Bone invasion in soft tissue sarcomas of the extremities: An underappreciated prognostic factor. Bone invasion in soft tissue sarcomas

BackgroundBone invasion is unfrequently reported in soft tissue sarcomas of the extremities (eSTS), it is difficult to assess preoperatively and its prognostic impact has not been extensively studied. The objective of this paper was to analyze the incidence and the clinical impact of histologically proven bone invasion in individuals with eSTS.MethodsA retrospective analysis was performed using the medical files patients who had eSTS and were treated between 2012 and 2016. A 5 years survival was estimated using the Kaplan-Meier method and a Cox proportional risk assessment. The outcomes of patients with and without bone invasion were compared.Results370 patients were included in the analysis. The median follow up was 25 months, the median age was 45 years (IQR 31–58). Bone invasion was found in 41 (11.08%). Median tumor size was 11.8 cm. The majority of individuals were diagnosed at stage IV (n = 116, 31.4%), followed by stage IIIB (n = 87, 23.5%). High histological grade was associated with worse OS (HR 2.23, CI 95% 1.36–3.65, p = 0.001). Absence of bone invasion was associated with better prognosis (HR 0.541, CI 95% 0.34–0.86, p = 0.009). OS was 27.3 vs 49.28 months. The disease-free survival (DFS) was 25.1 in bone invasion vs 45.23 without bone invasion.ConclusionBone invasion in individuals with eSTS is an independent adverse prognostic factor associated with lower OS and DFS; although infrequently reported, bone invasion might be considered as part of the staging in the future     

Efficacy and safety analysis according to histology for S-1 in combination with carboplatin as first-line chemotherapy in patients with advanced non-small-cell lung cancer: updated results of the West Japan Oncology Group LETS study

BackgroundA phase III study (Lung Cancer Evaluation of TS-1) previously demonstrated noninferiority in terms of overall survival (OS) at interim analysis for carboplatin–S-1 compared with carboplatin–paclitaxel for first-line treatment of advanced non-small-cell lung cancer (NSCLC).Patients and methodsA total of 564 patients were randomly assigned to receive either carboplatin on day 1 plus oral S-1 on days 1–14 or carboplatin–paclitaxel on day 1 every 21 days. Updated results and post hoc subgroup analysis according to tumor histology are presented.ResultsThe updated analysis revealed a median OS of 15.2 months in the carboplatin–S-1 arm and 13.1 months in the carboplatin–paclitaxel arm, with a hazard ratio (HR) of 0.956 [95% confidence interval (CI) 0.793–1.151], consistent with the previous primary analysis. Median OS was 14.0 months in the carboplatin–S-1 arm and 10.6 months in the carboplatin–paclitaxel arm (HR 0.713; 95% CI 0.476–1.068) for patients with squamous cell carcinoma (SCC), with corresponding values of 15.5 and 13.9 months (HR 1.060; 95% CI 0.859–1.308) for those with non-SCC.ConclusionsThese results establish the efficacy and safety of carboplatin–S-1 in patients with advanced NSCLC regardless of tumor histology.     

Randomized Study of Maintenance Pemetrexed Versus Observation for Treatment of Malignant Pleural Mesothelioma: CALGB 30901

BackgroundThe role of maintenance therapy for malignant pleural mesothelioma (MPM) is unknown. We performed a randomized phase II trial to determine if continuation of pemetrexed after first-line pemetrexed and platinum would improve progression-free survival (PFS).Patients and MethodsEligible patients with unresectable MPM, without disease progression following 4 to 6 cycles of pemetrexed and platinum were randomized 1:1 to observation or continuation of pemetrexed until progression, stratified by number of cycles (< 6 or 6), cis- or carboplatin containing regimen, and histology. Study size was calculated based on the assumption that observation would produce a median PFS of 3 months and pemetrexed would yield median PFS of 6 months.ResultsA total of 72 patients were registered from December 2010 to June 2016. The study closed early after 53 patients were randomized; 49 eligible (22 on the observation arm and 27 on the pemetrexed arm) were included in the analysis. The median PFS was 3 months (95% confidence interval [CI], 2.6-11.9 months) on observation and 3.4 months (95% CI, 2.8-9.8 months) on pemetrexed (hazard ratio [HR], 0.99; 95% CI, 0.51-1.90; P = .9733). The median overall survival (OS) was 11.8 months (95% CI, 9.3-28.7 months) for observation, and 16.3 months (95% CI, 10.5-26.0 months) for pemetrexed (HR, 0.86; 95% CI, 0.44-1.71; P = .6737). Grade 3 or 4 toxicities on the pemetrexed arm included anemia (8%), lymphopenia (8%), neutropenia (4%), and fatigue (4%). A higher baseline level of soluble mesothelin-related peptide was associated with worse PFS (HR, 1.86; 95% CI, 1.00-3.46; P = .049).ConclusionMaintenance pemetrexed following initial pemetrexed and platinum chemotherapy does not improve PFS in patients with MPM.     

Renal Sarcoma: A Population-Based Study

IntroductionRenal sarcomas are exceedingly rare and lack a prognostic stage classification. We thus aimed to investigate the contemporary clinicopathologic characteristics and outcomes of renal sarcomas at a national level.Patients and MethodsWe utilized the Surveillance, Epidemiology, and End Results database to extract data on patients with renal sarcoma diagnosed between 2004 and 2015. We estimated median, 1-, 3-, and 5-year overall survival (OS) probabilities via Kaplan-Meier curves and used multivariable regression to compare OS between different patient groups.ResultsWe identified 365 patients; at diagnosis, 104 patients (28.5%) had stage I disease (T1N0M0), 133 patients (36.4%) patients had stage II disease (T2-4N0M0), and 117 patients (32.1%) patients had stage III disease (any T, N1, or M1). Median survival was 105 months (interquartile range [IQR], 29 – not reached) for stage I disease, 46 months (IQR 14-118 months) for stage II disease, 8 months (IQR 3-28 months) for stage III disease, and 32 months (IQR, 8-116 months) for the entire cohort. Patient age (hazard ratio [HR] for death [per year] 1.02, 95% confidence interval [95% CI] 1.00-1.04), stage (II vs. I: HR 1.71, 95% CI 1.00-2.92; III vs. I: HR 4.93, 95% CI 2.68-9.05), grade (grade 3 vs. grade 1: 3.07, 95% CI 1.18-8.00; grade 4 vs. grade 1: HR 3.66, 95% CI 1.41-9.49), and possessing medical insurance (HR 0.40, 95% CI 0.16-0.94) were independently and significantly associated with OS. Performance of nephrectomy also trended towards independently improving OS (HR 0.23, 95% CI 0.05-1.09).ConclusionA novel staging classification for renal sarcomas into a 3-stage system based on Tumor Node Metastasis (TNM) criteria produces distinct survival curves, although further studies are needed to robustly assess its validity.     

Factors Associated With Survival in Complete Pathologic Response Non–Small Cell Lung Cancer

ObjectivesThere is a strong association with improved survival for patients with non–small cell lung cancer (NSCLC) who have developed a pathological complete response (pCR) after neoadjuvant therapy. A national database was used to investigate factors associated with long-term survival in this cohort of patients.PatientsRetrospective review was completed of the National Cancer Database of patients who obtained pCR and had neoadjuvant therapy for stage I to stage III NSCLC between 2004 and 2014. All patients had neoadjuvant chemotherapy with or without radiation therapy.MethodsUnivariate and multivariable analysis was performed on factors associated with overall survival (OS), including gender, clinical stage, and nodal count. Patients were divided into 2 groups based on the Commission on Cancer–recommended median number of lymph nodes (LNs) examined: 0 to 9 LNs and ≥10 LNs. Chi-square and Wilcoxon rank-sum tests were used to compare patient, hospital, and clinical variables between groups.ResultsIncreased age (hazard ratio [HR] 1.02, 95% confidence interval [CI], 1.00-1.03), neoadjuvant radiation therapy (HR 1.48, 95% CI, 1.10-2.00), and pneumonectomy (HR 1.64, 95% CI, 1.22-2.22) were associated with worse survival in the 759-patient cohort. Multivariable regression demonstrated having ≥10 nodes harvested (HR 0.71, 95% CI, 0.56-0.89) was associated with improved survival as was every increase in LN harvest up to 17 LNs. No significant differences in 5-year OS were found between clinical stage I, II, and III, respectively (66.1% vs. 60.9% vs. 58.6%, P = .288).ConclusionThis study shows that younger age, increasing LN harvest, female sex, the absence of neoadjuvant radiation therapy and non-pneumonectomy resections are all associated with improved OS in patients with NSCLC who have developed pCR.     

Primary non-Hodgkin's lymphoma of the nasopharynx: prognostic factors and outcome of 113 Indian patients

This single institutional study evaluated the prognostic factors and treatment outcome of 113 Indian patients with primary nasopharyngeal non-Hodgkin's lymphoma. At presentation, 28% had stage I and 62% had stage II disease. Treatment comprised of a combination of chemotherapy (CTh) and radiotherapy (RT) in the majority of the patients (76%). After a median follow-up of 56 months, the 5-year disease-free survival (DFS) and overall survival (OS) for the whole group were 55.8% and 57.9%, respectively. Multivariate analysis showed that; age > 30 years [hazard ratio (HR) = 6.59, 95% confidence interval (CI) = 2.59 - 16.7, P < 0.0001], WHO performance score > or = 2 (HR = 2.34, 95% CI = 1.01 - 5.46, P = 0.050), T-cell lymphomas (HR = 2.81, 95% CI = 1.14 - 6.96, P < 0.001) and the presence of B symptoms (HR = 3.65, 95% CI = 1.77 - 7.53, P = 0.025), had a negative influence on survival. Patients treated with a combination of CTh and RT had a significantly better outcome than those treated with CTh alone (OS: 69%vs. 31%, P < 0.00001). HR for death in the CTh alone group was 3.73 (95% CI = 1.95 - 7.13). The CR (P = 0.01), DFS (P = 0.01) and OS (P = 0.03) rates were significantly better for patients receiving a RT dose of > or =4500 cGy. HR in the subgroup that received a RT dose of <4500 cGy was 2.51 (95% CI = 1.04 - 6.06). These results suggest that combined modality treatment, comprising of CTh and RT (with an RT dose of > or =4500 cGy), results in satisfactory outcome in patients with this rare neoplasm.     

Optimal treatment of early-stage ovarian cancer

BackgroundThere is no clear consensus regarding systemic treatment of early-stage ovarian cancer (OC). Clinical trials are challenging because of the relatively low incidence and good prognosis. Initial results of the International Collaborative Ovarian Neoplasm (ICON)1 trial demonstrated benefit in both overall survival (OS) and recurrence-free survival (RFS) with adjuvant chemotherapy. We report results of 10-year follow-up to establish whether benefits are maintained longer term and discuss how this and other available evidence from randomised trials can be used to guide treatment options regarding the need for, and choice of, adjuvant chemotherapy regimen.Patients and methodsICON1 recruited women with OC following primary surgery in whom there was uncertainty as to whether adjuvant chemotherapy was indicated. Patients were randomly assigned to adjuvant or no adjuvant chemotherapy. Platinum-based chemotherapy was recommended and 87% received single-agent carboplatin. Analyses of long-term treatment benefits and interaction with risk groups were carried out. A high-risk group of women was defined with stage 1B/1C grade 2/3, any stage 1 grade 3 or clear-cell histology.ResultsWith a median follow-up of 10 years, the estimated hazard ratio (HR) for RFS was 0.69 [95% confidence interval (CI) 0.51–0.94, P = 0.02] and OS 0.71 (95% CI 0.52–0.98, P = 0.04) in favour of chemotherapy. In absolute terms, there was a 10% (60%–70%) improvement in RFS and a 9% (64%–73%) improvement in OS; the benefit of chemotherapy might be greater in high-risk disease (18% improvement in OS). Uncertainty remains about the optimal chemotherapy regimen. The only randomised trial data available are from a subset of 120 stage 1 patients in ICON3 where the treatment difference, comparing carboplatin with carboplatin/paclitaxel was estimated with relatively wide CIs [progression-free survival HR = 0.71 (95% CI 0.39–1.32) and OS HR = 0.98 (95% CI 0.49–1.93)].ConclusionsExtended follow-up from ICON1 confirms that adjuvant chemotherapy should be offered to women with early-stage OC, particularly those with high-risk disease.Clinical trial numbersISRCTN11916376 for ICON1 and ISRCTN57157825 for ICON3.     

Older Patients Treated for Lung and Thoracic Cancers: Unplanned Hospitalizations and Overall Survival

BackgroundLung cancer affects older adults and is the leading solid tumor in terms of death. A Comprehensive Geriatric Assessment (CGA) is recommended before cancer treatment to guide therapy management.Patients and MethodsThis study was conducted between September 2015 and January 2019. During this period of time, all consecutive older outpatients referred for a CGA before initiation of lung or thoracic tumor treatment were included. The objectives were to describe the impact of geriatric factors on unplanned hospitalizations and overall survival (OS). The study was approved by a local ethics committee.ResultsOverall, 228 patients were recruited. The median age was 78.7 ± 5 years. The majority (82%) of patients were diagnosed with non–small-cell lung cancer, and the most common (40.4%) treatment was systemic therapy. In multivariate analysis, factors associated with unplanned hospitalizations within the first 3 months were male gender (adjusted odds ratio [aOR], 3.3; 95% confidence interval [CI], 1.5-7.2), systemic therapy (aOR, 2.6; 95% CI, 1.1-6.2), and fall history (aOR, 3.6; 95% CI, 1.6-8.2). Factors associated with a decrease in OS in the multivariate Cox model analysis were male gender (hazard ratio [HR], 3.9; 95% CI, 2.1-7.3), stage IV (HR, 1.6; 95% CI, 1.0-2.6), G8 ≤ 14 (HR, 3.5; 95% CI, 1.1-11.4), systemic therapy (HR, 2.6; 95% CI, 1.2-5.5), Eastern Cooperative Oncology Group performance status ≥ 2 (HR, 2.0; 95% CI, 1.2-3.4), and impaired handgrip strength (HR, 1.6; 95% CI, 1.0-2.5).ConclusionG8 score and handgrip strength are important to predict OS in older adults treated for thoracic tumors. In the CGA, fall history was associated with unplanned hospitalization.     

Sarcopenia is an independent unfavorable prognostic factor of non-small cell lung cancer after surgical resection: A comprehensive systematic review and meta-analysis

BackgroundWhether sarcopenia has any impact on long-term survival of patients with surgically treated non-small cell lung cancer (NSCLC) remains unclear. We conducted a meta-analysis focusing on current topic comprehensively for the first time.MethodsWe systematically searched relevant studies in PubMed, Embase, and Cochrane Library up to July 3, 2018. Data of 5-year overall survival (OS) and disease-free survival (DFS) rates as well as hazard ratio (HR) of OS were collected for analysis by using the STATA 12.0 package.ResultsA total of 6 cohort studies consisting of 1213 patients (422 patients with sarcopenia and 791 patients without) were included for analysis. Meta-analysis showed that patients with sarcopenia had a significantly lower 5-year OS rate (risk ratio (RR) = 1.63; 95% confidence interval (CI) = [1.13, 2.33]; P = 0.008) than those without, which was more prominent in patients with early-stage NSCLC. Sarcopenia was found to be an independent predictor of poor OS in patients with surgically treated NSCLC (HR = 2.85; 95%CI = [1.67, 4.86]; P < 0.001). With a limited sample size, there was no sufficient evidence of significantly different 5-year DFS rate between the two groups (RR = 1.14; 95%CI = [0.59, 2.17]; P = 0.70). However, in the subgroup of patients with early-stage NSCLC, sarcopenia was associated with a significantly lower 5-year DFS rate (RR = 1.59; 95%CI = [1.01, 2.52]; P = 0.046).ConclusionPatients with sarcopenia had a significantly worse prognosis than those without after surgical resection of NSCLC especially in those at early stage. Sarcopenia is an independent unfavorable prognostic factor for patients with surgically treated NSCLC. (246 words).     

Prognostic Value of the Pretreatment Neutrophil-to-Lymphocyte Ratio in Different Phenotypes of Locally Advanced Breast Cancer During Neoadjuvant Systemic Treatment

PurposeNeutrophils are among the key cellular players in the inflammatory milieu produced in patients with breast cancer (BC), and strong evidence exists in terms of the prognostic value of assessing the neutrophil-to-lymphocyte ratio (NLR) in patients with BC. In this study we sought to determine whether the baseline NLR correlates with pathological complete response (pCR), disease-free survival (DFS), and overall survival (OS) in patients with locally advanced BC in the neoadjuvant chemotherapy (NAC) setting.MethodsWe analyzed the pretreatment NLR from the first blood count of patients treated from 2007 to 2015 in terms of pCR, DFS, and OS in patients with locally advanced BC. Patients received standard medical care based on national guidelines.ResultsA total of 1519 patients were included in the study. Median age was 49 years (22-88). The cutoff point for NLR was 2.0. NLR was not associated with pCR or DFS. However, patients with high NLR had worse OS in the presence of triple-negative BC (105.9 months; 95% confidence interval [CI], 100.2-111.5] vs. 98.7 months; 95% CI, 91.1-106.3; P = .029), Her2 overexpression (114.0 months; 95% CI, 110.5-118.0 vs. 100.8 months; 95% CI 95.7-105.9; P = .019), and residual disease after NAC for both phenotypes. Multivariate analysis showed that NLR was independently associated with OS (hazard ratio, 1.4; 95% CI, 1.02-1.95; P = .037).ConclusionsPretreatment NLR in patients with locally advanced BC correlates with OS as an independent prognostic factor. This influence depends on phenotype and residual disease. Routine assessment of this parameter could be an easy and affordable tool for defining prognosis.     

Influence of Androgen Receptor Expression on the Survival Outcomes in Breast Cancer: A Meta-Analysis

Purpose

Despite the fact that the androgen receptor (AR) is known to be involved in the pathogenesis of breast cancer, its prognostic effect remains controversial. In this meta-analysis, we explored AR expression and its impact on survival outcomes in breast cancer.

Methods

We searched PubMed, EMBASE, Cochrane Library, ScienceDirect, SpringerLink, and Ovid databases and references of articles to identify studies reporting data until December 2013. Disease-free survival (DFS) and overall survival (OS) were analyzed by extracting the number of patients with recurrence and survival according to AR expression.

Results

There were 16 articles that met the criteria for inclusion in our meta-analysis. DFS and OS were significantly longer in patients with AR expression compared with patients without AR expression (odds ratio [OR], 0.60; 95% confidence interval [CI], 0.40-0.90; OR, 0.53; 95% CI, 0.38-0.73, respectively). In addition, hormone receptor (HR) positive patients had a longer DFS when AR was also expressed (OR, 0.63; 95% CI, 0.41-0.98). For patients with triple negative breast cancer (TNBC), AR expression was also associated with longer DFS and OS (OR, 0.44, 95% CI, 0.26-0.75; OR, 0.26, 95% CI, 0.12-0.55, respectively). Furthermore, AR expression was associated with a longer DFS and OS in women (OR, 0.42, 95% CI, 0.27-0.64; OR, 0.47, 95% CI, 0.38-0.59, respectively). However, in men, AR expression was associated with a worse DFS (OR, 6.00; 95% CI, 1.46-24.73).

Conclusion

Expression of AR in breast cancer might be associated with better survival outcomes, especially in patients with HR-positive tumors and TNBC, and women. Based on this meta-analysis, we propose that AR expression might be related to prognostic features and contribute to clinical outcomes.     

Novel Prognostic Factors in Resected Small Bowel Adenocarcinoma

BackgroundSmall bowel adenocarcinoma (SBA) is a rare malignancy affecting approximately 3000 patients per year in the United States, and there is limited evidence prognosticating patients with resected SBA. We aimed to evaluate prognostic factors and the role of adjuvant therapy in patients with resected SBA.Patients and MethodsTwo hundred forty-one patients who had resected stage I-III SBA were retrospectively identified at a single tertiary referral institution. Overall survival (OS) analysis was performed by the Kaplan-Meier method, and Wilcoxon tests were used for statistical comparisons. Cox proportional hazards were performed to identify significant variables by univariate and multivariate analysis.ResultsMedian OS for the entire group was 54.5 months (95% confidence interval [CI], 37.2-81.2 months), with 5- and 10-year OS of 48% and 35%. Median follow-up was 113.7 months (95% CI, 97.9-126.6 months). For patients with stage III disease who received adjuvant therapy, the median OS was 33.8 months (95% CI, 27.8-78.8) compared to 24.7 months (95% CI, 11.5-37.8) for patients with no adjuvant therapy (P < .01). Male sex, advanced T stage, advanced N stage, increased positive lymph node ratio, lymphocyte-to-monocyte ratio < 1.56, presence of residual disease, and earlier date of diagnosis predicted worse survival on univariate analysis. Age > 60 years, lymphocyte-to-monocyte ratio < 1.56, and advanced T stage were identified as independent negative predictors of OS for all patients by multivariate analysis.ConclusionAdvanced age, advanced T stage, and lymphocyte-to-monocyte ratio < 1.56 independently predicted survival in resected SBA. Adjuvant therapy is associated with improved survival in patients with resected stage III SBA.     

A comparison of carboplatin and paclitaxel with cisplatinum and 5-fluorouracil in definitive chemoradiation in esophageal cancer patients

BackgroundIn esophageal cancer (EC) patients who are not eligible for surgery, definitive chemoradiation (dCRT) with curative intent using cisplatinum with 5-fluorouracil (5-FU) is the standard chemotherapy regimen. Nowadays carboplatin/paclitaxel is also often used. In this study, we compared survival and toxicity rates between both regimens.Patients and methodsThis multicenter study included 102 patients treated in five centers in the Northeast Netherlands from 1996 till 2008. Forty-seven patients received cisplatinum/5-FU (75 mg/m² and 1 g/m²) and 55 patients carboplatin/paclitaxel (AUC2 and 50 mg/m²).ResultsOverall survival (OS) was not different between the cisplatinum/5-FU and carboplatin/paclitaxel group {[P = 0.879, hazard ratio (HR) 0.97 [confidence interval (CI) 0.62–1.51]}, with a median survival of 16.1 (CI 11.8–20.5) and 13.8 months (CI 10.8–16.9). Median disease-free survival (DFS) was comparable [P = 0.760, HR 0.93 (CI 0.60–1.45)] between the cisplatinum/5-FU group [11.1 months (CI 6.9–15.3)] and the carboplatin/paclitaxel group [9.7 months (CI 5.1–14.4)]. Groups were comparable except clinical T stage was higher in the carboplatin/paclitaxel group (P = 0.008). High clinical T stage (cT4) was not related to OS and DFS in a univariate analysis (P = 0.250 and P = 0.201). A higher percentage of patients completed the carboplatin/paclitaxel regimen (82% versus 57%, P = 0.010). Hematological and nonhematological toxicity (≥grade 3) in the carboplatin/paclitaxel group (4% and 18%) was significantly lower than in the cisplatinum/5-FU (19% and 38%, P = 0.001).ConclusionsIn this study, we showed comparable outcome, in terms of DFS and OS for carboplatin/paclitaxel compared with cisplatinum/5-FU as dCRT treatment in EC patients. Toxicity rates were lower in the carboplatin/paclitaxel group together with higher treatment compliance. Carboplatin/paclitaxel as an alternative treatment of cisplatinum/5-FU is a good candidate regimen for further evaluation.     

Survival analysis of carboplatin added to an anthracycline/taxane-based neoadjuvant chemotherapy and HRD score as predictor of response—final results from GeparSixto

BackgroundIn the neoadjuvant GeparSixto study, adding carboplatin to taxane- and anthracycline-based chemotherapy improved pathological complete response (pCR) rates in patients with triple-negative breast cancer (TNBC). Here, we present survival data and the potential prognostic and predictive role of homologous recombination deficiency (HRD).Patients and methodsPatients were randomized to paclitaxel plus nonpegylated liposomal doxorubicin (Myocet®) (PM) or PM plus carboplatin (PMCb). The secondary study end points disease-free survival (DFS) and overall survival (OS) were analyzed. Median follow-up was 47.3 months. HRD was among the exploratory analyses in GeparSixto and was successfully measured in formalin-fixed, paraffin-embedded tumor samples of 193/315 (61.3%) participants with TNBC. Homologous recombination (HR) deficiency was defined as HRD score ≥42 and/or presence of tumor BRCA mutations (tmBRCA).ResultsA significantly better DFS (hazard ratio 0.56, 95% CI 0.34–0.93; P = 0.022) was observed in patients with TNBC when treated with PMCb. The improvement of OS with PMCb was not statistically significant. Additional carboplatin did not improve DFS or OS in patients with HER2-positive tumors. HR deficiency was detected in 136 (70.5%) of 193 triple-negative tumors, of which 82 (60.3%) showed high HRD score without tmBRCA. HR deficiency independently predicted pCR (ypT0 ypN0) [odds ratio (OR) 2.60, 95% CI 1.26–5.37, P = 0.008]. Adding carboplatin to PM significantly increased the pCR rate from 33.9% to 63.5% in HR deficient tumors (P = 0.001), but only marginally in HR nondeficient tumors (from 20.0% to 29.6%, P = 0.540; test for interaction P = 0.327). pCR rates with carboplatin were also higher (63.2%) than without carboplatin (31.7%; OR 3.69, 1.46–9.37, P = 0.005) in patients with high HRD score but no tmBRCA. DFS rates were improved with addition of carboplatin, both in HR nondeficient (hazard ratio 0.44, 0.17–1.17, P = 0.086) and HR deficient tumors (hazard ratio 0.49, 0.23–1.04, P = 0.059).ConclusionsThe addition of carboplatin to neoadjuvant PM improved DFS significantly in TNBC. Long-term survival analyses support the neoadjuvant use of carboplatin in TNBC. HR deficiency in TNBC and HRD score in non-tmBRCA TNBC are predictors of response. HRD does not predict for carboplatin benefit.     

FDA Approval Summary: Atezolizumab and Durvalumab in Combination with Platinum-Based Chemotherapy in Extensive Stage Small Cell Lung Cancer

The U.S. Food and Drug Administration (FDA) granted approval to atezolizumab and durvalumab in March of 2019 and 2020, respectively, for use in combination with chemotherapy for first‐line treatment of patients with extensive stage small cell lung cancer. These approvals were based on data from two randomized controlled trials, IMpower133 (atezolizumab) and CASPIAN (durvalumab). Both trials demonstrated an improvement in overall survival (OS) with anti–programmed death ligand 1 antibodies when added to platinum‐based chemotherapy as compared with chemotherapy alone. In IMpower133, patients receiving atezolizumab with etoposide and carboplatin demonstrated improved OS (hazard ratio [HR], 0.70; 95% confidence interval [CI], 0.54–0.91; p = .0069), with median OS of 12.3 months compared with 10.3 months in patients receiving etoposide and carboplatin. In CASPIAN, patients receiving durvalumab with etoposide and either cisplatin or carboplatin also demonstrated improved OS (HR, 0.73; 95% CI, 0.59–0.91; p = .0047) with median OS of 13.0 months compared with 10.3 months in patients receiving etoposide and either cisplatin or carboplatin. The safety profiles of both drugs were generally consistent with known toxicities of immune‐checkpoint inhibitor therapies. This review summarizes the FDA perspective and data supporting the approval of these two agents.Implications for PracticeEffective therapeutic options for small cell lung cancer (SCLC) are limited, and there has been modest improvement in the overall survival (OS) of patients with SCLC over the past 3 decades. The approvals of atezolizumab and of durvalumab in combination with chemotherapy for first‐line treatment of patients with extensive stage SCLC represent the first approved therapies with OS benefit for this patient population since the approval of etoposide in combination with other approved chemotherapeutic agents. Additionally, the efficacy results from IMpower133 and CASPIAN lay the groundwork for possible further evaluation in other treatment settings in this disease.     

Stereotactic radiofrequency ablation as first-line treatment of recurrent HCC following hepatic resection

BackgroundTo evaluate the therapeutic efficacy, safety and overall clinical outcome of multiprobe stereotactic RF ablation (SRFA) as first-line treatment of HCC recurrence after hepatic resection (HR).Study designIn this retrospective single-center study, 34 consecutive patients with previous HR were treated by SRFA between 2006 and 2018 for 140 HCCs in 60 ablation sessions.ResultsThe median treated tumor size was 3.0 cm (range 0.5–10 cm). SRFA was primarily successful for 133/140 (95%) tumors. Four tumors were successfully retreated, resulting in a secondary technical efficacy rate of 97.9%. Local tumor recurrence developed in 4 of 140 tumors (2.9%). The major complication rate was 4.8% (3 of 60 ablations). No periprocedural deaths occurred.The overall survival (OS) rates at 1-, 3-, and 5- years from the date of the first SRFA were 94.0%, 70.2%, and 53.3%, respectively, with a median OS of 69.1 months (95% CI 18.8–119.3). The disease-free survival (DFS) was 52.6%, 19.7% and 15.8%, at 1-, 3- and 5- years, respectively, with a median DFS of 12.8 months (95% CI 9.0–28.9).ConclusionStereotactic RFA is a safe, feasible and useful option in the management of recurrent HCC following HR with low morbidity paired with good clinical outcome.     

Prognostic Significance of Total Lymphocyte Count,Neutrophil-to-lymphocyte Ratio,and Platelet-to-lymphocyte Ratio in Limited-stage Small-cell Lung Cancer

BackgroundWe sought reliable markers of survival and disease control among patients treated for limited-stage small-cell lung cancer (LS-SCLC).Patients and MethodsSubjects were 122 patients given (chemo)radiotherapy for LS-SCLC at MD Anderson in 2002 through 2015. Pretreatment total lymphocyte count (TLC), neutrophil-to-lymphocyte ratio (NLR), and platelet-to-lymphocyte ratio (PLR) were analyzed for associations with overall (OS) and progression-free survival. Optimal cutoff values were identified with receiver operating characteristic curves and survival probabilities with the Kaplan-Meier method.ResultsPretreatment TLC was 1.86 × 10³/μL (±0.88); NLR, 3.44 (±3.69); and PLR, 170.53 (±101.56); corresponding cutoffs were 1.9, 2.9, and 140.1. Higher TLC was associated with superior median and 2-year OS (17.4 vs. 15.7 months and 33% vs. 29%; P = .029), and higher NLR and PLR with worse median and 2-year OS (NLR: 14.9 vs. 17.8 months, 29% vs. 31%; P = .026; PLR: 14.8 vs. 18.9 months, 24% vs. 37%; P = .009). Multivariate Cox regression adjusted for age, disease stage, number of chemotherapy cycles, and use of prophylactic cranial irradiation confirmed the links between high TLC and superior OS (hazard ratio [HR] 0.55; 95% confidence interval [CI], 0.32-0.94; P = .028) and between high NLR and PLR and inferior OS (NLR: HR, 1.86; 95% CI, 1.15-3.01; P = .011; PLR: HR, 1.72; 95% CI, 1.06-2.82; P = .030).ConclusionsBaseline lymphopenia was an indicator of poor prognosis in patients with LS-SCLC.     

Randomized phase III trial of prophylactic cranial irradiation versus observation in patients with fully resected stage IIIA–N2 nonsmall-cell lung cancer and high risk of cerebral metastases after adjuvant chemotherapy

This prospective, randomized, phase III trial shows that prophylactic cranial irradiation prolongs disease-free survival, decreases the rate of cerebral metastases and does not affect quality-of-life for patients with fully resected postoperative pathologically confirmed stage IIIA-N2 non-small-cell lung cancer and high risk of cerebral metastases after adjuvant chemotherapy.BackgroundThis study compared prophylactic cranial irradiation (PCI) with observation in patients with resected stage IIIA–N2 non-small-cell lung cancer (NSCLC) and high risk of cerebral metastases after adjuvant chemotherapy.Patients and methodsIn this open-label, randomized, phase III trial, patients with fully resected postoperative pathologically confirmed stage IIIA–N2 NSCLC and high cerebral metastases risk without recurrence after postoperative adjuvant chemotherapy were randomly assigned to receive PCI (30 Gy in 10 fractions) or observation. The primary end point was disease-free survival (DFS). The secondary end points included the incidence of brain metastases, overall survival (OS), toxicity and quality of life.ResultsThis trial was terminated early after the random assignment of 156 patients (81 to PCI group and 75 to control group). The PCI group had significantly lengthened DFS compared with the control group, with a median DFS of 28.5 months versus 21.2 months [hazard ratio (HR), 0.67; 95% confidence interval (CI) 0.46–0.98;P = 0.037]. PCI was associated with a decrease in risk of brain metastases (the actuarial 5-year brain metastases rate, 20.3% versus 49.9%; HR, 0.28; 95% CI 0.14–0.57;P < 0.001). The median OS was 31.2 months in the PCI group and 27.4 months in the control group (HR, 0.81; 95% CI 0.56–1.16;P = 0.310). While main toxicities were headache, nausea/vomiting and fatigue in the PCI group, they were generally mild.ConclusionIn patients with fully resected postoperative pathologically confirmed stage IIIA–N2 NSCLC and high risk of cerebral metastases after adjuvant chemotherapy, PCI prolongs DFS and decreases the incidence of brain metastases.     

Disease-free and overall survival at 3.5 years for neoadjuvant bevacizumab added to docetaxel followed by fluorouracil,epirubicin and cyclophosphamide,for women with HER2 negative early breast cancer: ARTemis Trial

BackgroundThe ARTemis trial previously reported that addition of neoadjuvant bevacizumab (Bev) to docetaxel (D) followed by fluorouracil, epirubicin and cyclophosphamide (D-FEC) in HER2 negative breast cancer improved the pathological complete response (pCR) rate. We present disease-free survival (DFS) and overall survival (OS) with central pathology review.Patients and methodsPatients were randomized to 3 cycles of D followed by 3 cycles of FEC (D-FEC), ±4 cycles of Bev (Bev + D-FEC). DFS and OS were analyzed by treatment and by central pathology reviewed pCR and Residual Cancer Burden (RCB) class.ResultsA total of 800 patients were randomized [median follow-up 3.5 years (IQR 3.2–4.4)]. DFS and OS were similar across treatment arms [DFS hazard ratio (HR)=1.18 (95% CI 0.89–1.57), P = 0.25; OS HR = 1.26 (95% CI 0.90–1.76), P = 0.19). Both local pathology report review and central histopathology review confirmed a significant improvement in DFS and OS for patients who achieved a pCR [DFS HR = 0.38 (95% CI 0.23–0.63), P < 0.001; OS HR = 0.43 (95% CI 0.24–0.75), P = 0.003]. However, significant heterogeneity was observed (P = 0.02); larger improvements in DFS were obtained with a pCR achieved with D-FEC than a pCR achieved with Bev + D-FEC. As RCB class increased, significantly worse DFS and OS was observed (P for trend <0.0001), which effect was most marked in the ER negative group.ConclusionsThe addition of short course neoadjuvant Bev to standard chemotherapy did not demonstrate a DFS or OS benefit. Achieving a pCR with D-FEC is associated with improved DFS and OS but not when pCR is achieved with Bev + D-FEC. At the present time therefore, Bev is not recommended in early breast cancer.ClinicalTrials.gov numberNCT01093235.