Significant Difference In DFS Research Articles

Abstract PO1-27-03: Studies on factors for pathological complete response after neoadjuvant chemotherapy in relation to HER2 status in primary breast cancer

Abstract Background: Neoadjuvant chemotherapy (NAC) has been increasingly used as the frontline therapy for the management of high-risk localized breast cancer (BC). Achieving pathological complete response (pCR) following NAC is associated with significantly better disease-free (DFS) and overall survival (OS), particularly for triple negative (TN) and HER2+ breast cancer. Among HER2 negative BC, HER2-low BC is a newly defined subset that has a HER2 immunohistochemical (IHC)-1+ or 2+/ISH negative phenotype. HER2 status is divided into 3 categories: HER2 positive, HER2-low, and HER2-zero. In this study, we investigated factors for pCR in relation to HER2 status and survival after NAC. Methods: A total of 197 cases with primary BC from January 2013 to July 2023 were enrolled in this study. There were 83 HER2 positive cases (including 7 HER2 2+/ISH+ cases) and 114 HER2 (78 HER2-low and 36 HER2-0) negative cases. HER2 3+ was dichotomized according to the staining cell rate (cut-off point; 90%) into the following two groups; HER2 3+/>90% (70 cases) and HER2 3+/< 90% (6 cases). The chemotherapy regimen was anthracycline and taxane with the addition of anti-HER2 therapy if the cases were HER2-positive. The clinicopathological factors examined were age, nodal status, tumor size, ER/PgR (cut-off points; 1% and 10%), and the Ki-67 index value (cut-off points: 20% and 40%). pCR was defined as the absence of residual invasive cancer on H&E evaluation of the complete resected breast specimen (ypT0/Tis). We investigated the correlation between pCR and clinicopathological factors. The DFS and OS were calculated using the Kaplan-Meier method and analyzed using the log-rank procedure. Uni- and multivariate analyses of factors for pCR were performed using regression analysis. Results: 1. pCR was observed in 48 cases (57.8%) after NAC in the HER2 positive group and 17 cases (14.9%) in the HER2 negative group. 2. There was no significant relationship between the pCR rate and ER, PgR, Ki-67, menopausal and nodal status in the HER2 positive group. However, pCR was significantly observed more often in smaller tumors. HER2 3+( >90%) had a significantly higher pCR rate than HER2 3+(≤90%) and HER2 2+(ISH+). Multivariate analysis revealed that HER2 3+( >90%) and tumor size (≤5cm) were significant factors for pCR in HER2 positive BC cases. 3. Patients with pCR after NAC had significantly better DFS in HER2 positive BC cases. 4. There was a significant correlation between the pCR rate and ER≤10%, PgR≤10% and tumor size < 5cm in the HER2 negative BC cases. There was no relationship between the pCR rate and the HER2 status; 19.4% in HER2-0 and 12.8% in HER2-low. 5. Multivariate analysis revealed that the PgR status and tumor size were significant factors for pCR in the HER2 negative BC cases. 6. There was no significant difference in DFS between patients with pCR and non-pCR, especially in the luminal type BC cases. Moreover, no significant difference was observed between HER2-low and HER2-0. Conclusion: pCR rate after NAC was 57.8% in the HER2 positive cases and 14.9% in the HER2 negative cases. Moreover, the HER2 3+( >90%) group had a significantly higher pCR rate than the HER2 3+(≤90%) and HER2 2+(ISH+) groups. There was no correlation between the HER2 status (HER2-low and HER2-0) and pCR rate in the HER2 negative BC cases. In addition, the ER/PgR negativity (≤10%) was a significant factor for pCR in the HER2 negative cases. These findings suggest that the IHC data on the HER2 and ER/PgR status may be effective in predicting the pCR rate after NAC in BC cases. Citation Format: Nobuyuki Arima, Reiki Nishimura, Kazuhiro Muramoto, Atsushi Inayoshi, Tomio Tanigawa, Sugiko Watanabe. Studies on factors for pathological complete response after neoadjuvant chemotherapy in relation to HER2 status in primary breast cancer [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 PO1-27-03.

Abstract PO1-13-07: LIV-1 and Trop2 expression using Immunohistochemistry as prognostic markers in early breast cancer

Abstract Backgrounds: Antibody-drug conjugate (ADC) has emerged as treatment option for breast cancer (BC). The ASCENT and TROPiCS-02 trial of Sacituzumab Govitecan, a Trop2 ADC, gained great success in TNBC and HR+ BC. Other targets, such as LIV-1, are being investigated for TNBC and HR+ BC. The clinical trials of Ladiratuzumab, an ADC of LIV-1 Ab and MMAE, are ongoing. However, unlike Her2 protein, the predictive and prognostic role of LIV-1 and Trop-2 has not been fully investigated. Therefore, we aimed to analyze the relationship between expression level and clinicopathological features and explore the value of the markers among subtypes of BC. Methods: TMA were selected from 1,349 breast cancer specimen of patients who received curative surgery from 2008 to 2012 at Seoul National University Hospital and IHC staining was performed on the TMA using LIV-1 antibody (HPA042377 manufactured by Sigma-Aldrich, St. Louis, MO, dilution ratio of 1:300) and Trop2 antibody(HPA055067, dilution ratio of 1:75). All IHC slides were carefully evaluated by trained pathologists. IHC expression was assessed as intensity (negative:0, weak:1, moderate:2, and strong:3). A modified histochemical score(H-score) was calculated from the intensity multiplied by the percentage of positive cells. Results: A total of 1119 patients from selected samples were included. The median age was 49 (range 25-90). Most patients had early T stage disease (n=513, 569, 29, 7, for pT1, pT2, pT3, pT4, respectively). The percentage of nodal metastasis (N=687 vs 432 in pN0 vs ≥pN1, 61.4 vs 38.6%) and LVI (N= 678 vs 441 in neg vs pos, 60.6% vs 38.6%). 713 pts (63.7%) were HR+ subtype, 200(17.9%) of Her2+ and 206(18.4%) of TNBC. We divided patients into negative/low/high expression groups according to LIV-1 expression by median expression level (cutoff H-score = 100): 479 of 1119 (42.8%) LIV-1-negative; 270 (42.2%) LIV-1-low expression and 370 (57.8%) LIV-1-high. Patients with LIV-1-low or -high tumors showed better DFS (156.2 vs 158.8 vs 159.95 mo for LIV-1-negative, -low, -high, respectively; P=0.0072) and OS(157.6 vs 163 vs 165.4 mo, P=0.0029) . HR+ subgroup, (N= 193 vs 228 vs 354 for neg vs low vs high), followed overall tendency (153.4vs 158.3 vs 159.9mo, P=0.0571 in DFS, 155.6vs160.2 vs165.4mo, P=0.0627 in OS, respectively) In contrast, for patients with TNBC, LIV-1-high expression showed the worst DFS and OS. (N = 183 vs 18 vs 5 in neg vs low vs high group, 159.7 vs 160.7 vs 93.1mo, P value=0.1854 for DFS, 160.8 vs 160.7 vs 93.1 mo, P=0.0334 for OS, respectively) LIV-1 expression failed to prove a prognostic value in Her2+ BC. We also analyzed Trop2 expression by dividing patients into low/intermediate/high by the method used previously in ASCENT trial. 1009 of 1119 (n=341 in low, 363 in intermediate, 305 in high expression) patients had Trop2 expression. There was no statistically significant difference in DFS and OS among all subtypes. In multivariate analysis, neither LIV-1 or Trop-2 had a prognostic role. Conclusion: The analysis of clinicopathological findings of LIV-1 protein indicates their values for prognosis markers, especially in HR+ BC and TNBC. Trop2 expression has no prognostic role in line with previous research. Further studies are warranted to explore targetable biomarkers for the development of appropriate ADCs. Citation Format: Yeonjoo Choi, Han Suk Ryu, Jiwon Koh, Dae-Won Lee, Kyung-hun Lee, Seock-Ah Im. LIV-1 and Trop2 expression using Immunohistochemistry as prognostic markers in early breast cancer [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 PO1-13-07.

Comparison of responses to neoadjuvant and adjuvant chemotherapies in muscle-invasive bladder cancer

BackgroundBladder cancer surgery is critical for treatment, and systemic treatment before or after cystectomy may be necessary. We aimed to investigate the efficacy and response to neoadjuvant and adjuvant treatments.MethodsData on 93 patients with resectable muscle-invasive bladder cancer were analyzed retrospectively. Patients who received neoadjuvant and adjuvant chemotherapies were included. The neoadjuvant treatment group was divided into pathological responders and non-responders. Overall survival and disease-free survival were calculated.ResultsThe median age was 61.5 years; there were 6 female and 87 male patients. Baseline characteristics were similar between the groups. While there was no difference in OS between the neoadjuvant and adjuvant treatment groups (20 months vs. not reached), DFS was significantly higher in the adjuvant group (20.6 vs. 25.3 months). While there was no significant difference in DFS between the responders and non-responders to neoadjuvant treatment (20.6 vs. 19.1 months), OS was significantly longer in the responders (Not reached vs. 12.3 months).ConclusionsOur results concluded that neoadjuvant and adjuvant chemotherapies have similar survival rates, but no response was associated with poor outcomes. Determining the group for patient selection may be helpful for optimal management.

Is Programmed Death Ligand 1(PD-L1) Expression in Vulvar Cancer Prognostic for Locoregional Control?

Vulvar cancer is a rare female genital neoplasm in which surgery and radiotherapy play an integral role in the treatment paradigm; however, locoregional recurrence remains the predominant pattern of failure. Little is known about the impact of PD-L1 status in vulvar cancer and its value for clinical outcomes and response prediction to immunotherapy. We sought to explore clinical outcomes of patients with positive PD-L1 expression in vulvar cancer. Single-institution retrospective analysis of patients with surgically resectable invasive vulvar carcinoma from 2001-2021 was performed. Patients with locally advanced disease not amendable to upfront surgery or de novo metastatic disease were excluded. Immunohistochemical PD-L1 expression was assessed using the Combined Positive Score (CPS) with positive expression defined as ≥1, and Tumor Proportion Score (TPS) with positive expression defined as ≥1%. Survival and disease control outcomes were calculated using the Kaplan-Meier Method with log-rank t-test. Multivariable analysis was conducted using a parsimonious cox regression analysis using forward conditional selection. A total of 85 patients were identified with a median age of 69 years old (IQR: 59-78), 54% (n = 46) FIGO stage I-II, 97% (n = 82) squamous cell carcinoma histology, 41% (n = 35) p16 positive status, 74% (n = 63) without a history of lichen sclerosis, 40% (n = 34) without co-existing vulvar intraepithelial neoplasm (VIN), and 49% (n = 42) treated with surgery alone. There were 72% (n = 61) with positive PD-L1 TPS (≥1%), and 81% (n = 69) with positive PD-L1 CPS (≥1) expression. The median follow up was 49 months (IQR: 21-75 months). The 5-year OS was 79% (95% CI, 70%-89%), DFS 55% (95% CI, 43%-67%), local control (LC) 59% (95% CI, 47%-72%), regional control (RC) 86% (95% CI, 78%-94%), and distant metastasis (DM) 96% (95% CI, 92%-100%). PD-L1 expression was associated with lower LC and DFS by TPS ≥1%. The 5-year LC of 82% (95% CI, 65%-98%) for PD-L1 negative versus 50% (95% CI, 34%-65%) positive disease (p = 0.03). The 5-year DFS was 77% (95% CI, 59%-95%) for PD-L1 negative versus 46% (95% CI, 31%-61%) positive disease (p = 0.03). No significant DFS or LC difference was noted by CPS levels ≥1. No significant difference was observed for RC, DM, or OS. On multivariable analysis, PD-L1 TPS remained a significant predictor for LC (HR = 3.01, 95% CI, 1.07-8.95, p = 0.04). No significant difference in DFS was observed for PD-L1 TPS on multivariable analysis. PD-L1 expression is associated with higher rates of local recurrence and may represents a potentially important actionable target independent of p16 status to improve the predominant pattern of relapse in this uncommon malignancy.

Effect of HER2-low expression on neoadjuvant efficacy in operable breast cancer.

To investigate the effects of HER2-low expression (HER2-low) and HER2-zero expression (HER2-0) on the pathological complete response (pCR) rate and survival of patients following neoadjuvant chemotherapy. Eighty-six patients were followed up. Patients were divided into HER2-0 (immunohistochemistry (IHC) score of 0 (IHC0)) and HER2-low (IHC1+ or IHC2+/in situ hybridization non-amplified (ISH-)) groups according to the IHC detection of puncture tissues. After neoadjuvant chemotherapy, the clinical characteristics, pCR rate and DFS were compared between the two groups. There were 24 (27.9%) cases with HER2-0 and 62 (72.1%) cases with HER2-low. Hormone receptor-positive (HR+) patients accounted for 77.4% of the HER2-low group, which was higher than 70.8% in the HER2-0 group, and there was no significant difference between the two groups (p = 0.524). There were statistical differences in the pT and pN stages between HER2-low and HER2-0 subgroups in the triple-negative breast cancer (TNBC) group after neoadjuvant chemotherapy. The HER2-low subgroup had an earlier T stage (p = 0.009), and the ratio of N0 to N1 in the HER2-low and HER2-0 subgroups was 92.9% and 71.4%, respectively (p = 0.037). The Ki-67 index and median PR value were significantly lower in the HER2-low group after neoadjuvant chemotherapy (p = 0.002, p = 0.018). The HER2 IHC score was altered in the HER2-low group, and the HER-2 (2+) score changed significantly (p = 0.002). Seventy-eight patients with complete immunohistochemical data were analyzed. The discordance rate of the IHC score of HER2 after neoadjuvant chemotherapy was 38.5%, and eight patients with HER2-low showed HER2-0 status, with a discordance rate of 10.3%. After neoadjuvant chemotherapy, The pCR rate was significantly lower in the HER2-low group compared with that in the HER2-0 group (4.8% vs. 8.3%; p = 0.914), but the recurrence and metastasis rates were lower in the HER2-low group (9.7% vs. 20.8%; p = 0.165). There were no differences in DFS between the two groups at 6, 12, 24, and 36months (p = 0.076; p = 0.518; p = 0.245; p = 0.406). The subgroup analysis demonstrated no significant difference in DFS between HER2-low and HER2-0 subgroups in the HR + and TNBC groups (p = 0.141, p = 0.637). This retrospective study indicates that HER2-low has no significant effect on neoadjuvant efficacy in operable breast cancer. There were no statistical differences in clinical characteristics, pCR rate, and DFS between the HER2-low and the HER2-0 groups. There was no evidence that a HER2-low status constitutes a unique biological subtype, suggesting that more clinical data might be needed to verify these observations.

56P Association between HER2 expression level and prognosis using RT-PCR in HER2-low breast cancer

The variation and heterogeneity of conventional immunohistochemistry (IHC) or in situ hybridization (ISH) techniques for measuring HER2 has long been pointed out, and the method of testing for HER2 has been discussed for the selection of appropriate treatment. Therefore, we compared HER2 expression in RT-PCR using OncotypeDX have correlation with conventional IHC, and evaluated HER2 expression in RT-PCR as a prognostic factor in HER2-negative early breast cancer. ER+/HER2- patients who underwent breast cancer surgery between 2004 and 2016 and underwent OncotypeDX testing were included. Data from 632 patients were collected and analyzed by retrospective chart review at 9 centers to determine if there was a correlation between HER2 expression by IHC and RT-PCR. HER2 expression was classified as negative, HER2-low, and positive when HER2 mRNA levels were ≤ 9.1, 9.2-11.4, and11.5≤, respectively, based on the median mRNA level in HER2 negative in IHC. Survival curves were estimated using the Kaplan-Meier method with a log-rank test between the three groups. The median age of the 632 patients was 51 years. Of the 632 patients, 311(49.2%) were pStage I, the 309 (48.9%) were pStage II, and 11(1.7%) were pStage III. 127 (20%) patients received postoperative chemotherapy, and 54 (8.5%) patients had relapse. HER2 IHC rates were HER2 0: 166 (26.3%), 1+: 304 (48.1%), and 2+: 162 (25.6%). There was a weak correlation between the IHC and RT-PCR methods for HER2 expression (Spearman rank correlation P<0.001, r=0.33). The recurrence rates of IHC 0, 1+, and 2+ were 1.8%, 3.9%, 2.6%, respectively. There was no statistically significant difference in DFS between the three groups of HER2 expression by the IHC method (P=0.59). In addition, in the study of HER2 expression and prognosis by RT-PCR, the patients were divided into HER2 negative: 269, HER2-low: 357, and HER2 positive: 1. There was no statistically significant difference between the three groups (P=0.832). The recurrence rates were 3.9%, 4.4%, and 0%, respectively. In the analysis of HER2 expression, there was a weak correlation between IHC and RT-PCR mRNA expression levels; in the HER2-negative population, RT-PCR mRNA expression of HER2 was not a prognostic factor in early breast cancer.

Prognosis of Patients Over 60 Years Old With Early Rectal Cancer Undergoing Transanal Endoscopic Microsurgery – A Single-Center Experience

AimTransanal endoscopic microsurgery (TEM) is widely performed in early rectal cancer. This technique offers greater organ preservation and decreases the risk of subsequent surgery. However, postoperative local recurrence and distant metastasis remain challenges for patients with high-risk pathological factors. This single-center study reports the prognosis of early rectal cancer patients over 60 years old after TEM.MethodsThe data of the patients over 60 years old who underwent local anal resection were collected retrospectively. Moreover, the 5-year follow-up data were analyzed to determine the 5-year DFS and OS.Results47 early rectal cancer patients over 60 years old underwent TEM. There were 27 patients with high-risk factors and 20 patients without high-risk factors. Two patients underwent radical surgery after TEM and ten patients received adjuvant treatment. Local recurrence occurred in 7 patients, of which 4 underwent salvage surgery. The 5-year progression-free survival rate was 75.6%, which was lower in the high-risk patients group (69.6%) than in the non-high-risk patients group (83.3%) (P>0.05). The 5-year OS was 90.2%, but there was no statistically significant difference between the two groups (high-risk patients 87.0%, non-high-risk patients 94.4%). Furthermore, there was no significant difference in DFS and OS between people over and under 70 years old.ConclusionSome high-risk factor patients over 60 years old do not have inferior 5-year DFS and OS to the non-high-risk patients. TEM is an option for old patients with high surgical risks. Even if postoperative pathology revealed high-risk factors, timely surgical treatment after local recurrence would be beneficial to improve the 5-year DFS and OS.

Evaluating the impact of the degree of extranodal extension on outcomes in locally advanced oral cavity cancer.

e18058 Background: The presence of extranodal extension (ENE) in oral cavity cancer is associated with a higher risk of distant metastasis and worse overall survival (OS). Trials show that patients with locally advanced head and neck cancer and ENE benefit from concurrent chemoradiation over radiation therapy alone.We explored whether degree of ENE impacts survival outcomes in individuals with oral cavity cancer. Methods: From an IRB-approved database of 303 pts with locally advanced oral cavity cancer treated with surgical resection between 2001-2020, patients with pathologic ENE who received adjuvant treatment were included. Patient demographics, tumor staging, treatment information, disease recurrence, and survival were collected. Surgical slides were reviewed to confirm the extent of ENE. All staging was updated to AJCC 8th edition. Cox proportional hazards regression was used to relate patient, tumor, or treatment characteristics with either disease-free survival (DFS, composite of disease recurrence and death) or OS, from the time of radiation therapy completion. ENE was analyzed as both a dichotomous variable (major if &gt; 2 mm, minor if ≤2 mm) and as a continuous variable in the subset of patients for whom exact ENE extent could be confirmed. Results: A total of 113 patients were identified who underwent surgery and adjuvant therapy for advanced oral cavity cancer with ENE, with 35 having major ENE and 78 having minor ENE. Forty-one patients had T1-T2 disease while 72 had T3-T4 disease. Additionally, 24 had N2a disease and 89 had N3b disease. Of these, 78 received concurrent chemoradiation while 35 received radiation therapy alone. Ninety-nine patients had pathologic slides available for review to determine exact ENE extent. Median ENE distance was 1 mm (IQR 1-2, range 0.1-10). With a median follow up time of 22.3 months, there were 48 recurrences and 67 deaths. Median DFS was 21.3 months (95%CI 11.1-33.2) and median OS was 29.9 months (95%CI 20.6-66.6). Between major vs minor ENE, there was no statistically significant difference in DFS (HR 1.18, 95%CI 0.72-1.92, p = 0.51) or OS (HR 1.17, 95%CI 0.70-1.96, p = 0.55). Furthermore, there was no statistically significant association between ENE as a continuous variable and DFS (HR 0.97 per mm, 95%CI 0.87-1.4, p = 0.96) or OS (HR 0.96 per mm, 95%CI 0.83-1.11, p = 0.58). The benefit of concurrent chemotherapy on OS was not seen (HR 0.74, 95%CI 0.44-1.22, p = 0.24), though those patients on average had more advanced nodal disease (85% N3b vs 66%). Conclusions: No significant relationship was seen between extent of ENE and DFS or OS in individuals with locally advanced oral cavity cancer. This analysis was limited by the small number of patients, that most patients had ≤2 mm of ENE, and the presence of confounding risk factors such as nodal stage and receipt of chemotherapy. Overall, the effect of the degree of ENE on outcomes in advanced oral cavity cancer remains unclear.

The Overweight Paradox: Impact of Body Mass Index on Patients Undergoing VATS Lobectomy or Segmentectomy

The aim of this study was to assess the impact of BMI on perioperative outcomes in patients undergoing VATS lobectomy or segmentectomy. Data from 5088 patients undergoing VATS lobectomy or segmentectomy, included in the VATS Group Italian Registry, were collected. BMI (kg/m2) was categorized according to the WHO classes: underweight, normal, overweight, obese. The effects of BMI on outcomes (complications, 30-days mortality, DFS and OS) were evaluated with a linear regression model, and with a logistic regression model for binary endpoints. In overweight and obese patients, operative time increased with BMI value. Operating room time increased by 5.54 minutes (S.E.=1.57) in overweight patients, and 33.12 minutes (S.E.=10.26) in obese patients (P < 0.001). Compared to the other BMI classes, overweight patients were at the lowest risk of pulmonary, acute cardiac, surgical, major, and overall postoperative complications. In the overweight range, a BMI increase from 25 to 29.9 did not significantly affect the length of stay, nor the risk of any complications, except for renal complications (OR: 1.55; 95% CI: 1.07-2.24; P=0.03), and it reduced the risk of prolonged air leak (OR: 0.8; 95% CI: 0.71-0.90; P < 0.001). 30-days mortality is higher in the underweight group compared to the others. We did not find any significant difference in DFS and OS. According to our results, obesity increases operating room time for VATS major lung resection. Overweight patients are at the lowest risk of pulmonary, acute cardiac, surgical, major, and overall postoperative complications following VATS resections. The risk of most postoperative complications progressively increases as the BMI deviates from the point at the lowest risk, towards both extremes of BMI values. Thirty days mortality is higher in the underweight group, with no differences in DFS and OS.

Racial Disparity in Pathologic Response to Neoadjuvant Chemotherapy in Resected Pancreatic Cancer

Introduction: Major pathologic response (MPR) following neoadjuvant chemotherapy (NAC) in pancreatic ductal adenocarcinoma (PDAC) patients undergoing resection is associated with improved survival. Populations at risk for worse MPR following NAC have not been clearly defined. Using the Central Pancreatic Consortium dataset, we sought to determine if racial disparities exist in MPR rates following modern NAC in PDAC patients undergoing resection. Methods: Patients with potentially operable PDAC receiving at least 2 cycles of neoadjuvant FOLFIRINOX or gemcitabine/nab-paclitaxel ±radiation followed by pancreatectomy (2010-2019) at 7 centers were reviewed. Cox regression evaluated the association between race and disease-free (DFS) and overall survival (OS). Results: Of 486 patients (median age 64) who underwent resection following NAC (mFOLFIRINOX 56%, gemcitabine/abraxane 25%, other 19%), 67 (13.8%) patients were AA while 419 were non-AA. AA patients had significantly reduced rates of MPR compared to non-AA patients (13.4% vs. 25.8% respectively; P=0.039). Furthermore, AA race was independently associated with worse MPR on multivariable logistic regression (OR 0.26, 95% CI 0.10-0.69; P=0.007) while controlling for duration of NAC, CA 19-9 decline, body mass index, age, and ECOG status. In this selected cohort of completely resected patients receiving NAC, there was no statistically significant difference in DFS (P=0.9) or OS (P=0.8) between AA and non-AA cohorts. Conclusion: Although the racial disparity associated with reduced MPR rates do not translate into differences in survival between AA and non-AA PDAC patients, further investigation is warranted to determine if these differences reflect biologic mechanisms of chemoresistance or non-biologic factors.

The Influence of Adjuvant Chemotherapy Dose Intensity on Five-Year Outcomes in Resected Colon Cancer: A Single Centre Retrospective Analysis.

There is evidence that achieving a dose intensity > 80% in adjuvant colon cancer treatment improves survival. In total, 192 consecutive patients with resected stage III and high-risk stage II colon cancer that received adjuvant chemotherapy were retrospectively analyzed. Patients who received at least 6 weeks of adjuvant therapy were included. The primary objective was to assess the influence of dose index (DI) and relative dose intensity (RDI) on DFS and OS at 3 and 5 years in patients receiving fluorouracil-based doublet therapy with oxaliplatin (FOLFOX) (5-FU and oxaliplatin assessed separately), or capecitabine monotherapy. In the capecitabine group, DFS rates for 3 and 5 years were 66.7% and 57.6%, respectively, while OS rates were 80.3% and 66.7%, respectively. Those who received FOLFOX had DFS rates of 76.9% and 71.2% at 3 and 5 years, respectively. OS rates were 86.4% and 76.7% at 3 and 5 years, respectively. Median RDI was 73.8% for capecitabine and 76.3% and 85.6% for the oxaliplatin and 5-FU components respectively. Based on a multivariate analysis in patients receiving FOLFOX, those with an oxaliplatin DI > 80% had improvements in DFS and OS compared to those with an oxaliplatin DI of ≤80%. Otherwise, there was no significant difference in DFS or OS when comparing patients who achieved an RDI or a DI of above versus below 80% in the patients receiving adjuvant chemotherapy for resected colon cancer.

Long-Term Oncological Outcome Comparison between Intermediate- and High-Dose Radioactive Iodine Ablation in Patients with Differentiated Thyroid Carcinoma: A Propensity Score Matching Study.

Background Radioactive iodine (RAI) ablation is recommended for most patients with differentiated thyroid carcinoma (DTC) after total thyroidectomy (TT). We aimed to compare long-term outcomes between intermediate-dose (100 mCi) and high-dose (150 mCi) RAI ablation therapy in patients with DTC using propensity score matching analysis. Methods This was a retrospective study of 1448 patients with DTC who underwent RAI ablation after TT. Propensity score matching was performed using the extent of operation, tumor size, extrathyroidal extension, multifocality, lymphatic invasion, vascular invasion, perineural invasion, number of positive lymph nodes (LNs), ATA risk stratification system, T stage, N stage, TNM stage, preoperative serum Tg and TgAb levels, and post-RAI serum Tg and TgAb levels. Results Recurrence rates in the intermediate- and high-dose groups were 3.1% and 5.6%, respectively. After propensity score matching, LN ratio >0.22 (HR, 2.915; 95% CI, 1.228–6.918; p=0.015) and serum Tg >10 ng/mL after RAI (HR, 3.976; 95% CI, 1.839–8.595; p < 0.001) were significant predictors of recurrence. Kaplan–Meier analysis showed no significant difference in DFS before or after propensity score matching (p=0.074 and p=0.378, respectively). Conclusions Intermediate-dose RAI ablation for the adjuvant treatment of DTC is sufficient as compared to high-dose RAI ablation. Further prospective or multicenter studies should be conducted to clarify the prognosis of intermediate-dose RAI ablation.

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

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

The role of hyperthermic intraperitoneal chemotherapy in the treatment of spontaneously ruptured hepatocellular carcinoma: a pilot study.

BackgroundSpontaneous tumor rupture is a distinctive disease pattern in patients with hepatocellular carcinoma (HCC). The application of hyperthermic intraperitoneal chemotherapy (HIPEC) in spontaneously ruptured hepatocellular carcinoma (srHCC) is debatable. Our study aimed to compare the long-term outcomes of srHCC vs. nrHCC and to test the role of postoperative HIPEC in patients with srHCC after hepatectomy.MethodsFrom 2014 to 2018, PSM was performed to compare 57 patients who performed liver resection for srHCC and met the research criteria with 57 nrHCC patients selected from 446 consecutive patients. Then patients with srHCC were divided into two groups according to whether they underwent HIPEC after hepatectomy.ResultsAfter 1:1 PSM, the clinical characteristics of the patients with srHCC and nrHCC were comparable. In terms of long-term outcomes, the nrHCC group had significantly longer OS (P=0.026) and DFS (P<0.001) than the srHCC group. Of the 57 srHCC patients, the HIPEC group showed added complications compared to the non-HIPEC group, including an increased length of hospital stay and higher in-hospital costs. However, there were no significant differences in the metastatic patterns of these recurrent patients, and there was no statistically significant difference in DFS (P=0.28) or OS (P=0.56) between the two groups.ConclusionsThe prognosis of ruptured HCC patients were worse than those of non-ruptured HCC patients. HIPEC may not be a robust treatment for srHCC now.

Multidrug-related protein 1 (MRP1) polymorphisms rs129081, rs212090, and rs212091 predict survival in normal karyotype acute myeloid leukemia

Resistant disease is still a main obstacle in acute myeloid leukemia (AML) treatment. Therefore, individual genetic variations affecting therapy response are gaining increasing importance. Both SNPs and ABC transporter genes could already be associated with drug resistance. Here, we report allelic variants of MRP1 (ABCC1) SNPs rs129081, rs212090, and rs212091 with significant influences on survival in AML patients. DNA was extracted from bone marrow samples (n = 160) at diagnosis. Genotyping 48 SNPs within seven different ABC transporter genes using real-time PCR revealed rs129081 GG variant with a significant higher OS (p = 0.035) and DFS (p = 0.01). Comparing TT and AA rs212090 variants showed significant influences on DFS (p = 0.021). SNP rs212091 GG expression was associated with worse OS (p = 0.006) and a significant difference in DFS between alleles GG and AA (p = 0.018). The multivariable models confirmed a significant influence on OS for rs212091 (AA HR = 0.296, 95% CI 0.113–0.774, p = 0.013 and GG p = 0.044). Rs129081 variant CG, TT of rs212090, AA, and AG of rs212091 demonstrated significant impact on DFS (p = 0.024, p = 0.029, p = 0.017, and p = 0.042, respectively). This analysis demonstrates a significant influence of MRP1 SNPs on survival in AML. As they were not associated to prognostic characteristics, we suggest these SNPs to be independent prognostic markers for AML.

Postoperative radiotherapy option based on mediastinal lymph node reclassification for patients with pN2 non-small-cell lung cancer.

In this research, we used the mediastinal lymph node reclassification proposed by the International Association for the Study of Lung Cancer (iaslc) to screen for patients with pathologic N2 (pN2) non-small-cell lung cancer (nsclc) who might benefit from postoperative radiotherapy (port). The study enrolled 440 patients with pN2 nsclc who received complete surgical resection and allocated them to one of three groups: N2a1 (single-station skip mediastinal lymph node metastasis), N2a2 (single-station non-skip mediastinal lymph node metastasis), and N2b (multi-station mediastinal lymph node metastasis). Rates of local recurrence at first recurrence in patients receiving and not receiving port were compared using the chi-square test. Overall (os) and disease-free survival (dfs) were then compared using Kaplan-Meier survival analysis with log-rank test. In addition, the factors potentially influencing os and dfs were analyzed using univariate and multivariate Cox regression. The rate of local recurrence for the N2a2 and N2b groups was significantly lower in patients receiving port (p = 0.044 and p = 0.043 respectively). The log-rank test revealed that, for the N2a1 group, differences in os and dfs were not statistically significant between the patients who did and did not receive port (p = 0.304 and p = 0.197 respectively). For the N2a2 group, os and dfs were markedly superior in patients who received port compared with those who did not (p = 0.001 and p = 0.014 respectively). For the N2b group, os was evidently better in patients who received port compared with those who did not (p = 0.025), but no statistically significant difference in dfs was observed (p = 0.134). Multivariate regression analysis revealed that, in the N2a1 group, port was significantly associated with poor os [hazard ratio (hr): 2.618; 95% confidence interval (ci): 1.185 to 5.785; p = 0.017]; in the N2a2 group, port was associated with improved os (hr: 0.481; 95% ci: 0.314 to 0.736; p = 0.001) and dfs (hr: 0.685; 95% ci: 0.479 to 0.980; p = 0.039). For patients with pN2 nsclc who receive complete resection, port might be beneficial only for patients with single-station non-skip metastasis (N2a2). Patients with single-station skip metastasis (N2a1) and multi-station metastasis (N2b) might not currently benefit from port.

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.

A single-center study of treatment outcomes of pediatric basal ganglia germinoma in Taiwan

A basal ganglia (BG) germinoma is a rare tumor, and the optimal treatment remains unknown. We evaluated the clinical outcomes of treatment of BG germinoma in pediatric patients in Taiwan. We retrospectively reviewed the medical records of 34 children with BG germinoma who were treated with radiotherapy (RT) at Taipei Veterans General Hospital between 1989 and 2016. The median follow-up time is 8.3years (1.8-25.2years). Survival was analyzed using the Kaplan-Meier estimate. Univariate Cox proportional-hazards models were used to identify the potential risk factors. Only four patients (11.8%) experienced recurrence and all successfully underwent salvage therapy. One patient (2.97%) died due to suspected radiotherapy (RT)-related sarcoma in the scalp. The 2-, 3-, and 5-year DFS rates were 91.2%, 88.2%, and 79.4%, respectively; the 2-, 3-, and 5-year OS rates were 97.1%, 94.1%, and 82.4%, respectively. Focal RT showed low DFS in the Kaplan-Meier survival curves (P = .028) compared with non-focal RT (whole ventricle, whole brain, or cranial spinal area). In the univariate Cox proportional-hazards model, there was a significant difference in DFS between focal and non-focal RT (P = .03). There is no difference in DFS and OS between BG germinoma patients and non-BG germinoma patients. We found an excellent DFS and OS in pediatric patients with BG germinoma treated with RT. Whole ventricle irradiation is recommended for good tumor control and low treatment-related toxicity. BG germinoma patients showed similar treatment results as germinoma patients in other common sites.

Differences in prognosis by p53 expression after neoadjuvant chemotherapy in triple-negative breast cancer.

119 Background: Triple negative breast cancer (TNBC) exhibits a higher rate of early recurrence and more aggressive behavior. Despite unfavorable prognoses, TNBCs are known to be highly reactive to chemotherapy and show higher pathologic complete response rates after neoadjuvant chemotherapy. However, TNBC patients with residual cancer have significantly worse prognoses than patients with non-TNBC associated residual cancer. TP53 mutations are the most common genetic alterations in breast cancer and are highly linked to basal subtype carcinomas. Past studies have investigated if TP53 mutation can predict the response of cancer to chemotherapy or affect a difference in prognosis; however, the lack of consistent results has hampered clinical applications. Because immunostaining studies can be easily performed, those results may be more useful until Next generation sequencing results are clinically applicable. The aim of this study was to determine whether p53 expression in TNBC could predict the response to neoadjuvant chemotherapy and the resulting prognosis. Methods: From 2009 to 2017, TNBC patients who underwent neoadjuvant chemotherapy were reviewed, including a total of 31 TNBC patients who had clinical lymph node metastasis. The status of p53 expression in patients before and after chemotherapy was evaluated. Results: Two patients (22.2%, 2/9) achieved pCR in p53(+) TNBC and four patients (50%, 5/10) achieved pCR in p53(-) TNBC. There was no correlation between pCR rate and p53 expression ( P= 0.350). Based on pre-chemotherapy p53 expression, there was no significant difference in DFS between p53(+) TNBC and p53(-) TNBC ( P= 0.335) . However, after chemotherapy, p53(+) TNBC had shown higher DFS than p53(-) TBNC ( P= 0.099). Based on pre-chemotherapy p53 expression, p53(+) TNBC had better OS than p53(-) TNBC, but the difference was not statistically significant ( P= 0.082). After chemotherapy, p53(+) TNBC showed significantly better OS than p53(-) TNBC ( P = 0.018). Conclusions: Immunohistochemically detected p53 expression in TNBC could not predict the response to neoadjuvant chemotherapy. However, p53 (+) TNBC had a better OS than p53 (-) TNBC in patients who underwent neoadjuvant chemotherapy.

Addition of zoledronic acid to neoadjuvant chemotherapy is not beneficial in patients with HER2-negative stage II/III breast cancer: 5-year survival analysis of the NEOZOTAC trial (BOOG 2010-01)

BackgroundAdjuvant bisphosphonates are associated with improved breast cancer survival in postmenopausal patients. Addition of zoledronic acid (ZA) to neoadjuvant chemotherapy did not improve pathological complete response in the phase III NEOZOTAC trial. Here we report the results of the secondary endpoints, disease-free survival, (DFS) and overall survival (OS).Patients and methodsPatients with HER2-negative, stage II/III breast cancer were randomized to receive the standard 6 cycles of neoadjuvant TAC (docetaxel/doxorubicin/cyclophosphamide) chemotherapy with or without 4 mg intravenous (IV) ZA administered within 24 h of chemotherapy. This was repeated every 21 days for 6 cycles. Cox regression models were used to evaluate the effect of ZA and covariates on DFS and OS. Regression models were used to examine the association between insulin, glucose, insulin growth factor-1 (IGF-1) levels, and IGF-1 receptor (IGF-1R) expression with survival outcomes.ResultsTwo hundred forty-six women were eligible for inclusion. After a median follow-up of 6.4 years, OS for all patients was significantly worse for those who received ZA (HR 0.468, 95% CI 0.226–0.967, P = 0.040). DFS was not significantly different between the treatment arms (HR 0.656, 95% CI 0.371–1.160, P = 0.147). In a subgroup analysis of postmenopausal women, no significant difference in DFS or OS was found for those who received ZA compared with the control group (HR 0.464, 95% CI 0.176–1.222, P = 0.120; HR 0.539, 95% CI 0.228–1.273, P = 0.159, respectively). The subgroup analysis of premenopausal patients was not significantly different for DFS and OS ((HR 0.798, 95% CI 0.369–1.725, P = 0.565; HR 0.456, 95% CI 0.156–1.336, P = 0.152, respectively). Baseline IGF-1R expression was not significantly associated with DFS or OS. In a predefined additional study, lower serum levels of insulin were associated with improved DFS (HR 1.025, 95% CI 1.005–1.045, P = 0.014).ConclusionsOur results suggest that ZA in combination with neoadjuvant chemotherapy was associated with a worse OS in breast cancer (both pre- and postmenopausal patients). However, in a subgroup analysis of postmenopausal patients, ZA treatment was not associated with DFS or OS. Also, DFS was not significantly different between both groups. IGF-1R expression in tumor tissue before and after neoadjuvant treatment did not predict survival.Trial registrationClinicalTrials.gov, NCT01099436, April 2010.