Favorable outcome with sentinel lymph node biopsy alone after neoadjuvant chemotherapy in clinically node positive breast cancer at diagnosis: Turkish Multicentric NEOSENTI-TURK MF-18-02-study

PurposeFactors affecting local outcome were evaluated in patients with clinically node-positive (cN+) breast cancer at diagnosis, who underwent sentinel lymph node biopsy (SLNB) alone after neoadjuvant chemotherapy (NAC).MethodsBetween 2004 and 2018, 303 cytopathology-proven cN (+) patients in a multicentric registry, who received NAC and underwent SLNB alone were analysed. All patients had regional nodal irradiation.ResultsMedian age was 46 (23–70). Of those, 211 patients had ypN0 disease (69.6%), whereas 92 patients had ypN (+) disease including 19 (20.6%) isolated tumor cells (ITC), 33 micrometastases (35.9%) and 40 macrometastases (43.5%). At a median follow-up of 36 months (24–172), one patient (0.3%) with macrometastatic SLN was found to have locoregional recurrence as chest wall and supraclavicular LN metastases at the 60th month. Five-year disease-free survival (DFS) and disease specific survival (DSS) rates were 87% and 95%, respectively. Patients with cT3/4 (HR = 2.41, 95% CI; 1.14–5.07), non-luminal molecular pathology (HR = 2.60, 95% CI, 1.16–5.82), and non-pCR in the breast (HR = 2.11, 95% CI, 0.89–5.01) were found to have an increased HR compared to others in 5-year DFS. However, no difference could be found between ypN0 and ypN ITC and micrometastasis (HR = 1.23, 95% CI, 0.44–3.47), whereas there was a slight increase in HR of patients with ypN macrometastasis versus ypN0 (HR = 1.91, 95% CI, 0.63–5.79).ConclusionALND could be avoided in meticulously selected cN (+) patients who underwent SLNB after NAC having breast and/or nodal pCR, cT1-2, or low volume residual nodal disease with luminal pathology, as long as axillary radiotherapy is provided.     

Nomograms for Predicting Overall and Recurrence-free Survival From Pathologic Stage IA and IB Lung Cancer After Lobectomy

BackgroundStage I non–small-cell lung cancer (NSCLC) is potentially curable with surgical resection. Significant proportions of patients may still experience recurrence and death despite undergoing curative surgery. This study describes predictive nomograms for recurrence-free (RFS) and overall survival (OS) after lobectomy.Patients and MethodsA total of 301 patients with the American Joint Committee on Cancer pathologic stage IA and IB NSCLC who underwent open, thoracoscopic, or robotic lobectomy from January 2011 to April 2017 were analyzed. Multivariate Cox proportional hazards regression models were used to create nomograms for OS and RFS. Kaplan-Meier survival curves were calculated for OS and RFS comparing high-risk and low-risk cohorts based on nomogram scores.ResultsHistology (hazard ratio [HR], 0.24; 95% confidence interval [CI], 0.10-0.56; P = .002), lymphovascular invasion (HR, 0.46; 95% CI, 0.29-0.74; P = .001), smoking status (HR, 3.46; 95% CI, 1.25-9.55: P = .02), and total lymph nodes removed (HR, 1.05; 95% CI, 1.01-1.10; P = .021) were significant predictors for OS in a multivariate model. Lymphovascular invasion (HR, 0.55; 95% CI, 0.36-0.83; P = .0040), smoking status (HR, 2.56; 95% CI, 1.16-5.62; P = .02), total lymph nodes removed (HR, 1.04; 95% CI, 1.00-1.08; P = .029), and tumor size (HR, 1.30; 95% CI, 1.30-1.68; P = .047) were significant predictors of RFS in a multivariate model.ConclusionNomograms can predict OS and RFS for pathologic stage IA and IB NSCLC after lobectomy regardless of operative approach. The risk for death and recurrence after stratification by the nomogram scores may provide guidance regarding adjuvant therapy and surveillance.     

Prognostic value of platelet-associated biomarkers in rectal cancer patients received neoadjuvant chemoradiation: A retrospective study

PurposePlatelet volume has been shown to prognostic value in patients with colorectal cancer. However, the changes of other platelet-associated biomarkers in rectal cancer patients, before and after the neoadjuvant chemoradiation therapy (NACRT), remain unclear. In this study, we investigated the prognostic value of platelet-associated biomarkers in rectal cancer patients with NACRT.Patients and methodsA total of 75 patients with locally advanced (T3–4 or N+) rectal cancer (LARC) cancer were selected and followed up from the Affiliated Cancer Hospital of Zhengzhou University between June 2013 and September 2016. The data of platelet-associated biomarkers, including the platelet count, platelet to lymphocyte ratio (PLR), lymphocyte to monocyte ratio (LMR), mean platelet volume (MPV), and platelet distribution width (PDW) both pre- and post- NACRT, were collected. The associations between these platelet-associated biomarkers and the overall survival (OS), as well as disease-free survival (DFS) of patients, were analysed. Patients were divided into groups with high or low values of the platelet-associated biomarkers, and the outcomes were compared by using Cox regression and Kaplan–Meier analysis.ResultsWe found that pre-PLR (HR: 4.104; 95%CI: 1.411–11.421; P = 0.009) and pre-LMR (HR: 0.384; 95%CI: 0.124–1.185; P = 0.066) could predict the OS in LARC patients after NACRT by multivariate Cox regression analysis, a cut-off value of pre-PLR > 7.02 and pre-LMR ≤ 7.10 could be used as independent prognostic factors for OS by Kaplan–Meier method. The pre-MPV value could be used as an independent prognostic factor for DFS by Kaplan–Meier analysis (P = 0.037). Moreover, post-CEA was correlated with OS and DFS in LARC patients with NACRT.ConclusionIn LARC patients with NACRT, the pre-PLR and pre-LMR are independent prognostic factors for OS, while pre-MPV has predictive value for DFS.     

Superior efficacy of neoadjuvant chemotherapy and radical cystectomy in cT3-4aN0M0 compared to cT2N0M0 bladder cancer

In this study, we compared complete pathological downstaging (pCD, ≤(y)pT1N0) and overall survival (OS) in patients with cT2 versus cT3–4aN0M0 UC of the bladder undergoing radical cystectomy (RC) with or without neoadjuvant chemo- (NAC) or radiotherapy (NAR). A population-based sample of 5,517 patients, who underwent upfront RC versus NAC + RC or NAR + RC for cT2-4aN0M0 UC between 1995–2013, was identified from the Netherlands Cancer Registry. Data were retrieved from individual patient files and pathology reports. pCD-rates were compared using Chi-square tests and OS was estimated by Kaplan–Meier analyses. Multivariable analyses were conducted to determine odds (OR) and hazard ratios (HR) for pCD-status and OS, respectively. We included 4,504 (82%) patients with cT2 and 1,013 (18%) with cT3–4a UC. Median follow-up was 9.2 years. In cT2 UC, pCD-rate was 25% after upfront RC versus 43% (p < 0.001) and 33% (p = 0.130) after NAC + RC and NAR + RC, respectively. In cT3–4a UC, pCD-rate was 8% after upfront RC versus 37% (p < 0.001) and 16% (p = 0.281) after NAC + RC and NAR + RC, respectively. In cT2 UC, 5-year OS was 57% and 51% for NAC + RC and upfront RC, respectively (p = 0.135), whereas in cT3–4a UC, 5-year OS was 55% for NAC + RC versus 36% for upfront RC (p < 0.001). In multivariable analysis for OS, NAC was beneficial in cT3–4a UC (HR: 0.67, 95%CI 0.51–0.89) but not in cT2 UC (HR: 0.91, 95%CI 0.72–1.15). NAR did not influence OS. In conclusion, NAC + RC was associated with superior pCD compared to RC alone and NAR + RC. Superior OS for NAC + RC compared to RC alone was especially evident in cT3–4a disease.     

Minimally invasive surgery versus percutaneous radiofrequency ablation for early-stage hepatocellular carcinoma: Results from a high-volume liver surgery center in East Asia

Background & aimsThe outcomes of minimally invasive surgery (MIS) vs. percutaneous radiofrequency ablation (RFA) in treating early-stage hepatocellular carcinoma (HCC) remain inconclusive. This study thus aimed to compare the outcomes of both treatments for early-stage HCCs.MethodsThis retrospective study consecutively enrolled patients with newly diagnosed early-stage HCCs treated with MIS or percutaneous RFA between 2011 and 2018. Outcomes were compared between the MIS and RFA groups both before and after 1:1 propensity score matching (PSM).ResultsA total of 119 and 481 patients underwent MIS and percutaneous RFA, respectively. Patients undergoing percutaneous RFA exhibited older age (p = 0.007) and higher rates of Child–Pugh class B (p < 0.001) and multifocal disease (p < 0.001). The median overall survival (OS) was 73.7 months in the MIS group, which was significantly higher than that for the RFA group of 65.1 months (p = 0.003). 50% HCC recurrence after MIS was not reached. The mean recurrence-free survival (RFS) was 49.6 months for the MIS group, which was significantly higher than the RFA group of 41.3 months (p < 0.001). On multivariate analysis, age ≥65 (HR: 1.61; 95% CI: 1.13–2.31, p = 0.009), RFA (HR: 2.21; 95% CI: 1.14–4.29, p = 0.019), and Child–Pugh class B (HR: 2.03; 95% CI: 1.29–3.21, p = 0.002) remained risk factors for OS, and RFA (HR: 2.18; 95% CI: 1.42–3.35; p < 0.001) remained a risk factor for RFS. After PSM, 103 patients were included in each group. No significant difference in OS was identified (p = 0.198), but RFS was higher in the MIS group than the RFA group (p = 0.003). Severe postoperative complications occurred at the same rate (1%) in both groups (p > 0.99).ConclusionAfter PSM, severe postoperative complication and OS rates were found to be comparable between the MIS and RFA groups, but RFS was higher in the MIS group than the RFA group, suggesting that MIS may have better outcomes for patients with early-stage HCC.     

Transarterial chemoembolization plus immune checkpoint inhibitor as postoperative adjuvant therapy for hepatocellular carcinoma with portal vein tumor thrombus: A multicenter cohort study

PurposeThis study aimed to assess the efficacy and safety of postoperative adjuvant transarterial chemoembolization (PA-TACE) plus immune checkpoint inhibitor (ICI) for hepatocellular carcinoma (HCC) with portal vein tumor thrombus (PVTT).Patients and methodsThis study was conducted on three centers from June 2018 to December 2020. Patients were divided into the PA-TACE (n = 48) and PA-TACE plus ICI groups (n = 42). The recurrence-free survival (RFS) and overall survival (OS) curves were depicted by Kaplan-Meier method, and the differences between the two groups were compared using log-rank test. Univariate and multivariate Cox analyses were performed to identify independent risk factors for RFS and OS. Adverse events (AEs) were assessed according to the Common Terminology Criteria for AEs (CTCAE) version 5.0.ResultsThe median RFS of the PA-TACE plus ICI group was significantly longer than the PA-TACE group (12.76 months vs. 8.11 months; P = 0.038). The median OS of the PA-TACE plus ICI group was also significanfly better than the PA-TACE group (24.5 months vs. 19.1 months; P = 0.032). PA-TACE plus ICI treatment was an independent prognostic factor for RFS (HR: 0.54, 95% CI: 0.32–0.9, P = 0.019) and OS (HR: 0.47, 95% CI: 0.26–0.86, P = 0.014). Only one patient experienced grade ≥3 immune-related AEs in the PA-TACE plus ICI group.ConclusionsPA-TACE plus ICI treatment had better efficacy in preventing recurrence and prolonging survival than PA-TACE alone for HCC patients with PVTT after R0 resection. This novel treatment modality may be an appropriate option for HCC with PVTT.     

Elevated serum carcinoembryonic antigen level after curative surgery is a prognostic biomarker of stage II-III colorectal cancer

BackgroundHigh preoperative carcinoembryonic antigen (CEA) is a well-known risk factor for stage II-III colorectal cancer (CRC); however, in most cases, cancer does not recur. Conversely, postoperative CEA (post-CEA) is occasionally measured, and high post-CEA patients often develop recurrence; however, the clinical significance of post-CEA testing is unknown. The purpose of this study was to determine whether post-CEA elevation might indicate a poor prognosis for stage II-III CRC patients who underwent curative surgery.Patients and methods482 patients with pathological stage II-III CRC were included. Univariate and multivariate analyses were performed to evaluate post-CEA levels.ResultsMultivariate analysis showed that elevated post-CEA (hazard ratio (HR): 3.14, P < 0.001), pathological lymph node metastasis (pN+), and pathological T4 (pT4) are associated with poor recurrence-free survival (RFS), and that elevated post-CEA (HR: 3.12; P = 0.002), pN+, pT4, age >70, and smoking are independently associated with poor overall survival. Subgroup analysis among stage III patients, in combination with the risk classification of the International Duration Evaluation of Adjuvant Chemotherapy (IDEA) study, showed that elevated post-CEA is a significant indicator of poor prognosis for RFS in both low-risk (73.8% vs. 21.2%, P < 0.001) and high-risk (49.9% vs. 25.0%, P = 0.04) groups.ConclusionsPost-surgical CEA elevation is independently associated with poor prognosis in stage II-III CRC. Adding post-CEA levels to the IDEA risk classification may provide a more reliable indicator of the need for individualized surveillance and adjuvant chemotherapeutic strategies.     

Clinical outcomes of elderly patients receiving neoadjuvant chemoradiation for locally advanced rectal cancer

BackgroundStudies of clinical outcomes of elderly patients treated with neoadjuvant chemoradiation (nCRT) for locally advanced rectal cancer (LARC) are limited. Our aim was to assess the impact of age on clinical outcomes in a large multi-institutional database.Patients and methodsData for patients diagnosed with LARC who received nCRT and curative-intent surgery between 2005 and 2012 were collected from five major Canadian cancer centers. Age was analyzed as a continuous and dichotomous variable (<70 versus ≥70 years) and correlated with disease-free survival (DFS), cancer-specific survival (CSS) and overall survival (OS). Cox regression models were used to adjust for important prognostic factors.ResultsOf 1172 patients included, 295 (25%) were ≥70 years, and they were less likely to receive adjuvant chemotherapy (ACT; 60% versus 79%, P < 0.0001), oxaliplatin-based ACT (12% versus 31%, P < 0.0001), less likely to complete nCT (76% versus 86%, P < 0.001), and more likely to be anemic at initiation of nCRT (42% versus 30%, P = 0.0004). In multivariate analyses, age ≥70 years was associated with similar DFS [hazard ratio (HR) 0.93, 95% confidence interval (CI) 0.68–1.26, P = 0.63], similar CSS (HR 0.81, 95% CI 0.46–1.41, P = 0.45), and similar OS (HR 1.28, 95% CI 0.88–1.86, P = 0.20), compared with the younger age group. As a continuous variable, increasing age was not predictive of DFS (HR 1.00, 95% CI 0.99–1.02, P = 0.49) or CSS (HR 1.002, 95% CI 0.98–1.02, P = 0.88); however, it correlated with an inferior OS (HR 1.02, 95% CI 1.00–1.03, P = 0.04).ConclusionsElderly patients (≥70 years) who receive nCRT followed by surgery appear to have similar outcomes compared with younger patients. Decisions regarding eligibility for nCRT and surgery should not be based on age alone.     

Prognostic impact of preoperative prognostic nutritional index in resected advanced gastric cancer: A multicenter propensity score analysis

BackgroundAdvanced gastric cancer (AGC) causes debilitating malnutrition and leads to deterioration of the immune response. However, the concept of the prognostic nutritional index (PNI) is controversial when applied to patients with AGC. The aim of the present study was to evaluate the effect of the PNI after gastrectomy in patients with AGC.Materials and methodsA multicenter retrospective study was conducted using propensity score matching (PSM) in gastric adenocarcinoma patients who underwent resection via laparoscopic or open surgery between 2014 and 2017. To overcome selection bias, we performed 1:1 matching using 5 covariates.ResultsThe resection margins (P < 0.001) and LNM (P = 0.004) were significantly different between the two groups. In univariate analysis, poor tumor differentiation (P = 0.038) (R1+R2, P = 0.004), vascular and neural invasion (P < 0.001), and a PNI<50 (P < 0.001) were associated with poor recurrence-free survival (RFS). In multivariate analysis, a PNI<50 (hazard ratio (HR), 12.993; P < 0.001) was a risk factor for RFS. Univariate analysis for overall survival (OS) revealed that a PNI<50 (P < 0.001) (R1+R2,P = 0.006) and vascular and neural invasion (P < 0.001) were risk factors. In subsequent multivariate analysis, a PNI<50 (HR, 24.501; P < 0.001) was a significant risk factor for OS. Clinical assessments performed during a 12.34 (±5.050) month follow-up revealed that OS (P < 0.001) and RFS (P < 0.001) were worse in patients with a low PNI (<50) than in matched patients with a high PNI.ConclusionA low PNI is a strong predictor of unfavorable RFS and OS in patients with AGC.     

Pathological downstaging and survival after induction chemotherapy and radical cystectomy for clinically node-positive bladder cancer—Results of a nationwide population-based study

BackgroundInduction chemotherapy (IC) for clinically node-positive bladder cancer is applied without clinical evidence of improved outcome. Our objective was to compare complete pathological downstaging (pCD) and overall survival (OS) for IC versus upfront radical cystectomy (RC) in cT1-4aN1-3M0 urothelial carcinoma (UC).MethodsThis population-based study included 659 cN+ patients treated with RC between 1995 and 2013. IC was applied in 212 (32%) patients. We defined pCD as ≤(y)pT1N0 at RC. Multivariable analyses were preformed to identify independent predictors of pCD and OS.ResultsIn cN1 and cN2–3 patients, 31% and 19% of patients proved to be pN0 at upfront RC. In cN1, pCD was achieved in 39% following IC versus 5% for upfront RC (P < 0.001). In cN2–3 UC, rates were 27% versus 3% (P < 0.001). Three-year OS for pCD and ypCD were 81% and 84%, respectively. Three-year OS rates were 66% versus 37% (cN1) and 43% versus 22% (cN2-3), again in favour of IC (P < 0.001). In multivariable analyses, IC was associated with pCD (Odds ratio, 14; 95% confidence interval [CI], 7.4–25) and a 53% decreased risk of death (Hazard ratio [HR], 0.47; 95% CI, 0.36–0.61). Indication bias and unequal distributions of factors associated with OS (e.g. patients proceeding to RC) limit interpretation of our results.ConclusionsPatients with clinical nodal involvement should not be neglected. Up to 1/4 of patients with cN+ disease had pN0 at upfront RC. Moreover, IC followed by RC for clinically node-positive UC was associated with improved pathological downstaging compared with RC alone. A potential OS benefit for IC needs to be validated in a randomised trial.Take home messageIC followed by RC for clinically node-positive UC is associated with improved pathological downstaging compared with RC alone. A potential OS benefit for IC needs to be validated in a randomised trial.     

Sarcopenia assessed by skeletal muscle mass volume is a prognostic factor for oncological outcomes of rectal cancer patients undergoing neoadjuvant chemoradiotherapy followed by surgery

IntroductionRecently, sarcopenia has been reported to be associated with poor postoperative outcomes in various cancers. However, its clinical significance for rectal cancer patients undergoing neoadjuvant chemoradiotherapy (NACRT) followed by surgery remains unknown.Materials and methodsThis study included 46 patients with locally advanced rectal cancer who underwent curative surgery after NACRT. Sarcopenia was assessed by measuring the cross-sectional psoas muscle area (PA) at L3 and total bilateral psoas muscle volume (PV). Patients with a lower PV or PA value than the median were assigned to the sarcopenia group while others were assigned to the non-sarcopenia group. Clinical outcomes were then compared between groups.ResultsThe sarcopenia group included 22 patients. The rate of overall postoperative complications did not differ between groups. Five-year relapse-free survival (RFS) was significantly lower in the sarcopenia group when sarcopenia was assessed by PV after NACRT (44.0% vs. 82.6%, P = 0.00494). In contrast, RFS did not differ between groups when sarcopenia was assessed by PA. Multivariable analysis identified PV after NACRT as the most significant risk factor for RFS (hazard ratio 4.00; 95% CI 1.27–12.66, P = 0.018).ConclusionSarcopenia assessed by total PV after NACRT may be an accurate and reliable predictor of poor oncological outcomes in rectal cancer patients.     

Surgery improves overall and cancer-specific survival of rare urinary cancers; population - based study

Numerous rare urinary tract (UT) cancers lack adequate understanding of survival and therapeutic options, and nearly all responses to systemic therapy are unsatisfactory, yet clinical research is scarce.MethodsBetween 2010 and 2015, a total of (14,622 patients) with uncommon UT cancer (62.5%) in the overall survival (OS) group and (37.5%) in the cancer specific survival (CSS)group were identified in the SEER database. multimodality therapeutic approach on OS and CSS were compared.ResultsIn uncommon UT malignancies, OS outperformed CSS in the locoregional stage (P < 0.05), but not in the distant stage (P = 0.34). Non-performed surgery had poor survival in both OS (HR 1.647; 95% CI (1.461–1.856)) and CSS (HR 1.573; 95% CI (1.399–1.769)) respectively (P < 0.05). There were no significant differences in survival in the CSS group between those who received or did not obtain chemotherapy.ConclusionsThe OS group survives substantially longer than the CSS group in the locoregional stage, but not at the distant stage. While both the OS and CSS groups of the locoregional stage were linked with improved survival after surgery, chemotherapy treatment decreased OS but not CSS in patients with uncommon urological cancers. There were no differences in radiation between the OS and CSS.     

The choice of a neoadjuvant chemotherapy cycle for breast cancer has significance in clinical practice: results from a population-based,real world study

Objective: Neoadjuvant chemotherapy(NAC) is currently used in both early stage and locally advanced breast cancers. The survival benefits of standard vs. non-standard NAC cycles are still unclear. This study aimed to investigate the relationship between NAC cycles and survival based on real world data.Methods: We identified patients diagnosed with invasive primary breast cancers who underwent NAC followed by surgery. Patients who received at least 4 NAC cycles were defined as having received sta...     

Validation of the Eighth Edition Clinical T Categorization System for Clinical Stage IA,Resected Lung Adenocarcinomas: Prognostic Implications of the Ground-Glass Opacity Component

IntroductionThere is controversy regarding the clinical T (cT) category of lung adenocarcinomas that manifest as part-solid nodules (PSNs). We aimed to validate the cT category and to evaluate the independent prognostic role of the nodule type (i.e., part-solid versus solid).MethodsWe retrospectively evaluated the prognostic value of clinico-radiologic factors regarding the overall survival of patients with clinical stage IA lung adenocarcinomas that were resected between 2008 and 2014. cT Category, nodule type, and their interaction term were included in the multivariable Cox regression analysis with other variables. In addition, a mixture cure model analysis was performed to investigate the association between the covariates and long-term survival.ResultsA total of 744 patients (420 women; 362 PSNs; median age, 63 y) were included. The multivariable-adjusted hazard ratio (HR) of the nodule type was not significant (1.30, 95% confidence interval [CI]: 0.80–2.10, p = 0.291). However, the cT categories were significantly associated with overall survival (HR of cT1b, 2.33 [95% CI: 1.07–5.06, p = 0.033]; HR of cT1c, 5.74 [95% CI: 2.51–13.12, p < 0.001]). There were no interactions between the nodule type and the cT categories (all p > 0.05). The multivariable mixture cure model revealed that solid nodules were associated with a decreased probability of long-term survival (OR = 0.40, 95% CI: 0.18–0.92, p = 0.030). In addition, cT1c was a negative predictor of long-term survival (OR = 0.26, 95% CI: 0.07–0.94, p = 0.040).ConclusionsThe cT categorization system is valid for PSNs and solid nodules. Nevertheless, PSNs are a prognostic factor associated with long-term survival.     

Hepatectomy for ruptured hepatocellular carcinoma classified as Barcelona Clinic Liver Cancer stage 0/A: The optimal treatment

Background and aimsRuptured hepatocellular carcinoma (rHCC) generally has a very poor prognosis and is currently classified as T4 in the tumor–node–metastasis (TNM) staging system. In this study, we aimed to demonstrate the actual impact of rHCC, as well as the positive effect of hepatectomy in patients with Barcelona Clinic Liver Cancer (BCLC) stage 0/A rHCC.MethodsWe enrolled 86 patients with rHCC after surgery and 526 patients with non-rHCC after surgery or transcatheter arterial chemoembolization (TACE). Survival curves were plotted using the Kaplan–Meier method to compare the postoperative prognosis of patients with rHCC with that of patients with non-rHCC. Univariate and multivariate Cox regression analyses were used to identify the risk factors affecting patient survival.ResultsBCLC stage 0/A rHCC treated with surgery had a worse prognosis than BCLC stage 0/A non-rHCC treated with surgery (overall survival [OS]: hazard ratio [HR] = 3.12 [2.24–4.34], P < 0.001; recurrence-free survival [RFS]: HR = 2.26 [1.65–3.09], P < 0.001). Rupture was an independent prognostic factor in patients with BCLC stage 0/A rHCC (OS: HR = 1.685 [1.416–2.006], P < 0.001; RFS: HR = 1.484 [1.267–1.737], P < 0.001), and patients with BCLC stage 0/A rHCC who underwent surgery had a comparable prognosis to patients with BCLC stage B HCC who underwent surgery or TACE (OS: P = 0.78).ConclusionsPatients classified as having BCLC stage 0/A rHCC can achieve comparable outcomes to patients with BCLC stage B HCC after hepatectomy. However, not all patients with rHCC should be classified as T4 in the TNM staging system.     

Afatinib versus cisplatin plus pemetrexed in Japanese patients with advanced non‐small cell lung cancer harboring activating EGFR mutations: Subgroup analysis of LUX‐Lung 3

In LUX‐Lung 3, afatinib significantly improved progression‐free survival (PFS) versus cisplatin/pemetrexed in EGFR mutation‐positive lung adenocarcinoma patients and overall survival (OS) in Del19 patients. Preplanned analyses in Japanese patients from LUX‐Lung 3 were performed. Patients were randomized 2:1 to afatinib or cisplatin/pemetrexed, stratified by mutation type (Del19/L858R/Other). Primary endpoint was PFS (independent review). Secondary endpoints included OS, objective response, and safety. Median PFS (data cut‐off: February 2012) for afatinib versus cisplatin/pemetrexed was 13.8 vs 6.9 months (hazard ratio [HR], 0.38; 95% confidence interval [CI], 0.20–0.70; P = 0.0014) in all Japanese patients (N = 83), with more pronounced improvements in those with common mutations (Del19/L858R; HR, 0.28; 95% CI, 0.15–0.52; P < 0.0001) and Del19 mutations (HR, 0.16; 95% CI, 0.06–0.39; P < 0.0001). PFS was also improved in L858R patients (HR, 0.50; 95% CI, 0.20–1.25; P = 0.1309). Median OS (data cut‐off: November 2013) with afatinib versus cisplatin/pemetrexed was 46.9 vs 35.8 months (HR, 0.75; 95% CI, 0.40–1.43; P = 0.3791) in all Japanese patients, with greater benefit in patients with common mutations (HR, 0.57; 95% CI, 0.29–1.12; P = 0.0966) and Del19 mutations (HR, 0.34; 95% CI, 0.13–0.87; P = 0.0181); OS was not significantly different in L858R patients (HR, 1.13; 95% CI, 0.40–3.21; P = 0.8212). Following study treatment discontinuation, most patients (93.5%) received subsequent anticancer therapy. The most common treatment‐related adverse events were diarrhea, rash/acne, nail effects and stomatitis with afatinib and nausea, decreased appetite, neutropenia, and leukopenia with cisplatin/pemetrexed. Afatinib significantly improved PFS versus cisplatin/pemetrexed in Japanese EGFR mutation‐positive lung adenocarcinoma patients and OS in Del19 but not L858R patients ( www.clinicaltrials.gov ; NCT00949650).     

The impact of postmastectomy and regional nodal radiation after neoadjuvant chemotherapy for clinically lymph node-positive breast cancer: a National Cancer Database (NCDB) analysis

BackgroundFollowing neoadjuvant chemotherapy (NAC), the optimal strategies for postmastectomy radiotherapy (PMRT) and regional nodal irradiation (RNI) after breast-conserving surgery (BCS) are controversial. In this analysis, we evaluate the impact of these radiotherapy (RT) approaches for women with clinically node-positive breast cancer treated with NAC in the National Cancer Database (NCDB).Patients and methodsWomen with cT1–3 cN1 M0 breast cancer treated with NAC were divided into four cohorts by surgery [Mastectomy (Mast) versus BCS] and post-chemotherapy pathologic nodal status (ypN0 versus ypN+). Overall survival (OS) was estimated using the Kaplan–Meier method and RT approaches were analyzed using the log-rank test, multivariate Cox models, and propensity score-matched analyses.ResultsFrom 2003 to 2011, 15 315 cases were identified including 3040 Mast-ypN0, 7243 Mast-ypN+, 2070 BCS-ypN0, and 2962 BCS-ypN+ patients. On univariate analysis, PMRT was associated with improved OS for both Mast-ypN0 (P = 0.019) and Mast-ypN+ (P < 0.001) patients. On multivariate analyses adjusted for factors including age, comorbidity score, cT stage, in-breast pathologic complete response, axillary surgery, ypN stage, estrogen receptor status and hormone therapy, PMRT remained independently associated with improved OS among Mast-ypN0 [hazard ratio (HR) = 0.729, 95% confidence interval (CI) 0.566–0.939, P = 0.015] and Mast-ypN+ patients (HR = 0.772, 95% CI 0.689–0.866, P < 0.001). No differences in OS were observed with the addition of RNI to breast RT for BCS-ypN0 or BCS-ypN+ patients. Propensity score-matched analyses demonstrated identical patterns of significance. On subset analysis, OS was improved with PMRT in each pathologic nodal subgroup (ypN0, ypN1, and ypN2-3) (all P < 0.05).ConclusionsIn the largest reported analysis of RT for cN1 patients treated with NAC, PMRT was associated with improved OS for all pathologic nodal subgroups. No OS differences were observed with the addition of RNI to breast RT.     

Prognostic implications of residual disease tumor-infiltrating lymphocytes and residual cancer burden in triple-negative breast cancer patients after neoadjuvant chemotherapy

BackgroundFor primary triple-negative breast cancer (TNBC) treated with neoadjuvant chemotherapy (NAC), higher pretreatment tumor-infiltrating lymphocytes (TILs) correlates with increased pathologic complete response (pCR) rates, and improved survival. We evaluated the added prognostic value of residual disease (RD) TILs to residual cancer burden (RCB) in predicting survival post-NAC.Patients and methodsWe combined four TNBC NAC patient cohorts who did not achieve pCR. RD TILs were investigated for associations with recurrence-free survival (RFS), and overall survival (OS) using Cox models with stromal TILs as a continuous variable (per 10% increment). The likelihood ratio test was used to evaluate added prognostic value of RD TILs.ResultsA total of 375 RD TNBC samples were evaluable for TILs and RCB. The median age was 50 years, with 62% receiving anthracycline/taxane chemotherapy. The RCB class after NAC was 11%, 50%, and 39% for I, II, and III, respectively. The median RD TIL level was 20% (IQR 10–40). There was a positive correlation between RD TIL levels and CD8+ T-cell density (ρ = 0.41). TIL levels were significantly lower with increasing post-NAC tumor (P = 0.005), nodal stage (P = 0.032), but did not differ by RCB class (P = 0.84). Higher RD TILs were significantly associated with improved RFS (HR: 0.86; 95% CI 0.79–0.92; P < 0.001), and improved OS (HR: 0.87; 95% CI 0.80–0.94; P < 0.001), and remained significant predictors in multivariate analysis (RFS P = 0.032; OS P = 0.038 for OS). RD TILs added significant prognostic value to multivariate models including RCB class (P < 0.001 for RFS; P = 0.021 for OS). The positive prognostic effect of RD TILs significantly differed by RCB class for RFS (P_Int=0.003) and OS (P_Int=0.008) with a greater magnitude of positive effect observed for RCB class II than class III.ConclusionsTIL levels in TNBC RD are significantly associated with improved RFS and OS and add further prognostic information to RCB class, particularly in RCB class II.     

Neoadjuvant chemotherapy followed by interval debulking surgery for advanced epithelial ovarian cancer: GOTIC-019 study

Introduction

Three randomized controlled trials have resulted in extremely extensive application of the strategy of using neoadjuvant chemotherapy (NAC) followed by interval debulking surgery (IDS) for patients with advanced epithelial ovarian cancer in Japan. This study aimed to evaluate the status and effectiveness of treatment strategies using NAC followed by IDS in Japanese clinical practice.

Patients and methods

We conducted a multi-institutional observational study of 940 women with Federation of Gynecology and Obstetrics (FIGO) stages III–IV epithelial ovarian cancer treated at one of nine centers between 2010 and 2015. Progression-free survival (PFS) and overall survival (OS) were compared between 486 propensity-score matched participants who underwent NAC followed by IDS and primary debulking surgery (PDS) followed by adjuvant chemotherapy.

Results

Patients with FIGO stage IIIC receiving NAC had a shorter OS (median OS: 48.1 vs. 68.2 months, hazard ratio [HR]: 1.34; 95% confidence interval [CI] 0.99–1.82, p = 0.06) but not PFS (median PFS: 19.7 vs. 19.4 months, HR: 1.02; 95% CI: 0.80–1.31, p = 0.88). However, patients with FIGO stage IV receiving NAC and PDS had comparable PFS (median PFS: 16.6 vs. 14.7 months, HR: 1.07 95% CI: 0.74–1.53, p = 0.73) and OS (median PFS: 45.2 vs. 35.7 months, HR: 0.98; 95% CI: 0.65–1.47, p = 0.93).

Conclusions

NAC followed by IDS did not improve survival. In patients with FIGO stage IIIC, NAC may be associated with a shorter OS.