Higher Disease-free Survival Research Articles

Neutrophil-to-lymphocyte and platelet-to-lymphocyte ratios as predictors of outcomes in inflammatory breast cancer.

Background: Inflammatory breast cancer (IBC) is uncommon, aggressive and associated with poor survival outcomes. The lack of prognostic biomarkers and therapeutic targets specific to IBC is an added challenge for clinical practice and research. Inflammatory biomarkers such as neutrophil-to-lymphocyte and platelet-to-lymphocyte ratios (NLR and PLR) demonstrated independent prognostic impact for survival in breast cancer. In our study, these biomarkers were investigated in a cohort of patients with nonmetastatic IBC. Methods: A retrospective cohort of 102 IBC patients with nonmetastatic disease was conducted at the Mohammed VI University Hospital (Oujda, Morocco) between January 2010 and December 2014. NLR and PLR were obtained from blood cell count at baseline before neoadjuvant chemotherapy (NACT) from patients' medical records. The receiver operating characteristic was used to find the optimal cut-off. Correlation between these blood-based biomarkers and response to NACT was analyzed by Chi-squared and Fisher's exact test. Their prognostic value for predicting disease-free survival (DFS) and overall survival (OS) was performed based on Cox regression models. Results: Totally, 102 patients with IBC were included in the analysis. Pathologic complete response (pCR) after NACT, defined by the absence of an invasive tumor in the breast tissues and nodes after surgery (ypT0 ypN0), was observed in eight patients (7.8%). NACT response was found to be associated with menopausal status (p=0.039) and nodal status (p<0.001). Patients with a low NLR had a higher pCR rate as compared with the high-NLR group (p=0.043). However, the pCR rate was not significantly associated with age (p=0.122), tumor side (p=0.403), BMI (p=0.615), histological grade (p=0.059), hormone receptors status(p=0.206), HER2 (p=0.491) and PLR (p=0.096). Pre-treatment blood-based NLR of 2.28 was used as the cut-off value to discriminate between high and low NLR according to the receiver operating characteristic curves. Similarly, a value of 178 was used as the cut off for PLR. Patients with low-NLR had a significantly better 5-year DFS (p<0.001) and OS (p<0.001) than the high-NLR group. Moreover, low-PLR was significantly associated with higher DFS (p=0.001) and OS (p=0.003). The NLR showed a significant prognostic impact for DFS (HR: 2.57; 95% CI: 1.43-4.61; p=0.01) and for OS (HR: 2.92; 95% CI: 1.70-5.02; p<0.001). Similarly, a meaningful association between PLR and 5-year DFS (HR: 1.95; 95% CI: 1.10-3.46; p=0.021) and OS (HR: 1.82; 95% CI: 1.06-3.14; p=0.03) was noticed. Conclusions: High NLR and PLR were found associated with reduced DFS and OS in nonmetastatic IBC. Further studies are awaited to confirm these findings.

P-94 Unicentric real-world data from esophageal cancer neoadjuvant treatment according to the CROSS trial protocol

Locally advanced esophageal cancer (EC) remains a disease with poor prognosis, with a 5-year survival of around 40%. In 2012, the CROSS trial was a changing point in the treatment of EC by introducing neoadjuvant (NA) chemoradiotherapy (CRT), with carboplatin/paclitaxel and reduced-dose RT (41.4Gy), as a valid approach, with higher disease-free survival (DFS) and overall survival (OS) than had been seen before. These results had subgroup variations, with better OS in squamous cell carcinoma (SCC) patients when compared to adenocarcinoma (AC).

Long-Term Outcomes of Total Body Irradiation Plus Cyclophosphamide Versus Busulfan Plus Cyclophosphamide As Conditioning Regimen for Acute Lymphoblastic Leukemia: A Comparative Study

Introduction: Total body irradiation-Cyclophosphamide (TBI-Cy) and Busulfan-Cyclophosphamide (Bu-Cy) are the most commonly used conditioning regimens in allogeneic hematopoietic stem cell transplantation (allo-HCT) for acute lymphoblastic leukemia (ALL). TBI-based conditioning regimens may have a better antitumor effect at sanctuary cites compared to chemotherapy regimens. However, some controversy still remains concerning the role of TBI in adult ALL. Therefore, we aimed to retrospectively investigate long-term treatment outcomes of ALL patients post allo-HCT and identify prognostic factors and the impact of the conditioning.Methods: We enrolled consecutive patients with ALL who underwent alloHCT from 1990 to 2016 in our center, following a TBI- or a Busulfan (Bu)-based conditioning regimen. TBI at 14.4Gy was divided at 6 fractions over 3 days and Bu (mainly oral) at 4mg/kg/day. Both regimens included 120mg/kg Cy. Graft source was mainly mobilized peripheral blood stem cells.Results: We studied 151 ALL (114 B-ALL, 35 T-ALL and 2 biphenotypic) patients aged 28±12 years, transplanted in CR1 (60), other CR (33) or relapsed/refractory disease (58) from sibling (87), HLA matched (42) or mis-matched (17) unrelated and alternative donors (5). TBI-based conditioning was administered in 84, whereas non-TBI in 67. No differences were observed in baseline characteristics, except for disease phase, disease risk index (DRI) and graft source. The majority of non-TBI patients had relapsed/refractory disease at transplant (50.7% versus 28.6% in TBI-conditioning, p=0.043) and subsequently significantly higher DRI (p=0.025). Furthermore, bone marrow was the graft source in significantly higher number of non-TBI patients (28.4% versus 8.3% in the TBI group, p=0.001).With a follow-up of 19.0 (0.5-170.5) in TBI and 14.5 (1.2-319.1) months in the non-TBI group, there was no difference in the incidence of acute (Grade 2-4) or chronic GVHD, thrombotic microangiopathy, bacterial or fungal infections. Only viral infections were significantly increased in the non-TBI group (59% versus 41% in the TBI group, p=0.03). Therefore, there was no significant difference in the cumulative incidence (CI) of treatment-related mortality (5-year CI of 24.1% in non-TBI versus 27.7% in the TBI group, p=0.678) or relapse mortality (5-year CI of 29.2% in non-TBI versus 37.1% in the TBI group, p=0.283).Overall survival (OS) was similar in the TBI and non-TBI group (5-year 46.7% compared to 35.8%, p=0.201). In the multivariate analysis, unfavorable pre-transplant predictors of OS were age (p=0.024), higher disease risk index (DRI) (p=0.007) and female to male donor (p=0.006). Disease-free survival (DFS) was similar in the TBI and non-TBI group (5-year 47.1% compared to 35.4%, p=0.134), with age, higher DRI and female to male donor being unfavorable predictors. When the analysis was limited to patients transplanted in CR1 (40 in the TBI versus 20 in the non-TBI group), there were also no significant differences.Interestingly, age predicted OS and DFS only in the TBI group. TBI patients younger than 40 years had significantly high OS (55.1%, p=0.023) and DFS (55.5%, p=0.02) versus the older ones. Older TBI patients had higher TRM (43.3% versus 20.1%, p=0.135) and relapse mortality (45.8 versus 24.7, p=0.238) that did not reach levels of statistical significance. However, the same was not true for the non-TBI group (p=0.233 for DFS, p=0.326 for OS).Conclusion: In our retrospective data of the last 3 decades, the type of conditioning regimen did not influence the outcome of transplantation. Based on our results, high dose TBI is a feasible conditioning in terms of a prolonged DFS and OS for younger patients and seems an efficient tool to cure high-risk ALL in CR1. It should be kept in mind that intravenous BU is also used with stable pharmacokinetics. Since our data were not powered to appraise superiority of one regimen in terms of efficacy and toxicity, the choice between TBI or Bu conditioning regimens is still under consideration. Treatment is complex for adult ALL patients and remains a field of debate and a challenge for prospective studies in the future. DisclosuresGavriilaki:European Hematology Association: Research Funding.

Arsenic trioxide dose capping to decrease toxicity in the treatment of acute promyelocytic leukemia.

Arsenic trioxide (ATO) and all-trans retinoic acid (ATRA) combination therapy yields high complete remission and disease-free survival rates in acute promyelocytic leukemia (APL). ATO is dosed on actual body weight and high ATO doses in overweight patients may contribute to increased toxicity. We performed a retrospective, two-center study comparing toxicities in patients who received the Lo-Coco et al ATRA/ATO regimen with capped ATO, ≤10 mg/dose, and non-capped ATO, >10 mg/dose. A total of 44 patients were included; 15 received doses ≤10 mg and 29 received >10 mg. During induction, there was no difference in the incidence of grade ≥3 hepatotoxicity, grade ≥3 QTc prolongation, neurotoxicity, and cardiac toxicity between groups. In consolidation, patients receiving >10 mg/dose experienced a greater incidence of neurotoxicity (66.7% vs 22.2%; p = 0.046). Capping doses saved $24634.37/patient and reduced waste of partially-used vials. At a median follow-up of 27 months, no disease relapses occurred in either group. This represents an opportunity to improve the safety profile of this highly effective regimen.

Prognostic influences of BCL1 and BCL2 expression on disease-free survival in breast cancer

We investigated the prognostic influences of BCL1 and BCL2 expression on disease-free survival in breast cancer patients. BCL1 and BCL2 expression statuses were assessed by immunohistochemistry using tissue microarrays from 393 breast cancer patients. The Kaplan–Meier estimator and log-rank test were used for survival analyses. The Cox proportional hazards model was used to calculate hazard ratio (HR) and the 95% confidence interval (CI) of survival analyses. BCL1 expression revealed no impact on survival. The high BCL2 group showed superior disease-free survival compared with the low BCL2 group (p = 0.002), especially regarding local recurrence-free survival (p = 0.045) and systemic recurrence-free survival (p = 0.002). BCL2 expression was a significant prognostic factor by univariable analysis (HR, 0.528; 95% CI, 0.353–0.790; p = 0.002) and by multivariable analysis (HR, 0.547; 95% CI, 0.362–0.826; p = 0.004). High BCL2 expression was associated with higher disease-free survival in the hormone receptor (HRc)-positive and human epidermal growth factor receptor 2 (HER2)-negative (HRc(+)/HER2(−)) subtype only (p = 0.002). The high BCL2 group was associated with positive estrogen receptor (ER), positive progesterone receptor (PR), low histologic grade, and age ≤ 50 years. BCL1 expression had no prognostic impact, but BCL2 expression was a significant independent prognostic factor. High BCL2 expression was associated with higher disease-free survival, especially regarding local recurrence and systemic recurrence. The prognostic effect of BCL2 expression was effective only in the HRc(+)/HER2(−) subtype. Favorable clinicopathologic features and a strong association with the ER/PR status could partly explain the superior prognosis of the high BCL2 group. BCL2 expression could be utilized to assess the prognosis of breast cancer patients in clinical settings.

Association of pathological response to neoadjuvant pembrolizumab with tumor PD-L1 expression and high disease-free survival (DFS) in patients with resectable, local-regionally advanced, head and neck squamous cell carcinoma (HNSCC).

6006 Background: Patients with resected HNSCC, with high-risk (positive margins, extracapsular spread [ECE]) or intermediate-risk pathological features have an estimated 1-year DFS of 65% and 69%, respectively. Immune checkpoint blockade improved survival of patients with recurrent/metastatic HNSCC, and preclinical models indicate radiotherapy (RT) synergizes with anti-PD-1. Therefore, we administered the PD-1 inhibitor pembrolizumab (pembro) pre- and post-surgery with adjuvant RT +/- cisplatin in patients with resectable, locoregionally advanced (clinical T3/4 and/or ≥2 nodal metastases) HNSCC (NCT02641093). Methods: Eligible patients received pembro (200 mg I.V. x 1) 1-3 weeks before resection. Adjuvant pembro (q3 wks x 6 doses) was administered with RT (60-66Gy) with or without weekly cisplatin (40mg/m2 X 6) for patients with high-risk and intermediate-risk features, respectively. The primary endpoint was 1-year DFS estimated by Kaplan Meier curves. Safety was evaluated by CTCAE v5.0. Pathological response (PR) to neoadjuvant pembro was evaluated by comparing pre- and post-surgical tumor specimens for treatment effect (TE), defined as tumor necrosis and/or histiocytic inflammation and giant cell reaction to keratinaceous debris. PR was classified as no (NPR, &lt; 20%), partial (PPR, ≥20% and &lt; 90%) and major (MPR, ≥90%). Tumor PD-L1 immunohistochemistry was performed with 22c3 antibody and reported as combined positive score (CPS). Results: Ninety-two patients were enrolled. Seventy-six patients received adjuvant pembro and were evaluable for DFS. Patient characteristics included: median age 58 (range 27 – 80) years; 32% female; 88% oral cavity, 8% larynx, and 3% human papillomavirus negative oropharynx; 86% clinical T3/4 and 65% ≥2N; 49 (53%) high-risk (positive margins, 45%; ECE, 78%); 64% (44/69 available) had PD-L1 CPS ≥1. At a median follow-up of 20 months, 1-year DFS was 67% (95%CI 0.52-0.85) in the high-risk group and 93% (95%CI 0.84-1) in the intermediate-risk group. Among 80 patients evaluable for PR, TE scoring resulted in 48 NPR, 26 PPR and 6 MPR. Patients with PPR/MPR had significantly improved 1-year DFS when compared with those with NPR (100% versus 68%, p = 0.01; HR = 0.23). PD-L1 CPS ≥ 1 was not independently associated with 1-year DFS, but was highly associated with MPR/PPR (p = 0.0007). PPR/MPR in PD-L1 CPS &lt; 1, ≥1 and ≥20, were estimated as 20, 55 and 90%, respectively. Grade ≥ 3 adverse events occurred in 62% patients with most common including dysphagia (15%), neutropenia (15%), skin/wound infections (10%), and mucositis (9%). Conclusions: PR to neoadjuvant pembro is associated with PD-L1 CPS≥1 and high DFS in patients with resectable, local-regionally advanced, HNSCC. Clinical trial information: NCT02641093.

Oncologic outcomes of human papillomavirus-associated oropharynx carcinoma treated with surgery alone: A 12-institution study of 344 patients.

The oncologic outcomes of surgery alone for patients with American Joint Committee on Cancer 7th edition (AJCC 7th) pN2a and pN2b human papillomavirus-associated oropharynx squamous cell carcinoma (HPV+OPSCC) are not clear. The authors performed a 12-institution retrospective study of 344 consecutive patients with HPV+OPSCC (AJCC 7th pT0-3 N3 M0) treated with surgery alone with 6 months or more of follow-up using univariate and multivariate analyses. The 2-year outcomes for the entire cohort were 91% (182 of 200) disease-free survival (DFS), 100% (200 of 200) disease-specific survival (DSS), and 98% (200 of 204) overall survival (OS). The 18 recurrences within 2 years were 88.9% (16 of 18) local and/or regional recurrences and 11.1% (2 of 18) distant metastases. Recurrences were not significantly associated with smoking, pT stage, or pN stage. The 16 patients with locoregional recurrences within 2 years all underwent successful salvage treatments (median follow-up after salvage: 13.1 months), 43.8% (7 of 16) of whom underwent salvage surgery alone for a 2-year overall salvage radiation need of 4.5% (9 of 200). The 2-year outcomes for the 59 evaluable patients among the 109 AJCC 7th pT0-2 N2a-N2b patients with 1 to 3 pathologic lymph nodes (LNs) were as follows: local recurrence, 3.4% (2 of 59); regional recurrence, 8.4% (5 of 59); distant metastases, 0%; DFS, 88.1% (52 of 59); DSS, 100% (59 of 59); OS, 96.7% (59 of 61); and salvage radiation, 5.1% (3 of 59). With careful selection, surgery alone for AJCC 7th pT0-T2N0-N2b HPV+OPSCC with zero to 3 pathologic LNs without perineural invasion, extranodal extension, or positive margins results in high DFS, DSS, OS, and salvage treatment success. Because of the short-term follow-up, these data support further investigation of treatment de-escalation in this population.

Docetaxel, carboplatin plus trastuzumab as neoadjuvant setting in patients with early-stage human epidermal growth factor receptor 2 positive breast cancer: a retrospective analysis

Objective: To examine the efficacy of docetaxel, carboplatin plus trastuzumab regimen (TCH) as neoadjuvant setting in early-stage human epidermal growth factor receptor 2 (HER2) positive breast cancer. Methods: Totally 522 patients diagnosed with early-stage HER2 positive breast cancer at Breast Disease Center, Peking University First Hospital between January 2013 to December 2018 were enrolled, which constituted 21.8% (522/2 394) of early-stage invasive breast cancer. Clinical pathological factors were retrospectively analyzed. There were 113 female patients underwent TCH neoadjuvant chemotherapy, aging 52(13) years (range: 23 to 69 years). Pathologic complete pathological response(pCR) was defined as ypT0N0M0, and the rate of pCR was calculated. Kaplan-Meier method and Log-rank test were used for survival comparison. Results: Patients who received trastuzumab-based therapy(n=294) had higher disease-free survival (DFS) compared with those who omitted trastuzumab(n=177) (84.4% vs. 72.4%, χ²=4.095, P=0.046). Eighteen of 113 patients (15.9%) experienced grade 3 to 4 chemotherapy-realted toxicity. Grade 3 to 4 neutropenia occurred in 12 patients, while grade 3 to 4 diarrhea occurred in 6 patients. Thirty-one of 113 (27.4%) patients achieved pCR. DFS and overall survival (OS) were similar between patients who achieved pCR and non-pCR (DFS: 91.8% vs. 85.0%, OS: 92.5% vs. 90.5%, all P>0.05). According to Miller-Payne system, patients who achieved G4 to G5 had improved DFS compared with G1 to G3 (89.6% vs. 81.5%, χ²=5.340, P=0.021), but they had similar OS (91.4% vs. 89.1%, χ²=1.008, P=0.315). Conclusions: TCH is an effective regimen in neoadjuvant setting for patients with HER2 positive breast cancer. Patients who achieved G4 to G5 had improved DFS.

Trastuzumab Provides a Comparable Prognosis in Patients With HER2-Positive Breast Cancer to Those With HER2-Negative Breast Cancer: Post Hoc Analyses of a Randomized Controlled Trial of Post-Mastectomy Hypofractionated Radiotherapy.

Background and PurposeWe investigated the locoregional effect of trastuzumab, and determined whether patients with human epidermal growth factor receptor (HER)2-positive breast cancer (BC) treated with trastuzumab could achieve comparable efficacy to that of patients with HER2-negative BC.Materials and MethodsThis was post hoc analyses of data of 793 BC patients from a randomized controlled trial comparing post-mastectomy hypofractionated radiotherapy with conventional fractionated radiotherapy. Survival rates were analyzed by the Kaplan–Meier method and compared by the log-rank test.ResultsPatients were classified into three groups: HER2-negative (HER2−; n = 547), HER2-positve with trastuzumab (HER2+ + T; n = 136), and HER2-positive without trastuzumab (HER2+ − T; n = 110). The HER2+ + T group had significantly lower locoregional recurrence (LRR, 6.0% vs. 13.9%), distant metastasis (DM, 17.4% vs. 33.8%) and higher disease-free survival (DFS, 81.2% vs. 61.9%) at 5 years than that of the HER2+ − T group (P <.05). The HER2− group had significantly lower LRR (6.8% vs. 13.9%), DM (22.4% vs. 33.8%) and higher DFS (76.1% vs. 61.9%) at 5 years than that of the HER2+ − T group (P <.05). The difference in LRR, DM and DFS at 5 years was not significant between the HER2+ + T group and HER2− group (P >.05). Different annual LRR patterns was found among groups according to HR status.ConclusionTrastuzumab reduces LRR in patients with locally advanced HER2-positive BC who have received post-mastectomy radiotherapy. It provides comparable DFS to that with patients with HER2-negative BC.

Disease-free and overall survival in nonmetastatic esophageal or gastroesophageal junctional cancer after treatment with curative intent: A nationwide population-based study.

246 Background: Among patients with potentially curable esophageal cancer (EC) or gastroesophageal junctional cancer (GEJC) treated with curative intent, survival remains poor and around half of these patients have disease recurrence within a few years. This study addresses the need for real-world data on disease-free survival (DFS) and overall survival (OS) in patients with EC or GEJC who underwent potentially curative treatment. Methods: Patients selected from the nationwide Netherlands cancer registry (NCR) had received a primary diagnosis of non-metastatic EC or GEJC (excluding patients with T4b tumors) in 2015 or 2016 and received treatment with curative intent. Curative intent was defined as receiving resection (with or without [neo]adjuvant therapy) or definitive chemoradiotherapy (dCRT) without surgery. DFS and OS were analysed using Kaplan-Meier curves with Log-Rank test from resection date or end of dCRT. A sub-analysis was performed for NCR patients selected to align with the population of the CheckMate-577 phase 3 study of adjuvant nivolumab, i.e. patients with non-cervical stage II/III disease, R0 resection and residual pathological disease after neoadjuvant CRT (nCRT) and surgery. Results: We identified 1916 patients of median age of 67 years and predominantly male (76%). The majority (79%) received surgery and 21% of patients received dCRT. In resected patients, 83% received nCRT, 10% neoadjuvant chemotherapy (with or without adjuvant CRT) and 7% received no (neo)adjuvant treatment. Compared to the resected group, the population receiving dCRT had significantly fewer males (65% vs 78%), a higher median age (72 vs 65 years) and worse performance status. Patients receiving dCRT significantly shorter median DFS (14.2 months) and OS (20.9 months) compared to resected patients (DFS: 26.4 months, p &lt; 0.001; OS: 40.5 months, p &lt; 0.001). The 1- and 3-year DFS probabilities were 68% and 44%, respectively, in resected patients, and 56% and 24%, respectively, in patients receiving dCRT. In patients receiving nCRT followed by surgery, the median DFS and OS were 25.2 and 38.0 months, respectively, and 1- and 3-year DFS probabilities were 67% and 43%, respectively. In the sub-analysis (n = 725) the median DFS and OS were 19.2 and 29.4 months, respectively, and the 1- and 3-year DFS rates were 62% and 36%, respectively. Conclusions: Although patients are treated with curative intent, a considerable amount of patients with non-metastatic EC or GEJC experienced recurrence within two years. Resected patients had a higher DFS and OS compared to patients receiving dCRT.

Effectiveness of Sequential Chemoradiation vs Concurrent Chemoradiation or Radiation Alone in Adjuvant Treatment After Hysterectomy for Cervical Cancer

There is no current consensus on the role of chemotherapy in addition to radiation for postoperative adjuvant treatment of patients with early-stage cervical cancer with adverse pathological factors. To evaluate the clinical benefits of sequential chemoradiation (SCRT) and concurrent chemoradiation (CCRT) compared with radiation alone (RT) as a postoperative adjuvant treatment in early-stage cervical cancer. After radical hysterectomy at 1 of 8 participating hospitals in China, patients with FIGO (International Federation of Gynecology and Obstetrics) stage IB to IIA cervical cancer with adverse pathological factors were randomized 1:1:1 to receive adjuvant RT, CCRT, or SCRT. Data were collected from February 2008 to December 2018. Patients received adjuvant RT (total dose, 45-50 Gy), CCRT (weekly cisplatin, 30-40 mg/m2), or SCRT (cisplatin, 60-75 mg/m2, plus paclitaxel, 135-175 mg/m2) in a 21-day cycle, given 2 cycles before and 2 cycles after radiotherapy, respectively. The primary end point was the rate of disease-free survival (DFS) at 3 years. A total of 1048 women (median [range] age, 48 [23-65] years) were included in the analysis (350 in the RT group, 345 in the CCRT group, and 353 in the SCRT group). Baseline demographic and disease characteristics were balanced among the treatment groups except that the rate of lymph node involvement was lowest in the RT group (18.3%). In the intention-to-treat population, SCRT was associated with a higher rate of DFS than RT (3-year rate, 90.0% vs 82.0%; hazard ratio [HR], 0.52; 95% CI, 0.35-0.76) and CCRT (90.0% vs 85.0%; HR, 0.65; 95% CI, 0.44-0.96). Treatment with SCRT also decreased cancer death risk compared with RT (5-year rate, 92.0% vs 88.0%; HR, 0.58; 95% CI, 0.35-0.95) after adjustment for lymph node involvement. However, neither DFS nor cancer death risk was different among patients treated with CCRT or RT. In this randomized clinical trial, conducted in a postoperative adjuvant treatment setting, SCRT, rather than CCRT, resulted in a higher DFS and lower risk of cancer death than RT among women with early-stage cervical cancer. ClinicalTrials.gov Identifier: NCT00806117.

Radical antegrade modular pancreatosplenectomy (RAMPS) versus conventional distal pancreatosplenectomy (CDPS) for left-sided pancreatic ductal adenocarcinoma.

The insufficient clearance of regional lymph nodes and unsatisfactory R0 resection rate may result in the metastasis of left-sided pancreatic ductal adenocarcinoma (PDAC) after conventional distal pancreatosplenectomy (CDPS). Radical antegrade modular pancreatosplenectomy (RAMPS) was designed to achieve R0 resection more successfully with better lymph-node clearance; however, there is still insufficient evidence of its short- and long-term results to confirm its superiority. We conducted this study to compare the efficiency of these two procedures. The subjects of this retrospective analysis were 103 patients with left-sided PDAC who underwent either RAMPS (n = 46) or CDPS (n = 57). We assessed perioperative data and surgical information and used univariate and multivariate analyses to identify prognostic factors for survival. There were no significant differences in baseline data between the groups. RAMPS was associated with a significantly shorter hospital stay (12.11days vs. 22.98days; P < 0.001), and significantly less blood loss (451.09ml vs. 764.04ml, P = 0.002), as well as a significantly lower rate of blood transfusion (15.22% vs. 33.33%, P = 0.035). RAMPS and CDPS had comparable perioperative complication rates. Moreover, RAMPS achieved more effective lymph-node retrieval (17.87 vs. 10.23; P < 0.001). The RAMPS group had a higher overall survival (OS) rate (28.73months vs. 18.30months; P = 0.003) and a higher disease-free survival (DFS) rate (21.97months vs. 9.40months; P < 0.001). RAMPS achieved better survival and surgical outcomes than CDPS for patients with left-sided PDAC.

Systematic Review of the Role of BCG in the Treatment of Urothelial Carcinoma of the Prostatic Urethra.

In patients with non-invasive urothelial carcinoma of the prostatic urethra (PUC), treatment with Bacillus Calmette-Guérin (BCG) could be beneficial. To assess the response rates to BCG in the different tumor stages, to describe the clinical impact of transurethral resection of the prostate (TURP) before BCG treatment, and to review the side effects of BCG treatment for PUC. A systematic search was conducted using the PubMed database to identify original studies between 1977 and 2019 reporting on PUC and BCG. Of a total of 865 studies, ten were considered for evidence synthesis. An indication for BCG treatment was found in non-stromal invasive stages (Tis pu, Tis pd) and in stromal infiltrating cases (T1) of primary and secondary PUC when transitional cell carcinoma was the histology of origin. Studies including patients treated with TURP before BCG showed a better local response in the prostatic urethra with a higher disease free survival (DFS) (80-100% vs. 63-89%) and progression free survival (PFS) (90-100% vs. 75-94%) than patients in studies in which no TURP was performed. However, this difference in recurrence and progression in the prostate neither affected the total PFS (57-75% vs. 58-93%), nor the disease specific survival (70-100% vs. 66-100%). The use of resection loop biopsies of the prostatic urethra in appropriate cases during the primary work-up for suspected PUC, as well as the use of the current TNM classification for PUC, need to be improved. BCG therapy for non-stromal invasive stages of PUC show a good local response. Local response is further improved by a TURP before BCG therapy, although the overall prognosis does not seem to be affected. Further evidence for BCG treatment in the rare cases of stromal invasive PUC is needed. Specific side effects of BCG treatment for PUC are not reported.

High level of CD73 predicts poor prognosis of intrahepatic cholangiocarcinoma.

Background: Despite recent improvements in the diagnosis and therapy of intrahepatic cholangiocarcinoma (ICC), the prognosis for ICC patients remains poor. Therefore, it is needed to identify new biological indicators for ICC progression.Methods: Immunohistochemistry was engaged to inspect the ecto-5ʹ-nucleotidase (CD73) and CD8 expressions in tissue microarrays including tissues from 140 ICC patients. Then, the association between the level of CD73/CD8 and clinicopathologic characteristics of ICC was analysed. Finally, the prognostic value of CD73 and CD8 levels in ICC patients was assessed by Kaplan-Meier and multivariate and univariate analyses.Results: The CD73 expression was evidently upregulated in ICC tissues compared to the corresponding peritumoral tissues. The elevated CD73 expression was positively related to the lymphatic metastasis (p=0.049). While the level of tumour-infiltrating CD8 T+ cells in tumour tissues was negatively associated with serum AFP (p=0.019), tumor size (p=0.028), and lymphatic metastasis (p=0.039). Additionally, patients with elevated CD73 expression or low tumour-infiltrating CD8+ T cells exhibited shorter overall survival (OS) and higher disease-free survival (DFS) rates than patients with low CD73 expression and/or high tumour-infiltrating CD8+ T cells. Notably, the overexpression of CD73 or low tumour-infiltrating CD8+ T cells was an independent indicator for predicting the OS and DFS of ICC patients.Conclusions: We revealed that CD73 expression and low tumour-infiltrating CD8+T cells are valuable predictors of survival and recurrence in patients with ICC.

Prognostic impact of neutrophils-to-lymphocytes ratio (NLR), PD-L1 expression, and tumor immune microenvironment in laryngeal cancer

PurposeIn laryngeal carcinoma (LSCC), tumor immune microenvironment is attracting increasing interest, given the recent progresses in immunotherapy. Immune cells migrate to tumors as a result of a tumor antigen-induced immune reaction and cancer cells recruit immune regulatory cells to induce an immunosuppressive network, resulting in the escape from host immunity. This interaction reflects both on tumor microenvironment and systemic inflammatory status. Blood neutrophil-to-lymphocyte ratio (NLR), reflecting a highly pro-inflammatory status, has been related to worse oncological survival outcomes.The aim of this study was to analyze in LSCC the relationship between circulating inflammatory cells (also in terms of NLR) and tumor immune microenvironment histopathological features (programmed cell death ligand 1 [PD-L1] expression, and tumor-infiltrating lymphocytes [TILs]), also investigating their clinical-pathological and prognostic significance. MethodsBlood pre-operative NLR, and, at pathology, PD-L1 (in terms of combined positive score [CPS]) and TILs were assessed on 60 consecutive cases of LSCC. ResultsBlood NLR, neutrophils, and lymphocytes counts showed a significant value in predicting DFS and recurrence risk. Moreover, PD-L1 CPS ≥ 1 and TILs count rate ≥30% were associated with higher disease-free survival (DFS) and reduced recurrence risk. A logistic regression model found a significant positive association between increasing NLR values, and PD-L1 CPS < 1 and TILs count rate <30%. ConclusionsFurther studies are needed to better characterize the role of pre-operative blood NLR in association with PD-L1 expression and tumor immune microenvironment features as prognostic factors and markers of anti-tumor immune response in LSCCs, also with regard to the effectiveness of immunotherapeutic protocols.

The pathological features and prognoses of intraductal papillary mucinous neoplasm and mucinous cystic neoplasm after surgical resection: a single institution series

BackgroundIntraductal papillary mucinous neoplasms (IPMNs) and mucinous cystic neoplasms (MCNs) represent the tumors with malignant transformation potential. The objective of the study was to verify their pathological characteristics, prognoses, and recurrence factors.MethodsTwo hundred eighteen IPMNs and 27 MCNs resected at a single institution were included. The demographic, preoperative, histopathological, and follow-up data of the patients were recorded and analyzed. Overall survival (OS) and disease-free survival (DFS) were defined as the interval from the date of initial surgery to death or the last follow-up (OS) and to diagnosis of recurrence or death at follow-up (DFS).ResultsOf the 218 IPMN and 27 MCN patients, 93 (42.7%) and 8 (29.6%) cases were malignant, respectively. IPMNs occurred in older patients compared with MCN patients (median 63 years vs 54 years, P < 0.0001), and MCNs occurred exclusively in females (100%). Of the overall study cohort, the pathological specimens presented peripheral invasion in 37 (15.1%) patients and incisal margin invasion was observed in 46 (18.8%) patients. After a median follow-up of 34 months, 37 (14.9%) patients relapsed. The 5-year OS and DFS rates of IPMNs were 97.5% and 80.6%; and the OS and DFS rates of MCNs were 95.7% and 87.0%, respectively. There were four independent risk factors associated with recurrence: pathological diagnoses with malignancy (odds ratio, OR = 3.65), presence of oncocytic type for IPMN (OR = 1.69), peripheral invasion (OR = 12.87), and incisal margin invasion (OR = 1.99).ConclusionsIPMNs and MCNs are indolent tumors with favorable prognoses after surgical resection in terms of their relatively high OS and DFS rate. Patients with malignant pathological-related diagnoses should accept strict tumor surveillance in view of their higher risk of recurrence.

Comparing prognostic factors of Glut-1 expression and maximum standardized uptake value by FDG-PET in patients with resectable pancreatic cancer

BackgroundThis study aimed to assess the prognostic values of preoperative maximum standardized uptake value (SUVmax) of primary pancreatic tumors and Glut-1 expression in patients with resectable pancreatic ductal adenocarcinoma (R-PDAC), and to investigate whether Glut-1 expression is more effective than SUVmax in predicting survival in patients with R-PDAC. MethodsWe investigated 101 R-PDAC patients who underwent pancreatectomy for pancreatic cancer treatment. SUVmax analyzed through 18F-fluoro-2-deoxyglucose positron emission tomography/computed tomography (18F-FDG-PET/CT), and Glut-1 expression, were assessed for predicting the prognosis of patients with R-PDAC. ResultsIn patients with R-PDAC, the high SUVmax group (≥4.25) had significantly shorter overall survival (OS) and disease-free survival (DFS) than the low SUVmax group (＜4.25). Surprisingly, Glut-1 expression was not significantly correlated with SUVmax. Moreover, the high Glut-1 expression group, which was related to higher levels of CA 19–9, had significantly shorter OS and DFS than the low Glut-1 expression group. Furthermore, among the high SUVmax group, OS and DFS were significantly shorter in the high Glut-1 expression group. Multivariate analyses revealed that Glut-1 overexpression was an independent prognostic factor in patients with R-PDAC. Glut-1 knockdown also induced cell cycle arrest in PDAC cells in vitro. ConclusionsThe study determined that Glut-1 overexpression is a more powerful prognostic factor than SUVmax for predicting OS and higher risk of recurrence in R-PDAC patients. Glut-1 overexpression is also more likely to be associated with malignant activity in PDAC patients.

Short- and long-term outcomes of surgery for colorectal and non-colorectal liver metastasis: a report from a single center in the Baltic country

BackgroundThe liver is a major target organ for metastases of various types of cancers. Surgery is a well-established option for colorectal liver metastases (CRLM). Regarding the improved surgical and anesthetic techniques, the safety of liver resection has increased. Consequently, the interest in the surgical management of non-colorectal liver metastases (non-CRLM) has gained significant attention. Therefore, this study was designed to investigate the surgical treatment outcomes for non-CRLM and to compare it with an outcome of CRLM in a tertiary care center in the Baltic country—Lithuania.MethodsWe retrospectively analyzed data from all patients who underwent liver resection for CRLM or non-CRLM between 2010 and 2017 in a tertiary care center—Vilnius University hospital Santaros Clinics. Demographic and metastasis characteristics, as well as disease-free and overall survival, were compared between the study groups.ResultsIn total, 149 patients were included in the study. Patients in the CRLM group were older (63.2 ± 1.01 vs 54.1 ± 1.8 years, p < 0.001) and mainly predominant by males. Overall postoperative morbidity rate (16.3% vs 9.8%, p = 0.402) and major complications rate (10% vs 7.8%, p = 0.704) after liver resection for CRLM and non-CRLM was similar. Kaplan-Meier analysis showed higher disease-free survival in the CRLM group with 89.4% vs 76.5% and 64.9% vs 31.4% survival rates at 1 and 3 years, respectively (p = 0.042), although overall survival was not different between the CRLM and non-CRLM groups with 89.4% vs 78.4% and 72.0% vs 46.1% survival rates at 1 and 3 years, respectively (p = 0.300).ConclusionsIn this study, we confirmed comparable short- and long-term outcomes after liver resection for CRLM and non-CRLM. Surgical resection should be encouraged as an option in well-selected patients with non-CRLM.

Sequential chemoradiation versus radiation alone or concurrent chemoradiation in adjuvant treatment after radical hysterectomy for stage IB1-IIA2 cervical cancer (STARS Study): A randomized, controlled, open-label, phase III trial.

6007 Background: There are limited data from previous studies regarding whether the addition of chemotherapy to adjuvant radiation after radical surgery improves outcomes among patients with early-stage cervical cancer and adverse pathological factors. Methods: This was a prospective randomized trial including patients with FIGO 2009 stage IB1-IIA2 cervical cancer and squamous-cell, adenocarcinoma, or adenosquamous carcinoma with at least one adverse factor after radical hysterectomy. Patients were randomized 1:1:1 to receive adjuvant radiation alone, concurrent chemoradiation with weekly cisplatin (30-40 mg/m2), or sequential chemoradiation with cisplatin (60-75 mg/m2) plus paclitaxel (135-175 mg/m2) in 21 day cycles, given 2 cycles before and 2 cycles after radiotherapy respectively. The primary outcome was the rate of disease-free survival at 3 years. Results: A total of 1,048 patients were included in the study (350, radiation alone; 345, concurrent chemoradiation; and 353, sequential chemoradiation). Overall, the median follow-up was 56 months and the median age of patients was 48 years. Most patients (75%) had stage IB1 or IIA1 disease. The three groups were similar with respect to histologic subtypes, the rate of lymphovascular invasion, parametrial, surgical margin and deep stromal involvement, tumor grade, rate of use of minimally invasive surgery, and neoadjuvant chemotherapy, except for lymph-node involvement that was lowest in radiation alone arm. In the intention-to-treat population, sequential chemoradiation was associated with a higher rate of disease-free survival than radiation alone (3-year rate, 90·0% vs. 82·0%; HR 0·52; 95% CI, 0·35 to 0·76) and concurrent chemoradiation (90·0% vs. 85·0%; HR 0·65; 95% CI, 0·44 to 0·96), differences remained after adjustment for lymph-node involvement. Sequential chemoradiation was also associated with a higher rate of overall survival than radiation alone (5-year rate, 92·0% vs. 88·0%; HR for death from cancer, 0·58; 95% CI, 0·35 to 0·95). However, neither disease-free survival nor cancer death risk was different between patients treated with concurrent chemoradiation or radiation alone. Conclusions: In this trial, sequential chemoradiation, rather than concurrent chemoradiation, resulted in a higher disease-free survival and lower risk of cancer death than radiation alone among women with early-stage cervical cancer after radical surgery. Clinical trial information: NCT00806117.

Machine learning radiomics signature on magnetic resonance imaging associated with phenotypes and disease-free survival in patients with breast cancer (RBC-01): A registry-based, multicenter cohort study.

3563 Background: The early stage breast cancer patients can vary in disease-free survival (DFS), innovative predictors evaluate the prognostic capacity are urgently needed. We aimed to develop and independently validate a radiomics signature based on MRI associated with phenotypes and DFS in patients with breast cancer and to establish a radiomics nomogram that incorporates the radiomics signature and clinicopathological findings using computational algorithms. Methods: In this multicenter, retrospective, cohort study, we analyzed preoperative contrast–enhanced MRI data from the prospective cohort study (n = 123) of patients who had been treated with neoadjuvant chemotherapy in phase 3 trials and independent cohort (n = 438) at the Sun Yat-sen Memorial Hospital as training cohort to develop the radiomic signature, and validated it in validation cohort (Foshan cohort, n = 121; Dongguan cohort, n = 89) between November 17, 2011, and September 21, 2019, and validated in TGCA cohort (n = 84). Machine-learning algorithm to identify robust imaging subtypes and evaluated their clinical and biologic relevance. A nomogram combining the radiomic signature and clinicopathological findings to predict individual survival based on Cox regression model. The primary endpoint was disease-free survival (DFS). This study is registered with ClinicalTrials.gov, number NCT04003558, and Chinese Clinical Trail Registry, number ChiCTR1900024020. Results: A total of 855 breast cancer patients were included. Radiomics signature was generated to classify patients into high-risk and low-risk groups in the Guangzhou training cohort. Patients with low-risk scores in the training cohort had higher DFS (hazard ratio [HR] 0.55, 95% CI 0.31 to 0.99; P= 0.045) than patients with high-risk scores, and validated in in validation cohort (HR 0.14, 95% CI 0.03 to 0.62; P= 0.003). The nomogram combined radiomics score with clinicopathological factors could accurately predict DFS benefits in training cohort (C-index = 0.83; AUC, 1, 2, 3-year were 0.80, 0.85, 0.82, respectively) and validated in validation cohorts. Conclusions: The radiomics signature are significantly associated with the DFS in patients with breast cancer. Combining the radiomics nomogram improved individualized DFS pretiction. Clinical trial information: NCT04003558 .