Higher Disease-free Survival Rate Research Articles

A clinical study of induction chemotherapy±concurrent chemoradiotherapy for stage N2-3M0 nasopharyngeal carcinoma with plasma Epstein-Barr virus DNA>4000 copies/ml

Objective To investigate the value of induction chemotherapy in the treatment of stage N2-3M0 nasopharyngeal carcinoma with plasma Epstein-Barr virus (EBV) DNA>4000 copies/ml. Methods A retrospective study was performed on clinical data from 210 patients with stage N2-3M0 nasopharyngeal carcinoma and plasma EBV DNA>4000 copies/ml who were admitted to our hospital from 2009 to 2013. In the 210 patients, 101 received induction chemotherapy plus concurrent chemoradiotherapy (NCRT) and 109 concurrent chemoradiotherapy alone (CCRT). The survival rates were calculated by the Kaplan-Meier method. The log-rank test was used for the analysis of survival rates and univariate analysis of the impacts of the changes in the plasma EBV DNA level after induction chemotherapy on the prognosis. Results The 3-year sample size was 154.The NCRT group had significantly higher 3-year disease-free survival (DFS) and distant metastasis-free survival (DMFS) rates than the CCRT group (80.1% vs. 70.6%, P=0.029; 87.1% vs. 76.0%, P=0.036), while there was no significant difference in 3-year overall survival (OS) rate between the two groups (88.0% vs. 80.4%, P=0.210). Patients with stage N2 disease in the NCRT group had significantly higher 3-year DFS and DMFS rates than those in the CCRT group (P=0.031, 0.014). Patients with stage N3 disease in the NCRT group had significantly higher 3-year OS, DFS, and DMFS rates than those in the CCRT group (P=0.029, 0.012, 0.019). In all the patients, the 3-year OS and DMFS rates were improved with the increase in the cycle number of induction chemotherapy (P=0.020, 0.021). In the NCRT group, patients treated with 2, 3, and 4 cycles of induction chemotherapy before radiotherapy had plasma EBV-DNA clearance rates of 51.85%, 76.92%, and 88.57%, respectively (P=0.004). Using the complete clearance of plasma EBV-DNA as a predictor of progression, the sensitivity for the above three groups was 62.50%, 66.67% and 75.00(P=0.910), respectively, and the specificity was 57.89%, 90.00% and 96.77%(P=0.000), respectively. Conclusions In the treatment of nasopharyngeal carcinoma with plasma EBV DNA>4000 copies/ml, induction chemotherapy improves DFS and DMFS in patients with stage N2-3M0 disease and OS in patients with stage N3 disease; induction chemotherapy dose not improve recurrence-free survival rate. The prognosis and plasma EBV DNA clearance rate are improved with the increase in the cycle number of induction chemotherapy. Using the complete clearance of plasma EBV DNA as a predictor of progression, the sensitivity and specificity in patients treated with 4 cycles of chemotherapy are superior over those in patients treated with 2 or 3 cycles of chemotherapy. Key words: Nasopharyngeal neoplasms/induction chemotherapy; Nasopharyngeal neoplasms/concurrent chemo-radiotherapy; Epstein-Barr virus; Deoxyribonucleic acid

Role of radiotherapy in patients with stage I-II diffuse large B-cell lymphoma of waldeyer’s ring in remission after chemotherapy

Objective To investigate the impacts of adjuvant radiotherapy on the prognosis of patients with stage Ⅰ-Ⅱ diffuse large B cell lymphoma of Waldeyer’s ring (WR-DLBCL) who achieved complete remission (CR) after chemotherapy. Methods Clinical data were collected from 130 patients with stage Ⅰ-Ⅱ WR-DLBCL who were admitted to our hospital from 2005 and 2013. All the patients achieved CR after at least two cycles of cyclophosphamide, doxorubicin/epirubicin, vincristine, and prednisone (CHOP)-based chemotherapy or rituximab plus CHOP (R-CHOP)-based chemotherapy. In the 130 patients, 43 received R-CHOP (including 25 patients undergoing radiotherapy) and 87 CHOP (including 76 patients undergoing radiotherapy); 29 received chemotherapy alone and 101 chemoradiotherapy. The survival rates were calculated by the Kaplan-Meier method and analyzed by the log-rank test. Univariate and multivariate prognostic analyses were made by the log-rank test and the Cox model, respectively. Results In all patients, the 5-year sample size was 101. The univariate analysis showed that patients with an Eastern Cooperative Oncology Group (ECOG) score of 0 had significantly higher 5-year overall survival (OS) and disease-free survival (DFS) rates than those with an ECOG score of 1(95.6% vs. 80.1%, P=0.000; 95.7% vs. 75.4%, P=0.029). Patients treated with chemotherapy alone had significantly lower 5-year OS and DFS rates than those treated with chemoradiotherapy (77.1% vs. 91.7%, P=0.048; 77% vs. 87.4%, P=0.037). The multivariate analysis by the Cox model showed that ECOG score was a prognostic factor for both OS and DFS (P=0.047, 0.003). Adjuvant radiotherapy was related to improved DFS rather than OS (P=0.039, 0.133). Conclusions Stage Ⅰ-Ⅱ WR-DLBCL patients with low ECOG scores have better prognosis than those with high ECOG scores. Patients with CR after chemotherapy may benefit from adjuvant radiotherapy. The conclusions need to be further confirmed by prospective randomized controlled trials. Key words: Diffuse large B cell lymphoma/chemotherapy; Diffuse large B cell lymphoma/radiotherapy; Prognosis

Efficacy and Toxicity of Intravitreous Chemotherapy for Retinoblastoma: Four-Year Experience

To investigate the efficacy and toxicity of intravitreous melphalan for treatment of retinoblastoma, as a single agent or with concomitant topotecan. A total of 130 eyes of 120 patients with retinoblastoma receiving 630 intravitreous (melphalan, topotecan) or topotecan periocular injections. A total of 83 (64%) of these eyes were treated with concomitant ophthalmic artery chemosurgery (OAC). Retrospective cohort study. Indirect ophthalmoscopy and clinical imaging were used to evaluate clinical response. Ocular survival and disease-free survival were estimated using Kaplan-Meier methods in 130 eyes. Ocular toxicity was evaluated by clinical findings and electroretinography (ERG) on 244 evaluable injections in 63 patients using 30-Hz flicker responses. Analysis was performed using linear mixed effects models with a random intercept and slope for each patient and a fixed effect for number of injections, in addition to any other fixed effect of interest. Ocular survival, disease-free survival, ERG: peak-to-peak ERG amplitudes in response to 30-Hz photopic flicker stimulation. There were no disease- or treatment-related deaths, and no patient developed externalization of tumor or metastatic disease. Two-year Kaplan-Meier estimates of ocular survival and disease-free survival were 94.2% (95% confidence interval, 89.2-99.4) and 86.2% (95% confidence interval, 78.7-94.5), respectively. There was a significant association between the number of injections and diminished ERG responses, such thaton average each intravitreous melphalan injection was associated with a 5.3-μV decrease in ERG amplitude (P < 0.001). Concomitant intra-arterial chemotherapy (P= 0.01) and greater inherent ocular pigment also were significantly associated with a reduction in ERG (P= 0.045). Patient age and weight, new injection site location, addition of topotecan, concomitant focal treatment, and time interval between injections were not significantly associated with toxicity. Intravitreous melphalan is an effective treatment for vitreous seeding in retinoblastoma, resulting in high rates of ocular survival and disease-free survival. However, in this study, each injection of melphalan was associated, on average, with a decrement in ERG response. The findings suggest increased toxicity (1) when OAC is given within 1 week of the intravitreous injection and (2) in more deeply pigmented eyes.

Outcomes in Patients with pT1-T2, pN0-N1 Breast Cancer After Conservative Surgery and Whole-breast Radiotherapy.

To evaluate locoregional recurrence, overall survival, disease-free survival and prognostic influence of the number of positive lymph nodes and other variables in breast cancer treatment. A total of 377 patients with pT1-T2, pN0-N1 invasive breast carcinoma treated from 2005 to 2013 were retrospectively evaluated. Patients underwent conservative surgery followed by whole-breast radiotherapy. Clavicular region irradiation was not performed. With a median follow-up of 4 years, locoregional recurrence rate was 3.4% (nodal recurrence=1.06%). Expression of progesterone receptors was significantly associated with better disease-free survival, tumor size (T>2 cm) with poorer disease-free survival, locoregional recurrence and poorer overall survival; the presence of three nodal metastases was related to significantly poorer overall survival (p=0.024). Whole-breast adjuvant radiotherapy without nodal irradiation after breast-conserving surgery led to low rate of locoregional recurrence and high rates of overall survival and disease-free survival in patients with pT1-T2 pN0-N1 breast cancer.

PROGNOSTIC SIGNIFICANCE OF MONORESISTANCE GENE EXPRESSION IN TUMORS OF PATIENTS WITH NON-SMALL CELL LUNG CANCER AFTER PREOPERATIVE CHEMOTHERAPY

A significant role in the development of lung tumor resistance to drug therapy play so called mono resistance genes that determine resistance/sensitivity of tumor cells to distinct chemotherapeutic agents, they include BRCA1, RRM1, ERCC1, TOP1, TOP2a, TUBB3, TYMS, ABCC5 genes. It is shown that the use of these biomarkers as a criteria to appoint the adequate postoperative chemotherapy is associated with the forecast. However in the course of neoadjuvant chemotherapy change the expression profile of these genes can occur, which can lead to misinterpretation of results. In this regard perspective is the development of new relevant prognostic factors, which take into account occurred molecular genetic alterations in lung tumors after preoperative therapy. We presented the results of the combined treatment of 52 patients with NSCLC IIA - IIIB stage, based on the analysis of chemotherapy resistance/sensitivity gene expression for appointment the suitable drugs. It was found that the lack of expression of ERCC1 gene in lung tumor derived after neoadjuvant chemotherapy is associated with high rates of disease-free survival (P. = 0,00913). Low level expression of RRM1 gene (less than 0.5) is also associated with high rates of patient's survival (log-rank test P. = 0,01808), while a high level is a marker of poor prognosis. It is found that the combination of enhanced expression (&gt;0.5) of any two or three genes: RRM1, ABCC5, TYMS, are the indicators of poor disease-free survival. We have shown that expression of ERCC1 gene is the independent prognostic factor. At zero ERCC1 expression in lung tumors, regardless of high or low level of expression of RRM1, ABCC5, TYMS genes, a high recurrence-free survival is observed. Thus, the data suggest the prognostic significance of the expression of ERCC1, TUBB3, RRM1, ABCC5 and TYMS genes in the lung tumor after neoadjuvant chemotherapy.

Alternative Donor/Unrelated Donor Transplants for the β-Thalassemia and Sickle Cell Disease.

Considerable progress with respect to donor source has been achieved in allogeneic stem cell transplant for patients with hemoglobin disorders, with matched sibling donors in the 1980s, matched unrelated donors and cord blood sources in the 1990s, and haploidentical donors in the 2000s. Many studies have solidified hematopoietic progenitors from matched sibling marrow, cord blood, or mobilized peripheral blood as the best source-with the lowest graft rejection and graft versus host disease (GvHD), and highest disease-free survival rates. For patients without HLA-matched sibling donors, but who are otherwise eligible for transplant, fully allelic matched unrelated donor (8/8 HLA-A, B, C, DRB1) appears to be the next best option, though an ongoing study in patients with sickle cell disease will provide data that are currently lacking. There are high GvHD rates and low engraftment rates in some of the unrelated cord transplant studies. Haploidentical donors have emerged in the last decade to have less GvHD; however, improvements are needed to increase the engraftment rate. Thus the decision to use unrelated cord blood units or haploidentical donors may depend on the institutional expertise; there is no clear preferred choice over the other. Active research is ongoing in expanding cord blood progenitor cells to overcome the limitation of cell dose, including the options of small molecule inhibitor compounds added to ex vivo culture or co-culture with supportive cell lines. There are inconsistent data from using 7/8 or lower matched unrelated donors. Before routine use of these less matched donor sources, work is needed to improve patient selection, conditioning regimen, GvHD prophylaxis, and/or other strategies.

Histopathologic risk stratification of stage IIB colorectal cancer.

To stratify stage IIB (pT4a PN0) colorectal cancer in terms of histopathologic findings. We reviewed the medical records of 80 patients who underwent surgery for stage IIB colorectal cancer. The disease-free survival (DFS) and overall survival (OS) rates were evaluated and correlated with the presence or absence of "Tumor Necrosis", "Crohn's-like lymphoid reaction", and "Perineural Invasion". Patients with "Tumor Necrosis" had significantly lower DFS rates (p<0.0001), those with "Crohn's-like lymphoid reaction" had significantly higher DFS rates (p=0.037), and those with "Perineural Invasion" had significantly lower DFS rates (p<0.0001). Patients with "Tumor Necrosis" had significantly lower OS rates (p=0.016), those with "Crohn's-like lymphoid reaction" had significantly higher OS rates (p=0.022), and those with "Perineural Invasion" had significantly lower OS rates (p=0.003). Since stage IIB colorectal cancers accompanied by the pathological findings of "Tumor Necrosis" and "Perineural Invasion", but with the absence of "Crohn's-like lymphoid reaction" carried a poor prognosis, the efficacy of adjuvant chemoradiation must be considered for these patients.

Results from Ongoing Phase 2 Trial of SL-401 As Consolidation Therapy in Patients with Acute Myeloid Leukemia (AML) in Remission with High Relapse Risk Including Minimal Residual Disease (MRD)

Results from Ongoing Phase 2 Trial of SL-401 As Consolidation Therapy in Patients with Acute Myeloid Leukemia (AML) in Remission with High Relapse Risk Including Minimal Residual Disease (MRD)

High Disease-Free and Overall Survival Rate Following Allogeneic Hematopoietic Stem Cell Transplantation for FLT3-Mutated Acute Myeloid Leukemia Even in Non-Remission Status

[Background] FMS like tyrosine kinase 3 (FLT3) mutations occur in about 30% of patients with acute myeloid leukemia (AML). Patients with FLT3-mutated AML have a poor prognosis and are referred for early allogeneic hematopoietic stem cell transplantation (allo-HSCT) in first complete remission (CR1). So far, there is still limited data available on allo-HSCT for FLT3-mutated AML in non-remission status.[Objective and method] To assess the clinical features and outcome of allo-HSCT for FLT3-mutated AML, we retrospectively analyzed patients underwent first allo-HSCT for FLT3-mutated AML excluding acute promyelocytic leukemia (FAB M3) from January 2011 to March 2016.[Result] During the study period, 332 patients received first allo-HSCT for AML in our institute. One hundred and thirty-eight were tested for the presence of FLT3-mutation and 35 showed positive results and were subjected to the analysis. The median follow-up day of survivors was 602 (101-1867). The median age of the patients was 55 years (range, 21-72). Twenty-one patients had de novo AML, 12 had AML with myelodysplasia related changes, and 2 had therapy related AML. Eighteen had normal karyotype, 4 had complex, and 13 had others. Seven were in remission (5 in CR1, and 2 in CR2), and 28 were in non-remission (8 in primary induction failure, 13 in relapse 1, and 7 in chemo naïve status). Twenty-nine patients used unrelated cord blood, 2 did unrelated bone marrow, and 4 did related peripheral blood stem cell as grafts. All but 1 received myeloablative pretransplant conditionings. At 2 years after transplantation, overall survival (OS), disease free survival (DFS), relapse rate (RR), and non-relapse mortality (NRM) of whole studied population were 65.9%, 50.2%, 28.4%, and 21.4%, respectively. Among those in non-remission before transplantation, OS, DFS, RR, and NRM at 2 years post-transplant were 62.2% (Figure 1A), 49.9%(Figure 1B), 24.3%, and 25.8%, respectively. Only younger age (<55 years) was the factor associated with better OS with statistical significance in multivariate analysis.[Conclusion] Our data indicated that allo-HSCT could overcome the poor prognosis of FLT3-mutated AML even for those in non-remission status, despite the profound chemo-resistant character of FLT3-mutated AML. [Display omitted] [Display omitted] DisclosuresIzutsu:Abbvie: Research Funding; Gilead: Research Funding; Celgene: Research Funding; Janssen Pharmaceutical K.K.: Honoraria; Eisai: Honoraria; Kyowa Hakko Kirin: Honoraria; Chugai Pharmaceutical: Honoraria, Research Funding; Takeda Pharmaceutical: Honoraria; Mundipharma KK: Research Funding.

Laryngeal Verrucous Carcinoma.

Objective Laryngeal verrucous carcinoma (LVC) is a rare, locally invasive neoplasm comprising 1% to 3.4% of laryngeal carcinomas. Management strategies are a topic of ongoing conversation, and no definitive treatment protocol based on T stage and presentation exists. This review examines characteristics, treatment modalities, and patient outcomes of LVC. Data Sources PubMed, MEDLINE, EMBASE, and Web of Science. Methods Databases were searched through October 29, 2015, for literature detailing individual patient cases of LVC. Variables analyzed included patient demographics, tumor characteristics, tumor size, treatment, and outcomes. Results Thirty-seven articles with 369 cases were included. LVC was found more commonly in males (13.8:1), at an average age of 58.7 years, and located in the glottis (74.0%). Most patients had local disease at presentation (94.9%). The most common presenting symptom was hoarseness (92.3%). The most common primary treatment was surgery alone (72.3%), with local excision as the most common technique (56.8%). In patients with data available on both surgical modality and T stage, most patients who presented as T1 and were managed surgically underwent local excision (79.2%). Surgical treatment alone led to high rates of disease-free survival at follow-up (86.8%). A large number of patients presenting with T1 disease were disease free at follow-up (88.6%). Overall survival was 80.3%. Conclusion LVC is most often managed surgically. The extent of surgical resection may be guided by T stage, with smaller tumors resected via local excision and larger tumors via partial or total laryngectomy. Regardless of T stage or therapy, LVC has a good posttreatment prognosis.

Extending Aromatase-Inhibitor Adjuvant Therapy to 10 Years

BackgroundTreatment with an aromatase inhibitor for 5 years as up-front monotherapy or after tamoxifen therapy is the treatment of choice for hormone-receptor–positive early breast cancer in postmenopausal women. Extending treatment with an aromatase inhibitor to 10 years may further reduce the risk of breast-cancer recurrence.MethodsWe conducted a double-blind, placebo-controlled trial to assess the effect of the extended use of letrozole for an additional 5 years. Our primary end point was disease-free survival.ResultsWe enrolled 1918 women. After a median follow-up of 6.3 years, there were 165 events involving disease recurrence or the occurrence of contralateral breast cancer (67 with letrozole and 98 with placebo) and 200 deaths (100 in each group). The 5-year disease-free survival rate was 95% (95% confidence interval [CI], 93 to 96) with letrozole and 91% (95% CI; 89 to 93) with placebo (hazard ratio for disease recurrence or the occurrence of contralateral breast cancer, 0.66; P=0.01 by a two-sided log-rank test stratified according to nodal status, prior adjuvant chemotherapy, the interval from the last dose of aromatase-inhibitor therapy, and the duration of treatment with tamoxifen). The rate of 5-year overall survival was 93% (95% CI, 92 to 95) with letrozole and 94% (95% CI, 92 to 95) with placebo (hazard ratio, 0.97; P=0.83). The annual incidence rate of contralateral breast cancer in the letrozole group was 0.21% (95% CI, 0.10 to 0.32), and the rate in the placebo group was 0.49% (95% CI, 0.32 to 0.67) (hazard ratio, 0.42; P=0.007). Bone-related toxic effects occurred more frequently among patients receiving letrozole than among those receiving placebo, including a higher incidence of bone pain, bone fractures, and new-onset osteoporosis. No significant differences between letrozole and placebo were observed in scores on most subscales measuring quality of life.ConclusionsThe extension of treatment with an adjuvant aromatase inhibitor to 10 years resulted in significantly higher rates of disease-free survival and a lower incidence of contralateral breast cancer than those with placebo, but the rate of overall survival was not higher with the aromatase inhibitor than with placebo. (Funded by the Canadian Cancer Society and others; ClinicalTrials.gov numbers, NCT00003140 and NCT00754845.)

Outcomes After Oncoplastic Breast-Conserving Surgery in Breast Cancer Patients: A Systematic Literature Review.

Surgeons have increasingly performed breast-conserving surgery (BCS) utilizing oncoplastic techniques in place of standard lumpectomy for early-stage breast cancer. We assess oncologic outcomes after oncoplastic BCS for T1-T2 breast cancer. A systematic literature review identified peer-reviewed articles in PubMed evaluating BCS with oncoplastic reconstruction. Selected studies reported on positive margin rate (PMR), re-excision rate (RR), conversion to mastectomy rate (CMR), overall survival (OS), disease-free survival (DFS), local recurrence (LR), distant recurrence (DR), complication rate, and/or cosmetic outcomes. The search yielded 474 articles; 55 met the inclusion criteria and collectively evaluated 6011 patients with a mean age 54.6years over a mean follow-up 50.5months. T1 (43.8%) and T2 (39.3%) invasive ductal carcinoma were the most common tumor histopathologies. PMR, RR, and CMR were 10.8, 6.0, and 6.2%, respectively, while OS, DFS, LR and DR were 95.0, 90.0, 3.2, and 8.7%, respectively. Margin widths were heterogeneously defined in studies that included margin assessment. The PMR was not significantly different when positive margins were defined as tumor<10,<5,<2, and<1mm from ink margin, or tumor on ink (p=0.162). Eleven studies reported specific margins for 1455 patients, of whom 143 (9.8%) had positive margins, including 113 (7.8%) with tumor on ink. This study is the largest comprehensive literature review to date on oncoplastic BCS. Our systematic review reveals high rates of OS and DFS with low LR, DR, PMR, RR, CMR and complication rates, thereby confirming the oncologic safety of this procedure in patients with T1-T2 invasive breast cancer.

Co-existence of IL7R high and SH2B3 low expression distinguishes a novel high-risk acute lymphoblastic leukemia with Ikaros dysfunction.

Acute lymphoblastic leukemia (ALL) remains the leading cause of cancer-related death in children and young adults. Compared to ALL in children, adult ALL has a much lower cure rate. Therefore, it is important to understand the molecular mechanisms underlying high-risk ALL and to develop therapeutic strategies that specifically target genes or pathways in ALL. Here, we explored the IL7R and SH2B3 expression in adult ALL and found that IL7R is significantly higher and Sh2B3 lower expressed in B-ALL compared to normal bone marrow control, and the IL7RhighSH2B3low is associated with high-risk factors, and with high relapse rate and low disease-free survival rate in the patients. We also found that Ikaros deletion was associated with the IL7RhighSH2B3low expression pattern and Ikaros directly binds the IL7R and SH2B3 promoter, and suppresses IL7R and promotes SH2B3 expression. On the other hand, casein kinase inhibitor, which increases Ikaros function, inhibits IL7R and stimulates SH2B3 expression in an Ikaros dependent manner. Our data indicate that IL7RhighSH2B3low expression distinguishes a novel subset of high-risk B-ALL associated with Ikaros dysfunction, and also suggest the therapeutic potential for treatment that combines casein kinase inhibitor, as an Ikaros activator, with drugs that target the IL7R signaling pathway.

Role of perineural invasion as a prognostic factor in laryngeal cancer.

The diffusion of laryngeal cancer cells in the perineural space is a parameter associated with a negative prognosis, high loco-regional recurrence and low disease-free survival rates. The spread of tumor cells on the perineural sheath highlights the histopathological and clinically aggressive behavior of this type of tumor, which may extend proximally or distally in the nerve for >10 cm. Therefore, the surgical resection margin is generally insufficient to treat patients with laryngeal cancer presenting with perineural invasion (PNI) with surgery alone. In PNI, the minor laryngeal nerves are frequently involved, rather than the superior and inferior laryngeal nerves. The aim of the present study was: i) To evaluate the prognostic importance of PNI; ii) to correlate the rate of infiltration with factors associated with the tumor, including histotype, site and tumor-node-metastasis stage, and with the type of surgery (total or partial laryngectomy); and iii) to evaluate the rate of disease-free survival according to the outcome of combined surgery and radiotherapy (RT) treatment, by means of retrospective analysis. The results of the present study highlighted the importance of performing a closer clinical and instrumental follow-up in patients with laryngeal cancer whose histopathological examination is positive for PNI. In such cases, it is important to complement the surgical therapeutic treatment with adjuvant RT.

Natural Killer (NK) Alloreactivity Seems Not to Play a Role in Preventing Leukemia Relapse in Unmanipulated Haploidentical Bone Marrow Transplantation with Post-Transplant Cyclophosphamide

BackgroundNatural Killer (NK) cells have been widely studied due to their non-major histocompatibility complex (MHC)-restricted cytotoxicity towards transformed or virally infected target cells. In the setting of hematopoietic stem cell transplantation (HSCT), donor NK cells may be "alloreactive" as their killer immunoglobuline-like receptors (KIRs) do not recognize their ligands on recipient human leukocyte antigen (HLA) class I molecules (i.e. KIR-ligands), leading to NK activation. NK alloreactivity can often occur in haploidentical HSCT (Haplo-HSCT), by means of KIR/KIR-L mismatch in graft versus host (GvH) direction, contributing to graft-versus leukemia (GvL) effect, clearing residual leukemic blasts. In the last decade, several studies have shown that NK cells alloreactivity plays a role in T-depleted Haplo-HSCT leading to higher disease free survival rates for patients transplanted from NK-alloreactive donors; recent studies have also shown that donors having KIR B haplotypes (characterized by the presence of more activating KIR) or expressing KIR2DS1 correlated with a better clinical outcome of transplantation. Thus, these NK cell features might be positively considered in the donor selection strategy.Materials and Methods:We analyzed NK-alloreactivity in the setting of unmanipulated Haplo-HSCT with post-transplant cyclophosphamide for patients affected by acute myeloid leukemia or myelodisplastic syndromes. 101 consecutive patients transplanted from September, 2010 to October, 2014 were enrolled, with the big majority of donors and patients studied for HLA-genotype and KIR.Results:Disease status at HSCT was the most relevant factor affecting outcome (p <0.0001), with 3 y 78% overall survival (OS) and 76% disease free survival (DFS) rates for "early" patients (CR1+CR2, n=61) versus 33% OS and 28% DFS rates for "advanced" patients (CR3 or active disease, n=40). Nor NK-alloreactivity nor the presence of donor KIR-B haplotype nor the presence of donor KIR2DS1 seemed to play a role in preventing leukemia relapse. NK alloreactive patients had DFS rate similar to non-NK alloreactive group (62% vs 59%, p 0.47) with a better, still non-significant trend in OS (72% vs 60%, p 0.14) for NK-alloreactive patients. Similarly, Haplo-HSCT from donors with KIR-B haplotype (with B-content score>=2) or who had KIR2DS1 was not associated with better outcome (p 0.67 and p 0.89, respectively). We observed an high expression of CD56 and inhibitory receptors such as NKG2A on surface of NK cells in post-HSCT samples, suggesting that NK-cell function could be inhibited in unmanipulated haploidentical setting.ConclusionsNK alloreactivity seems not to play a role in preventing leukemia relapse in unmanipulated haploidentical transplantation with post-transplantation. The different immunosuppressive approach of this Haplo-HSCT setting compared to T-depleted Haplo-HSCT, with concomitant use of cyclosporine from early transplant days, which has been shown to interact and possibly inhibit NK cells in vivo, and post transplant cyclophosphamide effects, selectively killing activated T-cell and inducing long-term tolerance, could affect NK efficacy. Further studies are needed to better understand the complexity of this intriguing issue, leading to a more complete definition of NK cell functions in this Haplo-HSCT setting. [Display omitted] [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Prognostic impact of tumor-infiltrating lymphocytes (TIL's) and stromal-infiltrating lymphocytes (SIL's) in triple-negative breast cancer.

83 Background: Immune response seems to improve outcome in women with Triple-Negative Breast Cancer (TNBC). Recent data suggests that the presence of Tumor-Infiltrating Lymphocytes is an independent factor associated with better prognosis. In this study, we evaluate the prognostic impact of both TIL´s and SIL´s in patients with TNBC. Methods: Data on women diagnosed with TNBC between 2005 and 2013, was collected by retrospectively reviewing at our institute. The rate of intratumoral and/or stromal lymphocytes was evaluated in all hematoxylin and eosin-stained histopathologic sections according to Denkert et al. The five-year disease-free survival (DFS) and overall survival (OS) were compared between groups with the presence or absence of TIL´s or SIL´s. Demographic and clinical characteristics were assessed, variables with a statistical significance between groups were analyzed in a multivariate analysis. Results: A total of 172 patients with TNBC treated at this institution were included with a mean age of 49.8 years. A complete absence of tumor lymphocytes was found in 88 patients while the presence of intratumoral, stromal or both was found in 84 (48.8%). A mean follow-up of 46.12 months showed significantly higher rates of both DFS and OS in women with SIL´s and TIL´s (p = 0.014 and 0.042 respectively) in locally advanced stages (LAS), regardless the rate of infiltrating lymphocytes found [Table 1]. SIL´s are correlated with a better prognosis compared with TIL´s (p = 0.028 and 0.091 respectively). Non-significant differences were found in early stages (p= 0.255). Conclusions: These results show that the presence of SIL´s or TIL´s are strongly associated with higher rates of DFS and OS in LAS, especially when SIL´s are found, suggesting that immunity seems to play a key role regarding the outcome in women with TNBC. Independent of the rate of lymphocytic infiltrate, its presence has a statistical significance. Because it is a feasible and inexpensive test that can be used as a prognostic predictor, we suggest assessing both SIL's and TIL's in histopathologic biopsies of patients with TNBC. [Table: see text]

Risk-Adapted Adjuvant Chemotherapy After Concomitant Fluoropyrimidine–Radiotherapy Neoadjuvant Treatment for Patients With Resectable CT3-4 or N+ Rectal Cancer: Five-Year Disease-Free Survival Results of a Single-Center Series

BackgroundProviding adjuvant chemotherapy in locally advanced rectal cancer after neoadjuvant chemoradiation is currently a matter of debate. Recommendations from clinical guidelines range from offering no treatment to oxaliplatin-based combinations. We present a risk-adapted approach based on the response to initial chemoradiation as the strongest prognostic factor for disease-free survival (DFS). Patients and MethodsOne hundred one patients were treated at a single institution with preoperative long-course radiotherapy plus concurrent fluoropyrimidines. Patients with disease downstaged to pT0-2N0 received adjuvant fluoropyrimidines alone, while the remaining received an oxaliplatin-based combination. The primary study end point was 5-year DFS. ResultsOverall, the disease of 54 patients was downstaged to pT0-2N0 (53.5%), while that of 47 patients was staged as pT3-4 or N+ (46.5%) after surgery. In the intention-to-treat analysis, 5-year DFS for patients in the good-prognosis group (downstaging to pT0-2 N0) and for those with poor prognosis (pT3-4 or N+) were 79.4% and 66.3%, respectively (hazard ratio, 0.489; P = .043). Downstaging and pN+ were independent prognostic factors for DFS. ConclusionA risk-adapted adjuvant therapy strategy based on pathologic stage after neoadjuvant chemoradiation is feasible and achieves high rates of 5-year DFS. Patients with good prognostic factors can be treated with adjuvant fluoropyrimidines alone, thus permitting the avoidance of oxaliplatin-derived toxicities.

Elective versus Therapeutic Neck Dissection in Node-Negative Oral Cancer

BackgroundWhether patients with early-stage oral cancers should be treated with elective neck dissection at the time of the primary surgery or with therapeutic neck dissection after nodal relapse has been a matter of debate.MethodsIn this prospective, randomized, controlled trial, we evaluated the effect on survival of elective node dissection (ipsilateral neck dissection at the time of the primary surgery) versus therapeutic node dissection (watchful waiting followed by neck dissection for nodal relapse) in patients with lateralized stage T1 or T2 oral squamous-cell carcinomas. Primary and secondary end points were overall survival and disease-free survival, respectively.ResultsBetween 2004 and 2014, a total of 596 patients were enrolled. As prespecified by the data and safety monitoring committee, this report summarizes results for the first 500 patients (245 in the elective-surgery group and 255 in the therapeutic-surgery group), with a median follow-up of 39 months. There were 81 recurrences and 50 deaths in the elective-surgery group and 146 recurrences and 79 deaths in the therapeutic-surgery group. At 3 years, elective node dissection resulted in an improved rate of overall survival (80.0%; 95% confidence interval [CI], 74.1 to 85.8), as compared with therapeutic dissection (67.5%; 95% CI, 61.0 to 73.9), for a hazard ratio for death of 0.64 in the elective-surgery group (95% CI, 0.45 to 0.92; P=0.01 by the log-rank test). At that time, patients in the elective-surgery group also had a higher rate of disease-free survival than those in the therapeutic-surgery group (69.5% vs. 45.9%, P<0.001). Elective node dissection was superior in most subgroups without significant interactions. Rates of adverse events were 6.6% and 3.6% in the elective-surgery group and the therapeutic-surgery group, respectively.ConclusionsAmong patients with early-stage oral squamous-cell cancer, elective neck dissection resulted in higher rates of overall and disease-free survival than did therapeutic neck dissection. (Funded by the Tata Memorial Centre; ClinicalTrials.gov number, NCT00193765.)

Clinical significance of neutrophil and albumin pretreatments in nasopharyngeal carcinoma prognosis

Objective: To investigate the association of pretherapeutic neutrophil, lymphocyte, monocyte, and serum albumin levels with nasopharyngeal carcinoma (NPC) prognosis in 401 patients. Methods: This study involved 401 NPC patients recently diagnosed and admitted in Sun Yat-sen University Cancer Center, China. Laboratory variables, such as immunology-related parameters and albumin level prior to treatment, were analyzed. The overall survival and disease-free survival rates were determined using the Kaplan-Meier method and were then compared using the log-rank test. Univariate and multivariate analyses were performed using the Cox proportional hazards model to identify prognostic factors. Results: Patients with neutrophil counts >5.20×10/L (n=172) had significantly lower overall survival and disease-free survival rates compared with those with neutrophil counts≤5.20×10/L (n=229) (P=0.014, P=0.009). In the 401 NPC cases, patients with high albumin levels (>43.00 g/L; n=253) had significantly higher overall survival (P=0.000) and disease-free survival (P=0.006) rates compared with those with low albumin levels (≤43.00 g/L; n=148). Multivariate analysis showed that the neutrophil level is an independent risk factor for disease-free survival, whereas the albumin level is a strong independent prognostic factor for overall survival. Conclusion: The pretherapeutic neutrophil and albumin levels are independent prognostic factors for survival in NPC patients.

Clinical efficacy of neoadjuvant chemoradiotherapy followed by surgery for locally advanced esophageal squamous cell carcinoma

Objective To explore the efficacy of neoadjuvant chemoradiotherapy (CRT) followed by surgery for locally advanced esophageal squamous cell carcinoma ( ESCC), and to investigate the correlation between a clinical complete response ( cCR) and a pathologic complete response ( pCR). Methods One hundred and fifty-eight patients with locally advanced thoracic ESCC from 2001 to 2013 were retrospectively analyzed. All patients received concurrent chemoradiotherapy followed by surgery. Platinum-based chemotherapy regimens were adopted in chemotherapy and a prescribed dose of 40 Gy in 20 fractions, 5 fractions per week, was used in radiotherapy. The overall survival (OS) and disease-free survival (DFS) rates were calculated using the Kaplan-Meier method, and pairwise comparisons and univariate prognostic analyses were performed using the log-rank test. Multivariable prognostic analyses were performed using the Cox regression model. Results The pCR rate was 41. 1% in all patients. After the treatment with neoadjuvant CRT, 32(72. 7% ) out of 44 patients with a cCR had a pCR, but only 33(28.9%) out of 114 patients with a non-cCR had a pCR (P = 0. 000 ). The sensitivity, specificity, positive predictive value, and negative predictive value of a cCR in predicting a pCR were 49.2%, 87.1%, 72.7%, and 71. 1%, respectively. The 3-year sample size was 91. The 3-year OS and DFS rates in all patients were 53. 9% and 48.6%, respectively. Patients with a cCR had significantly higher 3-year OS and DFS rates than those with a non-cCR (P =0. 012;P =0. 026), while patients with a pCR had significantly higher 3-year OS and DFS rates than those with a non-pCR (P =0. 000 ; P = 0. 000). The multivariate analyses demonstrated that the pathologic response after CRT and chemotherapy regimen were the influencing factors for OS. The most common grade acute adverse reaction was leucopenia (34.2%). Conclusions With a high pCR rate and tolerable adverse reactions, neoadjuvant CRT followed by surgery is a safe and effective option for locally advanced ESCC. The cCR rate after CRT is closely correlated with the pCR and OS rates. Key words: Esophageal neoplasms/neoadjuvant chemoradiotherapy; Clinical complete response; Pathologic complete response; Prognosis