left-sided breast cancer patients: A prospective study

PurposeOur study evaluated brain natriuretic peptide (BNP) changes over time after adjuvant radiotherapy (RT) in women with left-sided breast cancer investigating its correlation with heart dosimetric parameters.MethodsForty-three patients underwent clinical cardiac examination, electrocardiogram (ECG), echocardiography and BNP measurement before RT (T0) and 1 (T1), 6 (T6) and 12 months (T12) after. After T12 cardiac assessment was performed annually in each patient. Mean values and standard deviation (SD) of BNP, left ventricular ejection fraction (LVEF), V20, V25, V30, V45 and mean dose were calculated. Normalized BNP (BNPn) was calculated as follows: BNPnT1 = BNPT1/BNPT0, BNPnT6 = BNPT6/BNPT0, BNPnT12 = BNPT12/BNPT0. Absolute BNP and BNPn values were used for data analysis.ResultsMedian follow-up from the end of RT to the last check-up was 87 months (range 37–120 months). Minimum follow-up was 74 months except for two patients, who died at respectively 37 and 47 months after RT. In all patients LVEF did not change significantly (p = 0.22) after RT. BNP increased significantly (p < 0.001), particularly 1 and 6 months after RT. It slightly decreased after 12 months. BNP did not correlate with V20, V25, V30, V45, mean dose and MHD. All BNPn correlated significantly (p < 0.05) with V20, V25, V30, V45, mean dose and MHD. Four patients had a cardiac event; in the only subject who developed myocardial infarction, V20, V25, V30 and V45 were the highest and BNP increased from T1 and persisted high even at T12.ConclusionOur results confirm that BNP could be a useful minimally invasive marker of early RT related cardiac impairment.     

Outcome of radiotherapy for clinically overt metastasis to the internal mammary lymph node in patients receiving neoadjuvant chemotherapy and breast cancer surgery

PurposeThis study was aimed to assess the outcome of radiotherapy and determine prognostic factors for survival in breast cancer patients with clinically overt metastasis to the internal mammary lymph node (IMN+).MethodsWe retrospectively reviewed the medical records of 193 patients with IMN + breast cancer who received neoadjuvant chemotherapy (NAC), breast surgery without internal mammary lymph node (IMN) dissection, and postoperative radiotherapy at 9 hospitals between 2009 and 2013. Breast-conserving surgery or mastectomy was performed after taxane-based NAC. Radiotherapy was administered to the whole breast/chest wall and regional nodes. IMN-covering radiotherapy was performed in 92.2% of patients with median dose of 58.4 Gy (range, 44.9–69.1 Gy). The overall survival (OS), disease-free survival (DFS), and IMN failure-free survival (IMNFFS) were analyzed.ResultsAfter median follow-up of 71 months, 9 patients (4.7%) developed IMN failure and simultaneous distant metastasis. The 5-year DFS, OS, and IMNFFS was 68.6%, 81.8%, and 95.3%, respectively. Non-triple-negative breast cancer, Ki-67 ≤ 10%, pathological complete response (CR) in tumor and axillary node, and radiologic CR of IMN after NAC were significant factors for predicting higher DFS; however, IMN radiation dose was not significant determinants for DFS. The 5-year DFS of patients with IMN-dose ≤ 50.0 Gy and those with >50.0 Gy was 86.7% and 76.7%, respectively (p = 0.41).ConclusionsA multimodality strategy including NAC, breast surgery, and IMN-covering radiotherapy was effective for patients with overt IMN + breast cancer. Even without an IMN dissection, most patients were IMN failure-free with an IMN-focusing radiotherapy.     

Safety of cyclin-dependent kinase4/6 inhibitor combined with palliative radiotherapy in patients with metastatic breast cancer

IntroductionCyclin-dependent kinase (CDK)4/6 inhibitor is a first-line therapy for metastatic ER+/HER2-breast cancer. However, there are limited data on safety of combined radiotherapy (RT) and CDK4/6 inhibition.MethodsWe conducted a retrospective study of women with metastatic breast cancer who received palliative RT within 14 days of CDK4/6 inhibitor use. The primary endpoint was toxicity per Common Terminology Criteria for Adverse Events v5. Secondary endpoints were pain response and local control based on clinical assessment and imaging.ResultsThirty patients underwent 36 RT courses with palbociclib (n = 34 courses, 94.4%) or abemaciclib (n = 2, 5.6%). RT was delivered before, concurrently or after CDK4/6 inhibitors in 7 (19.4%), 8 (22.2%), and 21 (58.3%) of cases with median 3.5 days from RT to closest CDK4/6 inhibitor administration. Median RT dose was 30Gy (range 8–40.05Gy). Treated sites included brain (n = 5, 11.6%), spine (n = 19, 44.2%), pelvis (n = 9, 20.9%), other bony sites (n = 6, 14.0%) and others (n = 4, 9.3%). No acute grade ≥3 non-hematologic toxicity occurred. No increased hematologic toxicity was attributable to RT with grade 3 hematologic toxicities rates 16.7%, 0%, and 6.7% before, during, and 2 weeks after RT completion. All but one patient (29/30) achieved symptom relief. Local control rates were 94.4%, 91.7% at 6 and 12 months.ConclusionsThe use of RT within 2 weeks of CDK4/6 inhibitors had low acceptable toxicity and high efficacy, suggesting that it is safe for palliation of metastatic breast cancer.     

Eurolung risk score is associated with long-term survival after curative resection for lung cancer

ObjectiveThe study objective was to verify whether the Eurolung score was associated with long-term prognosis after lung cancer resection.MethodsA total of 1359 consecutive patients undergoing anatomic lung resection (1136 lobectomies, 103 pneumonectomies, 120 segmentectomies) (2014-2018) were analyzed. The parsimonious aggregate Eurolung2 score was calculated for each patient. Median follow-up was 802 days. Survival distribution was estimated by the Kaplan–Meier method. Cox proportional hazard regression and competing risk regression analyses were used to assess the independent association of Eurolung with overall and disease-specific survival.ResultsPatients were grouped into 4 classes according to their Eurolung scores (A 0-2.5, B 3-5, C 5.5-6.5, D 7-11.5). Most patients were in class A (52%) and B (33%), 8% were in class C, and 7% were in class D. Five-year overall survival decreased across the categories (A: 75%; B: 52%; C: 29%; D: 27%, log rank P < .0001). The score stratified the 3-year overall survival in patients with pT1 (P < .0001) or pT>1 (P < .0001). In addition, the different classes were associated with incremental risk of long-term overall mortality in patients with pN0 (P < .0001) and positive nodes (P = .0005). Cox proportional hazard regression and competing regression analyses showed that Eurolung aggregate score remained significantly associated with overall (hazard ratio, 1.19; P < .0001) and disease-specific survival after adjusting for pT and pN stage (hazard ratio, 1.09; P = .005).ConclusionsEurolung aggregate score was associated with long-term survival after curative resection for cancer. This information may be valuable to inform the shared decision-making process and the multidisciplinary team discussion assisting in the selection of the most appropriate curative treatment in high-risk patients.     

Association of mineral content outside of bone with coronary artery calcium and 1‐year cardiovascular prognosis in maintenance hemodialysis patients

Coronary artery calcifications (CACs) are common among maintenance hemodialysis (MHD) patients and associated with increased morbidity and mortality due to cardiovascular events. The insight into chronic kidney disease‐mineral and bone disorder (CKD‐MBD) established a correlation between dysregulated mineral metabolism and CACs. This study aimed to identify the association of mineral content outside of bone (MCOB) with CACs and cardiovascular events in MHD patients. In the pilot prospective study with no intervention, patients underwent body composition assessment by body composition monitor after hemodialysis and computed tomography examination using the Agatston scoring method simultaneously within a week. The primary end point included cardiovascular events and cardiovascular death. Correlations and receiver operating characteristic analysis elucidated the associations of MCOB with CACs; multivariate analysis assessed the cardiovascular risk for groups with different MCOB. One hundred three eligible patients with an average age of 48 (35‐63) years old were enrolled and followed up to 12 (11‐12.5) months, among which 52.4% had detectable CACs at baseline. MCOB showed an inverse correlation with Agatston score and significantly discriminated the patients with Agatston score > 0 (AUC = 0.737; P < 0.001) and 400 (AUC = 0.733; P < 0.001). MCOB ≤ 9.2657 mg/kg was an independent risk factor for CACs (OR = 4.853; P = 0.044) and strong predictor for cardiovascular morbidity and mortality (HR = 10.108; P = 0.042), as well as rehospitalization (HR = 2.689; P = 0.004). MCOB inversely correlated with the presence and extent of CACs, and could discriminate Agatston score > 0 and 400, which also presented as an independent indicator for CKD‐MBD and 1‐year cardiovascular prognosis in adult MHD patients. Additional studies are required for identifying this issue.     

Sentinel lymph node biopsy in Chinese patients with large operable breast cancer (≥4 cm): A decade's experience from a single institution

BackgroundPerforming sentinel lymph node biopsy (SLNB) in patients with large operable breast cancer is still controversial. Our aim is to find whether or not performing SLNB is feasible and safety in Chinese patients with large operable breast cancer.MethodsWe reviewed the data of patients in our center from 2003 to 2015, a series of 267 patients with large operable breast cancer (≥4 cm) who underwent SLNB were examined. All selected patients recieved preoperative axillary evaluation.ResultsThe successful rate for localizing SLNs was 96.3% (257 of 267). 31.1% (78 of 257) patients were found to have positive sentinel lymph nodes (SLN). The median follow-up was 52 months. 2.2% (4 of 179) SLN-negative patients developed axillary recurrence (AR) as first event. The 5-year axillary recurrence free survival in SLN-negative patients was 96.9% (95%CI, 93.8%–100%). Patients with suspicious nodes on ultrasonography (US) (P = 0.16) and undergoing breast conserving therapy (BCT) (P = 0.057) had a higher trend to be associated with AR. The 5-year recurrence free survival (RFS) was 86.1% (95%CI, 80.8%–93.0%) in SLN-negative patients and 76.3% (95%CI, 68.1%–90.1%) in SLN-positive patients (P = 0.246).ConclusionsSLNB is feasible and safety in patients with large operable breast cancer who underwent preoperative axillary evaluation.     

Incidence and Clinical Significance of Hyperkalemia Following Heart Transplantation

BackgroundHyperkalemia (HK) is a life-threatening complication following solid organ transplantation, and patients often need potassium-chelating agents and deviations from standard posttransplant protocols. This is the first study to report the incidence and clinical impact of hyperkalemia following heart transplantation.MethodsWe retrospectively included patients who underwent heart transplantation at our institution between April 2014 and December 2018. Patients with multiorgan transplantation were excluded. Clinical outcomes of patients who had serum potassium >5.5 mEq/L in the first year posttransplant (HK group) were compared to patients who did not have serum potassium >5.5 mEq/L in the first year posttransplant (non-HK group).ResultsA total of 143 patients were included in this study. During the first year posttransplant, cumulative incidence of serum potassium >5.0, >5.5, and >6.0 mEq/L was 96%, 63%, and 24%, respectively. Fifty-five percent of patients required treatment with potassium-chelating agents. Sulfamethoxazole-trimethoprim was discontinued because of HK in 39% of patients. Overall survival of patients in the HK group (n = 89) was comparable to that of patients in the non-HK group (n = 54, 91% vs 98% at 1 year, P = .19), whereas infection-free survival was significantly lower in the HK group (34% vs 53% at 1 year, P = .010). Multivariate analysis revealed pretransplant renal dysfunction (odds ratio = 2.62; 95% confidence interval, 1.18-5.80; P = .018) and use of mechanical circulatory support (odds ratio = 2.90; 95% confidence interval, 1.08-7.76; P = .035) as significant predictors of posttransplant hyperkalemia.ConclusionsThe incidence of HK following heart transplantation was high, with more than half of patients requiring any therapeutic interventions, and HK was related to an increase in infection events.     

Does fusion status following posterolateral lumbar fusion in the treatment for stable lumbar degenerative spondylolisthesis affect the long-term surgical outcomes? A propensity score-weighted analysis of consecutive patients

BackgroundThe surgical strategy of lumbar degenerative spondylolisthesis (LDS) is controversial, especially regarding whether or not fusion should be used. Although some reports have indicated that decompression combined with fusion may be better than decompression alone in the treatment of LDS, the effect of fusion status after uninstrumented posterolateral lumbar fusion (PLF) on the outcomes of patients with stable LDS remains unknown. This study aimed to evaluate the surgical outcomes of uninstrumented PLF for stable LDS and clarify whether radiographic fusion status could affect surgical outcomes.MethodsA total of 93 consecutive patients who had undergone single-level uninstrumented PLF for Meyerding grade I LDS without preoperative dynamic instability with a minimum follow-up period of 5 years were retrospectively studied. Patients were divided into two groups: nonunion (52 patients) and union (41 patients). The primary outcomes were the 5-year percent recovery of postoperative Japanese Orthopaedic Association (JOA) scores, Oswestry Disability Index (ODI), Visual analog scale (VAS) scores, and reoperation rate. The outcome scores were compared between the groups using the inverse probability weighting method using propensity scores.ResultsThe union and nonunion groups had comparable weighted means of the 5-year postoperative clinical score for the percent recovery of the JOA score (70.2% vs. 71.1%, P = 0.86), ODI (14.5 vs.14.6, P = 0.98), VAS of low back pain (20.3 vs. 18.7 mm, P = 0.72), and VAS of leg pain (24.0 vs. 19.4 mm, P = 0.43). The reoperation rate was 2.4% (one case of adjacent segment pathology) in the union group and 0% in the nonunion group (P = 0.44).ConclusionThe fusion status following uninstrumented PLF had no significant effect on the 5-year postoperative clinical outcomes and reoperation rate in patients with Meyerding grade I LDS without dynamic instability.     

The impact on clinical outcomes of post-operative radiation therapy delay after neoadjuvant chemotherapy in patients with breast cancer: A multicentric international study

IntroductionRadiation therapy (RT) is frequently used for post-operative treatment in breast cancer (BC) patients who received preoperative systemic therapy (PST) and surgery. Nevertheless, the optimal timing to start RT is unclear.Material and methodsData from BC patients who underwent chemotherapy as PST, breast surgery and RT at 3 Institutions in Brazil and Canada from 2008 to 2014 were evaluated. Patients were classified into three groups regarding to the time to initiation of RT after surgery: <8 weeks, 8–16 weeks and >16 weeks.ResultsA total of 1029 women were included, most of them (59.1%; N = 608) had clinical stage III. One hundred and forty-one patients initiated RT within 8 weeks, 663 between 8 and 16 weeks and 225 beyond 16 weeks from surgery. With a median follow-up of 32 months, no differences in disease-free survival (DFS), overall survival and locoregional recurrence-free survival (LRRFS) were observed of time to indicated RT (<8 weeks versus 8–16 weeks versus >16 weeks). However, in luminal subtype patients (46.5%; N = 478), initiation of RT up to 8 weeks after surgery was associated with better LRRFS (<8 weeks versus >16 weeks: HR 0.22; 95%CI 0.05–0.86; p = 0.03), with a tendency to a better DFS (<8 weeks versus >16 weeks: HR 0.50; 95%CI 0.25–1.00).ConclusionRT initiated up to 8 weeks after surgery was related to better LRRFS in luminal BC patients who underwent PST. Our results suggest that early start of RT is important for these patients.     

Proximal aortic repair in dialysis patients: A national database analysis

ObjectivesDialysis is a well-established risk factor for morbidity and mortality after cardiovascular procedures. However, little is known regarding the outcomes of proximal aortic surgery in this high-risk cohort.MethodsPerioperative (in-hospital or 30-day mortality) and 10-year outcomes were analyzed for all the patients who underwent open proximal aortic repair with the diagnosis of nonruptured thoracic aortic aneurysm (aneurysm, n = 325) or type A aortic dissection (dissection, n = 461) from 1987 to 2015 using the US Renal Data System database.ResultsIn patients with aneurysm, perioperative mortality was 12.6%. The 10-year mortality was 81% ± 3%. Age 65 years or more (hazard ratio [HR], 1.35; 95% confidence interval [CI], 1.03 to 1.78; P = .03), chronic obstructive pulmonary disease (HR, 1.68; 95% CI, 1.01-2.82; P = .047), and Black race (HR, 1.46; 95% CI, 1.09-1.97; P = .01) were independently associated with worse 10-year mortality. In patients with dissection, perioperative mortality was 24.3% and 10-year mortality was 87.9% ± 2.2%. Age 65 years or more (HR, 1.49; 95% CI, 1.19-1.86; P < .001), congestive heart failure (HR, 1.39; 95% CI, 1.11-2.57; P = .004), and diabetes mellitus as the cause of dialysis (HR, 1.75; 95% CI, 1.2-2.57; P = .004) were independently associated with worse 10-year mortality. Black race (HR, 0.74; 95% CI, 0.6-0.92; P = .008) was associated with a better outcome.ConclusionsWe described challenging perioperative and 10-year outcomes for dialysis patients undergoing proximal aortic repair. The present study suggests the need for careful patient selection in the elective repair of proximal aortic aneurysm for dialysis-dependent patients, whereas it affirms the feasibility of emergency surgery for acute type A aortic dissections.     

Triple-negative breast cancer outcomes: Does AJCC 8th staging improve chemotherapy decision-making

PurposeTo investigate the effect of the 8th American Joint Committee on Cancer (AJCC) pathological prognostic staging on chemotherapy decision-making for triple-negative breast cancer (TNBC) patients with T1-2N0M0 disease.MethodsPatients diagnosed with T1-2N0M0 TNBC were retrieved from the Surveillance, Epidemiology, and End Results program. Statistical methods including Kaplan-Meier survival curve, receiver operating characteristics curve, and Cox proportional hazard model.ResultsWe identified 12,156 patients, including 9371 (77.1%) patients who received chemotherapy. Overall, 57.4% of patients (n = 6975) were upstaged after being reassigned by the 8th AJCC staging. However, the 8th staging of AJCC did not have a greater prognostic value compared to the 7th staging (P = 0.064). The receipt of chemotherapy significantly improved the breast cancer-specific survival for stage T1c and T2 tumors (P < 0.001), but not for stage T1a (P = 0.188) and T1b (P = 0.376) tumors. Using AJCC 8th staging, chemotherapy benefit was only found in stage IIA patients (P = 0.002), but not for stage IA (P = 0.653) and IB (P = 0.492) patients. There were 9564 patients with stage T1c and T2 diseases and 4979 patients with 8th AJCC stage IIA disease. Therefore, approximately half of patients (47.9%, n = 4585) may be safe to omit chemotherapy using the AJCC 8th staging compared to the current chemotherapy recommendation for T1-2N0M0 TNBC.ConclusionThe 8th AJCC staging system did not demonstrate the superior discriminatory ability of prognostic stratification than the 7th AJCC staging system in T1-2N0M0 TNBC. However, this new AJCC staging could more accurately predict the chemotherapy benefit, thereby enabling more patients to avoid unnecessary chemotherapy.     

Should women with early breast cancer under 40 years of age have a routine 21-gene recurrence score testing: A SEER database study

PurposeTo investigate the effect of 21-gene recurrence score (RS) on chemotherapy-decision making and prognosis in breast cancer patients aged <40 years.MethodsUsing the Surveillance, Epidemiology, and End Results program, we included patients aged <40 years with tumor size ≤5 cm, node negative, and estrogen receptor-positive breast cancer between 2004 and 2015. Correlations among the 21-gene RS, chemotherapy decision-making and prognosis were analyzed.ResultsWe included 2721 patients in this study. According to TAILORx cutoffs, 352 (12.9%), 1814 (66.7%), and 555 (20.4%) patients were classified as low-, intermediate-, and high-risk cohorts, respectively. The 21-gene RS categories were associated with the probability of receiving chemotherapy, with 7.1%, 33.4%, and 77.1% of patients in low-, intermediate-, and high-risk cohorts treated with chemotherapy, respectively (P < 0.001). Those in the intermediate-risk cohort were significantly less likely to receive chemotherapy over time (P = 0.008), and the trends of chemotherapy receipt were stable in the low-risk and high-risk cohorts over time. Multivariate analysis showed that the 21-gene RS was an independent prognostic indicator for breast cancer specific survival. In the stratified analysis, the receipt of chemotherapy was associated with better breast cancer specific survival in the high-risk cohort (P = 0.028), but not in the intermediate-risk cohort (P = 0.223).Conclusions21-gene RS has clinical implications for young breast cancer patients with respect to optimizing chemotherapy-decisions. Despite increasing rates of chemotherapy receipt in young patients, more studies are needed to determine the definitive effect of chemotherapy in young patients with three RS categories.     

Radiotherapy concurrent versus sequential with endocrine therapy in breast cancer: A meta-analysis

IntroductionThis study compared treatment outcomes of radiotherapy concurrent with endocrine therapy and radiotherapy sequential with endocrine therapy in breast cancer.Materials and methodsEligible studies of radiotherapy concurrent and sequential with endocrine therapy in breast cancer were retrieved through extensive searches of the PubMed, Medline, Embase, Cochrane library, FEBM, FMJS, Web of science, Wiley, CBM, CNKI, Wang fang, Cqvip databases from 2000 to 2014. Original English and Chinese publications of radiotherapy concurrent and sequential with endocrine therapy in breast cancer were included. The primary endpoint was radiation-induced toxicity including upper than grade 2 skin related toxicity, radiation pneumonia and pulmonary fibrosis; the second endpoint was survival date, including local recurrence, distant metastasis, 5-year OS, 10-year OS.ResultsEleven eligible trials were identified, six in English and five in Chinese. Totally, there were 1291 women in concurrent groups, and 1179 in sequential groups. Statistical analysis showed that there was no statistical difference between concurrent and sequential groups in skin related toxicity (RR 1.20, 95% CI 0.92–1.56, P = 0.17), radiation pneumonia (RR 1.11, 95% CI 0.46–2.70, P = 0.81) and pulmonary fibrosis (RR 1.35, 95% CI 0.75–2.41, P = 0.32). Meanwhile, no statistical difference was found in survival data, (RR 0.97, 95% CI 0.79–1.28, P = 0.26), (RR 0.86, 95% CI 0.66–1.12, P = 0.27) in local recurrence and distant metastasis respectively, (RR 1.01, 95% CI 0.96–1.06, P = 0.65), (RR 0.98, 95% CI 0.93–1.02, P = 0.32) in 5-year and 10-year overall survival respectively. Stratification analysis was proceeded, grouped by tamoxifen and AI in different treatment timing, however, no statistical difference was found in radiation-induced toxicity and survival outcomes.ConclusionRadiotherapy concurrent with endocrine therapy didn't increase or decrease neither the incidence of radiation-induced toxicity nor the survival rate compared with that of sequential group; Endocrine therapy drugs didn't influence outcomes in different treatment timing.     

Proton beam therapy reirradiation for breast cancer: Multi‐institutional prospective PCG registry analysis

To investigate adverse events (AEs, CTCAE v4.0) and clinical outcomes for proton beam therapy (PBT) reirradiation (reRT) for breast cancer. From 2011 to 2016, 50 patients received PBT reRT for breast cancer in the prospective Proton Collaborative Group (PCG) registry. Acute AEs occurred within 180 days from start of reRT. Late AEs began or persisted beyond 180 days. Fisher's exact and Mann‐Whitney rank‐sum tests were utilized. Kaplan‐Meier methods were used to estimate overall survival (OS) and local recurrence‐free survival (LFRS). Median follow‐up was 12.7 months (0‐41.8). Median prior RT dose was 60 Gy (10‐96.7). Median reRT dose was 55.1 Gy (45.1‐76.3). Median cumulative dose was 110.6 Gy (70.6‐156.8). Median interval between RT courses was 103.8 months (5.5‐430.8). ReRT included regional nodes in 84% (66% internal mammary node [IMN]). Surgery included the following: 44% mastectomy, 22% wide local excision, 6% lumpectomy, 2% reduction mammoplasty, and 26% no surgery. Grade 3 AEs were experienced by 16% of patients (10% acute, 8% late) and were associated with body mass index (BMI) > 30 kg/m² (P = 0.04), bilateral recurrence (P = 0.02), and bilateral reRT (P = 0.004). All grade 3 AEs occurred in patients receiving IMN reRT (P = 0.08). At 1 year, LRFS was 93%, and OS was 97%. Patients with gross disease at time of PBT trended toward worse 1‐year LRFS (100% without vs. 84% with, P = 0.06). PBT reRT is well tolerated with favorable local control. BMI > 30, bilateral disease, and IMN reRT were associated with grade 3 AEs. Toxicity was acceptable despite median cumulative dose > 110 Gy.     

Comparison of the Nottingham Prognostic Index and OncotypeDX© recurrence score in predicting outcome in estrogen receptor positive breast cancer

IntroductionTraditionally, Nottingham prognostic index (NPI) informed prognosis in patients with estrogen receptor positive, human epidermal growth factor receptor-2 negative, node negative (ER+/HER2-/LN-) breast cancer. At present, OncotypeDX© Recurrence Score (RS) predicts prognosis and response to adjuvant chemotherapy (AC).AimsTo compare NPI and RS for estimating prognosis in ER + breast cancer.MethodsConsecutive patients with ER+/HER2-/LN- disease were included. Disease-free (DFS) and overall survival (OS) were determined using Kaplan-Meier and Cox regression analyses.Results1471 patients met inclusion criteria. The mean follow-up was 110.7months. NPI was calculable for 1382 patients: 19.8% had NPI≤2.4 (291/1471), 33.0% had NPI 2.41–3.4 (486/1471), 30.0% had NPI 3.41–4.4 (441/1471), 10.9% had NPI 4.41–5.4 (160/1471), and 0.3% had NPI>5.4 (4/1471). In total, 329 patients underwent RS (mean RS: 18.7) and 82.1% had RS < 25 (270/329) and 17.9% had RS ≥ 25 (59/329). Using multivariable Cox regression analyses (n = 1382), NPI independently predicted DFS (Hazard ratio (HR): 1.357, 95% confidence interval (CI): 1.140–1.616, P < 0.001) and OS (HR: 1.003, 95% CI: 1.001–1.006, P = 0.024). When performing a focused analysis of those who underwent both NPI and RS (n = 329), neither biomarker predicted DFS or OS. Using Kaplan Meier analyses, NPI category predicted DFS (P = 0.008) and (P = 0.026) OS. Conversely, 21-gene RS group failed to predict DFS (P = 0.187) and OS (P = 0.296).ConclusionIn our focused analysis, neither NPI nor RS predicted survival outcomes. However, in the entire series, NPI independently predicted both DFS and OS. On the 40th anniversary since its derivation, NPI continues to provide accurate prognostication in breast cancer, outperforming RS in the current study.     

A high neutrophil-lymphocyte ratio and platelet-lymphocyte ratio are associated with a worse outcome in inflammatory breast cancer

IntroductionInflammatory breast cancer (IBC) is an uncommon, but aggressive form of breast cancer that accounts for a disproportionally high fraction of breast cancer related mortality. The aim of this study was to explore the peripheral immune response and the prognostic value of blood-based biomarkers, such as the neutrophil-to-lymphocyte ratio (NLR), in a large IBC cohort.Patients & methodsWe retrospectively identified 127 IBC patients and collected lab results from in-hospital medical records. The differential count of leukocytes was determined at the moment of diagnosis, before any therapeutic intervention. A cohort of early stage (n = 108), locally advanced (n = 74) and metastatic breast cancer patients (n = 41) served as a control population.ResultsThe NLR was significantly higher in IBC compared to an early stage breast cancer cohort, but no difference between IBC patients and locally advanced breast cancer patients was noted. In the metastatic setting, there was also no significant difference between IBC and nIBC. However, a high NLR (>4.0) remained a significant predictor of worse outcome in IBC patients (HR: 0.49; 95% CI: 0.24–1.00; P = .05) and a lower platelet-lymphocyte ratio (PLR) (≤210) correlated with a better disease-free survival (DFS) (HR: 0.51; 95% CI: 0.28–0.93; P = .03).ConclusionPatients with a high NLR (>4.0) have a worse overall prognosis in IBC, while the PLR correlated with relapse free survival (RFS). Since NLR and PLR were not specifically associated with IBC disease, they can be seen as markers of more extensive disease.     

Molecular subtyping reveals uniqueness of prognosis in breast ductal carcinoma in situ patients with lumpectomy

BackgroundWe aimed to analyse the discrepancy in clinical features and prognosis between molecular subtypes in primary ductal carcinoma in situ (DCIS) patients with lumpectomy.MethodsPrimary DCIS patients were identified from the Surveillance, Epidemiology, and End Results registries database from 2010 to 2017. Based on immunohistochemistry markers of hormone receptor (HR) and human epidermal growth factor receptor-2 (HER2), enrolled DCIS cases were divided into four molecular subtypes, HR-HER2-, HR-HER2+, HR + HER2+, and HR + HER2-. Clinical features and prognosis were compared between molecular subtypes. Radiotherapy (RT) effects on prognosis were also analysed in each molecular subtype.ResultsA total of 5,628 DCIS cases were retrospectively enrolled in this study. HR-HER2-, HR-HER2+, HR+HER2+, and HR+HER2- are 299 (5.3%), 498 (8.8%), 1,086 (19.3%), and 3,745 (66.5%), respectively. HR + HER2- cases have smaller tumor size (72.6%, P < 0.001) and lower grade (23.5%, P < 0.001). Comedo necrosis is more frequent in HR-HER2- (24.4%, P < 0.001) and HR-HER2+ DCIS cases (24.3%, P < 0.001). In univariate analyses, HR-HER2+ cases have significantly higher ipsilateral breast event (IBE) recurrence than HR+HER2- cases (P = 0.010). HR-HER2- cases show higher disease-specific mortality than HR+HER2+ cases (P = 0.021). In high-risk DCIS cases, RT reduces the absolute 5-year IBE incidence by 1.3%, 0.7%, 1.9%, and 2.6%, respectively in HR-HER2-, HR-HER2+, HR+HER2+, and HR+HER2- cases, respectively.ConclusionIn this population-based study, DCIS cases have diverse clinical and prognostic features for different molecular subtypes. Adjusting treatment strategies according to DCIS molecular subtypes is worth advancing.     

ST2 levels increased and were associated with changes in left ventricular systolic function during a three-year follow-up after adjuvant radiotherapy for breast cancer

ObjectivesTo search for biomarkers of RT-induced cardiotoxicity, we studied the behavior of ST2 during RT and three years after RT, and the associations with echocardiographic changes.Materials and methodsWe measured soluble ST2 (ng/ml) in serum samples from 63 patients receiving RT for early breast cancer. Sampling and echocardiography were performed at baseline, after RT and at the three-year follow-up. Patients were grouped by >15% (group 1) and ≤15% (group 2) relative worsening in global longitudinal strain (GLS).ResultsST2 levels tended to increase during RT, from a median (interquartile range; IQR) of 17.9 (12.4–22.4) at baseline to 18.2 (14.1–23.5) after RT (p = 0.075). By the three-year follow up, ST2 levels increased to 18.7 (15.8–24.2), p = 0.018. The increase in ST2 level was associated with worsening cardiac systolic function at three-year follow-up, GLS (rho = 0.272, p = 0.034) and left ventricular ejection fraction (LVEF) (rho = ─0.343, p = 0.006). Group 1 (n = 14) had a significant increase in ST2 levels from 17.8 (12.3–22.5) at baseline to 18.4 (15.6–22.6) after RT, p = 0.035 and to 19.9 (16.0–25.1) three years after RT, p = 0.005. ST2 levels were stable in group 2 (n = 47): 17.8 (12.3–22.0) at baseline, 17.7 (12.6–23.5) after RT and 18.0 (15.5–22.4) at three years.ConclusionST2 may be useful for determining which patients are at risk for long-term cardiovascular toxicity following adjuvant breast cancer RT, but prospective clinical studies are needed to confirm this hypothesis.