Presence Of LVI Research Articles

Survival impact of number of removed para-aortic lymph nodes in stage I epithelial ovarian cancer.

The survival effect of presence or absence of lymphadenectomy in early-stage epithelial ovarian cancer (EOC) was priorly shown but the effect of number of removed lymph nodes kept in background. We aimed to evaluate the survival impact of number of removed lymph nodes and their localizations in stage I EOC. This study included 182 patients. The best cut-off levels for number of pelvic and para-aortic lymph nodes (PaLN) were 24 and 10, respectively. Univariate and multivariate survival analyses were performed for these cut-offs and other prognostic factors. The median age of the patients was 49. The median number of removed pelvic and paraartic lymph nodes were 29 and 9, respectively. The median overall (OS) and progression-free survival (PFS) were 67 and 50months, respectively. The 5-year OS rate was 89.6%. Recurrence occured in 24 (19.5%) patients. In univariate analyses tumor grade (p: 0.005), pelvic LN number (p: 0.041) and PaLN number (p: 0.004) were the factors that were significantly associated with PFS. Tumor grade and PaLN number were independently and significantly associated with PFS in multivariate analyses (p: 0.015 and p: 0.017, respectively). In OS analyses, age, tumor grade, presence of LVI, number of pelvic and PaLNs were the significantly associated factors (p < 0.05 for all). In multivariate analyses, age and PaLN number were independently and significantly associated with OS (p: 0.011 and p: 0.021, respectively). The number and localizations of removed lymph nodes may have a survival affect in stage I EOC. We also think that this study may constitute a kernel point for larger prospective series on lymph node number and lymphatic regions.

Predictive Factors for Submandibular Gland Involvement in Oral Cavity Squamous Cell Carcinoma-a Prospective Study from a Tertiary Cancer Center.

The oncological necessity of submandibular gland removal during neck dissection for oral cavity squamous cell carcinoma surgery has remained controversial. This study was aimed to determine the rate of SMG involvement and assess the feasibility of submandibular gland (SMG) preservation. We present a prospective study conducted at a tertiary cancer center from June 2017 to May 2019. All patients of oral squamous cell carcinoma who underwent primary surgery with neck dissection were included and analyzed for incidence and predictive factors for incidence of level IB nodal and SMG involvement as per CAP guidelines. A total of 60 patients were inducted in the study, wherein 63 neck dissections were performed including bilateral dissection in three cases. There was involvement of SMG in 6 patients with two cases each in floor of mouth cancer, gingivo-buccal, and alveolar lesions. The SMG was involved by direct contiguous spread from the primary lesion in two cases, extra-capsular extension from level IB lymph nodes in one and by both mode of spread in three glands. Perineural invasion was seen in 83.33% (n = 5) patients with SMG involvement (p- < 0.001), while 66.67% (4/6) patients had lympho vascular invasion (p-0.006) and all the cases with SMG involvement had extra-capsular extension (p < 0.001), suggesting PNI, LVI, and ECE as the strongest predictors of SMG involvement. This study demonstrates that oral cavity squamous cell carcinoma has low potential to metastasize to the SMG; however, high-risk factors include primary tumor site in floor of mouth or tongue, heavy level IB nodal burden, presence of LVI, PNI, and ECE. In the absence of these high-risk factors, SMG preservation with complete nodal clearance in level IB is a promising technique for reducing future complications.

Can Lymphovascular and Perineural Invasion be Additional Staging Criteria in Colorectal Cancer?

To identify additional staging information, venous, lymphatic, and neural invasionas potential prognostic factors in colorectal cancer (CRC). A descriptive study. Place and Duration of the Study: University of Health Sciences, Tepecik Training and Research Hospital, Izmir, Turkey; from May 2007 to June 2019. Retrospective analyses were performed on 855 CRC patients, who were treated with surgery. Patient and treatment characteristics, lymphovascular (LVI), and perineural (PNI) invasion were documented. The impact of LVI and PNI was determined using Cox proportional hazards model. The cohort examined had 346 (40.5%) LVI and 150 (17.5%) PNI positive patients. After surgery, mortality was 18.4% for LVI and 8% for PNI patients. Although increased ASA score (for ASA 2 hazard ratio [HR]=0.555, p=0.001 and ASA 3-4 HR=0.723, p=0.014), adjuvant chemotherapy (HR=2.5, p<0.001), LVI (HR=1.961, p<0.001) and PNI (HR=1.625, p<0.001) involvement increased the risk of death based on univariate analysis, multivariate Cox analysis showed a risk of death increase with increased ASA score (for ASA 2 HR=0.53, p<0.001 and ASA 3-4 HR=0.703, p=0.008), adjuvant chemotherapy (HR=2.114, p<0.001) and LVI involvement (HR=1.640, p<0.001). LVI and PNI may be useful in identifying CRC patients who might benefit the most from adjuvant systemic therapy. On the other hand, the presence of LVI and PNI reflects a shorter patient survival. Key Words: Lymphovascular invasion, Perineural invasion, Colorectal cancer, Cancer staging.

Dynamic contrast enhanced-MRI and diffusion-weighted image as predictors of lymphovascular invasion in node-negative invasive breast cancer

BackgroundLymphovascular invasion (LVI) is an important risk factor for prognosis of breast cancer and an unfavorable prognostic factor in node-negative invasive breast cancer patients. The purpose of this study was to evaluate the association between LVI and pre-operative features of dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) and diffusion-weighted imaging (DWI) in node-negative invasive breast cancer.MethodsData were collected retrospectively from 132 cases who had undergone pre-operative MRI and had invasive breast carcinoma confirmed on the last surgical pathology report. MRI and DWI data were analyzed for the size of tumor, mass shape, margin, internal enhancement pattern, kinetic enhancement curve, high intratumoral T2-weighted signal intensity, peritumoral edema, DWI rim sign, and apparent diffusion coefficient (ADC) values. We calculated the relationship between presence of LVI and various prognostic factors and MRI features.ResultsPathologic tumor size, mass margin, internal enhancement pattern, kinetic enhancement curve, DWI rim sign, and the difference between maximum and minimum ADC were significantly correlated with LVI (p < 0.05).ConclusionsWe suggest that DCE-MRI with DWI would assist in predicting LVI status in node-negative invasive breast cancer patients.

Role of Pelvic Exenteration in the Treatment of Persistent or Recurrent Gynecological Cancers

Objective: To assess the oncological outcomes of Persistent/Recurrent Gynaecological Cancers who underwent Pelvic Exenteration (PE) in terms of DFS and OS in a 23 years-single center experience. Secondary outcome was to identify factors associated with recurrence. Methods: From June 1996 to March 2019, data of all patients who underwent PE were retrospectively collected. The Kaplan-Meier method was used to estimate DFS and OS. Univariable and multivariable logistic regression analysis was performed to identify potential independently associated predictors of recurrence. Results: 192 patients were considered for final analysis. After surgery 77 women (40.1%) received a post-operative oncologic treatment. Overall 106 patients (55.2%) experienced a relapse with a median follow-up of 58 months (range, 2 to 236 months). Presence of LVI (adjusted HR 2.2, 95% CI 1-4.9, P=0.05) was the only factor that retained an independent association with relapse at multivariable analysis. Positive lymph nodes were associated with death at univariable analysis (HR 3.9, 95% CI 1.7-9.4, P=0.002). When stratifying patients by cervical cancer, among 115 women, 67 (58.3%) relapsed. Presence of LVI (HR 2.7, 95% CI 1.1-6.6, P=0.02) and patients with pathologic risk factors such as tumor size, positive lymph nodes and LVI (HR 3.1, 95% CI 1.4-6.8, P=0.005) were associated with recurrence both at univariable and multivariable analysis. Conclusion: Pelvic exenteration may have a therapeutic role in cervical and endometrial tumors that recur at least 6 months after primary treatment. Patients affected by vulvar cancer or either with tumor size &gt;5 cm, positive lymph nodes, LVI have worse oncologic outcomes.

Lymphovascular invasion predicts disease-specific survival in node-negative esophageal squamous cell carcinoma patients after minimally invasive esophagectomy.

IntroductionLymphovascular invasion (LVI) is reported to be a potential prognostic predictor in esophageal squamous cell carcinoma (ESCC) patients.AimTo investigate the prognostic value of LVI in ESCC node-negative patients after minimally invasive esophagectomy (MIE).Material and methods1406 consecutive ESCC patients who underwent MIE were reviewed retrospectively. After exclusion, 880 patients were enrolled, and 298 node-negative patients were used for the further analysis. The Kaplan-Meier method was used to examine the survival difference. Univariate and multivariate analyses were performed to identify prognostic predictors.ResultsLVI was observed in 29.4% of all patients. Totally, the proportion of LVI was increased with advanced T (p < 0.01) and N (p < 0.01) stage and poor tumor differentiation (p < 0.01). In the node-negative patients, a similar result was obtained in T stage (p = 0.0252) and tumor differentiation (p = 0.0080). In survival analysis, the disease-specific survival (DSS) (p = 0.0146) rate was significantly lower in node-negative patients with LVI than in those without. The difference was absent when calculating disease-free survival (DFS) (p = 0.0796). Additionally, the presence of LVI was associated with lower DSS (p = 0.0187) but not DFS (p = 0.0785) in univariate analysis in node-negative patients. Moreover, in multivariate Cox regression analysis, the presence of LVI was identified as an independent prognostic factor only in DSS (p = 0.0496) but not in DFS (p = 0.5670) in node-negative patients.ConclusionsLVI is associated with shorter DSS and an independent prognostic factor in ESCC node-negative patients after MIE.

Abstract P1-10-07: The presence of ductal carcinoma in situ in core needle biopsy and microcalcifications on mammography in TNBC is associated with a lower pCR and worse long term outcome

Abstract Purpose Predictors for pathological Complete Response (pCR) in TNBC are very important given pCR is considered a surrogate marker for breast cancer-related survival. Associated DCIS in TNBC (accom-DCIS) as well as presence of microcalcifications on initial mammography (micro-MG) have been correlated with Androgen Receptor positive TNBC, known to achieve lower pCR rates. We aim to investigate the predictive impact of accom-DCIS and micro-MG on pCR. We also validated known clinico-pathological predictors for pCR. Long term outcome was analyzed for pCR and accom-DCIS. Methods A retrospective cohort study (diagnosed 1/1/2000 - 31/12/2017) of prospectively registered consecutively treated TNBC patients was performed. TNBC was defined as IHC-ER&amp;lt;1%, IHC-PR&amp;lt;1% and IHC-HER2 0-1+ and FISH negative if HER2 IHC 2/3+. All patients had standard of care neoadjuvant chemotherapy (NAC) in our hospital. Patients with at least 2 years of documented follow up and only TNBC of no special type on core needle biopsy (CNB) were included. We evaluated the predictive value of patient factors (age, BMI, symptomatic/screening-detected), imaging (micro-MG) and tumor related factors as reported in the pathology-report (grade, cT, focality, cN, lymphovascular invasion, accom-DCIS) for pCR (defined as pT0-TisN0). We used distant relapse rate and death to evaluate outcome. The Cox proportional hazards model was used to analyze the effect of pCR and accom-DCIS on distant relapse rate as well as overall survival (OS) in a multivariate model (corrected for size, nodal state, grading). Results are presented as hazard ratios (HR) with 95% confidence intervals (CI). Results The study contains 219 patients; accom-DCIS was reported in 53/219 (24.2%) CNB’s; pCR was achieved in 90/219 (41,1%). Patient related factors were comparable in patients who achieved pCR and those who had residual disease. Unifocal, smaller clinical size tumors and high tumor grade were significant predictors for pCR in our series. Analysis of 194 available mammographies showed micro-MG in 63/194 (32.5%). Micro-MG predicted for residual disease after NAC [HR = 3.350; 95% CI (1.708 - 6.569), p=0.005]. Accom-DCIS was a strong negative predictor of pCR [HR = 3.333; 95% CI (1.558 - 7.143), p=0.002)] and was associated with more distant relapse and worse survival [HR = 2.664; 95% CI (1.575 - 4.505), p=0.003]. pCR was strongly associated with a lower distant relapse rate and a better OS [HR = 2.210; 95% CI (1.282 - n3.811), p=0.004]. In the 129 cases without pCR, remaining tumor size [HR = 1.019; 95% CI (1.012 - 1.025), p=&amp;lt; 0,001), ypN [HR = 1.917; 95% CI (1.539 - 2.388), p=&amp;lt; 0,001) and presence of LVI [HR = 3.720; 95% CI (2.057 - 6.728), p=&amp;lt; 0,001] significantly predicted for secondary metastasis. There was only a trend towards more distant relapses if accom-DCIS was found in the resection specimen in those who had residual disease [HR = 1.347; 95% CI (0.780 - 2.325), p=0.2855]. Conclusion Presence of accom-DCIS in CNB as well as micro-MG predicts for less pCR in TNBC. Accom-DCIS in CNB is associated with more distant relapse and worse OS. For accom-DCIS on resection specimen, there was only a tendency towards more distant relapses. Citation Format: Jan Ardui, Sophie Vandamme, Chantal Van Ongeval, Giuseppe Floris, Hava Izci, Hans Wildiers, Kevin Punie, Tatjana Geukens, Ignace Vergote, Patrick Berteloot, Toon Van Gorp, Ann Smeets, Els Van Nieuwenhuysen, Sileny Han, Annouschka Laenen, Caroline Weltens, Hilde Janssens, Patrick Neven. The presence of ductal carcinoma in situ in core needle biopsy and microcalcifications on mammography in TNBC is associated with a lower pCR and worse long term outcome [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P1-10-07.

Abstract P1-18-02: Outcomes of patients with ER+/HER2+ non-metastatic breast cancer treated with trastuzumab without chemotherapy

Abstract Purpose: The development of trastuzumab has significantly improved prognosis and treatment of Her2 positive breast cancer. The efficacy of trastuzumab monotherapy is limited and thus standard of care is to combine trastuzumab with chemotherapy. Yet for those who cannot tolerate chemotherapy, there is no randomized data comparing no trastuzumab with trastuzumab monotherapy in the non-metastatic setting. We therefore examined the outcomes of non-metastatic patients treated with trastuzumab without chemotherapy in the National Cancer Database (NCDB). Methods: We included female patients from 2013-2016 with clinical stage I-III breast cancer who received surgery with ER+/HER+ disease. Patients treated with Her2 therapy after 2013 had their treatment classified under immunotherapy, whereas those treated before 2013 had Her2 therapy classified under chemotherapy. Exclusion criteria included male sex, prior cancer history, and clinical stage IV disease. We also excluded patients with pathologic stage 0 (DCIS), stage IV, or unknown pathologic stage. Treatments compared included chemotherapy (CT), adjuvant hormone therapy alone (HT), combination HT + trastuzumab (HT+T), and no adjuvant treatment (NT). Pearson chi square analysis, one-way ANOVA, and the Kaplan Meier method was used to evaluate the differences in clinical characteristics for the treatment groups and effects of treatment on overall survival. Results: We identified 46,025 patients who met eligibility criteria. The median follow-up was 31 months (SD 13.16) for CT, 30 months (SD 14.07) for HT, 30 months (SD 12.87) for HT + T, and 27 months (SD 14.61) for NT. Most patients received standard of care with CT (78%, n=36008), 12% (n=5632) received adjuvant HT without T (HT), 3% (n=1157) were treated with HT+T, and 12% (n=2669) with NT. There was a higher representation of elderly patients &amp;gt;70 years old in the HT (41%) and HT +T (51%) and NT arm (38%) compared to the CT arm (13%). There was a higher representation of lobular histology specifically in the HT + T arm (52%) compared to CT (11%), HT (11%), or NT arm (11%). There was a higher representation of patients with Charlson Deyo Comorbidity Scores of 1-2 (vs. 0) in the HT (21%) and HT +T arms (21%) compared to the CT (15%) or NT (18%) arms. There was a higher representation of node positive patients (N1-3 vs. N0) in the CT (38%) and HT+T (27%) groups vs. the HT (13%) and NT (16%) arms. Similarly, there were more patients with high grade disease (G3) and lymphovascular invasion (+LVI) in the CT (48% G3, 25% +LVI) and HT+T (45% G3, 20% +LVI) arms vs. in the HT (30% G3, 12% +LVI) and NT (39% G3, 15% +LVI) arms. Medicare patients were more likely to be treated with HT +T (58%) or HT (50%) than CT (24%) or NT (45%) which likely reflects the overlap of Medicare and older age. As compared to the standard of care CT arm, the patients treated without CT, had significantly worse overall survival. There was no improvement in OS for HT+T vs. HT without T. Hazard ratios for treatment regimens without CT were significantly worse with a HR 2.26 (95% CI 0.4-1.9) for HT without T, 3.01 (95% CI 0.3-2.3) for HT + T, and 4.37 (95% CI 3.7-5.1) for NT (p&amp;lt;0.0001). Conclusions: This is the largest retrospective analysis of US patients with ER+/HER2+ non-metastatic breast cancer. Those treated with HT + T (vs. CT, HT, and NT) are more likely to have lobular histology. Patients treated with HT+T (vs. HT) are more likely to have more aggressive disease including higher nodal stage, higher grade, and the presence of LVI. Those treated with HT+T (vs. CT) are more likely to be older. We fail to identify an OS benefit with HT + T compared to HT alone though further analysis including a multivariate analysis and propensity score matching will further elucidate the outcome of this group. Citation Format: Susanna Nguy, S. Peter Wu, Cheongeun Oh, Naamit K Gerber. Outcomes of patients with ER+/HER2+ non-metastatic breast cancer treated with trastuzumab without chemotherapy [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P1-18-02.

Indication for endoscopic treatment based on the risk of lymph node metastasis in patients with undifferentiated early gastric cancer

BackgroundDespite the risk of lymph node metastasis (LNM), the indications of endoscopic submucosal dissection (ESD) has expanded to undifferentiated type (UD-type) early gastric cancer (EGC). There is debate as to whether the endoscopic resection can be used. This study was conducted to evaluate risk factors for LNM in undifferentiated early gastric cancer, implications for the indication of the ESD so as to providing evidence for proper clinical management for UD-type EGC. MethodWe retrospectively analyzed 203 patients with UD-type EGC who underwent gastrectomy for primary gastric adenocarcinoma between 2012 and 2017. We evaluated the relationship between the clinicopathological factors and the presence of LNM using univariable and multivariable logistic regression analyses. ResultsA total of 203 UD-type EGC patients were enrolled, and LNM was positive in 40 cases (19.7%). Multivariable logistic regression analysis identified three independent risk factors for LNM, the tumor size (≥2.0 cm, P < 0.001), depth of invasion (P < 0.001), and lymphatic vessel involvement (LVI, P < 0.001). LNM was observed in 5.9% patients without the three predictive factors in UD-type EGC, whereas 7.7% and 37.7% of patients with one and two risk factors had LNM, respectively. In contrast, the LNM rate was up to be 66.7% in patients with three factors. Of 41 patients satisfying the expanded indication of ESD, 3 patients (7.3%) showed LNM. LNM was not found in any of 12 patients with small intramucosal lesions (<1.0 cm) without LVI. ConclusionsLNM-related risk factors were tumor larger than 2.0 cm, submucosal invasion, and the presence of LVI in UD-type EGC. ESD alone may be sufficient treatment for the intramucosal UD-type EGC that is smaller than 1.0 cm in size. When endoscopically resected specimens show unexpectedly larger tumor size, unexpected submucosal and LVI than that determined at pre-ESD endoscopic diagnosis, an additional gastrectomy with lymphadenectomy should be considered.

Mucoepidermoid Carcinoma of the Salivary Gland: Long Term Outcomes from a Tertiary Cancer Center in India.

To analyze the patterns of failure and factors affecting recurrence and overall survival in mucoepidermoid carcinoma of the salivary gland. The hospital records were retrospectively analyzed from October 2010 to January 2016. Patients diagnosed as mucoepidermoid carcinoma of the salivary gland were eligible for analysis. All patients received surgery as the primary treatment modality with or without post operative radiotherapy. Statistical analysis for factors affecting recurrence was done by cox regression analysis and p value less than 0.05 was considered significant. A total of 116 patients were diagnosed to have malignant salivary gland tumors of which 69 were mucoepidermoid carcinomas (69.5%). The median age was 43years (8-75years). Majority of the tumors occurred in major salivary glands gland (77%). 51% patients were females. Most common stage was stage II (36%) followed by stage I (27.5%), stage IV (20.3%) and stage III (16%). High grade carcinomas comprised 34.8%, intermediate grade 30.4% and low grade 34.8%. 36 patients (52.2%) received adjuvant radiotherapy (60Gy in 30 fractions). At a median follow up of 42months (8-70months), 8 (11.6%) patients died (7 cancer related and 1 noncancer related). The locoregional recurrence rate was 4.3% whereas the distant metastasis rate was 11.6%. Most common site of distant metastasis was lung. The mean disease free survival time was 61.4months and the mean overall survival was 62months. On univariate analysis, age < 50years, node positive, presence of PNI, high grade, presence of LVI and local recurrence were significant factors for distant metastasis (p < 0.05). On multivariate analysis, high grade, presence of LVI and local recurrence were significant factors for distant metastasis (p < 0.05). Mucoepidermoid carcinomas of salivary gland have good long term local control and overall survival. Majority of the recurrences are distant metastasis. High grade, LVI and local recurrence are significant risk factors for distant relapse.

A Nomogram to Predict Factors Associated with Lymph Node Metastasis in Ductal Carcinoma In Situ with Microinvasion.

Ductal carcinoma in situ (DCIS) with foci of invasion measuring ≤ 1mm (DCISM), represents < 1% of all invasive breast cancers. Sentinel lymph node biopsy (SLNB) has been a standard component of surgery for patients with invasive carcinoma or extensive DCIS. We hypothesize that selective performance of SLNB may be appropriate given the low incidence of sentinel node (SN) metastasis for DCISM. We investigated the clinicopathologic predictors for SN positivity in DCISM, to identify which patients might benefit from SLNB. A retrospective review of the National Cancer Database was performed for cases from 2012 to 2015. Clinical and tumor characteristics, including SN results, were evaluated, and Pearson's Chi square tests and logistic regression were performed. Of 7803 patients with DCISM, 306 (4%) had at least one positive SN. Patients with positive SNs were younger, more often of Black race, had higher-grade histology and larger tumor size, and were more likely to have lymphovascular invasion (LVI; all p < 0.001). In an adjusted model, the presence of LVI was associated with the highest odds ratio (OR) for node positivity (OR 8.80, 95% confidence interval 4.56-16.96). Among women with DCISM, only 4% had a positive SN. Node positivity was associated with more extensive and higher-grade DCIS, and the presence of LVI was strongly correlated with node positivity. Our data suggest that LVI is the most important factor in determining which patients with DCISM will benefit from SN biopsy.

The Impact of Post-Mastectomy Chest-Wall Radiation on Overall Survival for Intermediate-Risk Breast Cancer Patients: A National Cancer Data Base Analysis

The recommendation of post-mastectomy radiation therapy (PMRT) to breast cancer women with intermediate risk disease still requires a great deal of clinical judgment without a single, validated formula. We aimed to assess the impact of PMRT on overall survival (OS) among patients with breast cancer considered intermediate risk for local recurrence by querying the National Cancer Data Base (NCDB) 2004-2014 for breast cancer. We replicated the SUPREMO phase III clinical trial by including patients (age >=18) with pT1-2N1 (or pT2N0 with either histologic Grade = 3 or presence of LVI) who underwent total mastectomy and did not receive neoadjuvant therapy. PMRT had a total radiation dose 40-70 Gy and was given within 6 months after surgery. OS was defined as months from the date of surgery. Logistic regression was applied to assess the pattern of PMRT utilization. Cox proportional hazard model was used for the association with OS. Propensity score (PS) overlap weighting was implemented to balance all observed baseline characteristics and to eliminate the selection bias. The effect of PMRT in the subgroups was estimated through the multivariable model (MVA) with interactions. We obtained 35,244 eligible subjects with a median follow up of 65.5 months. The median age was 57, 82.6% were white, 55.6% had 1 positive lymph node (PLN), 43.7% of tumors were pT1, the median tumor size was 2.2 cm, 38.4% had Grade III-IV, 96.2% had a negative surgical margin, and 68.3% received adjuvant chemotherapy. 4841 (13.7%) received PMRT while 30,403 (86.3%) received no radiation (NR). There was a clearly increasing trend of PMRT utilization over the years. In MVA by logistic regression, the factors associated with a higher probability of PMRT usage include PLN =2-3, present of LVI, pT2, and younger age. The 10-year survival rate was 72.1% (PMRT) vs. 68.7% (NR) by KM method. In MVA with OS by controlling for baseline demographic and disease characteristics, the hazard ratio (HR) for PMRT vs. NR was 0.81 (95%CI: 0.74-0.89), and it was 0.84 (95%CI: 0.74-0.95) by the PS weighting approach. In the subgroups, the HR was 0.75 (95%CI: 0.64-0.88) among patients with PLN = 3, 0.69 (95%CI: 0.59-0.81) among women not receiving adjuvant chemotherapy, 0.68 (95%CI: 0.60-0.77) among women with age > 60, and 0.72 (95%CI: 0.58-0.90) among patients whose tumors exhibited LVI. In this large retrospective study based on NCDB, on average, PMRT provided significant long-term survival benefit among intermediate risk breast cancer patients, with a larger survival benefits noted amongst patients with 3 PLN, age > 60, or the presence of LVI. More informative guidance for the utilization of PMRT may require additional information such as disease specific survival or recurrence (which is unavailable in NCDB), and we are looking forward to the results from the SUPREMO trial.

Breast Cancer Molecular Subtypes as a Predictor of Radiotherapy Fractionation Sensitivity

Breast cancer molecular subtypes have been shown to be predictive for certain systemic therapies; yet, there is a paucity of data regarding their use as a predictor of radiotherapy fractionation sensitivity. The hypothesis of this analysis is that the impact of hypofractionation (HF) in comparison to conventional fractionation (CF), does not differ across breast cancer subtypes in a population of women with invasive breast cancer treated with modern systemic therapy. Patients diagnosed with stage I - III breast cancer between 2005-2009 and referred to a population-based cancer care program were identified. Descriptive statistics were used to report clinico-pathologic and treatment parameters. Molecular subtype was determined using the American Joint Committee on Cancer (AJCC) classification system: Luminal A (ER+ AND PR+ AND HER2- AND Grade 1) OR (ER2-3+ AND PR2-3+ AND HER2- AND Grade 2); Luminal B (All other (ER+ OR PR+) AND HER2-); HER2+ (All Her2+); Triple Negative (ER- AND PR- AND Her2-). Radiotherapy fractionation was categorized as HF (16 fractions) versus CF (25-30 fractions). Multivariable Cox Regression modelling was used to identify predictors of local recurrence (LR). LR-free survival (LRFS) was determined using the Kaplan-Meier method and compared using the log-rank test. A total of 5,868 cases were identified. The median age was 58 years (range: 23 – 91). Patients with Luminal A subtype comprised 45% of the cohort (N=2,628), compared to 30% Luminal B (N=1,734), 15% HER2+ (N=903), and 10% Triple Negative (N=603). There was no difference between those that received HF versus CF in terms of margin status (p=0.67), presence of extensive ductal carcinoma in situ (p=0.30) or receipt of radiotherapy boost (p=0.54). On multivariable analysis, tumor grade (p=0.003), presence of LVI (p=0.006), use of systemic therapy (p=0.01) and receipt of endocrine therapy (p=0.001) were associated with the risk of LR. The overall 10-year LRFS was 97.1% (95 CI: 96.6-97.6) for the whole cohort. The 10-year LRFS based on molecular subtypes was 98.3% (95 CI: 97.6 – 98.7) Luminal A, 96.6% (95 CI: 95.5 – 97.4) Luminal B, 97.0% (95 CI: 95.5 – 98.0) HER2+, and 93.5% (95 CI: 91.1 – 95.3) Triple Negative (p <0.001). There was no difference in the 10-year LRFS between patients treated with HF versus CF in those with Luminal A (98.2% versus 98.4%; p=.42); Luminal B (96.6% versus 96.8%; p=.90); HER2+ (97.5% versus 95.8%; p=.12) or Triple Negative subtype (93.9% versus 92.2%; p=0.47). There was no significant interaction between breast cancer subtype and fractionation regimen. Within the AJCC’s four commonly recognized clinical subtypes of breast cancer, local recurrence-free survival was not affected by breast radiotherapy fractionation. This data supports the routine use of hypofractionated regimens across all breast cancer subtypes.

Abstract P5-17-05: Outcome of triple negative inflammatory breast cancer (TNIBC) treated with dose-dense dose intense neoadjuvant chemotherapy (NAC), prognostic impact of post NAC lymphovascular invasion and tumor infiltrating lymphocytes (TIL)

Abstract Background Inflammatory breast cancers (IBC) particularly triple negative (TN) subtype have poor prognosis. There are few series reporting IBC outcome according to their immunohistochemical profile. We have already shown the efficiency of dose dense dose intense chemotherapy in triple negative breast cancer (1). We report a series of TNIBC treated with dose dense anthracycline cyclophosphamide followed with taxane and analyzed the correlation between pathological complete response (pCR), pre and post NAC TIL, post NAC LVI and disease free survival (DFS). Methods Between January 2010 and December 2016, all patients with TNIBC seen at breast cancer disease center, St Louis hospital, Paris, France, were treated with neoadjuvant dose dense dose intense Cyclophophamide (1.2g/m2 d1) - Epirubicin (75mg/m2 d1) q2w (SIM regimen) followed with 12 injections of paclitaxel (80 mg/m2) qw or 4 injections of docetaxel (100 mg/m2) q3w. All patients have histologically proven TN tumors and no evidence of metastases assessed by initial FDG PET Scanner. Mastectomy and axillary clearance was performed after chemotherapy. pCR was defined as no residual invasive tumor in breast and lymph nodes. TIL and lymphovascular invasion were evaluated pre and post NAC by 2 independent anatomopathologists dedicated to breast cancer. Delta TILS was defined as the difference between post chemotherapy and pre chemotherapy TIL. Results Thirty TNIBC pts were treated, 28 underwent surgery and 2 progressed during chemotherapy. Median follow-up was 39 months (8 – 86). 9/30 patients (30%) achieved pCR. Median disease free survival (DFS) was 41 months (2 – 86). Median TIL infiltration at diagnosis was 11% (0-60) and dropped to 1% after chemotherapy (0 – 80). Median delta TIL was - 9% (-50% – +40%). TIL increase after chemotherapy was associated with a decrease of DFS (14 months vs not reached ; p = 0,0009). LVI was present on surgical specimens in 12 cases (12/30, 43%; 12/21 non pCR pts 57 %). Presence of LVI after chemotherapy was significantly associated with a decrease of DFS in the whole population (21 months vs not reached ; p = 0.008) and no significantly among the patients without pCR (23 months vs not reached; p = 0.07). Conclusion To the best of our knowledge, it is the best pCR rate reported in TNIBC (2). We showed in this retrospective series of 30 TNIBC that dose dense dose intense chemotherapy is efficient in this population. Presence of lymphovascular invasion and TIL after neoadjuvant chemotherapy in TNIBC are strong prognostic factors associated with DFS. Systematic determination of post NAC TIL and LIV could be a surrogate to propose adjuvant treatment after NAC in TNIBC.

Abstract P3-12-09: Dosimetric analysis of the pattern of local recurrence in breast cancer patients undergoing breast reconstruction and post-mastectomy radiotherapy

Abstract Background This study aims to identify spatial and dosimetric patterns of breast cancer relapse in a mono-institutional large series of patients treated with mastectomy and various forms of breast reconstruction. Material and Methods We retrospectively reviewed 196 patients with Stage II-III breast cancer treated with modified radical mastectomy between 1995 and 2016 at the Radiotherapy Department of Careggi Hospital, Florence. All patients performed Skin-sparing mastectomy or nipple-sparing mastectomy with immediate or delayed breast reconstruction and subsequently received post-mastectomy radiotherapy (PMRT). Systemic therapy was prescribed as per local and international guidelines both in neoadjuvant and adjuvant setting. All patients were treated with 3DCRT technique. Diagnostic imaging (e.g. CT, MRI) obtained at recurrence were registered with the original planning computed tomography (pCT) for the dosimetric analysis. Recurrence gross tumor volume (rGTV) were delineated and co-registered with pCT. All rGTV were compared dosimetrically to planned dose and spatially with planning target volumes. Locoregional recurrence (LR) were divided in three categories relative to the high dose region, 95% of prescription dose (D95%). We defined “in field LR” those with more than 90% of their volume within D95% region,“marginal LR” when recurrence volume was between 20 and 90% within D95% and “outfield LR” those with less than 20% of their volume D95%. Results The median age was 49 years (range, 26 - 83 years).163 women (83 %) were classified as stage III; 118 women (60 %) had more than three positive axillary nodes. The majority of lesions were estrogen receptor positive ( 75 %), grade 3 (52%) ,with the presence of LVI (60 %). Adjuvant RT at chest wall were performed in all patients, most of whom underwent a RT of chest wall +infra- supraclavicular nodes (71%).Prescribed RT dose was 50 Gy in 25 fractions. With a median follow-up of 60 months (range, 12-240 months), 22 (11%) patients experienced a locoregional relapse: 10 patients in the chest wall; 7 in ipsilateral axillary region +/- chest wall; 3 in internal mammary nodes -/+ chest wall; one locoregional relapse was observed in the supraclavicular nodes. Most of relapses were G3 (75%) with documented LVI (79%). The topographic analysis of the local failure patterns showed: thirteen (59 %) were “in-field LR”; 9 (41%) were “out-field LR” . For the spatial analysis, all relapses on the chest wall were observed above the breast tissue expander or mammary prosthesis. Free time from recurrence disease was 30 months (range 5-86 months). Conclusion This study suggests that chest wall recurrences are rare after PMRT and are related to biologic aggressiveness of the disease than to inadequate irradiation of target volumes. Prospective studies are warranted to evaluate the relationship between treatment volumes and patterns of recurrences in order to refine new delineation guidelines for women undergoing PMRT and breast reconstruction. Citation Format: Desideri I, Meattini I, Becherini C, Francolini G, Scotti V, Olmetto E, Perna M, Topulli J, Livi L. Dosimetric analysis of the pattern of local recurrence in breast cancer patients undergoing breast reconstruction and post-mastectomy radiotherapy [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P3-12-09.

Prognostic significance of lymphovascular infiltration in overall survival of gastric cancer patients after surgery with curative intent.

ObjectiveLymphovascular infiltration (LVI) is frequently detected in gastric cancer (GC) specimens. Studies have revealed that GC patients with LVI have a poorer prognosis than those without LVI.MethodsIn total, 1,007 patients with curatively resected GC at Department of Gastric Cancer, Tianjin Medical University Cancer Institute and Hospital were retrospectively enrolled. The patients were categorized into two groups based on the LVI status: a positive group (PG; presence of LVI) and a negative group (NG; absence of LVI). The clinicopathological factors corrected with LVI and prognostic variables were analyzed. Additionally, a pathological lymphovascular-node (lvN) classification system was proposed to evaluate the superiority of its prognostic prediction of GC patients compared with that of the eighth edition of the N staging system.ResultsTwo hundred twenty-four patients (22.2%) had LVI. The depth of invasion and lymph node metastasis were independently associated with the presence of LVI. GC patients with LVI demonstrated a significantly lower overall survival (OS) rate than those without LVI (42.8% vs. 68.9%, respectively; P<0.001). In multivariate analysis, LVI was identified as an independent prognostic factor for GC patients (hazard ratio: 1.370; 95% confidence interval: 1.094−1.717; P=0.006). Using strata analysis, significant prognostic differences between the groups were only observed in patients at stage I−IIIa or N0−2. The lvN classification was found to be more appropriate to predict the OS of GC patients after curative surgery than the pN staging system. The −2 log-likelihood of lvN classification (4,746.922) was smaller than the value of pN (4,765.196), and the difference was statistically significant (χ2=18.434, P<0.001). ConclusionsThe presence of LVI influences the OS of GC patients at stage I−IIIa or N0−2. LVI should be incorporated into the pN staging system to enhance the accuracy of the prognostic prediction of GC patients.

A Machine Learning Approach for the Association of ki-67 Scoring with Prognostic Factors.

ki-67 score is a solid tumor proliferation marker being associated with the prognosis of breast carcinoma and its response to neoadjuvant chemotherapy. In the present study, we aimed to investigate the way of clustering of prognostic factors by ki-67 score using a machine learning approach and multiple correspondence analysis. In this study, 223 patients with breast carcinoma were analyzed using the random forest method for classification of prognostic factors according to ki-67 groups (<14% and >14%). Also the relationship between subgroups of prognostic factors and ki-67 scores was examined by multiple correspondence analysis. There was a clustering of molecular classification LA, 0-3 metastatic lymph node, age <50, absence of LVI, T1 tumor size with ki-67 <14% and grade III, 10 or more metastatic lymph nodes, and presence of LVI and molecular classification LB, age >50, and T3-T4 tumor size categories with ki-67 >14%. The fact that the low scores of ki-67 correlate with early stage diseases and high scores with advanced disease suggests that 14% threshold value is crucial for ki-67 score.

Clinical Impact and Prognostic Role of KRAS/BRAF/PIK3CA Mutations in Stage I Colorectal Cancer.

Stage I colorectal carcinoma has excellent prognosis, with 5-year survival rate up to 95%. The occurrence of lymphovascular invasion, tumor budding, high number of PDC, or lymph node micrometastases is associated with tumor progression. The aim of this study was to evaluate the mutational status of 62 stage I colorectal carcinomas (CRC) (taken from 37 patients surviving more than five years since the initial diagnosis and from 25 patients who died of disease) and to correlate it with histopathological features and the clinical outcome. Mutations of KRAS, NRAS, BRAF, and PIK3CA genes were analyzed through Myriapod Colon Status Kit, using the high-throughput genotyping platform Sequenom MassARRAY System. Mutations in those genes were found in 31 cases (50%) and mainly in those with poor prognosis. The most frequent mutations occurred at codons 12 and 13 of the KRAS gene (40% of cases). We found concomitant PIK3CA mutations in 5 cases (8%). The presence of PIK3CA mutations was mainly observed in tumors with poor prognosis and with unfavorable histopathological prognostic features. High PDC grade (P = 0.0112), the presence of tumor budding (P = 0.0334), LVI (P < 0.0001), KRAS mutations (P = 0.0228), PIK3CA mutations (P = 0.0214), multiple genetic mutations in KRAS and PIK3CA genes (P = 0.039), and nodal micrometastases (P < 0.0001) were significant prognostic variables for CSS. The presence of LVI was the only independent and statistically significant prognostic variable for CSS in our cohort of pTNM stage I CRCs. The analysis of KRAS/PIK3CA mutational status may be used to identify patients with stage I CRC at high risk of bad outcome and who may need additional treatments, including biological therapies.

Concomitant CIS on TURBT does not impact oncological outcomes in patients treated with neoadjuvant or induction chemotherapy followed by radical cystectomy.

Cisplatin-based neoadjuvant chemotherapy (NAC) for muscle invasive bladder cancer improves all-cause and cancer specific survival. We aimed to evaluate whether the detection of carcinoma in situ (CIS) at the time of initial transurethral resection of bladder tumor (TURBT) has an oncological impact on the response to NAC prior to radical cystectomy. Patients were identified retrospectively from 19 centers who received at least three cycles of NAC or induction chemotherapy for cT2-T4aN0-3M0 urothelial carcinoma of the bladder followed by radical cystectomy between 2000 and 2013. The primary and secondary outcomes were pathological response and overall survival, respectively. Multivariable analysis was performed to determine the independent predictive value of CIS on these outcomes. Of 1213 patients included in the analysis, 21.8% had concomitant CIS. Baseline clinical and pathologic characteristics of the 'CIS' versus 'no-CIS' groups were similar. The pathological response did not differ between the two arms when response was defined as pT0N0 (17.9% with CIS vs 21.9% without CIS; p = 0.16) which may indicate that patients with CIS may be less sensitive to NAC or ≤ pT1N0 (42.8% with CIS vs 37.8% without CIS; p = 0.15). On Cox regression model for overall survival for the cN0 cohort, the presence of CIS was not associated with survival (HR 0.86 (95% CI 0.63-1.18; p = 0.35). The presence of LVI (HR 1.41, 95% CI 1.01-1.96; p = 0.04), hydronephrosis (HR 1.63, 95% CI 1.23-2.16; p = 0.001) and use of chemotherapy other than ddMVAC (HR 0.57, 95% CI 0.34-0.94; p = 0.03) were associated with shorter overall survival. For the whole cohort, the presence of CIS was also not associated with survival (HR 1.05 (95% CI 0.82-1.35; p = 0.70). In this multicenter, real-world cohort, CIS status at TURBT did not affect pathologic response to neoadjuvant or induction chemotherapy. This study is limited by its retrospective nature as well as variability in chemotherapy regimens and surveillance regimens.

Incidence and Predictive Model for Lateral Pelvic Lymph Node Metastasis in Lower Rectal Cancer.

The lateral pelvic lymph node recurrence after curative resection in rectal cancer has been reported in more than 20% of cases and the lateral pelvic lymph node (LPLN) metastasis is an independent risk factor for local recurrence. A prospective cohort study with diagnosis of lower rectal cancer stages II and III performed to identify the factors with significant correlation with LPLN metastasis was categorised based on the number of positive factors and proposed a risk stratification model to uncover a possible benefit of LPLD in specific patient subgroups. Forty-three patients with lower rectal cancer underwent curative surgery, total mesorectal excision with bilateral lateral pelvic lymph node dissection. Pre-operative, female gender, raised serum CEA (> 5ng/mL), cT4, enlarged mesorectal lymph nodes, borderline enlarged LPLN on MRI, lower location (< 5cm from anal verge), large size (> 5cm) and non-circumferential lesion were significant predictors for LPLN metastasis. Histopathological, higher tumour grade, higher pT and pN stage, and the presence of LVI were significant factors. On cox-proportional hazard model analysis, female gender, large tumour, cT4, enlarged mesorectal lymph nodes, borderline enlarged LPLN, pN1 and positive LVI were associated with significant hazard. In conclusion, a specific group of patients with lower rectal cancer of stages II and III might be have treated with LPND in spite of concurrent chemo-radiation to achieve satisfactory oncological outcome. The proposed stratification grouping is strongly guiding the patient for lateral pelvic lymph node dissection. Further study to prove the oncological advantage of LPND is warranted at large scale.