Level of evidence used in recommendations by the National Comprehensive Cancer Network (NCCN) guidelines beyond Food and Drug Administration approvals

BackgroundA previous analysis of 113 National Comprehensive Cancer Network® (NCCN®) recommendations reported that NCCN frequently recommends beyond Food and Drug Administration (FDA)-approved indications (44 off-label recommendations) and claimed that the evidence for these recommendations was weak.MethodsIn order to determine the strength of the evidence, we carried out an in-depth re-analysis of the 44 off-label recommendations listed in the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®).ResultsOf the 44 off-label recommendations, 14 were later approved by the FDA and/or are supported by randomized controlled trial (RCT) data. In addition, 13 recommendations were either very minor extrapolations from the FDA label (n = 8) or were actually on-label (n = 5). Of the 17 remaining extrapolations, 8 were for mechanism-based agents applied in rare cancers or subsets with few available treatment options (median response rate = 43%), 7 were based on non-RCT data showing significant efficacy (>50% response rates), and 2 were later removed from the NCCN Guidelines because newer therapies with better activity and/or safety became available.ConclusionOff-label drug use is a frequent component of care for patients with cancer in the United States. Our findings indicate that when the NCCN recommends beyond the FDA-approved indications, the strength of the evidence supporting such recommendations is robust, with a significant subset of these drugs later becoming FDA approved or supported by RCT. Recommendations without RCT data are often for mechanism-based drugs with high response rates in rare cancers or subsets without effective therapies.     

HER2-enriched subtype and pathological complete response in HER2-positive breast cancer: A systematic review and meta-analysis

BackgroundHER2-positive (HER2+) breast cancer (BC) comprises all the four PAM50 molecular subtypes. Among these, the HER2-Enriched (HER2-E) appear to be associated with higher pathological complete response (pCR) rates following anti-HER2-based regimens. Here, we present a meta-analysis to validate the association of the HER2-E subtype with pCR following anti-HER2-based neoadjuvant treatments with or without chemotherapy (CT).MethodsA systematic literature search was performed in February 2019. The primary objective was to compare the association between HER2-E subtype (versus others) and pCR. Selected secondary objectives were to compare the association between 1) HER2-E subtype and pCR in CT-free studies, 2) HER2-E subtype within hormone receptor (HR)-negative and HR+ disease and 3) HR-negative disease (versus HR+) and pCR in all patients and within HER2-E subtype. A random-effect model was applied. The Higgins’ I² was used to quantify heterogeneity.ResultsSixteen studies were included, 5 of which tested CT-free regimens. HER2-E subtype was significantly associated with pCR in all patients (odds ratio [OR] = 3.50, p < 0.001, I² = 33%), in HR+ (OR = 3.61, p < 0.001, I² = 1%) and HR-negative tumors (OR = 2.28, p = 0.01, I² = 47%). In CT-free studies, HER2-E subtype was associated with pCR in all patients (OR = 5.52, p < 0.001, I² = 0%) and in HR + disease (OR = 4.08, p = 0.001, I² = 0%). HR-negative status was significantly associated with pCR compared to HR + status in all patients (OR = 2.41, p < 0.001, I² = 30%) and within the HER2-E subtype (OR = 1.76, p < 0.001, I² = 0%).ConclusionsThe HER2-E biomarker identifies patients with a higher likelihood of achieving a pCR following neoadjuvant anti-HER2-based therapy beyond HR status and CT use. Future trial designs to escalate or de-escalate systemic therapy in HER2+ disease should consider this genomic biomarker.     

Risk factors for lymph node metastasis in early gastric cancer without lymphatic invasion after endoscopic submucosal dissection

BackgroundLymphatic invasion (LI) is a potent risk factor for lymph node metastasis (LNM) in early gastric cancer (EGC) after endoscopic submucosal dissection (ESD). However, there are also other risk factors for LNM. Hence, to identify the need for additional surgery in some case of EGC without LI, the present study aimed to identify the risk factors for LNM in patients with EGC without LI.MethodsData from 2284 patients diagnosed with EGC who underwent curative surgery at National Cancer Center in Korea from January 2012 to May 2019 were collected. The clinicopathological characteristics of patients with EGC without LI were compared on the basis of LNM status.ResultsThere were 339 (17.1%) and 1648 (82.9%) patients with and without LI respectively. Among these patients with and without LI, 118 (34.8%) and 91 (5.5%) patients presented with LNM, respectively. In patients with EGC without LI, tumor size larger than 3 cm (OR = 2.12, 95% CI = 1.22–3.68; p = 0.007), submucosal invasion (OR = 4.14, 95% CI = 2.57–6.65; p < 0.001), and undifferentiated histologic type (OR = 2.33, 95% CI = 1.45–3.76; p < 0.001) were significant risk factors for LNM. Rates of LNM in patients meeting absolute, expanded, and beyond expanded criteria without LI were 0%, 1.5% (OR = 3.27, 95% CI = 0.18–59.41; p = 0.423), and 7.3% respectively. When the expanded criteria were divided into four subtypes patients with EGC, without LI within each subtype did not show significant risk of incidence of LNM compared to the absolute criteria.ConclusionsThe current expanded criteria for endoscopic resection (ER) are tolerable in cases without LI, even though minimal risk LNM exists. Therefore, additional surgery may not be needed for patients meeting expanded criteria for ER.     

Metabolic syndrome-related sarcopenia is associated with worse prognosis in patients with gastric cancer: A prospective study

ObjectivesSarcopenia and metabolic syndrome (MetS) are associated with the prognosis from malignant tumors. However, evidence of the relationship between sarcopenia and MetS among gastric cancer (GC) patients following radical gastrectomy is lacking. This study assessed the association between preoperative sarcopenia and MetS among GC patients and analyzed the prognosis of patients with different malnutrition statuses.MethodsWe prospectively assessed the preoperative statuses of sarcopenia and MetS among patients who underwent radical gastrectomy from July 2014 to December 2017. We combined sarcopenia and MetS to generate four groups: MetS-related sarcopenia group (MSS), sarcopenia group (S), MetS group (MS), and normal group (N).ResultsA total of 749 patients with resectable GC were included in this study. Preoperative MetS was associated with sarcopenia (p < 0.001). Multivariate logistic regression presented that MetS-related sarcopenia (OR = 2.445; p = 0.010) and sarcopenia alone (OR = 2.117; p = 0.001) were independent predictors of grade Ⅱ and above complications, while MetS alone was not (p = 0.342). Cox regression analysis revealed that MetS-related sarcopenia led to the worst prognosis in the four groups (MSS vs MS: HR = 3.555, p < 0.001; MSS vs N: HR = 2.020, p = 0.003; MSS vs S: HR = 1.763, p = 0.021). However, the MetS group had better prognosis than the normal group (MS vs N: HR = 0.568, p = 0.048).ConclusionPreoperative MetS was associated with sarcopenia among GC patients. MetS-related sarcopenia resulted in a significantly worse prognosis. The long-term prognoses of patients with sarcopenia were impaired by preoperative MetS, while patients without sarcopenia benefited. Thus, patients with both sarcopenia and MetS require more medical interventions.     

Prospective geriatric assessment for perioperative risk stratification in partial nephrectomy

PurposeComorbidities and frailty are determinants of surgical outcome. The aim of the study was to examine various measures of frailty and comorbidities in predicting postoperative outcome of partial nephrectomy (PN).MethodsWe prospectively analyzed the frailty and comorbidity status of 150 patients undergoing PN between 2015 and 2018. Primary endpoint was the occurrence of major postoperative complications (MPC) and secondary endpoints were the failure of Trifecta achievement and the need for hospital readmissions. For the transfer into clinical practice the most significant frailty parameters were summarized in a multi-dimensional test.ResultsMedian age was 67 (33–93) years, 64.7% of the patients were male. Univariable regression analysis showed, that patients with increased frailty indices (Hopkins frailty score ≥2 (OR = 3.74, p = 0.005), Groningen frailty index ≥4 (OR = 2.85, p = 0.036)) are at higher risk to develop MPC. Furthermore, poor physical performance, such as a low handgrip strength or a Full-Tandem-Stand (FTS) < 10 s were associated with MPC (OR = 4.76, p = 0.014; OR = 4.48, p = 0.018) and Trifecta failure (OR = 3.60, p = 0.037, OR = 5.50, p = 0.010).Six measures were combined to the geriatric assessment in partial nephrectomy score (GAPN). A GAPN-score ≥3 proved to be a significant predictor for MPC (OR = 4.30, p = 0.029) and for Trifecta failure (OR = 0.20, p = 0.011) in multivariable regression analysis.ConclusionThe frailty status and comorbidities are important determinants of the postoperative course after PN. These parameters should be assessed preoperatively and included in the treatment planning, especially in light of available alternative therapies. In this context, the GAPN-score may be a suitable tool.     

Risk factors for sexual dysfunction after rectal cancer surgery in 948 consecutive patients: A prospective cohort study

BackgroundSexual dysfunctions seriously affect the quality of life of patients. The aim of this study was to identify the risk factors for sexual dysfunction after rectal cancer surgery.MethodsA total of 948 consecutive patients undergoing rectal cancer radical resection were included between January 2012 and August 2019. The sexual functions were evaluated by the 5-item version of the International Index of Erectile Function (IIEF-5) in men and Index of Female Sexual Function (IFSF) in women at 12 months postoperatively.ResultsPostoperative sexual dysfunction was observed in 228 patients with rectal cancer (24.05%), which included 150 cases in male patients (25.0%) and 78 cases in female patients (22.5%). A multivariate logistic regression analysis results showed that age ≥45 years old (OR = 1.72, p = 0.001), tumor below the peritoneal reflection (OR = 1.64, p = 0.005), receiving preoperative radiotherapy (OR = 4.12, p < 0.001) and undergoing abdominoperineal resection (APR), intersphincteric resection (ISR) and Hartmann surgery (OR = 2.43, p < 0.001) were the independent risk factors of sexual dysfunction for patients with rectal cancer.ConclusionAge ≥45 years old, tumors below the peritoneal reflection, receiving preoperative radiotherapy, and undergoing APR, ISR and Hartmann surgery were the independent risk factors of sexual dysfunction. Patients should be informed about the sexual dysfunctions in the pre-operative consultations. More attention should be paid to intraoperative pelvic autonomic nerve preservation on rectal cancer patients with these risk factors for clinic surgeons.     

Occult contralateral central neck metastasis in papillary thyroid carcinoma with preoperatively documented ipsilateral lateral neck metastasis

BackgroundThis study was conducted to evaluate risk factors and long-term prognosis of contralateral central neck metastasis (CCNM) in papillary thyroid cancer (PTC) patients with ipsilateral lateral neck metastasis. We present clinical evidence to aid in surgical decision-making regarding the extent of central neck dissection (CND), focusing on separation between ipsilateral and contralateral sides.MethodsA total of 379 PTC patients who underwent total thyroidectomy and concomitant bilateral central neck dissection with ipsilateral lateral neck dissection (LND) at a single institution was retrospectively included between January 1997 and December 2015.ResultsThe median follow-up time was 83.2 months, the mean age was 44.3 years, and the mean tumor size was 1.5 cm. Among the study sample, 266 patients were female (70.2%) and 113 (29.8%) were male. Of 379 patients, CCNM was present in 34.6%. In multivariate analysis, male sex (adjusted OR = 2.46, p = 0.002), bilaterality (adjusted OR = 2.58, p = 0.004), number of metastatic ipsilateral central lymph nodes (adjusted OR = 1.15, p = 0.002), number of metastatic lateral lymph nodes (adjusted OR = 1.48, p < 0.001), and three-level metastasis (adjusted OR = 2.46, p = 0.012) were identified as risk factors of CCNM. Overall recurrence occurred in 6.0% and 11.5% of patients in the CCNM (-) group and CCNM (+) group, respectively. In addition, contralateral recurrence was observed in 1.2% patients and 0.8% patients in the CCNM (-) group and CCNM (+) group, respectively. However, CCNM did not significantly increase risk of recurrence (adjusted HR = 1.01, p = 0.981).ConclusionsAlthough the probability of pathological CCNM is not negligible, CCNM was not associated with higher risk of recurrence. This study suggest that central neck dissection may be limited to the ipsilateral side, and the result regarding prognosis of CCNM may help to avoid bilateral CND so that it could have potential to minimize unnecessary surgery-related complications such as recurrent laryngeal nerve(RLN) injury or hypoparathyroidism.     

Phase II study of neratinib in older adults with HER2 amplified or HER2/3 mutated metastatic breast cancer

ObjectiveThe tolerability and efficacy of targeted therapy in older adults with cancer has not been adequately studied. Neratinib is a novel HER1, HER2, HER4 tyrosine kinase inhibitor that has recently been granted FDA approval for treatment of breast cancer. The major toxicity of neratinib is diarrhea, which affects up to 90% of patients. This phase II trial evaluates the safety and tolerability of neratinib in adults ≥60.MethodsPatients aged 60 or older with histologically proven metastatic breast cancer and HER2 amplification (defined by ASCO/CAP guideline) or HER2/HER3 activating mutation were enrolled to receive neratinib at 240 mg daily in 28-day cycles. The association between tolerability, defined as dose reduction and number of completed courses, and log₂ Cancer and Aging Research Group (CARG) toxicity risk score was assessed using a Student's t-test and linear regression, respectively. Response rate, progression free survival, and overall survival were also evaluated.Results25 patients were enrolled with median age of 66 (range 60–79). Seventy-six percent of patients were white, 16% Asian, and 8% African-American. Seventy-six percent were patients with hormone receptor (HR) positive metastatic breast cancer (MBC) and 24% were patients with HR negative MBC. Median number of prior lines of metastatic therapy were 3 (range 0–11). 20/25 (80%) had worst grade toxicities ≥2. A total of 9/25 (36%) had grade 3 toxicities including 5/20 (20%) diarrhea, 2/20 (8%) vomiting, and 2/20 (8%) abdominal pain. There were no grade 4 or 5 toxicities. A total of 9/25 (36%) had dose reduction, and 2/25 (8%) discontinued therapy due to toxicity. The association between dose reductions and CARG toxicity score reached borderline statistical significance suggesting a trend with participants with higher CARG toxicity risk scores being more likely to require a dose modification (p = 0.054). 1/25 (4%) had a partial response, 11/25 (44%) had stable disease, 12/25 (48%) had progression of disease, and 1/25 (4%) was not assessed. Median progression free survival (PFS) was 2.6 months (95% CI [2.56–5.26]), and median overall survival (OS) was 17.4 months (95% CI [10.3, NA]).ConclusionsNeratinib was safe in this population of older adults with HER2 amplified or HER2/3 mutated metastatic breast cancer (BC). Higher CARG toxicity risk score may be associated with greater need for dose adjustments. Future studies are needed to confirm this finding.     

Systematic review of aromatase inhibitors in the first-line treatment for hormone sensitive advanced or metastatic breast cancer

To undertake a systematic review of three first-line treatments (letrozole, anastrozole and exemestane) for hormone sensitive advanced or metastatic breast cancer (MBC) in post-menopausal women. We searched six databases from inception up to January 2009 for relevant trials regardless of language or publication status. Randomised controlled clinical trials assessing the safety and efficacy of first-line AIs for post-menopausal women with hormone receptor-positive (HR+, i.e. ER+ and/or PgR+) with or without ErbB2 (HER2)-positive MBC, who have not received prior therapy for advanced or metastatic disease were included. Where meta-analysis using direct or indirect comparisons was considered unsuitable for some or all of the data, we employed a narrative synthesis method. Four studies (25 papers) met the inclusion criteria. From the available evidence, it was possible to directly compare the three AIs with tamoxifen. In addition, by using a network meta-analysis it was possible to compare the three AIs with each other. Based on direct evidence, letrozole seemed to be significantly better than tamoxifen in terms of time-to-progression (TTP) (HR = 0.70 (95% CI: 0.60, 0.82)), objective response rate (RR = 0.65 (95% CI: 0.52, 0.82)) and quality-adjusted time without symptoms or toxicity (Q-Twist difference = 1.5; P < 0.001). Exemestane seemed significantly superior to tamoxifen in terms of objective response rate (RR = 0.68 (95% CI: 0.53, 0.89)). Anastrozole seemed significantly superior to tamoxifen in terms of TTP in one trial (HR = 1.42 (95% CI: 1.15, NR)), but not in the other (HR = 1.01 (95% CI: 0.87, NR)). In terms of adverse events, no significant differences were found between letrozole and tamoxifen. Tamoxifen was associated with significantly more serious adverse events in comparison with exemestane (OR = 0.61 (95% CI: 0.38, 0.97)); while exemestane was associated with significantly more arthralgia in comparison with tamoxifen (OR = 2.33 (95% CI: 1.07, 5.11)). Anastrozole was associated with significantly more total adverse events (OR = 1.04 (95% CI: 1.00, 1.09)) and hot flushes (OR = 1.39 (95% CI: 1.03, 1.89)) in comparison with tamoxifen in one trial; however, the other trial showed no significant differences in adverse events between anastrozole and tamoxifen. The indirect comparison of AIs with each other in women with post-menopausal, hormone sensitive advanced or MBC showed that letrozole and exemestane were better in terms of objective response rate than anastrozole; while the more clinically relevant outcomes overall survival (OS) and progression-free survival (PFS) showed no significant differences between AIs. OS and PFS showed no significant differences between AIs and hence based on these results a class effect for all AIs is possible. However, these results are based on indirect comparisons and a network analysis for which the basic assumptions of homogeneity, similarity and consistency were not fulfilled. Therefore, despite the fact that these are the best available data, the results need to be interpreted with appropriate caution. Head-to-head comparisons between letrozole, anastrozole and exemestane in the first-line MBC setting are warranted.     

Development of a predictive score of axillary lymph node dissection based on targeted axillary dissection in patients with breast cancer diagnosis,affected lymph nodes,and neoadjuvant treatment

AimTo determine predictive factors of axillary lymph node dissection (ALND) results in breast cancer (BC) patients undergoing neoadjuvant chemotherapy (NACT), and subsequent staging using Targeted Axillary Dissection (TAD).Material and methodCase-control study between January 2016 and August 2019. Patients with BC, cN1 staging, marked with a metallic clip prior to NACT, and subsequently staged with TAD and ALND were included. They were divided into 2 groups: ALND patients with or without metastatic involvement (group 1 and group 2, respectively). We carried out a univariate analysis comparing clinical, radiological, surgical and pathological variables, and a logistic regression, (dependent variable: positive result of ALND; independent variables: number of suspicious lymph nodes in diagnostic ultrasound, positive hormone receptors, HER2 positive, complete clinical-radiological response to NACT, positive TAD, and biopsy of ≤2 nodes in TAD). A score for prediction of a metastatic ALND was proposed, with an internal validation study.Results60 patients were included: Group 1: 33 (55.0%); Group 2: 27 (45.0%). Tumor size (Odds Ratio (OR) = 1.67; 95%CI 1.02–2.74), number of suspected nodes in ultrasound (OR = 2.20; 95%CI 1.01–4, 77), HER2 positive (OR 0.04; 95%CI 0.003–0.54), clinical-radiological response to NACT (OR = 0.07; 95%CI 0.01–0.75), and positive TAD (OR 15.48; 95%CI 1.68–142.78) were independent predictors of a positive result in ALND. We developed a “positive ALND predictive score”, with good calibration (Hosmer-Lemeshow test: p = 0.65), and discrimination (AUC = 0.93; 95% CI 0, 87–0.99), with highest Youden index (0.7) at cut-off point of 17% risk of positive ALND (sensitivity = 100%; specificity = 70%).ConclusionTumor size, number of suspected nodes, positive HER2, response to NACT, and metastatic TAD are independent predictors of ALND. The predictive score for positive ALND would be a good indicator to safely omit ALND.     

Survival in breast cancer patients with spine metastases: Prognostic assessment involving molecular markers

BackgroundTo clarify and update the prognostic assessment for heterogeneous population of patients with breast cancer and spine metastases (SpM), using molecular markers.MethodsThe patient data used in this study was obtained from a French national multi-center database of patients treated for breast cancer with SpM between 2014 and 2017. 556 SpM cases were diagnosed.ResultsMedian overall survival (OS) time for all patients following the SpM event was 43.9 months. First, we confirmed 3 previously known significant prognostic factors for survival of patients with SpM: young age [HR: 2.019, 95% CI 1.343–3.037; p = 0.001], good WHO status [ Status 0 HR: 2.823, 95% CI 1.231–3.345; p < 0.0001] or [ Status 1 HR: 1.956, 95% CI 0.768–2.874; p = 0.001] and no-ambulatory neurological status: Frankel A-C [HR: 0.438, 95% CI 0.248–0.772; p = 0.004]. Secondly, we determined the effect of gene mutations on survival in patients with SpM, and we identified that HER2+ cancer subtype [HR: 1.567, 95% CI 0.946–2.557; p = 0.008] was an independent predictor of longer survival, whereas basal cancer subtype [HR: 0.496, 95% CI 0.353–0.699; p < 0.0001] was associated with a poorer prognosis. Other factors including the number of SpM, surgery, extraspinal metastases, synchrone metastases, metastasis-free survival, and SpM recurrence were not identified as prognostically relevant to survival.ConclusionSurvival and our ability to estimate it in breast cancer patients with SpM has improved significantly. Therefore, SpM prognostic scoring algorithms should be updated and incorporate genotypic data on subtypes to make treatment more adaptive.     

Uptake and survival effects of minimally invasive surgery for lung cancer: A population-based study

IntroductionDespite growing evidence supporting the safety of minimally invasive surgery (MIS) in the treatment of lung cancer, its uptake is still variable and its outcomes debated. This study examines the factors associated with MIS uptake and its effects on survival in patients with non-small cell lung cancer (NSCLC).MethodsAll patients in the Canadian province of Ontario with early stage NSCLC (stage I/II) from 2007 to 2017 were included. A logistic regression identified the predictors of MIS uptake, and a flexible parametric model was used to estimate survival rates based on MIS versus open resection.ResultsIn total, 8,988 patients underwent surgical resection; 53.6% had MIS. Year of diagnosis was associated with MIS uptake (OR = 1.33, p < 0.001); patients in later years were more likely to receive MIS. Rurality was a significant predictor of MIS, though distance from nearest regional cancer center did not predict MIS utilization. Patients with stage II disease were less likely to receive MIS compared to those with stage I disease (OR = 0.44, p < 0.001). MIS had a significantly higher 5-year survival compared to open resection for stage I and II disease. Patients >70 years had the greatest 5-year survival benefit from MIS.ConclusionsWe observed a substantial long-term survival benefit in patients undergoing MIS for early stage NSCLC. This difference was most pronounced in the oldest age group. These findings support the use of MIS in the treatment of lung cancer and challenge the notion that MIS compromises oncologic outcomes.     

Effect of DPYD,MTHFR, ABCB1, XRCC1, ERCC1 and GSTP1 on chemotherapy related toxicity in colorectal carcinoma

ABCB1, DPYD, MHTFR, XRCC1, ERCC1, GSTP1 and UGT1A1 genetic variants affect proteins related to CRC chemotherapy toxicity.A retrospective cohort study was conducted in 194 CRC patients.In first line treatment, DPYD rs17376848 AG genotype was associated with hematological toxicity (OR = 4.85; p = 0.03); GSTP1 G-allele (OR = 3.01; p = 0.005) and MTHFR rs1801133 T allele (OR = 2.51; p = 0.03) with respiratory toxicity; GSTP1 G-allele with cardiovascular toxicity (OR = 4.05; p = 0.01); ERCC1 rs11615 GG genotype with neurological toxicity (OR = 3.98; p = 0.01) and with asthenia (OR = 2.91; p = 0.08); XRCC1 rs1799782 T allele (OR = 0.31; p = 0.03) and GSTP1 G-allele (OR = 1.81; p = 0.01) with cutaneous toxicity. In second line treatment, XRCC1 rs1799782 T-allele was associated with asthenia (OR = 0.17; p = 0.03) and XRCC1 rs25487 T-allele with gastrointestinal toxicity (OR = 3.03; p = 0.005). After stratifying by treatment, in the 5-Fluorouracil group, the DPYD rs17376848 AG genotype was associated with hematological toxicity (OR = 2.76; p = 0.003), ABCB1 rs1045642 T-allele with the need of treatment adjustment due to toxicity (OR = 3.06; p = 0.01), and rs1045642 CC genotype with gastrointestinal toxicity (OR = 5.80; p = 0.03). In the capecitabine group, the MTHFR rs1801131 CC genotype was associated with asthenia (OR = 3.48; p = 0.009). In the oxaliplatin group, rs1045642 TT genotype was associated with the need to adjust treatment (OR = 0.32; p = 0.02), ERCC1 rs11615 GG genotype with asthenia (OR = 3.01; p = 0.01) and rs1615 GSTP1 GG genotype with respiratory toxicity (OR = 5.07; p = 0.009).ABCB1 rs1045642 T-allele reduces the need for treatment modification with both 5FU and oxaliplatin. Although several biomarkers predicted different toxic effects, they cannot be considered as risk factors for severe toxicity.     

Assessment of prognostic factors in long-term survival of male and female patients with colorectal cancer using non-mixture cure model based on the Weibull distribution

ObjectiveColorectal cancer (CRC) is known as one of the malignant form of cells growing in the inner lining of colon and rectum which could seriously affect the cure rate of patients. We aimed to evaluate the effect of prognostic factors on cure fraction of CRC patients.MethodsA total of 1043 CRC patients were included to the study from December 2001 to January 2007 at the Research Center of Gastroenterology and Liver Disease in Shahid Beheshti University of Medical Sciences, Tehran, Iran. Patients’ information was extracted from their medical records, then they were followed to identify their death status via phone-call. Weibull non-mixture cure model was used to evaluate the effect of the risk factors on cure fraction of CRC patients.ResultsThe five-years survival rate was 0.66 (males: 0.64 and female: 0.69). The median survival time for non-cured CRC patients were 3.45 years (males: 3.46; females = 3.45 years). In the single Weibull model, BMI≥30 (OR = 4.61, p-value = 0.033), poorly differentiated tumor grade (OR = 0.36, p-value = 0.036), tumor size≥25 mm (OR = 0.22, p-value = 0.046), and N1-stage (OR = 0.42, p-value = 0.005) had significant effect on females’ cure fraction. Also, cure fraction of male CRC patients significantly affected by BMI (levels:25.0–29.9-OR = 12.13-p-value<0.001; ≥30-OR = 7.00-p-value = 0.017), T1-stage (OR = 0.52, p-value = 0.021), M1-stage (OR = 0.45, p-value = 0.007), IV-staging (OR = 0.36, p-value = 0.041) and IBD (OR = 0.26, p-value = 0.017). In multiple Weibull model, females were associated with tumor size≥25 mm (OR = 0.20, p-value = 0.044) and N1-stage (OR = 0.45, p-value = 0.013) and males were affected by M1-stage (OR = 0.41, p-value = 0.011) and IBD (OR = 0.20, p-value = 0.022).The cure fraction of males and females CRC patients was 64% and 69%, respectively.ConclusionsThe prognostic factors for cure fraction of patients with CRC may be different among males and females. Further multicenter studies are required to assess the effect of common prognostic factors between males and females.     

Lack of association between HER2 codon 655 polymorphism and breast cancer susceptibility: meta-analysis of 22 studies involving 19,341 subjects

Epidemiological studies have investigated the association between HER2 codon 655 polymorphism and breast cancer susceptibility. However, the results are still inconclusive. To obtain a more precise estimation of the relationship, this meta-analysis was performed. A total of 22 studies including 9,209 cases and 10,132 controls were collected. The strength of association between HER2 codon 655 polymorphism and breast cancer susceptibility was assessed by calculating crude ORs with 95% CIs. When all the 22 studies were pooled into the meta-analysis, there was no evidence for significant association between HER2 codon 655 polymorphism and breast cancer susceptibility (for Val/Ile vs. Ile/Ile: OR = 1.069, 95% CI = 0.976–1.172; for Val/Val vs. Ile/Ile: OR = 1.191, 95% CI = 0.922–1.538; for dominant model: OR = 1.093, 95% CI = 0.991–1.206; for recessive model: OR = 1.141, 95% CI = 0.902–1.444). In the subgroup analysis by the source of controls and ethnicity, no significant increased risk was found in all genetic models. However, the current results indicated the modest association between the HER2 Ile655Val polymorphism and Asian population (Val/Ile vs. Ile/Ile: OR = 1.207, CI = 1.006–1.450). In summary, the meta-analysis suggests that HER2 codon 655 polymorphism is not associated with the increased breast cancer risk.     

Colonoscopy,imaging, and carcinoembryonic antigen: Comparison of guideline adherence to surveillance strategies in patients who underwent resection of colorectal cancer - A systematic review and meta-analysis

IntroductionAlmost one-third of patients with colorectal cancer (CRC) experience recurrence after resection. Adherence to surveillance guidelines largely dictates efficacy in early detection of recurrence. We sought to assess and compare adherence to postoperative surveillance guidelines for colonoscopy, imaging, and Carcinoembryonic Antigen (CEA).MethodsPubMed, Medline, Embase, Scopus, Cochrane, Web of Science, and CINAHL were systematically searched. Random-effects meta-analysis was performed and pooled adherence to each surveillance strategy was assessed for CEA, imaging, and colonoscopy.ResultsOverall 14 studies (55,895 patients) met the inclusion criteria. Adherence to colonoscopy guidelines was the highest (70%, 95%CI 67–73), followed by imaging (63%, 95%CI 47–80), and CEA (54%; 95%CI 42–66). Among 7 (50%) studies that examined adherence to the American Society of Clinical Oncology guidelines, compliance with colonoscopy was the highest (73%; 95% CI 70–76), followed by imaging (58%; 95% CI 37–78), and CEA (45%; 95%CI 37–52). Of note, guideline adherence to CEA testing was much lower than colonoscopy among patients with colon (OR 0.21; 95%CI 0.20–0.22) and rectal cancer (OR 0.25; 95%CI 0.23–0.28) (both p < 0.05). This was also noted when compared with imaging recommendations among older patients (OR = 0.62; 95%CI 0.42–0.93) and patients with stage II, (OR = 0.80; 95%CI 0.76–0.84) and stage III disease (OR = 0.88; 95%CI 0.82–0.94) (all p < 0.05).ConclusionWhile guideline adherence to postoperative surveillance with colonoscopy was high, adherence to CEA testing and imaging surveillance strategies was markedly lower following CRC resection. Future studies should investigate avenues to improve compliance with surveillance guidelines among health care providers and patients to optimize postoperative follow-up for CRC.     

Surgical results of non-small cell lung cancer involving the heart and great vessels

BackgroundThe surgical treatment of advanced non-small-cell-lung-cancer (NSCLC) invading mediastinal organs and great vessels is still controversial. The aim of this multicentre study is to analyse oncological outcomes, surgical outcomes and prognostic factors of patients with NSCLC involving heart and great vessels.Methods362 patients treated surgically for locally advanced T4-NCSLC between 1990 and 2020 were retrospectively reviewed. Patients were divided into five subgroups: pulmonary artery(n = 129), left atrium(n = 82), superior vena cava(n = 80), aorta(n = 43), and multiple vascular structures(n = 28). Resection was complete in 327(90%) patients.ResultsOverall 90-day mortality was 8.8%, influenced by poly-transfusions, pneumonectomy, bronchopleural fistula and previous cardiovascular disease (4.5HR.p = 0.03, 3.7HR p = 0.01, 14.0HR.p < 0.001 and 3.0HR p < 0.01). One-, 3- and 5-year survival rates were 75%, 43%, 33%, respectively and there were significant differences among the five groups(p < 0.001). Survival was significantly affected by induction radiotherapy, nodal status, pTNM-stage and radicality (3.8HR p = 0.03, 2.6HR p = 0.001, 1.6HR p < 0.05 and 1.6HR p < 0.05).ConclusionsSurgery provided acceptable results in selected patients with T4-NSCLC with major vascular infiltration in expert centres. Nodal-status and radicality influenced the overall-survival and disease-free survival. Neoadjuvant chemotherapy appears to have a positive effect on long-term results, particularly in N2-patients.     

The importance of surgical resection in the management of rectal sarcoma: A national cancer database analysis of 133 cases

Background and purposeRectal sarcomas (RS) are rare malignant tumors with a very poor prognosis. This study aimed to assess the characteristics, treatment, and outcomes of RS in the United States.MethodsThis study was a retrospective analysis of the National Cancer Database (NCDB) from 2004 to 2019 of patients with a diagnosis of RS. The main outcome measures were overall survival (OS) and its predictors.Results133 RS patients (39.1% female) with a mean age of 65.7 ± 15.6 years were included in the study. Mean tumor size was 6.1 ± 3 cm. The crude OS rate was 22.5% and median survival duration was 10.1 (IQR: 3.2–21) months. Factors associated with an improved OS on were private insurance (HR = 0.23, p = 0.001) and undergoing surgery (HR 0.23, p < 0.001), Factors associated with poor survival were age (HR 1.02, p = 0.005), male sex (HR 2.27, p = 0.001), Charlson score of 3 (HR 5.17, p = 0.003), and positive resection margins (HR: 2.64, p = 0.01). Multivariate Cox regression analysis revealed that male sex (HR 2.16, p = 0.04) and positive resection margins (HR 2.31, p = 0.03) were predictors of poor survival whereas surgery was an independent predictor of improved OS (HR 0.321, p < 0.001)ConclusionsRS is a very rare rectal malignancy with an even poorer prognosis than previously reported. However, undergoing surgery with curative intent while obtaining negative margins may confer better OS.     

Psychosocial needs of older patients with metastatic breast cancer treated at community centers

IntroductionPsychosocial status contributes to overall quality of life (QOL) for patients with cancer as psychosocial distress is commonly seen in this population. We sought to describe the psychosocial needs of older adults with metastatic breast cancer (MBC) treated in the community. We evaluated the correlation between the patient's psychosocial status and the presence of other geriatric abnormalities in this patient population.Materials and MethodsThis is a secondary analysis of a completed study evaluating older adults (≥65 years) with MBC treated at community practices who received a geriatric assessment (GA). This analysis evaluated psychosocial factors collected during GA, including depression assessed by Geriatric Depression Scale (GDS), perceived social support (SS) assessed by Medical Outcomes Study Social Support Survey (MOS), and objective social supportassessed by demographic variables (living situation and marital status). Perceived SS was further subdivided into tangible social support (TSS) and emotional social support (ESS). Kruskal-Wallis tests, Wilcoxon tests, and Spearman's correlations were used to assess the relationship between psychosocial factors, patient characteristics, and geriatric abnormalities.ResultsOne hundred older patients with MBC were enrolled and completed GA with a median age of 73 years (65–90). Almost half of the participants (47%) were either single, divorced, or widowed and 38% lived alone, demonstrating a significant number of patients with objective social support deficits. Patients with HER2+ or triple negative MBC had lower overall SS scores compared to patients with ER/PR+ or HER2- MBC (p = 0.033). Patients on fourth line of therapy were more likely to screen positive for depression compared to patients on earlier lines of therapy (p = 0.047). About half (51%) of the patients indicated at least one SS deficit on the MOS. A higher GDS and lower MOS score correlated with greater total GA abnormalities (p = 0.016). Evidence of depression correlated with poor functional status, decreased cognition, and a high number of co-morbidities (p < 0.005). Abnormalities in functional status, cognition, and high GDS are associated with lower ESS (p = 0.025,0.031,0.006 respectively).DiscussionPsychosocial deficits are common among older adults with MBC treated in the community and are associated with the presence of other geriatric abnormalities. These deficits require a thorough evaluation and management to optimize treatment outcomes.