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

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

Microvascular Invasion Does Not Predict Long-Term Survival in Hepatocellular Carcinoma up to 2 cm: Reappraisal of the Staging System for Solitary Tumors

Background

Excellent long-term outcomes have been reported recently for patients with small (≤2 cm) hepatocellular carcinoma (HCC). However, the significance of microvascular invasion (MVI) in small HCC remains unclear. The purpose of this study was to determine the impact of MVI in small HCC up to 2 cm.

Methods

In 1,109 patients with solitary HCC from six major international hepatobiliary centers, the impact of MVI on long-term survival in patients with small HCC (≤2 cm) and patients with tumors larger than 2 cm was analyzed.

Results

In patients with small HCC, long-term survival was not affected by MVI (p = 0.8), whereas in patients with larger HCC, significantly worse survival was observed in patients with MVI (p < 0.0001). In multivariate analysis, MVI (hazard ratio [HR] 1.59; 95 % confidence interval (CI) 1.27–1.99; p < 0.001), elevated alpha-fetoprotein (HR 1.41; 95 % CI 1.11–1.8; p = 0.005), and higher histologic grade (HR 1.29; 95 % CI 1.01–1.64; p = 0.04) were significant predictors of worse survival in patients with HCC larger than 2 cm but were not correlated with long-term survival in small HCC. When the cohort was divided into three groups—HCC ≤2, >2 cm without MVI, and HCC >2 cm with MVI—significant between-group survival difference was observed (p < 0.0001).

Conclusions

Small HCC is associated with an excellent prognosis that is not affected by the presence of MVI. The discriminatory power of the 7th edition of the AJCC classification for solitary HCC could be further improved by subdividing tumors according to size (≤2 vs. >2 cm).     

The short- and long-term outcomes in living-donor liver transplantation using small-for-size graft: A systematic review and meta-analysis

BackgroundA standard graft-to-recipient weight ratio (GRWR) ≥0.8% is widely accepted in living-donor liver transplantation (LDLT); however, the potential donor pool is expanded to patients adopting small-for-size graft (SFSGs) with GRWR <0.8%. This study aimed to investigate the effect of SFSG on short- and long-term outcomes following LDLT.MethodsElectronic databases were searched from January 1995 to January 2022 for studies comparing short- or long-term outcomes between patients with SFSG (GRWR <0.8%, SFSG group) and sufficient volume graft (GRWR ≥0.8%, non-SFSG group). The primary outcomes were one-, three-, and five-year overall survival (OS) and graft survival (GS), while the secondary outcome was postoperative complications.ResultsTwenty-four studies comprising 7996 patients were included. In terms of OS, SFSG group had poor three-year OS (HR: 1.48, 95% CI [1.01, 2.15], p = 0.04), but there were no significant differences between two groups in one-year OS (HR: 1.50, 95% CI [0.98, 2.29], p = 0.06) and five-year OS (HR: 1.40, 95% CI [0.95, 2.08], p = 0.02). In GS, there were no significant differences in one-year (HR 1.31, 95% CI [1.00, 1.72], p = 0.05), three-year (HR 1.33, 95% CI [0.97, 1.82], p = 0.07), and five-year GS (HR 1.17, 95% CI [0.95, 1.44], p = 0.13). The SFSG group had comparable postoperative complications, except for a high incidence of vascular complications and small-for-size syndromes.ConclusionsExpanding the potential donor pool in LDLT to SFSG with GRWR <0.8% can be acceptable in terms of comparable long-term OS and GS, despite the risk for vascular complications and small-for-size syndrome.     

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.     

Comparison Between Salvage Liver Transplantation and Repeat Liver Resection for Recurrent Hepatocellular Carcinoma: A Systematic Review and Meta-analysis

Introduction

Repeat liver resection (RLR) has been adopted by surgeons as the first-line treatment in the case of intrahepatic recurrence of hepatocellular carcinoma (HCC), whereas salvage liver transplantation (SLT) is considered a second-line option. The aim of our study was to evaluate the results of SLT and RLR for HCC.

Surgical and oncologic outcomes between laparoscopic and radical abdominal hysterectomy for IB1-IIA2 cervical cancer

ObjectiveTo compare sugrical and survival outcomes between laparoscopic radical hysterectomy (LRH) and radical abdominal hysterectomy (RAH).MethodsAll the patients with IB1-IIA2 cervical cancer who performed LRH or RAH in Fudan University Shanghai Cancer Center between 1/2016 and 12/2017 were retrospectively analyzed.ResultsThere were no significant differences between LRH and RAH groups except deep stromal invasion (35.2% vs 54.4%, p = 0.000), operating time (232.3 ± 61.9 min vs. 106.7 ± 36.2 min, p = 0.000), blood loss (169.5 ± 96.2 ml vs. 219.6 ± 149.3 ml, p = 0.000), and lymph node counts (21.1 ± 7.1 vs. 23.2 ± 8.7 min, p = 0.012). The LRH group displayed poorer disease-free survival (DFS) (5-year rate, 79.4% vs. 90.0%; p = 0.046) and overall survival (OS) (5-year rate, 74.7% vs. 90.0%; p = 0.026) compared to the RAH group. On multivariate analysis, LRH was an independent risk factor for DFS (hazard ratio, 0.377; 95% confidence interval [CI], 0.227–0.625; p = 0.000) and OS (hazard ratio, 0.434; 95% CI, 0.254–0.740; p = 0.003).ConclusionsLRH affected the survival of cervical cancer patients with tumor size >2 cm (p < 0.05). Adjuvant therapy could not improve the prognosis of laparoscopic patients (p < 0.05).     

Living vs. deceased donor liver transplantation for hepatocellular carcinoma: a systematic review and meta‐analysis

Experimental studies suggest that the regenerating liver provides a “fertile field” for the growth of hepatocellular carcinoma (HCC). However, clinical studies report conflicting results comparing living donor liver transplantation (LDLT) and deceased donor liver transplantation (DDLT) for HCC. Thus, disease‐free survival (DFS) and overall survival (OS) were compared after LDLT and DDLT for HCC in a systematic review and meta‐analysis. Twelve studies satisfied eligibility criteria for DFS, including 633 LDLT and 1232 DDLT. Twelve studies satisfied eligibility criteria for OS, including 637 LDLT and 1050 DDLT. Altogether, there were 16 unique studies; 1, 2, and 13 of these were rated as high, medium, and low quality, respectively. Studies were heterogeneous, non‐randomized, and mostly retrospective. The combined hazard ratio was 1.59 (95% confidence interval [CI]: 1.02–2.49; I² = 50.07%) for DFS after LDLT vs. DDLT for HCC, and 0.97 (95% CI: 0.73–1.27; I² = 5.68%) for OS. This analysis provides evidence of lower DFS after LDLT compared with DDLT for HCC. Improved study design and reporting is required in future research to ascribe the observed difference in DFS to study bias or biological risk specifically associated with LDLT.     

Antiviral Therapy Decreases Recurrence of Hepatitis B Virus-related Hepatocellular Carcinoma after Curative Resection: A Meta-analysis

Background

The long-term outcome after curative resection of hepatocellular carcinoma (HCC) remains unsatisfactory because of the high incidence of recurrence. The present study was intended to assess the impact of hepatitis B virus (HBV) DNA level and nucleos(t)ide analog therapy on posthepatectomy recurrence of HBV-related HCC.

Methods

Eligible studies were identified through a computerized literature search. The pooled relative risk ratio (RR) with 95 % confidence interval (CI) was calculated using Review Manager 5.1 Software.

Results

Twenty studies with a total of 8,204 participants were included for this meta-analysis. Pooled analysis showed that high viral load was significantly associated with risk of recurrence (RR: 1.85, 95 % CI: 1.41–2.42; P < 0.001), poorer disease-free survival (DFS) (RR: 1.96, 95 % CI: 1.62–2.38; P < 0.001), and poorer overall survival (OS) (RR: 1.47, 95 % CI: 1.22–1.77; P < 0.001) of HBV-related HCC after surgical resection. Nucleos(t)ide analog therapy significantly decreased the recurrence risk (RR: 0.69, 95 % CI: 0.59–0.80; P < 0.001) and improved both DFS (RR: 0.70, 95 % CI: 0.58–0.83; P < 0.001) and OS (RR: 0.46, 95 % CI: 0.32–0.68; P < 0.001).

Conclusions

High DNA level is associated with posthepatectomy recurrence of HBV-related HCC. Nucleos(t)ide analog therapy improves the prognosis of HBV-related HCC after resection.     

New onset vasomotor symptoms but not musculoskeletal symptoms associate with clinical outcomes on extended adjuvant letrozole – Analyses from NCIC CTG MA.17

PurposeNew onset symptoms on adjuvant aromatase inhibitors for hormone receptor positive early breast cancer may associate with clinical outcomes. We performed this exploratory analysis of the association of new onset musculoskeletal (MSK) and vasomotor (VM) symptoms with clinical outcomes in the NCIC CTG MA.17 trial 5 years of extended adjuvant endocrine therapy with letrozole after tamoxifen.MethodsSymptoms were collected at baseline, 1, 6, and every 12 months on study. Multivariate Cox Models adjusting for age, nodal status, duration of tamoxifen and prior chemotherapy were used to compare disease-free survival (DFS), distant disease-free survival (DDFS), and overall survival (OS) based on data collected before, and after, the unblinding between women with VM or MSK symptoms and those without.ResultsData post-unblinding showed new VM symptoms on extended letrozole significantly improved DFS and DDFS when occurring 1 month (DFS HR 0.52, 95% CI, 0.28–0.96; p = 0.04; DDFS HR 0.49, 95% CI, 0.24–0.99; p = 0.046) and 6 months (DFS HR 0.43, 95% CI, 0.24–0.78; p = 0.006; DDFS HR 0.44, 95% CI, 0.22–0.85; p = 0.02) after treatment initiation. Those with new VM symptoms at 12 months also had a significantly better DFS (HR 0.47, 95% CI 0.26, 0.84; P = 0.01) and a trend in improved DDFS. Only a trend to improved OS was found for those with VM symptoms 6 month after treatment. No significant improvement was found for those with new MSK symptoms at any time point or for any endpoint.ConclusionsNew onset VM symptoms with extended letrozole may be useful in predicting treatment benefit.     

Significance of HER2 expression in patients with upper tract urothelial carcinoma: A meta-analysis

ObjectiveSeveral studies have explored the prognostic values of HER2 expression in upper tract urothelial carcinoma (UTUC), however, the results obtained are not consistent. We aimed to calculate the clinical significance of HER2 expression on the outcome of UTUC patients using a meta-analysis.Materials and methodsUsing published evidence, we performed a meta-analysis to examine the clinical values of HER2 expression in patients with UTUC. Thirty-five articles from 679 articles related to the epidermal growth factor receptor family expression assessment in UTUC patients were reviewed and seven papers were found to be fit for analyses. The estimates included the odds ratio (OR), distribution related to stage and grade, hazard ratios (HRs), and 95% confidence intervals (CIs) from survival analyses of intravesical recurrence, progression, and overall survival (OS).ResultsThe pooled results showed that HER2 expression is significantly associated with higher stage, but not with tumor grade in patients with UTUC (OR, 2.05; 95% CI, 1.15–3.68; p = 0.016 and OR, 4.73; 95% CI, 0.80–27.8; p = 0.086, respectively). In addition, the pooled survival analyses demonstrated that HER2 expression yielded a worse recurrence-free survival in UTUC patients (HR, 4.32; 95% CI, 2.17–8.60; p < 0.0001). However, there is lack of statistical significance in terms of progression-free survival and OS (HR, 2.08; 95% CI, 0.46–9.32; p = 0.339 and HR, 1.06; 95% CI, 0.48–2.37; p = 0.879, respectively).ConclusionExisting studies on UTUC are heterogeneous and limited. Our analysis suggests that HER2 expression plays an important role in cancer recurrence in the urinary bladder after the primary treatment of UTUC.     

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 systematic review and meta-analysis of BRCA1/2 mutation for predicting the effect of platinum-based chemotherapy in triple-negative breast cancer

IntroductionPlatinum-based chemotherapy (PBC) remains the mainstay of treatments for triple-negative breast cancer (TNBC). TNBC is a heterogeneous group, the issue of whether BRCA1/2 mutation carriers have a particular sensitivity to platinum agents is inconclusive. We conducted a meta-analysis to explore the relationship between BRCA1/2 mutation and PBC susceptibility in individuals with TNBC, aiming to gain more information on the size of the benefit of PBC in BRCA1/2 mutation carriers.Materials and methodsAll studies applying PBC with a subgroup of BRCA1/2 status were included. All endpoints, including pCR and RCB in the neoadjuvant phase, DFS in the adjuvant phase, ORR, PFS, and OS in the advanced phase, were assessed using HRs and 95% Cl.ResultsFrom the 22 studies included, there were 2158 patients with TNBC, with 392 (18%) bearing the BRCA1/2 gene mutation. Based on 13 studies applying neoadjuvant PBC, we discovered that BRCA1/2 mutation was substantially associated with a 17.6% increased pCR rate (HR 1.32, 95% CI 1.17–1.49, p < 0.00001; I² = 51%). Same result was observed in RCB0/I index (HR 1.38, 95% CI 1.08–1.76, P = 0.009; I² = 0%). The meta-analysis of 6 trials addressing advanced therapy revealed that ORR rates were significantly higher in patients with BRCA1/2 mutation (HR 1.91, 95% CI 1.48–2.47, p < 0.00001; I² = 32%), as well as PFS(HR 1.13, 95% CI 0.81–1.57, P = 0.47; I² = 0%) and OS (HR 1.89, 95% CI 1.22–2.92, P = 0.004; I² = 0%).ConclusionAccording to our meta-analysis of 22 trials in TNBC, BRCA1/2 mutation carriers were significantly more sensitive to PBC regimens, especially in neoadjuvant and advanced therapy.     

Clinical impact of adjuvant radiation therapy delay after neoadjuvant chemotherapy in locally advanced breast cancer

Backgroundand Purpose: Post-operative radiation therapy (PORT) is usually indicated for patients with breast cancer (BC) after neoadjuvant chemotherapy (NAC) and surgery. However, the optimal timing to initiation of PORT is currently unknown.Material and methodsWe retrospectively evaluated data from patients with BC who received PORT after NAC and surgery at our institution from 2008 to 2014. Patients were categorized into three groups according to the time between surgery and PORT: <8 weeks, 8–16 weeks and >16 weeks.ResultsA total of 581 patients were included; 74% had clinical stage III. Forty-three patients started PORT within 8 weeks, 354 between 8 and 16 weeks and 184 beyond 16 weeks from surgery. With a median follow-up of 32 months, initiation of PORT up to 8 weeks after surgery was associated with better disease-free survival (DFS) (<8 weeks versus 8–16 weeks: HR 0.33; 95% CI 0.13–0.81; p = 0.02; <8 weeks versus >16 weeks: HR 0.38; 95% CI 0.15–0.96; p = 0.04) and better overall survival (OS) (<8 weeks versus 8–16 weeks: HR 0.22; 95% CI 0.05–0.90; p = 0.036; <8 weeks versus >16 weeks: HR 0.28; 95% CI 0.07–1.15; p = 0.08).ConclusionPORT started up to 8 weeks after surgery was associated with better DFS and OS in locally-advanced BC patients submitted to NAC. Our findings suggest that early initiation of PORT is critically important for these patients. However, the low numbers of patients and events in this study prevent us from drawing firm conclusions.     

Prognostic Significance of Post-Operative Morbidity Severity Score After Potentially Curative D2 Gastrectomy for Carcinoma

Background

Survival and relapse after gastric cancer surgery are largely attributed to tumor biology and surgical radicality; yet, other prognostic factors have been reported, including respiratory sepsis and anastomotic leakage, but not global morbidity severity score (MSS). The hypothesis tested was that MSS would be associated with both disease-free (DFS) and overall survival (OS).

Methods

Consecutive 373 patients undergoing potentially curative surgery for gastric adenocarcinoma between 2004 and 2016 in a UK cancer network were studied. Complications were defined prospectively as any deviation from a pre-determined post-operative course within 30 days of surgery and classified according to the Clavien-Dindo severity classification (CDSC). Primary outcome measures were DFS and OS.

Results

Post-operative complications were identified in 127 (34.0%) patients, which was associated with 9 (2.4%) post-operative deaths. Five-year DFS and OS were 35.9 and 38.5% for patients with a post-operative complication compared with 59.5 and 61.5% in controls (p?<?0.001, p?=?0.001, respectively). On multivariable DFS analysis, post-operative morbidity [hazard ratio (HR) 1.63, 95% confidence interval (CI) 1.06–2.50, p?=?0.026] was independently associated with poor survival. On multivariable OS analysis, post-operative morbidity HR 2.25 (95% CI 1.04–4.85, p?=?0.039) and CDSC HR 1.76 (95% CI 1.35–2.29, p?<?0.001) were independently associated with poor survival. These associations were also observed in patients with TNM stage I and II disease with morbidity HR 7.06 (95% CI 1.89–26.38, p?=?0.004) and CDSC HR 2.93 (95% CI 1.89–4.55, p?<?0.001) offering independent prognostic value.

Conclusion

Post-operative CDSC was an important independent prognostic factor after potentially curative gastrectomy for carcinoma associated with both DFS and OS. Prehabilitation strategies to minimize complications are warranted.

     

Aromatase inhibitors versus tamoxifen as adjuvant hormonal therapy for oestrogen sensitive early breast cancer in post-menopausal women: Meta-analyses of monotherapy,sequenced therapy and extended therapy

Adjuvant tamoxifen reduces relapses and prolongs survival in patients with oestrogen sensitive breast cancer. Development of resistance is however common. Tamoxifen can be given for a maximum of five years; although the risk of recurrences remains high after this period. This review examines nine randomised controlled trials including 28 632 women, which studied aromatase inhibitors (AIs) as an alternative to tamoxifen in three treatment settings: monotherapy (instead of tamoxifen), sequenced therapy (tamoxifen is switched to an AI) and extended therapy (following adjuvant tamoxifen). Disease free survival was significantly improved for monotherapy (HR 0.89, [95% CI 0.83–0.96] p = 0.002) and sequenced therapy (HR 0.72, [0.63–0.83] p < 0.00001). There was no difference in overall survival for monotherapy (HR 0.94, [0.82–1.08] p = 0.39) or extended therapy (HR 0.86 [0.79–1.16] p = 0.67). Importantly, overall survival was prolonged for patients who switched from tamoxifen to AI therapy (HR 0.78 95%CI 0.68–0.91, p = 0.001).     

PSA nadir and time to PSA nadir during initial androgen deprivation therapy as prognostic factors in metastatic castration-resistance prostate cancer patients treated with docetaxel

Prostate-specific antigen nadir (nPSA) and time to nPSA (TTN) have been proved to be associated with the prognosis of prostate cancer. In this study, we explored the prognosis effect of nPSA and TTN during initial androgen deprivation therapy (ADT) in patients with metastatic castration-resistant prostate cancer (mCRPC) after treatment with docetaxel-based chemotherapy. The data of 153 mCRPC patients received docetaxel followed by ADT were retrospectively reviewed. Multivariate Cox regression analysis demonstrated that TTN (overall survival (OS): Hazard ratio [HR] 0.096, 95% confidence interval [CI] 0.045–0.206, p < .001; progression-free survival (PFS): HR 0.128, 95% CI 0.078–0.211, p < .001) and nPSA (OS: HR 2.849, 95% CI 1.318–6.157, p = .008; PFS: HR 1.573, 95% CI 1.008–2.454, p = .046) acted as independent predictors of chemotherapy prognosis. Kaplan-Meier analysis showed that patients with nPSA ≥ 0.2 ng/ml or TTN < 6.5 months had shorter OS and PFS. These results suggest that TTN and nPSA during ADT can affect the prognosis of docetaxel-based chemotherapy prognosis post-castration resistance in patients with mCRPC, and higher nPSA and shorter TTN lead to poor chemotherapy prognosis. What is more, TTN has a greater impact during ADT on the prognosis of chemotherapy than nPSA.     

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

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

Loco‐regional Control After Neo‐adjuvant Chemotherapy and Conservative Treatment for Locally Advanced Breast Cancer Patients

Breast‐conserving treatment (BCT) has been validated for breast cancer patients receiving adjuvant chemotherapy. Our objective was to evaluate the difference in loco‐regional recurrence (LRR) rates between BCT and mastectomy in patients receiving radiation therapy after neo‐adjuvant chemotherapy (NCT). A retrospective data base was used to identify all patients with breast cancer undergoing NCT from 2002 to 2007. Patients with initial metastatic disease were excluded from this analysis. LRR was compared between those undergoing BCT and mastectomy. Individual variables associated with LRR were evaluated. Two hundred eighty‐four patients were included, 111 (39%) underwent BCT and 173 (61%) mastectomy. Almost all patients (99%) in both groups received postoperative radiation. Pathologic complete response was seen in 37 patients, of which 28 underwent BCT (p < 0.001). Patients receiving mastectomy had more invasive lobular carcinoma (p = 0.007) and a higher American Joint Committee on Cancer (AJCC) stage (p < 0.001) at diagnosis than those with BCT. At a median follow‐up of 6.3 years, the loco‐regional control rate was 91% (95% CI: 86–94%). The 10‐year LRR rate was similar in the BCT group (9.2% [95% CI: 4.9–16.7%]) and in the mastectomy group (10.7% [95% CI: 5.9–15.2%]; p = 0.8). Ten‐year overall survival (OS) rates (63% [95% CI: 46–79%] in the BCT group; 60% [95% CI: 47–73%] in the mastectomy group, p = 0.8) were not statistically different between the two patient populations. Multivariate analysis showed that AJCC stage ≥ III (HR: 2.6; 95% CI: 1.2–5.8; p = 0.02), negative PR (HR: 6; 95% CI: 1.2–30.6, p = 0.03), and number of positive lymph nodes ≥3 (HR: 2.5; 95% CI: 1.1–5.9; p = 0.03) were independent predictors of LRR. Ten‐year OS was similar in the BCT and in the mastectomy group (p = 0.1). The rate of LRR was low and did not significantly differ between the BCT and the mastectomy group after NCT. Randomized trials assessing whether mastectomy can be safely omitted in selected breast cancer patients (nonstage III tumors or those which do not require adjuvant hormone suppression) which respond to NCT are required.     

Combination of sarcopenia and prognostic nutritional index to predict long-term outcomes in patients undergoing initial hepatectomy for hepatocellular carcinoma

ObjectiveTo determine if preoperative sarcopenia and prognostic nutritional index (PNI) could accurately predict the postoperative outcomes of patients with hepatocellular carcinoma (HCC) undergoing initial hepatectomy.MethodsThree hundred three patients who underwent curative hepatectomy for HCC between January 2010 and August 2021 were enrolled and their data were retrospectively analyzed. Sarcopenia was determined from computed tomography images obtained 3 weeks prior to surgery, and PNI was calculated from preoperative albumin and whole lymphocyte count data in receiver operating characteristic (ROC) curve analysis, with a cutoff value of 46.2 to categorize high and low groups.ResultsOne hundred six (35%) patients had sarcopenia prior to surgery. Kaplan–Meier analysis revealed that sarcopenia and low PNI were associated with significantly worse overall survival (OS) compared with no sarcopenia and high PNI, respectively (P = 0.023 and P = 0.035, respectively). In addition, patients with sarcopenia had worse OS than those without sarcopenia in the high and low PNI groups (P = 0.058 and P = 0.038, respectively). Sarcopenia (hazard ratio [HR] 1.66; 95% confidence interval [CI] 1.00–2.76; P = 0.048) and PNI ≤46.2 (HR 1.96; 95% CI 1.17–3.27; P = 0.011) were independent prognostic factors on multivariate analysis, and combined sarcopenia and PNI had a higher AUC value (AUC = 0.722, P < 0.001) than either one alone in ROC analysis.ConclusionCombined sarcopenia and PNI as a prognostic marker can better predict the postoperative prognostic outcomes of HCC patients following hepatectomy than either sarcopenia or PNI alone.     

Clinical factors that affect the outcomes after anatomical versus non-anatomical resection for hepatocellular carcinoma

Purpose

For hepatocellular carcinoma (HCC), the superiority of anatomical resection (AR) over non-anatomical resection (NR) is still controversial. In this study, we assessed the potential benefits of AR for HCC.

Methods

We enrolled 173 consecutive patients with HCC who underwent hepatectomy in our hospital from August 2003 to May 2013 and compared the outcomes for the AR group (n = 125) with those for the NR group (n = 48).

Results

The median observational period was 790 days. The 1- and 2-year overall survival (OS) rates were 92.1 and 85.8 %, respectively; the 1- and 2-year disease-free survival (DFS) rates were 78.2 and 63.0 %, respectively. The AR and NR groups did not significantly differ in the OS or DFS. However, the 2-year DFS was significantly better for the AR group than the NR group among HCV patients (68.2 vs. 32.2 %; P = 0.004) and patients with alpha-fetoprotein (AFP) within the normal range (<20 ng/ml; 76.7 vs. 60.9 %; P = 0.031), total bilirubin <0.8 mg/dl (70.8 vs. 47.0 %; P = 0.034), and tumors 2–5 cm in diameter (82.0 vs. 62.5 %; P = 0.025).

Conclusions

If a patient is HCV-negative, has low AFP, low total bilirubin, or a tumor diameter of 2–5 cm, AR is recommended.