Number of negative lymph nodes should be considered for incorporation into staging for breast cancer

This study aimed to investigate the prognostic value of the number of involved lymph nodes (pN), number of removed lymph nodes (RLNs), lymph node ratio (LNR), number of negative lymph nodes (NLNs), and log odds of positive lymph nodes (LODDS) in breast cancer patients. The records of 2,515 breast cancer patients who received a mastectomy or breast-conserving surgery were retrospectively reviewed. The log-rank test was used to compare survival curves, and Cox regression analysis was performed to identify prognostic factors. The median follow-up time was 64.2 months, and the 8-year disease-free survival (DFS) and overall survival (OS) were 74.6% and 82.3%, respectively. Univariate analysis showed that pN stage, LNR, number of RLNs, and number of NLNs were significant prognostic factors for DFS and OS (all, P < 0.05). LODDS was a significant prognostic factor for OS (P = 0.021). Multivariate analysis indicated that pN stage and the number of NLNs were independent prognostic factors for DFS and OS. A higher number of NLNs was associated with higher DFS and OS, and a higher number of involved lymph nodes were associated with poorer DFS and OS. Patients with a NLNs count > 9 had better survival (P < 0.001). Subgroup analysis showed that the NLNs count had a prognostic value in patients with different pT stages and different lymph node status (log-rank P < 0.05). For breast cancer, pN stage and NLNs count have a better prognostic value compared to the RLNs count, LNR, and LODDS. Number of negative lymph nodes should be considered for incorporation into staging for breast cancer.     

Role of Postoperative Radiotherapy After Curative Resection and Adjuvant Chemotherapy for Patients With Pathological Stage N2 Non–Small-Cell Lung Cancer: A Propensity Score Matching Analysis

BackgroundThe objective of this study was to evaluate the role of postoperative radiotherapy (PORT) in the setting of adjuvant chemotherapy for pathological stage N2 (pN2) non–small-cell lung cancer (NSCLC).Materials and MethodsA retrospective review of 219 consecutive pN2 NSCLC patients who underwent curative surgery followed by adjuvant chemotherapy was performed. Forty-one patients additionally received PORT. Propensity scores for PORT receipt were individually calculated and used for matching to compare the outcome between patients who did (+) and did not (-) receive PORT. One hundred eleven patients in the PORT (-) group and 38 patients in PORT (+) group were matched. Clinical and pathologic characteristics were well-balanced.ResultsThe median follow-up duration was 48 months. In the matched patients, PORT resulted in a significantly lower crude locoregional relapse (43.2% vs. 23.7%; P = .032). Also, PORT was associated with improved locoregional control (LRC) rate (5-year LRC 63.7% vs. 48.6%; P = .036), but not distant metastasis-free survival, disease-free survival (DFS), and overall survival. An exploratory subgroup analysis suggested a potential DFS benefit of PORT in patients with multiple station mediastinal lymph node metastases (5-year DFS, 43.2% vs. 16.6%; P = .037) and squamous cell carcinoma histology (5-year DFS, 70.1% vs. 23.3%; P = .011).ConclusionsEven in the setting of adjuvant chemotherapy, PORT significantly increased LRC for patients with curatively resected pN2 NSCLC. Some subgroups appear to benefit from PORT in terms of DFS and LRC. Individualized strategies based on risk factors might be considered.     

Systematic review and meta-analysis of long-term oncological outcomes of lateral lymph node dissection for metastatic nodes after neoadjuvant chemoradiotherapy in rectal cancer

BackgroundStandard Western management of rectal cancers with pre-treatment metastatic lateral lymph nodes (LLNs) is neoadjuvant (chemo)radiotherapy (nCRT) followed by total mesorectal excision (TME). In recent years, there is growing interest in performing an additional lateral lymph node dissection (LLND). The aim of this systematic review and meta-analysis was to investigate long-term oncological outcomes of nCRT followed by TME with or without LLND in patients with pre-treatment metastatic LLNs.MethodsPubMed, Ovid MEDLINE, Embase, Cochrane Library and Clinicaltrials.gov were searched to identify comparative studies reporting long-term oncological outcomes in pre-treatment metastatic LLNs of nCRT followed by TME and LLND (LLND+) vs. nCRT followed by TME only (LLND-). Newcastle-Ottawa risk-of-bias scale was used. Outcomes of interest included local recurrence (LR), disease-free survival (DFS), and overall survival (OS). Summary meta-analysis of aggregate outcomes was performed.ResultsSeven studies, including 946 patients, were analysed. One (1/7) study was of good-quality after risk-of-bias analysis. Five-year LR rates after LLND+ were reduced (range 3–15%) compared to LLND- (11–27%; RR = 0.40, 95%CI [0.25–0.62], p < 0.0001). Five-year DFS was not significantly different after LLND+ (range 61–78% vs. 46–79% for LLND-; RR = 0.72, 95%CI [0.51–1.02], p = 0.143), and neither was five-year OS (range 69–91% vs. 72–80%; RR = 0.72, 95%CI [0.45–1.14], p = 0.163).ConclusionIn rectal cancers with pre-treatment metastatic LLNs, nCRT followed by an additional LLND during TME reduces local recurrence risk, but does not impact disease-free or overall survival. Due to the low quality of current data, large prospective studies will be required to further determine the value of LLND.     

The impact of radiological retroperitoneal lymphadenopathy on survival after cytoreductive surgery and hyperthermic intraperitoneal chemotherapy for colorectal peritoneal metastases

ObjectivesTo investigate the impact of retroperitoneal lymphadenopathy (RPLP) on pre-operative CT scan on overall survival (OS) and disease-free survival (DFS) after cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS-HIPEC) for peritoneal metastases (PM) of colorectal cancer.BackgroundIn patients with PM enlarged retroperitoneal lymph nodes (RPLP) are usually considered extra-regional lymph node metastases and therefore these patients may be excluded from CRS-HIPEC. This is a clinical dilemma since it is often hard to obtain histology from these nodes.MethodsIn this multicenter, retrospective study all consecutive patients with colorectal PM treated with CRS-HIPEC between 2004 and 2013 were included. The preoperative CT-scan was re-analyzed for the presence of RPLP based on the radiological appearance of enlarged lymph nodes. Outcomes were OS and DFS. Kaplan-Meier methods and Cox regression modeling were used to analyze the impact of RPLP on OS and DFS.ResultsIn 25 of 401 patients (6.1%) RPLP was observed on the preoperative CT-scan. Patient, tumor and surgical characteristics did not statistically significantly differ between groups with and without RPLP. After a median follow-up of 46 months, the one-, three- and five-year survival was 80%, 59%, 38% and 90%, 50%, 36% in the group with and without RPLP respectively. Median OS (47 vs. 35 months, logrank: p = 0.70) and median DFS (14 vs. 15 months, logrank: p = 0.81) did not statistically significantly differ between groups. In multivariable analysis, RPLP did not significantly influence survival.ConclusionEnlarged retroperitoneal lymph nodes on a pre-operative CT-scan should not automatically exclude patients from CRS-HIPEC.     

Promoter methylation of BRCA1 in triple-negative breast cancer predicts sensitivity to adjuvant chemotherapy

BackgroundBRCA1 function is inactivated through BRCA1 promoter methylation in a substantial number of triple-negative breast cancers. We investigated the impact of BRCA1-methylation status on the efficacy of adjuvant chemotherapy in patients with triple-negative breast cancer or with non-triple-negative breast cancer.MethodsBRCA1 promoter methylation was assessed in 1163 unselected breast cancer patients. Methylation was evaluated using a methylation-specific PCR (MSP) assay.ResultsIn the subgroup of 167 triple-negative breast cancer patients who received adjuvant chemotherapy, patients with BRCA1-methylated tumors had a superior 10-year disease-free survival (DFS)(78% versus 55%, P = 0.009) and 10-year disease-specific survival (DSS) (85% versus 69%, P = 0.024) than those with BRCA1-unmethylated tumors, and BRCA1 methylation was an independent favorable predictor of DFS and DSS in a multivariate analysis in this subgroup [DFS: hazard ratio (HR) = 0.45; 95% confidence interval (CI) 0.24–0.84; P = 0.019; DSS: HR = 0.43; 95% CI = 0.19–0.95; P = 0.044]. In contrast, in 675 non-triple-negative breast cancer patients who received adjuvant chemotherapy, BRCA1 methylation was an unfavorable predictor of DFS and DSS in univariate analysis (DFS: HR = 1.56; 95% CI 1.16–2.12; P = 0.003; DSS: HR = 1.53; 95% CI = 1.05–2.21; P = 0.026).ConclusionsTriple-negative breast cancer patients with BRCA1-methylated tumors are sensitive to adjuvant chemotherapy and have a favorable survival compared with patients with BRCA1-unmethylated triple-negative tumors.     

The impact of lymph node dissection and adjuvant chemotherapy on survival: A nationwide cohort study of patients with clinical early-stage ovarian cancer

IntroductionTo establish the impact of lymph node dissection and chemotherapy on survival in patients with early-stage epithelial ovarian cancer (EOC).MethodsAll Dutch patients with International Federation of Gynaecology and Obstetrics (FIGO) stage I–IIA and IIIA1 EOC between 2000 and 2012 were included. Data concerning age, stage, tumour grade, histological subtype, hospital type, lymph node dissection, adjuvant chemotherapy and survival were extracted from the Netherlands Cancer Registry.ResultsOf 3658 patients included, 1813 (49.6%) had lymph nodes removed. Relative survival of patients with lymph node dissection (including those with lymph node metastases) was significantly better than that of patients without, also after correcting for stage, tumour grade, histology and age (89% and 82%, respectively; relative excess risk [RER], 0.64; 95% confidence interval [CI]: 0.52–0.78). There was a positive correlation between the number of removed lymph nodes and overall survival (after excluding patients with lymph node metastases). Of patients with stage I–IIA EOC who had ≥10 lymph nodes removed, there was no difference in relative survival between those who received chemotherapy and those who did not (RER, 0.51; 95% CI: 0.15–1.64). This was also true for a subgroup of patients with high-risk features (stage IC and IIA and/or tumour grade 3 and/or clear cell histology [RER, 0.90; 95% CI: 0.46–1.99]).ConclusionAdequate dissection of at least 10 but preferably ≥20 lymph nodes should be standard procedure for the staging of early-stage EOC. Adjuvant chemotherapy after an adequate lymph node dissection does not seem to contribute to a better relative survival.     

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.     

Long-term Outcomes of Local and Metastatic Small Cell Carcinoma of the Urinary Bladder and Genomic Analysis of Patients Treated With Neoadjuvant Chemotherapy

IntroductionSmall cell carcinoma of the bladder (SCCB) is a rare variant of bladder cancer with poor outcomes. We evaluated long-term outcomes of nonmetastatic (M0) and metastatic (M1) SCCB and correlated pathologic response with genomic alterations of patients treated with neoadjuvant chemotherapy (NAC).Patients and MethodsClinical history and pathology samples from SCCB patients diagnosed at our institution were reviewed.ResultsOne hundred and ninety-nine SCCB patients were identified. (M0: 147 [74%]; M1: 52 [26%]). Among M0 patients, 108 underwent radical cystectomy (RC) (NAC: 71; RC only: 23; adjuvant chemotherapy: 14); 14 received chemoradiotherapy; the rest received chemotherapy alone or no cancer-directed therapy. RC-only patients had a median follow-up of 9.1 years, and median disease-free survival (DFS) and overall survival (OS) were 1.1 and 1.2 years, respectively. NAC patients had pathologic response (<pT2pN0) and pathologic complete response (pT0pN0) rates of 48% and 38%, respectively, with median follow-up of 7.2 years, and median DFS and OS of 5.6 and 14.5 years, respectively. NAC responders (<ypT2N0) had superior median DFS (14.5 vs. 0.6 years, hazard ratio [HR] 0.24, P< .001) and OS (14.5 vs. 2.5 years, HR 0.31, P = .002). DFS rates for responders and nonresponders were 76% and 27% at 5 years, and 71% and 23% at 10 years, respectively. Local and central nervous system recurrences were infrequent. Median progression-free survival (PFS) and OS for M1 disease were 6.9 and 10.3 months, respectively. Genomic profiling was performed on 47 NAC patients. Loss of ERCC2 function was significantly enriched among those with pathologic complete response to NAC (mutations present in 50% of pathologic complete responders vs. 15% nonresponders, P = .045).ConclusionM0 SCCB is chemo-sensitive and patients have excellent long-term survival following response to NAC. Patients with M1 disease have poor survival despite systemic therapy. Loss-of-function mutations of ERCC2 were associated with pathologic complete response to NAC.     

Effect of adjuvant chemotherapy in postmenopausal patients with invasive ductal versus lobular breast cancer

BackgroundOn the basis of the lack of response of invasive lobular breast cancer to neoadjuvant chemotherapy, we questioned the effectiveness of adjuvant chemotherapy in relation to histology.Patients and methodsWomen with primary nonmetastatic invasive ductal or (mixed type) lobular breast cancer, aged 50–70 years, diagnosed between 1995 and 2008, were selected from the Netherlands Cancer Registry and followed until January 1, 2010. The patients were divided in two groups: one group receiving adjuvant hormonal therapy only and the other receiving adjuvant hormonal therapy in combination with adjuvant chemotherapy.ResultsIn total, 19 609 patients had ductal cancer and 3685 had lobular cancer. The 10-year overall survival rate in ductal cancer when treated with hormonal therapy alone was 69%, compared with 74% with the combination therapy (P < 0.0001). In lobular cancer, 10-year survival rates were 68% after hormonal treatment alone and 66% after the combination therapy (P = 0.45). The hazard ratio (HR) for mortality in ductal cancer after combination therapy was 0.70 [95% confidence interval (CI) 0.64–0.76; P < 0.0001], compared with hormonal treatment alone. The HR in lobular cancer was 1.00 (95% CI 0.82–1.21; P = 0.97).ConclusionAdjuvant chemotherapy seems to confer no additional beneficial effects in postmenopausal patients with pure or mixed type lobular breast cancer receiving hormonal therapy.     

Chronicle: results of a randomised phase III trial in locally advanced rectal cancer after neoadjuvant chemoradiation randomising postoperative adjuvant capecitabine plus oxaliplatin (XELOX) versus control

BackgroundIn stage III colon cancer, oxaliplatin/5-fluorouracil (5-FU)-based adjuvant chemotherapy (FOLFOX) improves disease-free survival (DFS) and overall survival (OS). In rectal adenocarcinoma following neoadjuvant chemoradiation (CRT), we examined the benefit of postoperative adjuvant capecitabine and oxaliplatin (XELOX) chemotherapy.MethodsEligible patients were randomly assigned following fluoropyrimidine-based CRT and curative resection to observation or six cycles of XELOX. The primary end point was DFS; secondary end points were acute toxicity and OS. 390 patients were required in each arm, to detect an improvement in 3-year DFS from 40% to 50.5%, with 85% power and two-sided 5% significance level.ResultsThe study closed prematurely in 2008 because of poor accrual. Only 113 patients were randomly assigned to either observation (n = 59) or XELOX (n = 54). Compliance was poor, 93% allocated chemotherapy started and 48% completed six cycles. Protocolised dose reductions in XELOX were 39%, and levels of G3/G4 toxicity 40%. After a median follow-up of 44.8 months, 16 patients (27%) in the observation arm had relapsed or died compared with 12 patients (22%) in XELOX. The 3-year DFS rate was 78% with XELOX and 71% with observation [hazard ratio (HR) for DFS = 0.80; 95% confidence interval (CI) 0.38–1.69; P = 0.56]. The 3-year OS for XELOX and observation were 89% and 88%, respectively (HR for OS = 1.18; 95% CI 0.43–3.26; P = 0.75).ConclusionsThe observed improvement in DFS for adjuvant XELOX and similar OS were not statistically significant, as expected given the small number of patients and consequent low power. Our findings support the need for trials that test the role of neoadjuvant chemotherapy.ClinicalTrials.gov IdentifierNCT00427713.     

Adjuvant Management of Pathologic Node–Positive Disease After Definitive Surgery for Clinical T1-2 N0 Rectal Cancer

Introduction

Patients with cT1-2N0M0 rectal cancer are often treated with up-front surgical resection, with adjuvant treatment reserved for patients upstaged with pathologic node-positive (pN+) disease at surgery. This study evaluates practice patterns and clinical outcomes when comparing different forms of adjuvant treatment for this patient population.

Outcomes of Patients With Breast Cancer Who Present With Ipsilateral Supraclavicular or Internal Mammary Lymph Node Metastases

BackgroundThe prognostic implications of internal mammary (IM) and supraclavicular (SC) node involvement in locally advanced breast cancer is still unclear.Patients and MethodsWe evaluated 107 patients with IM (n = 65) or SC (n = 42) node involvement who underwent operation at the European Institute of Oncology between 1997 and 2009 to assess their prognostic features. We subsequently analyzed matched cohorts, using the 107 patients as cases and another group of patients as a control cohort, to evaluate prognostic differences between patients with and those without IM or SC node involvement.ResultsFive-year disease-free survival (DFS) was 84% in IM vs. 38.8% in SC node involvement (P < .0001), and 5-year overall survival (OS) was 96.9% in IM node vs. 57.1% in SC node involvement (P < .0001). No difference in outcome was found between patients with and controls without IM node involvement. Conversely, a statistically significant difference in DFS and locoregional recurrence was observed in patients with SC node involvement compared with controls without SC node involvement.ConclusionSC node involvement correlated with a significantly poorer outcome in patients with locally advanced breast cancer. Adequate staging, including biopsy of suspicious locoregional ipsilateral lymph nodes, is mandatory in these patients. Patients with IM or SC node involvement should be treated with curative intent using combined-modality treatments.     

Increased adjuvant treatment and improved survival in elderly stage III colon cancer patients in The Netherlands

BackgroundWe determined to what extent patients with colon cancer stage III ≥ 75 years received adjuvant chemotherapy and the impact on overall and disease-specific survival.Patients and methodsData from The Netherlands Cancer Registry on all 8051 patients with colon cancer stage III ≥ 75 years diagnosed in 1997–2009 were included. Trends in adjuvant chemotherapy administration were analysed and multivariable overall and disease-specific survival analyses were performed.ResultsThe proportion of stage III colon cancer patients ≥ 75 years who received adjuvant chemotherapy increased from 12%in 1997–2000 to 23% in 2007–2009 (P < 0.0001), with a marked age gradient and large geographic variation. Five-year overall survival increased over time from 28% in 1997–2000 to 35% in 2004–2006 (P < 0.0001). Sixty percent of patients died of colorectal cancer. Adjuvant chemotherapy was the strongest positive predictor of survival in this retrospective study (hazard ratio = 0.5; 95% confidence interval: 0.4–0.5).ConclusionThere has been an increase in administration of adjuvant chemotherapy to elderly patients with stage III colon cancer in The Netherlands since 1997. Survival of elderly patients with stage III colon cancer increased over time, at least partly due to stage migration. The large effect of adjuvant chemotherapy on survival in this study is likely to be associated with the selection of fitter patients for adjuvant treatment.     

Association between the HER2 Ile655Val polymorphism and response to trastuzumab in women with operable primary breast cancer

BackgroundHuman epidermal growth factor receptor 2 (HER2) Ile655Val polymorphism may affect the efficacy of trastuzumab treatment of breast cancer.Patients and methodsHER2 Ile655Val polymorphism was determined in 4167 patients with primary breast cancer using a polymerase chain reaction–restriction fragment length polymorphism (PCR–RFLP) assay. We investigated the associations between the HER2 Ile655Val polymorphism and clinical outcomes in women with HER2-negative breast cancer and with HER2-positive breast cancer who received trastuzumab or who did not.ResultsAt a median follow-up of 44 months, HER2 Ile655Val polymorphism was not significantly associated with survival either in the entire study population of 4167 patients or in 2976 HER2-negative breast cancer patients. Among 816 HER2-positive patients who received adjuvant chemotherapy and/or endocrine therapy without trastuzumab treatment, patients with the Val/Ile or the Val/Val genotype had a significantly worse disease-free survival (DFS) and distant DFS (DDFS) than those with the Ile/Ile genotype (DFS, adjusted hazard ratio [HR] 1.5; 95% confidence interval [CI] 1.0–2.3; P = 0.037; DDFS, adjusted HR 1.9; 95% CI 1.2–2.9 P = 0.005). In contrast, among 212 HER2-positive patients who received chemotherapy in combination with trastuzumab treatment, patients with the Val/Ile or the Val/Val genotype had a significantly better DFS and DDFS than those with the Ile/Ile genotype (5-year DFS, 100% versus 83%; P = 0.008; 5-year DDFS, 100% versus 89%; P = 0.031).ConclusionsHER2 Ile655Val polymorphism affects the function of HER2 gene only restricted in HER2-positive breast cancers. HER2-positive breast cancer patients with the Val variant have an aggressive phenotype, but are sensitive to trastuzumab treatment.     

The Impact of Age and Adjuvant Chemotherapy Modifications on Survival Among Black Women With Breast Cancer

BackgroundBlack women receive less relative dose intensity with more dose reductions and early chemotherapy cessation compared with White women. Adding further risk, older patients with breast cancer are most at risk for treatment modifications; however, it is unclear if this remains true for Black patients. Furthermore, the clinical implications of treatment modifications and delays on survival is uncertain, particularly in Black patients.Patients and MethodsThe purpose was to investigate whether age was a moderator for the association between treatment modifications (dose held, dose delayed, and early cessation) and overall survival and disease-free survival (DFS) in Black women with breast cancer using a retrospective cohort study of patients with early stage breast cancer treated with adjuvant chemotherapy.ResultsAcross the entire sample (n = 115), 37.4% (n = 43) of patients experienced a treatment modification. There was a significant interaction between age group and held dose for DFS (P = .026). Specifically, those diagnosed at 55 years of age and older, who had doses of chemotherapy held, experienced worse DFS compared with those who did not (hazard ratio, 4.185; 95% confidence interval, 1.187-14.75). In contrast, there was no difference in DFS between those who did and did not have doses held in patients diagnosed below 55 years of age (hazard ratio, 0.626; 95% confidence interval, 0.177-2.218).ConclusionIn this study, Black women receiving adjuvant chemotherapy for treatment of early stage breast cancer had roughly equal treatment modifications across age groups. However, held doses of chemotherapy in older Black patients were associated with worse DFS. Age may impact clinical outcomes seen with adjuvant chemotherapy treatment modifications.     

Effect of Coexisting KRAS and TP53 Mutations in Patients Treated With Chemotherapy for Non–small-cell Lung Cancer

BackgroundKRAS and TP53 are common mutations in non–small-cell lung cancer (NSCLC). The Lung Adjuvant Cisplatin Evaluation Biological Program group found adjuvant chemotherapy to be deleterious in patients with coexisting KRAS/TP53 mutations.Patients and MethodsTo validate these results, patients with NSCLC tested for KRAS and TP53 mutations and receiving chemotherapy for any stage NSCLC were selected. Mutation status was analyzed using next generation sequencing (Illumina) or multiplex recurrent mutation detection (MassARRAY, Agena Biosciences) assays, and was correlated with clinical and demographic data. Disease-free (DFS) or progression-free survival (PFS) was the main endpoint, and overall survival (OS) was the secondary endpoint.ResultsAmong 218 patients, 28 had coexisting KRAS/TP53 mutations, 77 TP53, 37 KRAS, 76 had neither KRAS nor TP53 mutation (WT/WT). There was no DFS/PFS difference for the KRAS/TP53 group versus all others among 99 patients who received adjuvant chemotherapy (hazard ratio [HR], 1.22; 95% confidence interval [CI], 0.61-2.44; P = .57), 27 stage III patients who received chemo-radiation (HR, 0.87; 95% CI, 0.32-2.38; P = .8), and 63 patients who received palliative chemotherapy (HR, 0.68; 95% CI, 0.31-1.48; P = .33). OS was longer in the WT/WT group compared with any other group (KRAS: HR, 1.87; 95% CI, 1.02-3.43; P = .043; TP53: HR, 2.17; 95% CI, 1.3-3.61; P = .0028; KRAS/TP53: HR, 2.06; 95% CI, 1.09-3.88; P = .026). No OS difference was seen for KRAS/TP53 compared with the other groups (HR, 1.26; 95% CI, 0.75-2.13; P = .38).ConclusionsThere was no significant difference in DFS/PFS between the 4 groups. However, OS was longer for patients with TP53 and KRAS wild-type NSCLC who received chemotherapy for any stage compared with patients with KRAS, TP53 mutation, or double mutant tumors.     

Differential efficacy of three cycles of CMF followed by tamoxifen in patients with ER-positive and ER-negative tumors: Long-term follow up on IBCSG Trial IX

BackgroundThe benefit of adjuvant chemotherapy in postmenopausal patients with estrogen receptor (ER)-positive lymph node-negative breast cancer is being reassessed.Patients and methodsAfter stratification by ER status, 1669 postmenopausal patients with operable lymph node-negative breast cancer were randomly assigned to three 28-day courses of ‘classical’ CMF (cyclophosphamide, methotrexate, 5-fluorouracil) chemotherapy followed by tamoxifen for 57 months (CMF→tamoxifen) or to tamoxifen alone for 5 years.ResultsERs were positive in 81% of tumors. At a median follow-up of 13.1 years, patients with ER-positive breast cancers did not benefit from CMF [13-year disease-free survival (DFS) 64% CMF→tamoxifen, 66% tamoxifen; P = 0.99], whereas CMF substantially improved the prognosis of patients with ER-negative breast cancer (13-year DFS 73% versus 57%, P = 0.001). Similarly, breast cancer-free interval (BCFI) was identical in the ER-positive cohort but significantly improved by chemotherapy in the ER-negative cohort (13-year BCFI 80% versus 63%, P = 0.001). CMF had no influence on second nonbreast malignancies or deaths from other causes.ConclusionCMF is not beneficial in postmenopausal patients with node-negative ER-positive breast cancer but is highly effective within the ER-negative cohort. In the future, other markers of chemotherapy response may define a subset of patients with ER-positive tumors who may benefit from adjuvant chemotherapy.     

Epidermal Growth Factor Receptor Mutation Status and Adjuvant Chemotherapy in Resected Advanced Non–Small-Cell Lung Cancer

IntroductionThis study was to assess the association of epidermal growth factor receptor (EGFR) mutation status and efficacy of adjuvant chemotherapy in patients with fully resected IIIA-N2 non–small-cell lung cancer (NSCLC).Materials and MethodsTumor samples (n = 150) from patients with IIIA-N2 NSCLC who either had or had not received paclitaxel plus carboplatin or vinorelbine plus carboplatin doublet adjuvant chemotherapy were analyzed for EGFR mutations. The association of the presence of EGFR mutations and survival was assessed.ResultsMutations were identified in 43 (28.7%) patients (n = 25 in the no chemotherapy [observation] arm and n = 18 in the chemotherapy arm). Patients with EGFR mutations had statistically significant improved disease-free survival (41 months [95% CI, 25.1-56.9 months] vs. 20 months [95% CI, 15.0-25.0 months]; 2P = .005) and overall survival (50 months [95% CI, 37.6-62.4 months] vs. 25 months [95% CI, 20.8-29.2 months]; 2P = .001), regardless of treatment. The patients with wild-type EGFR had greater overall survival with chemotherapy compared with no adjuvant therapy (hazard ratio [HR] 4.748 [95% CI, 2.844-7.928]; 2P < .001). In contrast, in patients with EGFR mutation in the observation group compared with the chemotherapy group had longer median disease-free survival (49 months [95% CI, 35.1-62.9 months] for the observation arm vs. 30 months [95% CI, 23.8-36.2 months] for the chemotherapy arm, 2P = .195) and overall survival (59 months [95% CI, 43.9-74.1 months] vs. 33 months [95% CI, 24.7-41.3 months]; 2P = .050).ConclusionsIn this exploratory study, the status of EGFR mutations was associated with different clinical outcomes in patients with resected IIIA-N2 NSCLC. Further studies are required to confirm that a patient's adjuvant treatment may be customized to their EGFR mutational status.     

A multicenter phase III prospective randomized trial of high-dose epirubicin in combination with cyclophosphamide (EC) versus docetaxel followed by EC in node-positive breast cancer. GOIM (Gruppo Oncologico Italia Meridionale) 9902 study

BackgroundThe Gruppo Oncologico Italia Meridionale 9902 trial compared four cycles of high-dose epirubicin plus cyclophosphamide (EC) with four cycles of docetaxel (Taxotere, D) followed by four cycles of EC as adjuvant treatment of node-positive breast cancer.Patients and methodsPatients were randomly assigned to EC (E 120 mg/m², C 600 mg/m², arm A) for four cycles or four cycles of D (100 mg/m²) followed by four cycles of EC (arm B), both regimens every 21 days. Hormone receptor-positive patients were given hormonal therapy for 5 years. Primary end point was 5-year disease-free survival (DFS). Secondary objectives were overall survival (OS) and safety.ResultsThere were 750 patients enrolled. With a median follow-up of 64 months, 5-year DFS was 73.4% in both arms, and 5-year OS was 89.5% versus 90.7% in arm A and B [hazard ratio was 0.99 (95% confidence interval for DFS 0.75–1.31; P = 0.95)], respectively. Grade 3–4 toxicity was more common in arm B.ConclusionsThis study did not show advantages from the addition of docetaxel to high-dose EC as adjuvant chemotherapy in node-positive breast cancer. The small sample size and low number of DFS events may have limited the ability to observe statistically significant difference between the two arms.     

The Prognostic Significance of the Lymph Node Ratio in Axillary Lymph Node Positive Breast Cancer

Purpose

This study evaluated the prognostic impact of the lymph node ratio (LNR; i.e., the ratio of positive to dissected lymph nodes) on recurrence and survival in breast cancer patients with positive axillary lymph nodes (LNs).

Methods

The study cohort was comprised of 330 breast cancer patients with positive axillary nodes who received postoperative radiotherapy between 1987 and 2004. Ten-year Kaplan-Meier locoregional failure, distant metastasis, disease-free survival (DFS) and disease-specific survival (DSS) rates were compared using Kaplan-Meier curves. The prognostic significance of the LNR was evaluated by multivariate analysis.

Results

Median follow-up was 7.5 years. By minimum p-value approach, 0.25 and 0.55 were the cutoff values of LNR at which most significant difference in DFS and DSS was observed. The DFS and DSS rates correlated significantly with tumor size, pN classification, LNR, histologic grade, lymphovascular invasion, the status of estrogen receptor and progesterone receptor. The LNR based classification yielded a statistically larger separation of the DFS curves than pN classification. In multivariate analysis, histologic grade and pN classification were significant prognostic factors for DFS and DSS. However, when the LNR was included as a covariate in the model, the LNR was highly significant (p<0.0001), and pN classification was not statistically significant (p>0.05).

Conclusion

The LNR predicts recurrence and survival more accurately than pN classification in our study. The pN classification and LNR should be considered together in risk estimates for axillary LNs positive breast cancer patients.