Difference In Disease-free Survival Research Articles

Abstract PO4-16-11: De-escalation of anthracyclines during adjuvant therapy based on Oncotype RS: A single institution experience in Mexico City

Abstract Introduction: In Mexico, hormone positive HER2 negative breast cancer is the most frequent subtype, accounting for 76.6% of cases. For patients undergoing local control management through surgery; adjuvant chemotherapy is usually followed depending on different risk factors. In order to avoid overtreatment, different genomic firms have been approved aiding in a more objective decision. One of these genomic firms is the Oncotype Recurrence score. The TAILORx and RxPONDER trials have provided guidance in determining which patients are candidates for chemotherapy depending on their menopausal status. However, it has not yet been determined whether patients requiring chemotherapy can receive an anthracycline-free regimen. In the Plan B clinical trial, a non-inferiority analysis was conducted on early-stage breast cancer patients who received anthracycline-based or non-anthracycline-based chemotherapy, with the non-anthracycline regimen being non-inferior, including patients with a RS > 25. We intend to reevaluate these findings in our Mexican population. Methods: We evaluated 217 patients with early stage hormone sensitive HER2 negative breast cancer who had an Oncotype Recurrence score (RS) result. This retrospective cohort study took place by analyzing electronic records from January 2011 to December 2017 with patients treated at the National Cancer Institute in Mexico City. We included patients 18 years of age or older, any sex with an Oncotype RS ≥ 16 in premenopausal patients or ≥ 26 in postmenopausal patients who received adjuvant chemotherapy with or without anthracyclines. Our primary endpoint was iDFS comparing TC vs AC-T. Overall survival was set as a secondary endpoint. Results: Of the 217 patients with an Oncotype recurrence score, only 46 patients received adjuvant chemotherapy of which 71.7% were premenopausal with a median age of 45 years. Stage II was the most common stage with 91.3% of the population, as well as ductal carcinoma with 82.6%. All patients had positive lymph nodes, 54.3% at least 1 lymph node. Most patients received AC-T adjuvant chemotherapy (60.9%), and only 39.1% received TC. Of the 46 patients analyzed, only 19.6% (9) had a recurrence upon follow-up (Table 1). Median time of follow up was 87.5 months. Difference in Disease free survival could not be established between patients receiving AC-T with 105 months (CI 95% 94.36-117.43 months) vs TC with 94.09 months (CI 95% 83.85-104.34 months, < p.918) (Figure 1). Overall survival did not have a statistical difference between both chemotherapy regimens, p< 0.649 (Figure 2A), when comparing Oncotype RS, overall survival was better in those with Oncotype OS < 26, p< 0.023 (Figure 2B). Discusion As described previously in the Plan B trial, TC was non inferior to the conventional adjuvant regimen of AC-T in Hormone positive HER2 negative early-stage breast cancer. Our results tend to show similar results when compared to the Plan B. An important aspect to our study was that 71.7% of our patients were premenopausal, where in the Plan B trial only 35% were premenopausal, considered a higher risk group of patients. Although a statical difference couldn´t be established due to our small sample size, in DFS or OS when comparing the chemotherapy regimen. Premenopausal patients with an Oncotype RS < 26 could receive an anthracycline free regimen, without impact in their overall survival. Larger prospective studies are necessary to assure this conclusion. Figure 1 DFS (TC vs AC-T) Figure 2 A and B Overall Survival Table 1 (Baseline characteristics) Citation Format: Carlos Arturo González Núñez, Paula Cabrera-Galeana, Juan Enrique Bargalló Rocha, Rafael Vazquez-Romo, Sergio Aguilar-Villanueva, Alexandra Garcilazo, Areli Velazquez-Martinez, Andrea Maliachi, Ruben Rodriguez, Esmeralda Romero-Bañuelos. De-escalation of anthracyclines during adjuvant therapy based on Oncotype RS: A single institution experience in Mexico City [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO4-16-11.

HER2 categorical changes after neoadjuvant chemotherapy: A study of 192 matched breast cancers with the inclusion of HER2-Low category

Understanding the changes of HER2 expression after neoadjuvant chemotherapy (NAC) in breast cancer (BC) is more important than ever, since it may allow more patients to access the effective therapeutic drugs targeting HER2-low BC. 192 matched pre- and post-NAC BCs were analyzed. HER2 immunohistochemistry (IHC) was re-evaluated with consensus according to the current ASCO/CAP guidelines. Tumors were categorized into HER2-0 (IHC0+), HER2-low (IHC1+ or IHC2+/ISH-) and HER2-positive (IHC3+ or IHC2+/ISH+) subgroups. 55 (28.6 %) patients achieved pathologic complete response (pCR). HER2-low BC accounted for 75/192 (39.1 %) baseline tumors, and 48/133 (36.1 %) residual tumors. In the non-pCR cohort, 53 (39.9 %) patients had HER2 categorical change after NAC, most commonly converting from HER2-low to HER2-0 (20.3 %, n = 27). Among patients with residual tumor, 25.6 % (11/43) of patients with baseline HER2-0 expression experienced a categorical change to HER2-low after NAC, significantly higher (p < 0.05) in the hormone receptor (HR) positive (9/23, 39.1 %) compared to the HR negative tumors (10 %, 2/20). Exploratory analysis failed to reveal a statistically significant difference in disease free survival and overall survival in non-pCR patients with or without HER2 change. Our results suggest that a substantial number of patients may experience HER2 categorical change after NAC, supporting re-testing of HER2 status in post-NAC residual tumors. Retesting HER2 status may be particularly important for evaluating post-NAC HER2-low status, in order to better assess which patients will more likely benefit from therapeutic drugs targeting HER2-low BC.

Oncologic efficacy of gonadotropin-releasing hormone agonist in hormone receptor-positive very young breast cancer patients treated with neoadjuvant chemotherapy.

Breast cancer in young women has been shown to have an aggressive behavior and poor prognosis. To evaluate the outcomes of young hormone receptor (HR)-positive patients with breast cancer treated with neoadjuvant chemotherapy (NAC), and the oncologic efficacy of gonadotropin-releasing hormone (GnRH) agonists. This retrospective study involved a prospectively enrolled cohort. We included patients diagnosed with invasive breast cancer who were treated with NAC followed by curative surgery at the Samsung Medical Center and Samsung Changwon Hospital between January 2006 and December 2017. Among patients with HR-positive and human epidermal grow factor 2 (HER2)-negative breast cancer, we analyzed the characteristics and oncology outcomes between the patients equal to or younger than 35 years and the patients older than 35 years. Among 431 patients with NAC and HR-positive/HER2-negative breast cancer, 78 were 35 years old or younger, and 353 patients were older than 35 years. The median follow-up was 71.0 months. There was no statistically significant difference in disease free survival (DFS, P = 0.565) and overall survival (P = 0.820) between the patients equal to or younger than 35 years and the patients older than 35 years. The two groups differed in that the GnRH agonist was used more frequently in the group of patients equal to or younger than 35 years than in the other group (52.4% vs 11.2%, P < 0.001). Interestingly, for the DFS according to the GnRH agonist in the group of patients equal to or younger than 35 years, patients treated with the GnRH agonist had better DFS (P = 0.037). Administration of GnRH agonists might improve the DFS rate of HR-positive/HER2-negative breast cancer in the equal to or younger than 35 years group of patients with NAC.

Tumor regression grade combined with post-therapy lymph node status: A novel independent prognostic factor for patients treated with neoadjuvant therapy followed by surgery in locally advanced gastroesophageal junction and gastric carcinoma.

Tumor regression grade (TRG) is a measure of histopathological response to neoadjuvant therapy (NAT). Post-therapy lymph node (ypN) metastasis was reported as a prognostic factor. However, the evaluation of the treatment effectiveness of NAT has not been well studied. Here, we explored whether TRG combined with ypN status could be a prognostic factor for gastroesophageal junction (GEJ) and gastric cancer (GC). Besides, we aimed at making clear the association of different neoadjuvant regimens with different TRG and ypN status. 376 patients with GEJ or GC accepting NAT in Peking University Cancer Hospital were retrospectively collected from January 1, 2003 to June 30, 2021. According to TRG and ypN status, patients were innovatively categorized into four groups: TRG0N0, TRG1-3N0, TRG0-1N+, and TRG2-3N+. We applied Kaplan-Meier method and log-rank test to testify the differences in disease free survival (DFS) and overall survival (OS) among four groups. Univariate and multivariate analyses were performed to examine the relationships between TRG combined with ypN status and prognosis. We observed significant survival differences among the four groups (p < 0.001, respectively). Median DFS and OS of patients with TRG0N0, TRG1-3N0, and TRG0-1N+ were not reached, whereas these of patients with TRG2-3N+ were 17.37 months (95% CI, 14.14-20.60 months) and 39.97 months (95% CI, 27.05-52.89 months). TRG combined with ypN status was still an independent predictor for both DFS (p < 0.001) and OS (p < 0.001) in multivariate analysis. Chi-squared test showed TRG combined with ypN status was significantly associated with different preoperative treatments (p < 0.001). Patients receiving immunotherapy achieved the highest TRG0N0 rate (31.9%). Our results demonstrate that TRG combined with ypN status is a novel independent predictor of both DFS and OS in resectable, locally advanced GEJ and GC. Neoadjuvant immunotherapy achieved the highest TRG0N0 rate.

78P Multiplex immunohistochemistry and digital pathology analysis examining the prevalence and prognostic value of tertiary lymphoid structures in early stage hormone positive, HER2-negative breast cancer

Tertiary lymphoid structures (TLS) are ectopic lymphoid organs that arise in nonlymphoid tissue sites of chronic inflammation including tumours. The presence of TLS, has been associated with increased tumour antigen presentation and improved cytokine-mediated signalling activity against tumour cells. Due to this, TLS have been associated with favourable outcomes in a number of cancer types. There is limited data regarding the prevalence and prognostic implication of TLS in hormone positive, HER2-negative (ER+/HER2-) breast cancer. Formalin-fixed paraffin embedded blocks from a cohort of 429 patients with early stage hormone positive/ HER2-negative breast cancer were used to construct a TMA with three x 1 mm cores per patient. Multiplex chromogenic immunohistochemistry staining was performed to stain for CD3+ T cells, CD20+ B cells and DCLamp + dendritic cells. Digital image analysis was performed using Qupath open source software. On the basis of staining with the TLS panel, samples could broadly be divided into three categories; immune cold with minimal immune infiltrate, T-cell only infiltrate and TLS defined by the presence of CD20+ B cells. TLS were seen in 14% (n=60) of patient samples which was similar to the rate of patients with a significant T-cell only immune infiltrate which was also 14% (n=60). The majority of samples had no infiltrate, comprising of 72% (n=312) of the cohort. The median CD3+ cells/mm2 in the entire cohort was 295mm2. When divided into these categories, there was no statistically significant difference in disease free survival (p value= 0.39) although there was a trend towards worse disease free survival in those with a high T-cell only infiltrate. In contrast to other breast cancer subtypes, tumour infiltrating lymphocytes in ER+/HER2- breast cancer may be a poor prognositc feature. However this may be dependant on the subpopulation of immune infiltrate, with TLS presence perhaps differing from T-cell only infiltrate. Further research with larger cohorts would be required to investigate this further.

Abstract 6748: Tumor regression grade combined with post-therapy lymph node status: A novel independent prognostic factor for patients treated with neoadjuvant therapy followed by surgery in resectable, locally advanced gastroesophageal junction and gastric carcinoma

Abstract Background: Tumor regression grade (TRG) is a measure of histopathological response to neoadjuvant therapy (NAT). Post-therapy lymph node (ypN) metastasis was reported as a prognostic factor. However, the evaluation of the treatment effectiveness of NAT has not been well studied. Here, we explored whether TRG combined with ypN status could be a prognostic factor for gastroesophageal junction (GEJ) and gastric cancer (GC). Methods: 376 patients with GEJ or GC receiving NAT in Peking University Cancer Hospital were retrospectively collected from January 1, 2003 to June 30, 2021. According to TRG and ypN status, patients were innovatively categorized into four groups: TRG0N0, TRG1-3N0, TRG0-1N+, and TRG2-3N+. We applied Kaplan-Meier method and log-rank test to examine the differences in disease free survival (DFS) and overall survival (OS) among four groups. Univariate and multivariate analyses were performed to elucidate the relationships between TRG combined with ypN status and prognosis. Results: We observed significant survival differences among the four groups (P &amp;lt; 0.001, respectively). Median DFS and OS of patients with TRG0N0, TRG1-3N0 and TRG0-1N+ were not reached, whereas median DFS and OS of patients with TRG2-3N+ were 17.37 months (95%CI, 14.14 to 20.60 months) and 39.97 months (95%CI, 27.05 to 52.89 months). TRG combined with ypN status was an independent predictor for both DFS (P &amp;lt; 0.001) and OS (P &amp;lt; 0.001) in multivariate analysis. Additionally, TRG combined with ypN status was significantly associated with different NAT (P &amp;lt; 0.001). The TRG0N0 rate in patients accepting immunotherapy was 31.9%, which was the highest in all regimens. Conclusion: Our results demonstrate that TRG combined with ypN status is a novel independent predictor of both DFS and OS in resectable, locally advanced GEJ and GC. Neoadjuvant immunotherapy achieved the highest TRG0N0 rate. Citation Format: Hongyan Yin, Qian Yao, Keren Jia, Dongfeng Niu, Xiaoyi Chong, Yanyan Li, Xujiao Feng, Yilin Li, Lin Shen, Yang Chen. Tumor regression grade combined with post-therapy lymph node status: A novel independent prognostic factor for patients treated with neoadjuvant therapy followed by surgery in resectable, locally advanced gastroesophageal junction and gastric carcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 6748.

SCOT: Tumor Sidedness and the Influence of Adjuvant Chemotherapy Duration on Disease Free Survival (DFS)

AimPatients with loco-regional right-sided colorectal tumors have a worse overall survival (OS). Here we investigate the difference in disease free survival (DFS) between colorectal patients with right and left sided tumors in the SCOT study. MethodsThe SCOT study showed 3-months of oxaliplatin-containing adjuvant chemotherapy (OxFp) is non-inferior to 6-months for patients with stage III and high-risk stage II colorectal cancer. We divided the cohort into patients with left and right sided tumors, and evaluated the effect on DFS and the principle 3 versus 6-months analysis. Results6088 patients with Stage III/high risk Stage II colorectal cancers were randomized between 27th March 2008 and 29th November 2013 from 244 centers internationally. In February 2017 (3-years FU) information on sidedness was available for 3309 patients (1238 R-sided, 2071 L-sided). Patients with right-sided tumors had a significantly worse DFS (3-year DFS right: 73.3% (se = 1.3%), left: 80.2% (se = 0.9%) HR 1.423 (95% CI 1.237-1.637; P < .0001). Adjusting for T and N-stage reduced the HR to 1.230 (95% CI 1.066-1.420, P = .005). The data did not suggest that sidedness affected the impact of chemotherapy duration on 3-year DFS (R: HR 1.024 [0.831-1.261], L: HR 0.944 [0.783-1.139]). Test for heterogeneity, P = .571. Further sub-set analysis was limited due to cohort size. ConclusionsThis is the first study to show that unselected patients with right-sided tumors had a worse DFS compared to left-sided tumors. Tumor sidedness did not impact upon the 3-months versus 6-months comparison in SCOT.

Meme Kanseri Nedeni ile Meme Koruyucu Cerrahi Uygulanan Hastalarda Re-eksizyon Uygulanmasını Etkileyen Faktörler

Abstract Objective: A significant proportion of patients undergoing breast-conserving surgery require re-excision for residual cancer. This study aims to determine the factors associated with residual tumor in patients undergoing breast conserving surgery, and to evaluate the follow-up results of the patients. Material and Methods: Patients underwent breast-conserving surgery in a 6-year period were included in this study. Patients were divided in 2 groups; no re-excision (Group A), and required re-excision (Group B). Patients who underwent mastectomy in the follow-up were excluded. Results: In this study, 190 patients were assessed; those 153 in Group A, and 37 in Group B. A total 192 masses were found; 154 in Group A, and 38 in Group B. The median follow-up time, and disease free survival were 9.2 (Inter Quantile Range [IQR]=5.9-11.1) years, and 8.8 (IQR=5.0-11.0) years respectively. There was no difference in disease free survival, and local recurrence between groups (p=0.246, and p=0.601; respectively). Axillary lymph node involvement, lymphovascular invasion, extensive intraductal companent, multifocality, large tumor diameter and younger age patients were higher in re-excision group. Multivariate anlysis identified, absence of lymphovascular invasion (Odds Ratio [OR]=0.05; %95Cl 0.01-0,44), and age &amp;gt;50 years (OR=0.17; %95Cl 0.04-0.73) were associated with lower re-excision requirement; however, tumor diameter &amp;gt;2 cm (OR=4.52;%95Cl 1.28-15.98) was associated with re-excision. Conclusion: There was no difference in disease free survival, and local recurrence between 2 groups. Patients should be informed for the risk of re-excision after initial breast conservig surgery and wider surgical excision or oncoplastic surgery should be performed in risky patients. Key Words: Breast conserving surgery, Re-excision, Early stage breast cancer.

Upfront surgery versus self-expanding metallic stent as bridge to surgery in left-sided colonic cancer obstruction: A multicenter observational study

BackgroundOncological outcomes of self-expanding metallic stent used as a bridge to surgery in potential curative patients with left-sided colonic cancer obstruction remain unclear. The aim of this study was to investigate perioperative and mid-term oncological outcomes of 2 of the currently most commonly performed treatments in left-sided colonic cancer obstruction. MethodsThis is a retrospective multicenter study including patients with left-sided colonic cancer obstruction treated with curative intent between 2013 and 2017. The presence of metastasis at diagnosis was an exclusion criterion. The primary outcome was to evaluate the noninferiority, in terms of overall survival, of bridge to surgery strategy compared with emergency colonic resection. The secondary outcomes were perioperative morbimortality, disease free survival, local recurrence, and distant recurrence. ResultsA total of 564 patients were included, 320 in the emergency colonic resection group and 244 in the bridge to surgery group. Twenty-seven patients of the bridge-to-surgery group needed urgent operation. Postoperative morbidity rates were statistically higher in the emergency colonic resection group (odds ratio [95% confidence interval] 0.37 [0.24–0.55], P < .001). There was no difference in 90-day mortality between groups (odds ratio [95% confidence interval] 0.85 [0.36–1.99], P = .702). The median follow-up was 3.80 years (2.29–4.92). The results show the noninferiority of bridge to surgery versus emergency colonic resection in terms of overall survival (hazard ratio [95% confidence interval) 0.78 [0.56–1.07], P = .127). There were no differences in disease free survival, distant recurrence, and local recurrence rates between bridge to surgery and emergency colonic resection groups. ConclusionSelf-expanding metallic stent as bridge to surgery might not lead to a negative impact on the long-term prognosis of the tumor compared with emergency colonic resection in expert hands and selected patients.

Prevalence of EGFR mutation testing in early-stage lung cancer: Implications of the ADAURA trial for clinical practice.

e20507 Background: It is reported that about 20% of patients with resected NSCLC adenocarcinoma harbor an EGFR driver mutation in the United States. Up to the recent approval of osimertinib in the adjuvant setting for resected EGFR + NSCLC based on the ADAURA trial, routine molecular profiling of early-stage lung cancer had not been standard of care. We hypothesize that there is a significant proportion of patients with resected adenocarcinoma with unknown EGFR status who could benefit from treatment that are missed with our current testing practices. Methods: We performed a retrospective analysis of Stage IB-IIIA lung adenocarcinomas resected at the University of Miami from 2014 to 2019. Eligible patients were identified from the Cancer Registry and information on EGFR mutation testing and treatment was obtained from chart review. We evaluated the prevalence of EGFR mutation testing in this population and outcomes based on EGFR mutation status. Disease free survival (DFS) and clinico-pathologic characteristics were evaluated. We estimated the number of patients that would have been eligible for EGFR testing and adjuvant osimertinib therapy in the pre-ADAURA era in our patient cohort. Results: A total of 120 patients had resected stage IB-IIIA adenocarcinoma during this five-year period (Stage IB 42.5%; Stage IIA 13.3%; Stage IIB 25%; Stage IIIA 19.2%) with a median age of 66 years. Most were females (59%), NHWs (51.5%), Hispanics (46.9%), and former smokers (66.7%). Out of patients with Stage IB-IIIA NSCLC with adenocarcinoma, 42.5% completed recommended adjuvant platinum-based chemotherapy. Only 40% of patients were referred for EGFR testing during this study period. The prevalence of EGFR mutations in this population was 10.8% (13 /120), but 59% of cases had no available EGFR testing. The most prevalent mutation was L858R (53.8%) followed by exon-19 deletions (30.8%). A total of 6 patients received an EGFR TKI therapy during the follow up period (2 in the adjuvant setting). With a median follow up of 12 mos, the rate of recurrence by stage was: Stage IB (3.9%); Stage IIB (10%); Stage IIIA (13%). Median time to disease progression or death was 13 months in this subgroup. There was no difference in disease free survival for patients with EGFR testing and those without results available in this short follow up period. Conclusions: Based on this retrospective review, up to 60% of patients with early-stage NSCLC with non-squamous histology have no available EGFR testing in the pre-ADAURA era. Of the anticipated 20% of patients with expected EGFR mutations based on historical controls, we have only identified half of patients that would have been eligible for adjuvant osimertinib. This study establishes the importance of upfront EGFR mutation testing in all NSCLC patients, not only to prognosticate, but also to identify the subset of patients who could benefit from adjuvant EGFR therapy.

The influence of harvest method on dendritic cell function and clinical outcomes in a randomized trial of a dendritic cell vaccine to prevent recurrences in high-risk melanoma.

9548 Background: A randomized, double-blind, placebo-controlled phase IIb trial of the tumor lysate, particle loaded, dendritic cell (TLPLDC) vaccine was conducted to prevent recurrence in patients (pts) with resected stage III/IV melanoma. Two methods for dendritic cell (DC) harvest were used for vaccine production, including no pretreatment or pretreatment with granulocyte-colony stimulating factor (G-CSF) in an attempt to reduce blood draw volumes. This analysis investigates differences in clinical outcomes and RNA gene expression between these DC harvest methods for TLPLDC vaccine creation. Methods: The TLPLDC vaccine is created by loading autologous tumor lysate into yeast cell wall particles (YCWPs) and exposing them to phagocytosis by DCs. By investigator/pt choice, pts had 120mL of blood drawn for DC harvest, or pts received 300μg of G-CSF for pre-DC mobilization and a 50-70 mL blood draw 24-48 hours later. Total vaccine production time was 72 hrs. Pts were randomized 2:1 to receive TLPLDC or placebo (DCs exposed to empty YCWPs). 1-1.5 x10^6 cells/dose were injected intradermally at 0, 1, 2, 6, 12, and 18 months. Differences in disease free survival (DFS) and overall survival (OS) were evaluated by Kaplan Meier analysis between pts who did not receive pretreatment (TLPLDC), pts who did receive pretreatment with G-CSF (TLPLDC+G), and pts receiving placebo. RNA-seq analysis was performed on the total RNA of pts’ prepared TLPLDC vaccines to assess gene expression. Relative RNA expression (RRE) was compared between TLPLDC and TLPLDC+G. Results: As previously reported, 144 pts were randomized: 103 received TLPLDC (46 TLPLDC, 57 TLPLDC+G) and 41 received placebo. There were no significant clinicopathologic or treatment differences between the three treatment arms. Survival was significantly improved in TLPLDC compared to TLPLDC+G or placebo, including 36-month OS (92.9% vs 62.8% vs 72.3% respectively, p = 0.022) and DFS (51.8% vs 23.4% vs 27.1%, p = 0.027). When compared to TLPLDC+G (n = 3) vaccine, RNA-seq from TLPLDC vaccine (n = 3) showed upregulation of genes associated with DC maturation, including HLA-DMB (RRE: 3.60), IFIT1 (3.38), CD27 (3.26), IFI44L (3.24), MX1 (2.96), HLA-DQA1 (2.67), HLA-DRA (2.40), CD49D (2.34) and CD74 (2.09), while downregulated genes were associated with DC suppression or immaturity including SERPINA1 (RRE:7.8), TLR2 (6.65), CCR1 (5.11), IL10 (4.19), CD93 (3.84) and CD14 (3.25). Conclusions: Pts receiving TLPLDC vaccine had significantly improved OS and DFS, while outcomes remained similar between those who received TLPLDC+G vs placebo. Pts who did not receive G-CSF had higher expression of genes linked to DC maturation and antigen processing and presentation, likely explaining the improvement in clinical efficacy. A phase III trial to further assess the TLPLDC vaccine to prevent recurrence is planned. Clinical trial information: NCT02301611.

Comparison of Hematopoietic Stem Cell Transplantation Results in Patients with β-Thalassemia Major from Three Different Graft Types

Allogeneic hematopoietic stem cell transplantation (HSCT) is the curative therapy for β-thalassemias that induces severe life-threatening complications. The human leukocyte antigen (HLA) registries and umbilical cord blood banks have carried out diligent searches to find matched unrelated donors (MUDs) for about 70.0% of patients from 2000 onwards. The chance of finding a non-sibling fully matched family donors is higher in some ethnic groups in which consanguineous marriages are common. We have studied and compared transplant complications and outcomes in different graft types (sibling, non-sibling family and unrelated). The non-sibling matched family donor (MFD) group consisted of four mothers, three fathers, five cousins, one paternal uncle and one paternal aunt. There was no significant difference in the mean transfused CD34+ cells, engraftment, median days of neutrophil and platelet recovery were achieved (p > 0.05). The distribution of postttransplant complication did not show any significant difference between groups (p > 0.05). In univariate analysis and multivarite analyses, age, gender, Pesaro risk group (I-II vs. III) and ABO incompatibilty demonstrated a significant difference in disease free survival (p < 0.05). Furthermore, in the second step of investigating overall survival (OS), age, gender and Pesaro risk group (I-II vs. III) showed a significant difference (p < 0.05). There was no significant difference in transplant-related mortality (TRM) between groups. Non-sibling related donor transplants are important for populations where consanguineous marriages are common. Transplant groups according to graft type had similar thalassemia-free survival (TFS) and OS when using a treosulfan-based regimen in our study.

Is age just a number or a serious consideration for outcomes after pancreaticoduodenectomy in a developing country?

Background: The effect of age on outcomes after pancreaticoduodenectomy has been reported inconsistently. The objective of our study was to review the impact of age on perioperative and oncological outcomes in patients following pancreaticoduodenectomy. Methods: All patients who underwent pancreaticoduodenectomy from January 2014 to December 2018 at Shaukat Khanum Memorial Cancer Hospital and Research Center were reviewed. Postoperative morbidity and oncological outcomes were compared between patients with age ≤ 60 years (Group A) and age > 60 years (Group B). Results: A total of 161 patients underwent pancreaticoduodenectomy during the study period including 117 (73%) in group A and 44 (27%) in group B. Mean age was 46±11 years in group A and 67±5 years in group B. Most common pathology was adenocarcinoma (81%), commonest site was periampullary (53%) and most common pancreatic reconstruction technique was pancreaticogastrostomy (68%). Patients in group B had significantly higher comorbidities including hypertension (p=0.00) and ischemic heart disease (p=0.030). There was no significant difference in morbidity (p=0.856), reoperation (p= 1.000) and 30-day readmission rate (p=0.097) betweenthe two groups. Similarly, there was no difference in disease free survival (p=0.957) and overall survival (p=0.070) in both groups. On multivariate analysis, soft pancreas (p=0.00) and non-dilated pancreatic duct (p=0.00) were associated with postoperative complications while ECOG performance status and ASA score did not show significant association. Conclusion: Pancreaticoduodenectomy can be performed in elderly patients with comparable morbidity and oncological outcomes as younger patients. Comorbid conditions remain higher in elderly patients and preoperative optimization can prevent worse postoperative outcomes.

Different surgical outcome and follow-up status between dMMR and pMMR colorectal cancer patients who fulfilled with Amsterdam-II criteria

BackgroundAlthough hereditary non-polyposis colorectal cancer (HNPCC) could be subtyped into proficient or deficient mismatch repair gene expression (pMMR or dMMR), distinct clinical features between these two subgroups patients were rarely reported.MethodsWe retrospectively analyzed 175 hereditary non-polyposis colorectal cancer (HNPCC) patients between January 1995 and December 2012. Cox proportional hazards model was used to compare the differences between two subgroups.ResultsSignificant differences of disease free survival (DFS) and overall survival (OS) exist between dMMR and pMMR. In addition to other factors including younger mean age of diagnosis for dMMR patients (48.6 years vs. 54.3 years), operation type (more extended colectomy for dMMR 35.8% vs. 14.5%), tumor location (right colon predominance for dMMR 61.7% vs. 27.3% and more rectum cases for pMMR 41.8% vs. 11.7%), tumor differentiation (more poor differentiation for dMMR 23.3% vs. 9.0%), N staging (more N0 cases for dMMR 70.8% vs. 50.9%), more frequently presence of extra-colonic tumors for dMMR (16.7% vs.1.8%), and lower recurrence rates (9.1% vs.35.3%). Significantly different cumulative incidences of developing metachronous colorectal cancer were observed with 6.18 for pMMR patients and 20.57 person-years for dMMR patients (p < 0.001).ConclusionsDistinct clinicopathological features significantly exist between dMMR and pMMR subtypes patient, MMR status should be consider to tailor operation types and follow up surveillance between these two subgroups patients who all fulfilled with Amsterdam-II criteria.

Induction chemotherapy for locally advanced laryngeal and hypopharyngeal cancer: Single institution experience.

The role of induction chemotherapy (IC) in locally-advanced head and neck squamous cell carcinoma (LAHNSCC) is unclear. A retrospective study of 104 patients with LAHNSCC of the larynx and hypopharynx, treated with IC or up-front chemoradiotherapy (CRT). Eighty patients received CRT and 24 IC followed by CRT; median follow up was 51.33 months. IC significantly improved median overall survival (OS) in the hypopharyngeal cancer group (64.7 vs 21 months, P = .003); with significant difference in the proportion of complete response at first imaging assessment post definitive CRT; no significant difference in disease free survival (DFS), loco-regional or distant failure in the hypopharyngeal cancer group; or OS and DFS in the laryngeal cancer group. Patients with laryngeal cancer had significantly better median OS than those with hypopharyngeal cancer. IC significantly improved complete response rates after CRT, and improved outcomes for patients with locally advanced hypopharyngeal, not laryngeal, cancers.

Measurement of circulating free DNA in squamous cell carcinoma of the anus and relation to risk factors and recurrence

BackgroundMeasuring circulating-free-deoxyribonucleic-acid (cfDNA) has created a new framework for personalized treatment in oncology. The aim of this study was to analyze the relation between cfDNA and risk factors and outcome in squamous cell carcinoma of the anus (SCCA). MethodsPatients treated with radiotherapy for localized SCCA were included in Aarhus, Denmark from 2016 to 2019. Serum samples from baseline, during and after therapy, were measured for the level of cfDNA in ng per µL by a direct fluorescent assay. ResultsEighty patients were included. Samples were available at baseline (n = 73) mid-therapy (n = 74), end-therapy (n = 67) and one-year follow-up (1Y) (n = 29). P16-positivity was found in 89% (n = 55). The median level of cfDNA was higher for P16 negative tumors (1.48) compared with the P16 positive tumors (0.90, P = 0.04). Data showed a correlation between baseline cfDNA levels and Gross Tumor Volume (R2 = 0.13, P < 0.01), and increasing levels with increasing T-stage (T1 = 0.80, T2 = 0.94, T3 = 1.11, T4 = 1.3). Higher cfDNA levels were observed in patients with poor performance status (P < 0.01). The cfDNA level decreased from baseline to mid-therapy (0.92–0.78, P < 0.01) and from baseline to 1Y (0.92–0.71, P < 0.01). Baseline levels for patients with treatment failure (n = 8) were above the 25th percentile (p = 0.05) which translates into difference in disease free survival. ConclusionResults indicate an association between baseline cfDNA levels and risk factors in SCCA and a low baseline level correlates to lower risk of treatment failure. Findings contribute with new knowledge of the biological role of cfDNA in SCCA and holds potential knowledge for personalized treatment of SCCA.

Treatment failure pattern of oropharyngeal cancer, especially for the aspect of retropharyngeal lymph node.

e18565 Background: In radiotherapy for head and neck cancer, it is very important to define the appropriate treatment volumes that determine the treatment outcome and toxicity. We examined the feasibility of omitting elective retropharyngeal (RP) nodal irradiation in oropharyngeal cancer. Methods: We performed a retrospective review from 2009 to 2016; 197 patients with oropharyngeal squamous cell carcinomas were treated with definitive or postoperative radiation therapy at the Seoul National University Hospital or Seoul National University Bundang Hospital. Of these patients, 151 patients (76%) were treated ipsilateral RP nodal areas up to the upper edge of C1 vertebral body, while the other 46 patients (24%) were not. We reviewed patterns of failures, disease free survival, and patient-reported chronic xerostomia status in each patient group. Results: During follow-up period, 2 patient developed RP nodal recurrences (4-108 months, median =46 months). There was no significant between-group difference in disease free survival, with a rate of 80.7% in the high RP nodal-irradiation group and 87.2% in the RP nodal spared group (P=0.17). Patients in the high RP nodal-irradiation group had higher mean ipsilateral parotid gland dose (median 28.7±7.5 Gy vs. 21.3±7.6 Gy, P&lt;0.001) and higher rates of chronic xerostomia (72.2% vs. 58.7%, P=0.030). Conclusions: Only 2 patients with omission of high RP node irradiation developed high RP node failure, and no significant difference in DFS was shown. Omission of high RP nodal irradiation resulted in reduced ipsilateral parotid gland dose, consequently with less chronic xerostomia.

SUN-LB77 Incidental Anaplastic Thyroid Carcinoma: An Uncommon Entity

Background:Anaplastic thyroid cancer is an aggressive thyroid malignancy with a median survival of 3 to 9 months. It is rare and represents 2-5% of all thyroid tumors. Even more uncommonly in about 2%–6% of all ATC cases, it is identified as a small, incidental finding after surgical resection of a predominantly non-anaplastic tumor.Clinical Case:We report a case of 67 year old Caucasian male who presented with history of hoarseness of voice for one month. Fine needle aspiration biopsy of right dominant thyroid nodule revealed papillary thyroid cancer. Pre-operative imaging was negative for involvement of surrounding structures or distant metastasis. He underwent total thyroidectomy and final pathology revealed Anaplastic carcinoma arising in papillary carcinoma measuring 3.6cm in greatest dimension. Undifferentiated (Anaplastic) Carcinoma comprised approximately 5% of the tumor. Areas from anaplastic and papillary tumor were dissected separately. DNA separated from these two specimens were analyzed by PCR amplification and both were positive for BRAF mutation. External beam radiation and radioactive iodine therapy were administered after surgery. Given absence of invasion or metastasis adjuvant therapy was not initiated. His positron emission tomography, computed tomography imaging and whole-body scan has been negative for residual/ recurrent or metastatic disease. He remains disease free at 18 months after diagnosis.Discussion:Anaplastic thyroid cancer is a rare but highly aggressive tumor. In most cases it develops from a pre-existing well differentiated thyroid cancer. ATC incidence typically peaks at the 6-7th decade of life, predominantly in women. The median survival is between 3 to 9 months with less than 10% of patients alive 3 years after the time of diagnosis. Because of its aggressive behavior, the American Joint Committee on Cancer Staging Manual classifies all Anaplastic thyroid cancer Stage IV tumors. Surgery, chemotherapy and radiotherapy are the conventional therapeutic strategies performed in the attempt to improve survival.However, incidental anaplastic thyroid cancer is rare variant with very few reported cases. American Thyroid Association (ATA) Guidelines for Management of Patients with ATC do not include specific recommendations for this form of ATC. There is no consensus to define best treatment approach as to whether intrathyroidal incidentally detected ATC is best treated with surgery alone, surgery followed by radiotherapy, or surgery followed by chemotherapy plus radiation therapy.Conclusion:Based on review of our case as well as outcomes of similar reported cases, prognosis is favorable for incidental anaplastic thyroid cancer. Hopefully, with more data from similar cases to demonstrate difference in disease free survival we should be able to define the role of chemotherapy and adjuvant therapy for incidental ATC better. The question remains open, as to whether incidental anaplastic thyroid cancer should be considered as a separate entity from aggressive form of ATC.

Expression of key regulatory genes in necroptosis and its effect on the prognosis in non-small cell lung cancer.

Background: Accumulating evidence suggests that necroptosis, or programmed necrotic cell death, may play a significant role in cancer. We evaluated the expression of key molecules in necroptosis and their association with clinical features and prognosis in NSCLC.Methods: A total of 253 NSCLC patients (96 squamous cell carcinoma [SCC] cases and 157 adenocarcinoma [AC] cases) who underwent curative resection were included. Tumor tissues and corresponding normal tissues were investigated for relative mRNA expression levels of RIPK1, RIPK3, and MLKL. Difference in disease free survival (DFS) was analyzed according to the expression levels of these molecules in tumor tissues.Results: NSCLC tissues had significantly lower expression of RIPK1, RIPK3, and MLKL than normal tissues (P = 1 x 10-4, P = 8 x 10-6, and P = 4 x 10-8, respectively). In subgroup analysis, SCCs had significantly lower RIPK1, RIPK3, and MLKL expression (P = 5 x 10-4, P = 3 x 10-15, P = 1 x 10-5, respectively), and ACs had significantly lower RIPK1 and MLKL expression (P = 0.01 and P = 6 x 10-4, respectively) than normal tissues. Low expression of RIPK1, RIPK3, and MLKL in tumors was associated with a worse DFS (HR = 1.71, P = 0.01; HR = 1.53, P = 0.04; and HR = 1.53, P = 0.04, respectively) in a multivariate analysis. In SCC, none of the RIPK1, RIPK3, and MLKL expression was significantly associated with DFS. However, in AC, low expression of RIPK1, RIPK3, and MLKL was significantly associated with worse DFS (HR = 1.67, P = 0.03; HR = 1.70, P = 0.03; and HR = 1.81, P = 0.02, respectively).Conclusions: Key regulatory genes in necroptosis, RIPK1, RIPK3, and MLKL, were downregulated in NSCLC, and their lower expression in NSCLC may be used to predict early recurrence after curative resection, especially in AC.

Integrative Bioinformatics Analysis of iNOS/NOS2 in gastric and colorectal cancer

Abstract Objective The aim of the present work was to investigate the expression of nitric oxide synthase 2 (iNOS/ NOS2) in colorectal and gastric cancers and evaluate its association with patient’s prognosis by integrated bioinformatics analysis. Methods The data for present study was obtained from the TCGA, GTEx, and STRING database. iNOS/NOS2 mRNA expression in normal tissue and colorectal, and gastric cancer tissuea were investigated through the GTEx and TCGA database. iNOS/NOS2 gene mutations and frequency were analyzed in the TCGA database using the cBioPortal online data analysis tool. The protein-protein interaction (PPI) network of iNOS/NOS2 was constructed by STRING database. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway of iNOS/NOS2 and relevant proteins involved in the PPI network were enriched and demonstrated by the bubble plot. Comparison of the overall survival(OS) and disease free survival(DFS) between samples expressing high and low levels of iNOS/NOS2 was analysis based on the TCGA databases through the GEPIA online data analysis tool. Results For colon adenocarcinoma (COAD) and rectal adenocarcinoma(READ) iNOS/NOS2 mRNA expression levels in tumor tissue were significant higher than those of corresponding normal colorectal tissue (p&lt;0.05). iNOS/NOS2 mutations were identified in both colorectal cancer and gastric cancer. Missense substitutions and synonymous substitution were the top two mutation types for colorectal and gastric cancer. The top positive and negative co-expressed genes correlated with iNOS/ NOS2 were TRIM40 (rpearson=0.56, p&lt;0.05) and GDPD5 (rpearson=-0.41, p&lt;0.05) in colorectal cancer respectively andCASP5 (rpearson=0.63,p&lt;0.05) and PIAS3 (rpearson=-0.43,p&lt;0.05) in gastric cancer. Twenty one proteins were included in the PPI network with 51 nodes and 345 edges which indicated the PPI enrichment wassignificant (p=1.0e-16). The KEGG of the included genes were mainly enriched in metabolic pathway and Jak-STAT signaling pathway. There was a significant difference indisease free survival (DFS) between samples expressing high and low iNOS/NOS2 (HR=0.37, p=0.044) in rectal cancer. The difference was not statistical between iNOS/NOS2 high and low expressing groups for overall survival(OS) or DFS in the colon cancer or gastric cancer(p&gt;0.05). Conclusions iNOS/NOS2 mRNA isup-regulated in tumor tissue compared to corresponding normal tissue in colorectal and gastric cancer which implement it in the development of colorectal and gastric cancers.