DFS Rates Research Articles

Prognostic value of tumor deposits in stage III colon cancer patients, a post-hoc analysis of CALGB/SWOG 80702 phase III study.

10 Background: In colon cancer, tumor deposits (TD) have been associated with worse prognosis, but they are included in the TNM staging system only in the absence of lymph node metastasis (i.e., stage III pN1c tumors). Here we aimed at evaluating the prognostic value of TD and the impact of the addition of TD in the count of lymph node metastases in patients with stage III colon cancer from the CALGB/SWOG 80702 phase III trial (NCT01150045). Methods: Pathological reports of all patients were reviewed for the presence and the count of TD, primary tumor sidedness, lymphovascular invasion and perineural invasion. Cases without available pathological report or without specific information of TD were excluded. Prognostic associations were evaluated by multi-variable Cox models adjusting for treatment arm, T-stage, N-stage, lymphovascular invasion, perineural invasion and lymph node ratio. Results: Overall, 2028 patients were included, with 524 (26%) TD-positive and 1504 (74%) TD-negative stage III tumors. Of the TD-positive patients, 80 (15.4%) were node negative (i.e., pN1c), 239 (46.1%) were pN1a/b and 200 (38.55%) were pN2. 17.2% and 37.0% of all pN1a/b and pN2 tumors had TD. Overall median follow-up was 69.3 months. The presence of TD was associated with poorer DFS (adjusted hazard ratio (aHR) = 1.59, 95%CI 1.28-1.91) and OS (aHR = 1.52, 95%CI 1.18-1.95) in the overall population. The negative effect of TD on DFS and OS was observed for both pN1a/b and pN2 groups and confirmed in multivariate Cox model. Among TD-positive patients, the number of TD had a linear negative effect on DFS and OS. Adding TD to the count of lymph node metastases, 104 of 1570 (6.6%) patients initially considered as pN1 were re-staged as pN2. Re-staged pN2 patients experienced worse DFS (3-year DFS rate: 65.5% versus 80.3%, P = .0003) and OS (5-year OS rate: 69.1 versus 87.8%, P = .0005) than patients confirmed as pN1. Re-staged pN2 patients had similar DFS than patients initially staged as pN2 (3-year DFS rate: 65.5% versus 63.1%, P = .1992). OS curves of these 2 groups crossed, with better outcomes during the first 3 years of follow-up but poorer 5-year estimates for re-staged pN2 patients (5-year OS rate: 69.1% versus 74.8%, P = .0436). Conclusions: TD are found in more than one fourth of stage III colon cancer specimens. The number of TD has a linear deleterious effect on patients’ prognosis. Adding the number of TD to the count of lymph node metastases improves the prognostication accuracy of the TNM staging. Support: U10CA180821, U10CA180882; https://acknowledgments.alliancefound.org . Clinical trial information: NCT01150045.

Complete intersphincteric longitudinal muscle excision May Be key to reducing local recurrence during intersphincteric resection

BackgroundAlthough total mesorectal excision (TME) is regarded as a standard procedure for rectal cancer, technical definition and evaluation method have not yet been investigated for intersphincteric resection (ISR). This study was performed to introduce a complete ISR procedure, and to assess whether total intersphincteric longitudinal muscle excision (TILME) facilitated the completeness of ISR and reduced recurrence. MethodsA total of 1080 patients with rectal adenocarcinoma who underwent robot-assisted low anterior resection (LAR) over 10 years were consecutively enrolled. Propensity-score matching of the two LAR groups (ISR vs LAR group, 1:1) and three ISR subgroups (partial vs subtotal vs total ISR subgroup, 2:2:1) was performed by strict adjustment of baseline characteristics. Archived specimens and video-/photo-records were reevaluated to examine completeness of TILME. ResultsComplete-TILME was performed in 84.5% of patients who underwent ISR. Multivariate analysis showed that incomplete-TILME was the only parameter independently associated with increased 5-year cumulative local recurrence (odds ratio = 23.385; 95% confidence interval = 1.492–366.421; p = 0.03), and that incomplete-TILME was independently associated with adipose tissue surrounding the intersphincteric longitudinal muscle, coloanal anastomosis, and total ISR (p < 0.001–0.05). Although mean incontinence scores and anorectal manometry deteriorated to some degree 12–24 months after surgery in all patients, they remained acceptable. The 5-year cumulative DFS (74.1% vs 60%, p = 0.18) and OS (85.9% vs 70%, p = 0.10) rates tended to be higher in patients with complete than incomplete-TILME. ConclusionsThe completeness of TILME appears to be an independent indicator of complete ISR, reducing local recurrence following lower rectal cancer surgery.

Impact of Intraoperative Blood Loss on the Survival of Patients With Stage II/III Colorectal Cancer: A Multicenter Retrospective Study.

Resection of the primary lesion with radical lymph node dissection is the most promising treatment avenue for patients with cancer. On the other hand, these procedures often induce excessive intraoperative blood loss (IBL) and require perioperative blood transfusion. The influence of IBL on the long-term postoperative outcomes of patients with digestive cancer is controversial. We investigated the impact of IBL on survival and recurrence after curative surgery in patients with colorectal cancer (CRC) in a single study group. In total, 1,597 patients who underwent radical resection for CRC at three group hospitals between 2000 and 2019 were reviewed. Patients were classified into a group with high IBL (≥200 ml) or low IBL (<200 ml). The risk factors for disease-free (DFS) and overall (OS) survival were analyzed. A total of 489 and 1,108 patients were classified into the high and low IBL groups, respectively. The OS and DFS rates at 5 years after surgery were 89.3% and 63.4%, respectively, for the high IBL group and 96.9% and 77.8% for the low IBL group; these differences were statistically significantly (p<0.001). The multivariate analysis demonstrated that IBL was a significant independent risk factor for OS and DFS. The amount of IBL was associated with significant differences in the OS and DFS of patients with stage II/III CRC who received curative resection. The surgical procedure, surgical strategy, and perioperative care should be carefully planned to avoid causing IBL.

Assessment of HPV16 infection in patients with laryngeal cancer.

The purpose ofthestudy was to investigate HPV16 infection in laryngeal cancer patients treated with surgery and adjuvant radiotherapy as well as to analyze treatment results in relation to HPV16 infection and selected clinical, histopathological, and radiotherapy parameters. A retrospective analysis was performed in agroup of60 patients with squamous cell carcinoma ofthelarynx treated surgically and qualified for adjuvant radiotherapy at theOncology Center in Cracow between 1995 and 2001. Thestudied group consisted of57 men (95%) and 3 women (5%) ofmean age of56 years. In 13 patients (22%) underweight was noted. In theanalyzed material, locally advanced laryngeal cancer prevailed (pT3-pT4) - 52 cases (87%), with theinvolvement ofcervical lymph nodes (pN+) - 32 cases (53%). Histopathological examination revealed that microscopic radicality was not obtained in 18 patients (30%). Human papillomavirus 16 infection status as well as infection type (integrated, episomal, or mixed) were assessed in each patient by means ofquantitative polymerase chain reaction (qPCR) using real-time detection. The 5-year OS, DFS, and LC rates were 45%, 61%, and 69%, respectively. Multivariate analysis revealed that local relapse risk and local failure risk were statistically significantly influenced by underweight and positive surgical margin. Underweight had also astatistically significant impact on death risk. TheHPV16 infection was noticed in 4 cancers (6.8%). In all cases it was thesame episomal type. On thebasis ofour observations it can be assumed that HPV infection does not play animportant role in etiology oflaryngeal cancer. Although, further study is needed in larger patient populations; optimal methodology for detecting HPV infection should also be determined. Positive surgical margin has asignificant effect on worse treatment outcomes. Underweight before radiotherapy diminishes theprobability oftreatment success and survival oflaryngeal cancer patients.

Role of matrix metalloproteinase MMP-2, MMP-9 and tissue inhibitor of metalloproteinase (TIMP-1) in the clinical progression of pediatric acute lymphoblastic leukemia

ABSTRACT Background Matrix metalloproteinases (MMPs) play a crucial role in cancer progression and metastasis, however their role in pediatric Acute lymphoblastic leukemia (ALL) is still unrevealed. Methods The diagnostic, prognostic and predictive value of tissue inhibitor of metalloproteinase (TIMP-1), MMP-2, MMP-9 and CD34+CD38− cancer stem cells (CSCs) were assessed in bone marrow (BM) samples of 76 ALL children using Flow Cytometry analysis. Results There was a significant increase in TIMP-1 [1.52 (0.41–10) versus 0.91(0.6–1.12); respectively, p < 0.001], and CSCs CD34+CD38− [1 (0.03–18.6) versus 0.3 (0.01–1.1), p < 0.001] expression in ALL patients compared to controls. While there were no significant differences regarding MMP-2 and MMP-9 expression between the two groups. The sensitivity, specificity, area under curve (AUC) of MMP-2 were (80.3%, 53.3% and 0.568, p = 0.404), and of MMP-9 were (53.9%, 40% and 0.660, p = 0.053). While that of TIMP-1 were (78.9%, 100% and 0.892, p < 0.001), and that of CD34+CD38− CSCs were (78.9%, 73.3% and 0.855, p < 0.001). Increased TIMP-1 expression associated with the high-risk disease (p < 0.001). CD34+CD38− CSCs and MMP-2 overexpression associated with MRD at day-15, increased BM blast cell count at diagnosis and at day-15 ( p < 0.05). TIMP-1 overexpression is associated with shorter DFS and OS rates ( p = 0.009 and p = 0.048). Multivariate logistic regression analysis showed that both TIMP-1 [OR: 4.224, p = 0.046], and CD34+CD38− CSCs [OR: 6.873, p = 0.005] could be potential independent diagnostic factors for pediatric ALL. Conclusion TIMP-1 and CD34+CD38− CSCs could be possible useful diagnostic markers for pediatric ALL. Also, TIMP-1 is a promising prognostic marker for poor outcome of the patients.

Clinical Value of Postoperative Neutrophil-to-Lymphocyte Ratio Change as a Detection Marker of Bladder Cancer Recurrence.

PurposeThis study investigated the clinical significance of postoperative neutrophil-to-lymphocyte ratio (NLR) changes in bladder cancer recurrence.Patients and MethodsFor evaluating the predictive value of postoperative dynamic change of NLR, a retrospective cohort study was performed to analyze 213 patients with bladder cancer who underwent surgical treatment from January 2013 to December 2019 at the Affiliated Tumor Hospital of Guangxi Medical University. Baseline characteristics and recurrence-free survival (RFS) were statistically compared, and a multivariate analysis was used to identify prognostic factors.ResultsCompared with preoperative NLR levels, postoperative decreased NLR in 130 patients and postoperative increased NLR in 83 patients were detected. The 1-, 3- and 5-year RFS rates were 88.0%, 75.4% and 75.4% in the decreased postoperative NLR group, respectively, and 51.2%, 25.8% and 16.1% in the increased postoperative NLR group, respectively (P < 0.05). Kaplan–Meier curves showed that the cumulative DFS rate in the increased group was significantly lower than that in the decreased group (P < 0.05). The preoperative NLR showed significant difference with postoperative NLR in the total cohort, high-grade non-muscle-invasive bladder cancer (HG-NMIBC) and muscle-invasive bladder cancer (MIBC) group, while there was no significant difference between postoperative NLR and NLR of recurrence or last follow-up. Multivariate analysis suggested that postoperative-preoperative NLR was an independent predictor for RFS (HR=6.206, 95% CI: 3.826–10.067, P < 0.001) in the total cohort, RFS (HR=9.373, 95% CI: 2.724–32.245, P < 0.001) in the LG-NMIBC group, RFS rates (HR=6.873, 95% CI: 2.486–18.999, P < 0.001) in the HG-NMIBC group and RFS rates (HR=6.109, 95% CI: 2.847–13.109, P < 0.001) in the MIBC group.ConclusionThe dynamic change of postoperative NLR is a potential marker for the early detection of bladder cancer recurrence. Patients with increased NLR after surgery tend to have higher risk of recurrence.

Redefining Adequate Surgical Resection Margins for Oral Squamous Cell Carcinoma: Our Institutional Experience in 5 Consecutive Years

Background: Resection margin status is an important predictor of prognosis in patients with surgically treated OSCC. We introduced the concept of “adequate” versus inadequate” resection margins. Methods: A sample of 87 consecutive patients who underwent surgical treatment for OSCC between 2014 and 2019 were retrospectively examined. Patient demographics, tumour characteristics, adjuvant therapy, recurrence status and patient survival (overall -OS- and disease-free -DFS) were evaluated. According to pathological findings, margins were considered clear (≥5 mm), close (1-5 mm) or involved (<1 mm). Using statistical analysis, a binomial cut-off point was established at 3 mm, and patients were classified into two groups according to primary tumour resection margins: “adequate” (margins ≥3 mm) and “inadequate” (margins <3 mm). Results: Clear surgical margins (≥5 mm) were reported in 72% tumour specimens, close in 12% and involved in 16%. Applying the 3 mm cutt-off, 21% patients were considered to have “inadequate” and 79% “adequate” resections. Adjuvant therapy was provided in 60% of cases, in accordance with Clinical Practice Guidelines. OS rate was 63% and DFS rate 64%. OS was significantly lower (p 0.05). Conclusions: An adequate surgical margin for OSCC could be defined at our institution by ≥3 mm, a close margin (≤2.99 mm) being an adverse risk factor in OSCC survival although further studies are needed to analyse the impact in terms of cancer recurrence rates.

The dawn of a new era, adjuvant EGFR inhibition in resected non-small cell lung cancer.

Background:Adjuvant platinum-based chemotherapy is standard of care for patients with resected stage IIA/B or IIIA NSCLC. Overall survival is suboptimal due to the high metastatic potential of early-stage NSCLC and there is substantial clinical need for additional efficacious adjuvant treatment options.Methods:PubMed (all time to 4 February 2021) and related conference databases were searched using the key search terms ‘NSCLC’ AND ‘Adjuvant’ AND ‘EGFR inhibitor’ OR respective aliases.Results:The literature search identified five adjuvant phase III trials of EGFR inhibitors in early NSCLC. The earlier BR19 and RADIANT trials failed to demonstrate statistically significant improvements in either OS or DFS for gefitinib and erlotinib, respectively, compared with placebo in patients with EGFR mutation-unselected NSCLC. Three subsequent phase III trials, ADAURA, CTONG1104, and IMPACT, were conducted in EGFR-mutant NSCLC. IMPACT showed no statistically significant DFS benefit for adjuvant gefitinib, and although CTONG1104 did report improved DFS for gefitinib (HR = 0.56, p = 0.001), this benefit was not enduring, resulting in comparable 5-year DFS rates. Statistically significant and clinically meaningful DFS benefits were observed in ADAURA for osimertinib compared with placebo in patients with stage IB-IIIA and II-IIIA disease (7th Edition Staging), and these benefits, coupled with a meaningful improvement in 2-year CNS DFS and favorable HRQoL, make osimertinib an important new treatment option for the adjuvant treatment of EGFR exon 19 deletion or exon 21 L858R-mutated stage II-IIIA NSCLC (UICC/AJCC 8th Edition Staging), with final mature OS data eagerly awaited.Conclusion:Adjuvant osimertinib used alone or following platinum-based chemotherapy is now recommended in patients with stage II-IIIA EGFR-mutated NSCLC.

Resection of the inferior vena cava in different neoplasm

Purpose: The involvement of the inferior vena cava (IVC) in advanced abdominal tumors is a surgical challenge, given the high postoperative morbidity and poor long-term prognosis. IVC reconstruction is not always required due to the formation of collateral veins. Our goal was to analyze our experience, perioperative management, and results. Methods: We retrospectively evaluated short and long-term results of surgical resections of tumors with associated inferior vena cava resection performed in our facilities between 2012 and 2020. Results: 15 patients were selected for our retrospective study: 1 with renal carcinoma, 4 with sarcoma, 7 with colorectal metastases, 2 with adrenal tumors, and 1 with hepatocellular carcinoma. 7 were male with an average age of 59.06 years. The postoperative severe complications (Dindo-Clavien ≥ IIIa) affected 40% of patients and the mortality rate was 13.3%. Partial resection with primary repair was performed in 7 patients (46.7%), with patch reconstruction in 1 (6.7%), thrombectomy in 2 (13.3%), and vascular reconstruction with prosthesis in 5 patients (33.3%). The average follow-up was 30.62 months. The 1, 3 and 5-year OS rates were 100%, 91% and 43%, respectively; excluding the postoperative mortality. The mean DFS was 11.53 months. The 1, 3 and 5-year DFS rates were 46%, 18% and 18%, respectively. Graft thrombosis occurred in 3 patients (20%) during follow-up. Six patients were prescribed follow-up anticoagulation. Conclusion: IVC resection, though a technically demanding procedure, can be safely performed to achieve complete tumor resection with relative survival improvement and acceptable mortality and morbidity rates in selected patients.

The effect of adding concurrent chemotherapy to radiotherapy for stage II nasopharyngeal carcinoma with undetectable pretreatment Epstein-Barr virus DNA: Retrospective analysis with a large institutional-based cohort

Little is known about the value of adding concurrent chemotherapy (CC) to radiotherapy for stage II nasopharyngeal carcinoma (NPC) with undetectable (0 copies/mL) pretreatment Epstein-Barr Virus (EBV) DNA in the intensity-modulated radiotherapy (IMRT) era. To address this question, the present study retrospectively reviewed 514 patients with newly diagnosed stage II NPC and undetectable pretreatment EBV DNA from Sun Yat-sen University Cancer Center between March 2008 and October 2016. Clinical characteristics and survival outcomes between concurrent chemoradiotherapy (CCRT) and IMRT alone groups were compared. Propensity score matching analysis was conducted to control for confounding factors. Although CCRT group had significantly higher proportions of stage N1 disease than IMRT alone group before matching (85% vs. 61%, p < 0.001), no statistically significant differences were noted for OS (97.8% vs. 98.1%, p = 0.700), DFS (93.4% vs. 94.5%, p = 0.846), DMFS (96.0% vs. 96.9%, p = 0.762), and LRFS (97.3% vs. 98.1%, p = 0.701). After 1:1 propensity-score matching, 177 pairs were identified. Patients in each group were found to be well balanced in baseline characteristics and risk factors (all P > 0.05). The five-year OS (96.9% vs. 98.2%, p = 0.302), DFS (92.0% vs. 95.2%, p = 0.777), DMFS (95.2% vs. 97.6%, p = 0.896), and LRFS (97.3% vs. 97.6%, p = 0.328) rates remain comparable for both CCRT and RT alone groups. Additionally, subgroup analysis still failed to observe any significant survival benefit for the addition of CC to IMRT for N1 disease (P>0.05 for all). Our results indicated that IMRT alone appeared to achieve comparable survival to CCRT for stage II NPC with undetectable pretreatment EBV DNA.

Elevated neutrophil-to-lymphocyte ratio and predominance of intrahepatic cholangiocarcinoma prediction of poor hepatectomy outcomes in patients with combined hepatocellular-cholangiocarcinoma.

Although elevated neutrophil-to-lymphocyte ratio (NLR) has been associated with survival in some liver cancers, its prognostic relevance has not been studied in the context of combined hepatocellular cholangiocarcinoma CHCC-CC, a rare primary liver cancer. We investigated whether elevated NLR and a predominance of cholangiocarcinoma might predict poor prognosis in patients with resectable CHCC-CC. We retrospectively reviewed the clinicopathologic data of forty-two patients with CHCC-CC receiving hepatectomies at our hospital. We used Kaplan-Meier and Cox regression to analyze survival. Two-year disease-free survival and five-year overall survival rates were 43.2% and 32.9%, respectively. Univariate analyses showed that patients with NLR ≥3 had significantly worse 2-year DFS and 5-year OS rates. Univariant Kaplan-Meier survival analysis also associated these rates with a predominance in intrahepatic cholangiocarcinoma, AJCC tumor stage, pathological T stage and lymph-vascular invasion. However, our multivariate analysis found NLR ≥3 to be the only independent predictor of disease recurrence and poorer survival. Neutrophil-to-lymphocyte ratio was the most important independent predictor of poorer survival in patients with resectable CHCC-CC. Predominance of intrahepatic cholangiocarcinoma, advanced AJCC tumor stage and pathological T stage, and lymph-vascular invasion also may affect poor prognosis in patients receiving complete tumor resections.

Multiple Microinvasion Foci in Ductal Carcinoma In Situ Is Associated With an Increased Risk of Recurrence and Worse Survival Outcome.

BackgroundDuctal carcinoma in situ with microinvasion (DCISM) was defined as one or more foci of invasion beyond the basement membrane within 1 mm. The size of primary lesion is associated with axillary status and prognosis in patients with invasive breast cancer; thus, it is of interest to determine whether multiple foci of microinvasion are associated with a higher risk of positive axillary status or worse long-term outcomes in patients with DCISM.MethodsThis study identified 359 patients with DCISM who had undergone axillary evaluation at our institute from January 2006 to December 2015. Patients were categorized as one focus or multiple foci (≥2 foci) according to the pathological results. Clinicopathological features, axillary status, and disease-free survival rate were obtained and analyzed.ResultsOf 359 patients, 233 (64.90%) had one focus of microinvasion and 126 (35.10%) had multiple foci. Overall, 242 (67.41%) and 117 (32.59%) patients underwent sentinel lymph nodes biopsy (SLNB) and axillary lymph nodes dissection (ALND), respectively. Isolated tumor cells were found in four (1.11%) patients and axillary metastasis rate was 2.51%. Neither axillary evaluation methods (P = 0.244) nor axillary metastasis rate (P = 0.559) was significantly different between patients with one focus and multiple foci. In univariate analysis, patients with multiple foci tended to have larger tumor size (P < 0.001), higher nuclear grade (P = 0.001), and higher rate of lymphatic vascular invasion (P = 0.034). Also, the proportion of positive HER2 (P = 0.027) and Ki67 level (P = 0.004) increased in patients with multiple foci, while in multivariate analysis, only tumor size showed significant difference (P = 0.009). Patients with multiple foci were more likely to receive chemotherapy (56.35 vs 40.77%; P = 0.028). At median 5.11 years follow-up, overall survival rate was 99.36%. Patients with multiple microinvasive foci had worse disease-free survival rate compared with one-focus patients (98.29 vs 93.01%, P = 0.032).ConclusionEven though the numbers of microinvasion were different and patients with multiple foci of microinvasion tended to have larger tumor size, there was no higher risk of axillary involvement compared with patients with one focus of microinvasion, while patients with multiple microinvasive foci had worse DFS rate. Thus, DCISM patients with multiple foci of microinvasion may be the criterion for more aggressive local–regional treatment. Optimization of adjuvant therapy in DCISM patients is required.

The Correlation of Minimal Residual Disease with Prognosis in TCF3-PBX1+ Acute Lymphoblastic Leukemia in Children

To investigate the consistency between FCM and PCR on the detecting of MRD in TCF3-PBX1+ ALL, and to investigate the prognosis value of these 2 methods. 55 cases of paediatric TCF3-PBX1+ ALL patients from April 2008 to April 2015 were enrolled and analyzed. The FCM and PCR was used to detect the MRD in 239 bone marrow samples of 55 patients. All statistical analyses were carried out by using SPSS software version 16. Among the 55 children with TCF3-PBX1+ ALL, there were 30 male and 25 female. The median age was 5 (1-14) years. 20 patients relapsed during follow-up. The MRD results from PCR and FCM showed a strong correlation between both methods (K=0.774, P<0.001). There was no significant difference in 5-years DFS and OS between the patients in PCR+ and PCR- groups on day 15 or day 33. The 5 year DFS rate between the patients in FCM- and FCM+ was 63.9%±7.0% and 0; the 5 year OS rate was 66.5%±7.9% and 0. Combined with the result of FCM and PCR, at the d 33 of treatment, the 5-year DFS rate in FCM-/PCR- and single positive group was 65.4%±7.2% and 25.0%±15.3% (P<0.01). The detection result of MRD in TCF3-PBX1 detect by FCM and PCR shows better consistency. MRD positivity detected by FCM at the end of induction therapy (day 33) predicts a high risk of relapse in TCF3-PBX1 ALL patients.

Is the Oncological Outcome of Early Stage Uterine Carcinosarcoma Different from That of Grade 3 Endometrioid Adenocarcinoma?

Aim: The clinicopathologic characteristics, recurrence patterns, and survival of patients with grade 3 endometrial cancer (G3-EAC) and uterine carcinosarcoma (UCS) were compared. Materials and Methods: The medical records of patients treated for G3-EAC and UCS between January 1996 and December 2016 at 11 gynecologic oncology centers in Turkey and Germany were analyzed. Results: Of all patients included in the study, 161 (45.1%) were diagnosed with UCS and 196 (54.9%) with G3-EAC at FIGO stage I–II (early stage) disease. The recurrence rate was higher in patients with UCS than in those with G3-EAC (17.4 vs. 9.2%, p = 0.02). The 5-year disease-free survival (DFS; 75.2 and 80.8%, respectively; p = 0.03) and overall survival (OS; 79.4 and 83.4%, respectively; p = 0.04) rates were significantly lower in the UCS group compared to the G3-EAC group. UCS histology was an independent prognostic factor for decreased 5-year DFS (HR 1.8, 95% CI 1.2–3.2; p = 0.034) and OS (HR 2.7, 95% CI 1.3–6.9; p = 0.041) rates. Conclusions: The recurrence rate was higher in UCS patients than in G3-EAC patients, regardless of disease stage. DFS and OS were of shorter duration in UCS than in G3-EAC patients. Adequate systematic lymphadenectomy and omentectomy were an independent prognostic factor for increased 5-year DFS and OS rates.

Mucoepidermoid carcinoma of salivary glands: A French Network of Rare Head and Neck Tumors (REFCOR) prospective study of 292 cases

BackgroundTo describe the characteristics of the largest European study of MEC of salivary glands and to determine the prognostic factors for overall and disease free survival. Patients and methodsPatients with MEC were prospectively included in the Réseau d’Expertise Français sur les Cancers ORL Rares (REFCOR, French Network of Rare Head and Neck Tumors) database between 2009 and 2015. ResultsA total of 292 patients were included. Tumors were classified as low grade in 175 cases (60%), intermediate in 39 (13%) and high grade in 78 (27%). Median follow-up was 26 months. The 5-year OS and DFS rates were respectively 83% and 69%. In multivariate analysis, age (p = 0.004), diabetes (p = 0.02) and advanced stage (p = 0.03) were found to have a significant negative impact on OS. Diabetes (p = 0.001), alcohol consumption (p = 0.003) and advanced stage (p = 0.001) were found to have a significant negative impact on DFS. Compare to low grade, high grade tended to have a negative impact on OS (p = 0.05) and had a significant effect on DFS (0.002) while intermediate grade had no significant influence on survival. The surgical treatment had a positive impact on both OS (p = 0.00005) and DFS (p = 0.0005). Postoperative radiotherapy had no impact in multivariate analysis. ConclusionAdvanced clinical stage, high grade tumor, high age, the impossibility of carrying out a complete surgical resection, and diabetes are the main prognostic factors in this prospective series of patients with MEC. Such findings open new research perspectives on the influence of these components on initial patient care.

Preoperative Hepatic and Regional Arterial Chemotherapy in Patients Who Underwent Curative Colorectal Cancer Resection: A Prospective, Multi-center, Randomized Controlled Trial.

To evaluate the effects of the addition of preoperative hepatic and regional arterial chemotherapy (PHRAC) on prognosis of stage II and III colorectal cancer (CRC) in a multicenter setting. Our previous single-center pilot trial suggested that PHRAC in combination with surgical resection could reduce the occurrence of liver metastasis (LM) and improve survival in CRC patients. A prospective multi-center randomized controlled trial was conducted from December 2008 to December 2012 at 5 hospitals in China. Eligible patients with clinical stage II or III CRC who underwent curative resection were randomized to receive PHRAC plus adjuvant therapy (PHRAC arm) or adjuvant therapy alone (control arm). The primary endpoint was DFS. Secondary endpoints were cumulative LM rates, overall survival (OS), and safety (NCT00643877). A total of 688 patients from 5 centers in China were randomly assigned (1:1) to each arm. The five-year DFS rate was 77% in the PHRAC arm and 65% in the control arm (HR = 0.61, 95% CI 0.46-0.81; P = 0.001). The 5-year LM rates were 7% and 16% in the PHRAC and control arms, respectively (HR = 0.37, 95% CI 0.22-0.63; P < 0.001). The 5-year OS rate was 84% in the PHRAC arm and 76% in the control arm (HR = 0.61, 95% CI 0.43-0.86; P = 0.005). There were no significant differences regarding treatment related morbidity or mortality between the two arms. The addition of PHRAC could improve DFS in patients with stage II and III CRC. It reduced the incidence of LM and improved OS without compromising patient safety. ClinicalTrials.gov identifier: NCT00643877.

Operative and Oncological Outcomes After D2 Versus D1 Gastrectomy of Operable Gastric Cancer: an Observational Study.

The optimal surgery for operable gastric carcinoma is still controversial. The aim of the current study was to assess the outcomes of D2 compared with D1 gastrectomy. This observational study included 80 patients with operable gastric cancer treated by D2 gastrectomy at Alexandria University Hospital between January 2010 and January 2016. Another 68 patients treated by D1 gastrectomy during the same period were included. Both groups were compared regarding operative mortality, morbidities, tumor recurrence, and 5-year survival rates. D2 gastrectomy had a significantly higher postoperative mortality and morbidity rates compared with D1 group (19.4% and 41.9% versus 6.3% and 18.8%). Mean number of LNs retrieved was statistically increased in D2 compared with D1 group with more frequency of adequate lymphadenectomy (LN retrieved > 15). D2 gastrectomy demonstrated significant lower recurrence and cancer-specific mortality rates compared with D1 group (18.6% and 14.5% versus 34.9% and 30.8%) with no significant difference in DFS and OS rates. Spleen-saving D2 gastrectomy showed no significant difference in early postoperative mortality with significant increase in DFS and OS compared with D1 gastrectomy (78.7% and 82% versus 61.5% and 64.6%). D2 gastrectomy had a lower recurrence and cancer-specific mortality rates than D1 gastrectomy but it had higher postoperative mortality and morbidity rates that resulted in no overall survival benefit of D2 compared with D1 gastrectomy. Spleen-saving D2 gastrectomy can be done safely in selected patients by expert surgeons without increased morbidity and mortality and better survival outcomes.

The role of circulating tumor cells and K-ras mutations in patients with locally advanced rectal cancer: a prospective study.

Rectal cancer is a common malignancy with a relatively poor prognosis. We assessed the possible prognostic and predictive role(s) of circulating tumor cells (CTCs) and K-ras mutations in locally advanced rectal carcinoma (LARC) patients. CTCs number and K-ras mutation status were assessed in the Peripheral blood and tumor tissue samples of 60 patients with LARC compared to control group (normal rectal mucosa). Data were correlated to relevant clinico-pathological features, response to treatment, disease free (DFS) and overall survival (OS) rates. K-ras mutations were present in 24/60 (40%) patients. Baseline CTCs (< 5 cells/7ml blood) were detected in 23/60 (38.3%) patients, and 37 (61.7%) had baseline CTCs (≥ 5 cells/7ml) blood (P = 0.071). Serial sampling showed a decrease in CTCs levels in 40 (66.7%) patients and increase in 20 (33.3%) patients (P = 0.01). Patients with K-ras mutations had a significantly poor response to treatment, with reduced DFS and OS rates (P = 0.001, 0.004, and 0.001; respectively). Similarly, decreased CTCs levels during treatment associated significantly with better pathological responses (P = 0.003). Multivariate analysis demonstrated that K-ras mutation and baseline CTCs are independent prognostic factors for DFS (P = 0.014 and 0.045; respectively) and OS (P = 0.002 and 0.045; respectively). The presence of mutant K-ras and baseline CTCs ≥ 5 cells associated significantly with poor pathological response, shorter DFS and OS rates compared to those with either K-ras mutation or CTCs ≥ 5 cells only (P = 0.014, 0.005 and 0.001, respectively). K-ras mutations, baseline and serial CTCs changes represent good prognostic and predictive factors for LARC patients.

Ibrutinib (Ibr) Plus Venetoclax (Ven) for First-Line Treatment of Chronic Lymphocytic Leukemia (CLL)/Small Lymphocytic Lymphoma (SLL): 1-Year Disease-Free Survival (DFS) Results From the MRD Cohort of the Phase 2 CAPTIVATE Study

Ibrutinib (Ibr) Plus Venetoclax (Ven) for First-Line Treatment of Chronic Lymphocytic Leukemia (CLL)/Small Lymphocytic Lymphoma (SLL): 1-Year Disease-Free Survival (DFS) Results From the MRD Cohort of the Phase 2 CAPTIVATE Study

Prognostic significance of PD-1/PD-L1 expression in uveal melanoma: correlation with tumor-infiltrating lymphocytes and clinicopathological parameters.

To understand how to improve the effect of immune checkpoint inhibitors in uveal melanoma (UM), we need a better understanding of the expression of PD-1 and PD-L1, their relation with the presence of tumor-infiltrating lymphocytes (TILs), and their prognostic relevance in UM patients. Expression of PD-1 and PD-L1 was assessed in 71 UM tissue samples by immunohistochemistry and quantitative real-time PCR (qRT-PCR), and further validated by western blotting. The effect of interferon gamma (IFN-γ) on PD-1/PD-L1 expression was determined on four UM cell lines. Immunoreactivity of PD-1 was found in 30/71 cases and of PD-L1 in 44/71 UM samples. Tumor-infiltrating lymphocytes were found in 46% of UM tissues. PD-1 was expressed on TILs while tumor cells expressed PD-L1. UM with and without TILs showed expression of PD-1 in 69% and 18% cases, respectively (p = 0.001). Similarly, PD-L1 was found in 75% of UM with TILs and in 50% of cases without TILs, respectively (p = 0.03). DFS rate were lower in patients with TILs with expression of PD-1 and PD-L1, but the rate of DFS was higher with expression of PD-L1 in patients without TILs. After treatment of UM cell lines with IFN-γ, PD-1 expression was induced in all UM cell lines whereas PD-L1 expression was found at a lower level in untreated cells, while expression also increased following treatment with IFN-γ. Our study suggests that increased infiltration with TILs promotes the aggressive behavior and suppresses the immune response of UM cells, thereby inhibiting immunotherapy.