The cell composition of infused donor lymphocyte has different impact in different types of allogeneic hematopoietic stem cell transplantation

Donor lymphocyte infusion (DLI) is often used to enhance the graft‐versus‐leukemia (GVL) effect after allogeneic hematopoietic stem cell transplantation (allo‐HSCT). In this study, we first evaluated the impact of the cell composition of a modified DLI (mDLI) on the prognoses of patients. A total of 194 patients undergoing allo‐HSCT were enrolled and received mDLI for various clinical reasons. The infused cellular components of the mDLI were examined by flow cytometry. The results showed that infusion with a lower dose of CD14⁺ cells (<0.33 × 10⁸/kg) was an independent risk factor for the occurrence of II–IV acute graft‐versus‐host disease (aGVHD) (HR = 0.104, p = 0.032) in human leukoctye antigen‐identical transplant patients. In addition, a dose of CD14⁺ cells greater than the 50th percentile was associated with a lower incidence of hematological relapse and longer disease‐free survival (DFS) after the mDLI (relapse: HR = 0.193, p = 0.007; DFS: HR = 0.259, p = 0.016). However, we also found that a greater number of CD14⁺ cells were an independent risk factor for II–IV aGVHD (HR = 1.758, p = 0.034) in haploidentical allo‐HSCT. In conclusion, our data were the first to demonstrate that the cell composition of a 56 mDLI played a distinct role in different types of allo‐HSCT. This finding provided a novel approach for the development of cellular therapies by manipulating the components of infused cells.     

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.     

Prognostic impact of proliferation for resected early stage ‘pure’ invasive lobular breast cancer: Cut-off analysis of Ki67 according to histology and clinical validation

IntroductionThe intent of this analysis was to investigate and validate the prognostic potential of Ki67 in a multi-center series of patients affected by early stage ‘pure’ invasive lobular carcinoma (ILC).MethodsClinical-pathological data of patients affected by ILC were correlated with overall survival and disease-free survival (OS/DFS); data from a parallel invasive ductal carcinoma (IDC) patients' cohort were gathered as well. The maximally selected Log-Rank statistics analysis was applied to Ki67 continuous variable to estimate the appropriate cut-off. The Subpopulation Treatment Effect Pattern Plot (STEPP) analysis was performed as well.ResultsData from overall 1097 (457/222 ILC: training/validation set; 418 IDC) patients were gathered. The identified optimal Ki67 cut-offs were 4% and 14% for DFS in ILC and IDC cohort, respectively. In ILC patients, the Ki67 cut-off was an independent OS predictor. Ten-years OS and DFS were 89.9% and 77.2% (p = 0.007) and 79.4% and 69.2% (p = 0.03) for patients with Ki67 ≤ 4% and >4%, respectively. In IDC patients, 10-years OS was 93.8% and 71.7%, p = 0.02, DFS was 84.0% and 52.6%, p = 0.0003, for patients with Ki67 ≤ 14% and >14%, respectively. In the validation set, the optimal Ki67 OS cut-off was 5%. The STEPP analysis showed that in the presence of low Ki67 values, IDC patients have a better DFS than ILC patients, while with the increase of values the prognosis tends to overlap.ConclusionsDespite the retrospective design of the study, the prognostic relevance of Ki67 (as well as its optimal cut-off) seems to significantly differ according to breast cancer histology.     

Influence of age as a continuous variable on the prognosis of patients with pT1-2N1 breast cancer

PurposeTo assess the influence of age as a continuous variable on the prognosis of pT1-2N1 breast cancer and examine its decision-making value for postmastectomy radiotherapy (PMRT).MethodsWe retrospectively evaluated 5438 patients with pT1-2N1 breast cancer after mastectomy in 11 hospitals. A multivariable Cox proportional hazards regression model with penalized splines was used to examine the relationship between age and oncologic outcomes.ResultsThe median follow-up was 67.0 months. After adjustments for confounding characteristics, nonsignificant downward trend in locoregional recurrence (LRR) risk was observed with increasing age (P-non-linear association = 0.640; P-linear association = 0.078). A significant non-linear association was found between age and disease-free survival (DFS) and overall survival (OS) (P-non-linear association <0.05; P-linear association >0.05, respectively). The DFS and OS exhibited U-shaped relationships, with the hazard ratios (HRs), reaching a nadir at 50 years old. A decreased risk of LRR with PMRT vs. no PMRT (HR = 0.304, 95% CI: 0.204–0.454) was maintained in all ages. The HR of PMRT vs. no PMRT for DFS and OS gradually increased with age. In patients ≤50 years old, PMRT was independently associated with favorable LRR, DFS, and OS, all P < 0.05). In patients >50 years old, PMRT was independently associated with reduced LRR (P = 0.004), but had no effect on DFS or OS.ConclusionsAge was an independent prognostic factor for pT1-2N1 breast cancer; PMRT provided survival benefits for patients ≤50 years old, but not for patients >50 years old.     

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.     

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.     

Clinical outcome of patients after recurrent laryngeal nerve lymph node dissection for oesophageal squamous cell carcinoma

 Open in a separate windowOBJECTIVESRecurrent laryngeal nerve lymph node dissection (LND) has been incorporated into oesophagectomy for patients with oesophageal squamous cell carcinoma, but with uncertain oncological efficacy.METHODSThe data of patients with oesophageal squamous cell carcinoma, including who underwent upfront surgery (surgery group) and those who received neoadjuvant therapy followed by surgery (neoadjuvant chemoradiotherapy group), were retrospectively examined. The overall survival (OS) and disease-free survival (DFS) were compared between patients with and without recurrent laryngeal nerve LND.RESULTSAmong the 312 patients, no significant differences were found in 3-year OS and DFS between patients with and without recurrent laryngeal nerve LND in the entire cohort (OS: 57% vs 52%, P = 0.33; DFS: 47% vs 41%, P = 0.186), or the surgery group (n = 173, OS: 69% vs 58%, P = 0.43; DFS: 52% vs. 48%, P = 0.30) and the neoadjuvant chemoradiotherapy group (n = 139, OS: 44% vs 43%, P = 0.44; DFS: 39% vs 32%, P = 0.27). However, among patients with clinical positive recurrent laryngeal nerve lymph node involvement before treatment, there was significant OS and DFS differences between patients with and without recurrent laryngeal nerve LND (OS: 62% vs 33%, P = 0.029; DFS: 49% vs 26%, P = 0.031).CONCLUSIONSRecurrent laryngeal nerve LND is not a significant prognostic factor in patients with oesophageal squamous cell carcinoma; however, it is associated with better outcomes in patients with pre-treatment radiological evidence of recurrent laryngeal nerve lymph node involvement.     

Improvement Over the Years of Long-Term Survival in High-Risk Lymphoma Patients Treated with Hematopoietic Stem Cell Transplantation as Consolidation or Salvage Therapy

The role of hemopoietic stem cell transplantation (HSCT) is not well established in certain types of lymphoma, such as those with a high relapse risk or relapsing after initial therapy. New chemotherapeutic schemes and immunotherapy have improved survival of these patients. Nevertheless, there is not enough evidence regarding whether transplantation is the best therapeutic approach. Moreover, published data on long-term follow-up of high-risk lymphoma patients treated with HSCT are scarce. We analyzed 177 consecutive patients diagnosed with a high risk of relapse or with relapsed lymphoma who underwent HSCT after induction with standard chemotherapy in a tertiary academic center from 1989 to 2013. The median age was 40 years. Diagnoses were Hodgkin disease (n = 56), diffuse large B-cell lymphoma (n = 44), follicular lymphoma (n = 29), mantle cell lymphoma (n = 15), T-cell lymphoma (n = 18), and others (n = 15). Patients received either an autologous graft (n = 154) in first complete remission (1CR; n = 59) or more advanced stages (AS; n = 95), or an allogeneic graft (n = 23) in 1CR (n = 4) or AS (n = 19). In the autologous group, overall survival (OS) at 5 years was 57% and 75% in the periods 1989–2001 and 2002–2013, respectively (P = .05). Patients receiving an allogeneic graft presented an OS of 25% and 43% in the 2 periods. With a mean follow-up of 5 years (95% confidence interval 3.5–6.6), for patients receiving a transplant in 1CR, OS at 5 years was 80%, and for those receiving a transplant in AS it was 59% (P = .003). Nonrelapse mortality (NRM) at 5 years was 3.1% in the autologous group and 27.9% in the allogeneic group (P < .001). The main cause of NRM was infection (44%) in the whole cohort. All this leads to the conclusion that transplantation, as a therapeutic strategy, has shown a high long-term OS in this subgroup of patients with such a poor prognosis. OS improved over the years and reaching 1CR was a good prognostic feature. Infections were the main cause of NRM.     

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.     

Influence of the tumor site and histopathology after resection for non-colorectal non-neuroendocrine liver metastases. A single center experience

IntroductionIt remains unclear whether liver resection is justified in patients with non-colorectal non-neuroendocrine liver metastases (NCNNLM). A single-center study was conducted to analyse overall survival (OS), disease-free survival (DFS), and potential prognostic factors in patients with different types of NCNNLM.MethodA retrospective analysis of all patients who underwent liver resection of NCNNLM from January 2006 to July 2019 was performed.ResultsA total of 62 patients were analyzed. 82.3% presented metachronous metastases and 74.2% were unilobar. The most frequent primary tumor site (PTS) were breast (24.2%), urinary tract (19.4%), melanoma (12.9%), and pancreas (9.7%). The most frequent primary tumor pathologies were breast carcinoma (24.2%), non-breast adenocarcinoma (21%), melanoma (12.9%) and sarcoma (12.9%). The most frequent surgical procedure performed was minor hepatectomy (72.6%). R0 resection was achieved in 79.5% of cases. The major complications’ rate was 9.7% with a 90-day mortality rate of 1.6%. The 1, 3 and 5-year OS/DFS rate were 65%/28%, 45%/36% and 46%/28%, respectively. We identified the response to neoadjuvant therapy and PTS as possible prognostic factors for OS (P =0.06) and DFS (P =0.06) respectively.ConclusionBased on the results of our series, NCNNLM resection produces beneficial outcomes in terms of OS and DFS. PTS and the response to neoadjuvant therapy could be the main prognostic factors after resection.     

Dual-phase FDG PET/CT for predicting prognosis in operable breast cancer

PurposeWe aimed to investigate the role of dual-phase FDG PET/CT in predicting the prognosis of patients with operable breast cancer.MethodsWe retrospectively reviewed the data of 998 patients who underwent radical treatment for breast cancer. Before treatment, PET/CT scans were performed 1 and 2 h after FDG administration. The maximum standardized uptake value (SUVmax) at both time points (SUVmax1 and SUVmax2) in the primary tumor and the retention index (RI) were calculated. PET recurrence risk (PET-RR) was determined based on the SUVmax1 and RI, and disease-free survival (DFS) and overall survival (OS) were evaluated according to the metabolic parameters. Propensity score matching was performed to adjust for biological characteristics.ResultsThe cut-off values for SUVmax1 and RI were 3 and 5%, respectively. The 5-year DFS was 94.9% and 86.1% (P < 0.001), and the 5-year OS was 97.6% and 92.7% (P < 0.001) in the low and high PET-RR groups, respectively. In multivariate analysis, high T status, nodal metastasis, the triple-negative subtype, and high PET-RR were independent factors of poor DFS. Propensity score matching revealed similar findings (5-year DFS 91.8% vs. 88.6%, P = 0.041 and 5-year OS 97.1% vs. 94.2%, P = 0.240, respectively).ConclusionThe combined parameters of SUVmax1 and RI on dual-phase FDG PET/CT were useful for predicting prognosis of patients with breast cancer. Patients with a high SUVmax1 and a negative time course of FDG uptake had a favorable prognosis.     

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.     

Prognostic nutritional index and prognosis in renal cell carcinoma: A systematic review and meta-analysis

PurposeTo perform a systematic review and meta-analysis of the Prognostic Nutritional Index (PNI) as a prognostic factor for renal cell carcinoma (RCC).Materials and methodsEligible studies that evaluated the prognostic impact of pretreatment PNI in RCC patients were identified by comprehensive searching the electronic databases PubMed, Cochrane Central Search library, and EMBASE. The end points were overall/cancer-specific survival (OS/CSS) and recurrence-free/disease-free survival (RFS/DFS). Meta-analysis using random-effects models was performed to calculate hazard ratios (HRs) with 95 % confidence intervals (CIs).ResultsIn total, 9 retrospective, observational, case-control studies involving 5,976 patients were included for final analysis. Eight studies evaluated OS/CSS, and 5 evaluated RFS/DFS. Our results showed that lower PNI was significantly associated with unfavorable OS/CSS (HR = 1.68, 95% CI 1.44-1.96, P < 0.001, I² = 9.2%, P = 0.359) and RFS/DFS (HR = 1.98, 95% CI 1.57-2.50, P < 0.001, I² = 18.2%, P = 0.299) in patients with RCC. Subgroup and meta-regression analysis based on ethnicity, study sample size, presence of metastasis, PNI cut-off value, Newcastle–Ottawa quality assessment scale (NOS) score, and gender ratio all showed that lower PNI was associated with poorer OS/CSS and RFS/DFS. Funnel plots and Egger's tests indicated significant publication bias in OS/CSS (P = 0.001), but not in RFS/DFS (P = 0.757).ConclusionThis meta-analysis indicated that lower PNI was a negative prognostic factor and associated with tumor progression and poorer survival of patients with RCC. Therefore, PNI could be a potential prognostic predictor of treatment outcomes for patients with RCC.     

Comparison Between Resection and Transplantation in Combined Hepatocellular and Cholangiocarcinoma

Objective

The treatment of choice for combined hepatocellular and cholangiocarcinoma (cHCC-CC) is surgical resection. However, the efficacy of liver transplantation is not clear. We compared the surgical outcome of hepatic resection and liver transplantation for cHCC-CC.

Patients and methods

From 1995 to 2012, 89 patients were diagnosed with cHCC-CC after hepatic resection and 8 patients diagnosed with cHCC-CC after liver transplantation. We excluded 21 patients who were American Joint Committee on Cancer Staging Stage III or IV and lost to follow-up. The outcomes were reviewed retrospectively.

Results

The poor prognostic factors in cHCC-CC patients who underwent hepatectomy were large tumor size (>5 cm), small safety margin (<2 cm), and low preoperative albumin level. The disease-free survival (DFS) and overall survival (OS) between the hepatectomy group (n = 68) and the liver transplant group (n = 8) was not statistically different (5-year DFS: 26.2% vs 37.5%, P = .333; 5-year OS: 42.1% vs 50%, P = .591). In the small tumor subgroup (tumor size <5 cm), the DFS and OS between the 2 surgical procedures was not different, and in the adequate resection margin subgroup (safety margin >2 cm), survival was comparable.

Conclusions

In well-selected cases with small tumor size and with preserved liver function, liver resection should be considered when complete resection is possible.     

Anatomic versus non-anatomic resection of hepatocellular carcinoma with microvascular invasion: A systematic review and meta-analysis

The efficacy of anatomical resection (AR) and non-anatomical resection (NR) in the treatment of hepatocellular carcinoma (HCC) patients with microvascular invasion (MVI) remains unknown. This study compared the safety and outcomes of these surgical procedures. A systematic literature search was conducted. The main outcomes were overall survival (OS), disease-free survival (DFS). Overall hazard ratio (HR) was calculated from Kaplan–Meier plots and outcomes using random-effects models. There was no significant difference in postoperative complications between the AR and NR groups (risk ratio [RR]: 0.92, 95% confidence interval [CI]: 0.72–1.17, p = 0.496). OS was higher with AR at 1 year (RR: 0.66, 95% CI: 0.45–0.98, p = 0.037), 3 years (RR: 0.64, 95% CI: 0.50–0.82, p = 0.000), and 5 years (RR: 0.76, 95% CI: 0.65–0.89, p = 0.001). AR was associated with a higher OS rate (HR: 0.62, 95% CI: 0.47–0.82, p = 0.001). AR was associated with improved DFS at 1 year (RR: 0.65, 95% CI: 0.52 to 0.82, p = 0.000), 3 years (RR: 0.75, 95% CI: 0.66 to 0.86, p = 0.000), and 5 years (95% CI: 0.75 to 0.94, p = 0.002). Compared with NR, AR had significant advantages on overall HR of DFS (HR: 0.64, 95% CI: 0.45 to 0.91, p = 0.012). In conclusion, AR was associated with higher rates of OS and DFS in HCC patients with MVI. Thus, for well-presented liver function HCC patients which are predicted to have positive MVI, AR is recommended.     

UK national survey of venous thromboembolism prophylaxis in ankle fracture patients treated with plaster casts

BackgroundAnkle fractures are one of the commonest orthopaedic injuries. A substantial proportion of these are treated non-operatively at outpatient clinics with cast immobilization. We conducted this survey to assess the current practice in UK regarding thromboembolism prophylaxis in these patients.MethodsA telephonic survey was carried out on junior doctors within orthopaedic departments of 56 hospitals across the UK. A questionnaire was completed regarding venous thromboembolism risk assessment, prophylaxis, hospital guidelines, etc.Results84% (n = 47) hospitals did not routinely use any prophylaxis for these patients, while 7% (n = 4) hospitals used chemo-prophylaxis. Only 5.3% (n = 3) hospitals had DVT prophylaxis guidelines regarding these patients while other 9% (n = 5) hospitals were in process of developing such guidelines. In 64% (n = 36) hospitals, no formal DVT risk assessment was carried out.ConclusionA large variation exists across NHS hospitals and a poor risk assessment is being carried out in these patients. Development of local guidelines and extension of national guidelines to include high risk outpatients may improve the situation.     

Impact of cyclosporine‐A concentration in T‐cell replete haploidentical allogeneic stem cell transplantation

This paper aims to study whether cyclosporine‐A (CSA) levels have an impact on the clinical outcome of patients with T‐cell replete haploidentical allogeneic hematopoietic stem cell transplantation (allo‐HSCT). We analyzed 140 consecutive patients who had been given T‐cell replete haploidentical allo‐HSCT in our institute to assess the effect of CSA concentration in the early stages of allo‐HSCT on clinical outcomes, such as hematopoietic recovery, acute graft vs host disease (aGVHD), infection, disease‐free survival (DFS), and overall survival (OS). The median concentrations of CSA in the blood in the 1st, 2nd, 3rd, and 4th week after allo‐HSCT were 218, 235, 263, and 270 ng/mL, respectively. Additionally, 46%, 40%, 27%, and 18% of the patients had CSA blood levels below 200 ng/mL during those weeks. In total, 39 patients developed aGVHD (grade II‐IV), for a cumulative incidence of 27.8%, at a median of 32 days. Patients having a low CSA concentration (below 200 ng/mL) in the 3rd week had a higher cumulative incidence of grade II‐IV aGVHD (P = .02). In addition, multivariate logistic regression analysis showed that low CSA concentration (below 200 ng/mL) in the 3rd week was an independent risk factor of grade II‐IV aGVHD (P = .02; odds ratio = 2.66; 95% CI, 1.15‐6.17). However, CSA levels during the first 4 weeks did not have a significant impact on the patients’ hematopoietic recovery, infection, DFS, and OS. Our data indicated that adequate management of CSA levels during the peri‐engraftment period might improve clinical outcomes for those with T‐cell replete haploidentical allo‐HSCT.     

Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (HIPEC) for colorectal and appendiceal peritoneal metastases – The Hong Kong experience and literature review

IntroductionCytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) is increasingly used to treat peritoneal metastases from appendiceal or colorectal origin. We evaluate our institution's experience and survival outcomes with this procedure, and its efficacy in symptom relief.MethodsThis is a single-centre retrospective observational study on patients with peritoneal metastases (PM) from appendiceal neoplasm or colorectal cancer who underwent CRS/HIPEC in Queen Mary Hospital. Our primary endpoints were overall survival (OS) and morbidity and mortality of this procedure; secondary endpoints included disease-free survival (DFS) and symptom-free survival.ResultsBetween 2006 and 2018, thirty CRS/HIPEC procedures were performed for 28 patients – 17 (60.7%) had appendiceal PM while 11 (39.9%) had colorectal PM. The median peritoneal cancer index was 20; complete cytoreduction was achieved in 83.3% patients. High-grade morbidity occurred in 13.3% cases. There was no 30-day mortality. Two-year OS were 71.6% and 50% for low-grade appendiceal PM and colorectal PM patients (p = 0.20). Complete cytoreduction improved OS (2-year OS 75.4% vs 20%, p = 0.04). Median DFS was 11.8 months. Median symptom-free duration was 36.8 months; patients with complete cytoreduction were more likely to remain asymptomatic (82.9% at 1 year, vs 60% in incomplete cytoreduction group, p < 0.01). 91.7% low-grade appendiceal PM patients and 58.4% colorectal PM patients remained asymptomatic at post-operative one year (p = 0.31).ConclusionCRS/HIPEC is beneficial to appendiceal PM and selected colorectal PM patients – improving survival and offering prolonged symptom relief, with reasonable morbidity and mortality. Complete cytoreduction is key to realising this benefit.     

Impact of locoregional treatment on survival in patients presented with metastatic breast carcinoma

ObjectivesIn this study, we tried to evaluate the efficacy of locoregional treatment (LRT) in patients with metastatic breast carcinoma (MBC).Materials and methodsThe medical records of 227 patients with MBC at initial presentation between April 1999 and January 2013 were retrospectively evaluated. The median age at diagnosis was 50 years (range, 27–83 years). Thirty-nine patients (17%) had no LRT. Among patients who had LRT, 2 (1%) had locoregional radiotherapy (RT) alone, 54 (29%) had surgery alone [mastectomy, n = 50; breast conserving surgery (BCS), n = 4] and 132 (70%) had surgery (mastectomy, n = 119; BCS, n = 13) followed by locoregional RT.ResultsThe median follow-up time was 35 months (range, 4–149 months). Five-year OS and PFS rates were 44% and 20%, respectively. In both univariate and multivariate analysis LRT per se did not affect OS and PFS rates. However, the 5-year OS and PFS rates were significantly higher in patients treated with locoregional RT than the ones who were not. The corresponding rates were 56% vs. 24% for OS and 27% vs. 7% for PFS (p < 0.001). Median survival was 67 months and 37 months, respectively.ConclusionOur study showed that patients with MBC who received postoperative locoregional RT may have a survival advantage compared with patients who were only treated by surgery. A phase III trial testing the role of adjuvant locoregional RT may help to distinguish patients who will benefit from adjuvant RT.