Distant Recurrence-free Survival Rates Research Articles

Proton therapy for intracranial meningioma: a single-institution retrospective analysis of efficacy, survival and toxicity outcomes.

To report the outcomes of a large series of intracranial meningiomas (IMs) submitted to proton therapy (PT) with curative intent. We conducted a retrospective analysis on all consecutive IM patients treated between 2014 and 2021. The median PT prescription dose was 55.8Gy relative biological effectiveness (RBE) and 66 GyRBE for benign/radiologically diagnosed and atypical/anaplastic IMs, respectively. Local recurrence-free survival (LRFS), distant recurrence-free survival (DRFS), overall survival (OS), and radionecrosis-free survival (RNFS) were evaluated with the Kaplan-Meier method. Univariable analysis was performed to identify potential prognostic factors for clinical outcomes. Toxicity was reported according to the latest Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. Overall, 167 patients were included. With a median follow-up of 41 months (range, 6-99), twelve patients (7%) developed tumor local recurrence after a median time of 39 months. The 5-year LRFS was 88% for the entire cohort, with a significant difference between benign/radiologically diagnosed and atypical/anaplastic IMs (98% vs. 47%, p < 0.001); this significant difference was maintained also for the 5-year OS and the 5-year DRFS rates. Patients aged ≤ 56 years reported significantly better outcomes, whereas lower prescription doses and skull base location were associated with better RNFS rates. Two patients experienced G3 acute toxicities (1.2%), and three patients G3 late toxicities (1.8%). There were no G4-G5 adverse events. PT proved to be effective with an acceptable toxicity profile. To the best of our knowledge this is one of the largest series including IM patients submitted to PT.

Clinical outcomes of patients with HER2-positive microinvasive breast cancer.

544 Background: Although previous studies have reported that adjuvant trastuzumab with paclitaxel resulted in excellent survival outcomes in small, node-negative HER2-positive breast cancer, the necessity of adjuvant chemotherapy in HER2-positive microinvasive breast cancer (MIBC) remains controversial. Methods: Between January 2000 and January 2020, women with curatively resected pT1mi N0 and/or N1mi in Asan Medical Center were retrospectively identified and their survival outcomes including invasive disease-free survival (IDFS, excluding second primary cancer), distant recurrence-free survival (DRFS), and overall survival (OS) and the effect of adjuvant chemotherapy were analyzed. Results: A total of 833 patients were included. The median age was 51 years, and 51% (n = 426) were premenopausal. Pathologic nodal stage was pN0 in 96% (n = 799) and pN1mi in 0.7% (n = 6), and estrogen receptor (ER) was positive in 30% (n = 247). Adjuvant chemotherapy was administered to 18% (n = 147) of patients, of which 95% were fluorouracil-based. Six patients (0.7%) received adjuvant trastuzumab. With the median follow-up of 118.7 months, the 8-year IDFS and DRFS rates were 90.6% (95% CI, 88.4-92.7), and 97.3% (95% CI, 96.1-98.4), respectively, and the 8-year OS were 98.6% (95% CI, 97.8-99.5). IDFS did not differ by adjuvant chemotherapy, as the 8-year IDFS rates for patients who did and did not receive adjuvant chemotherapy were 91.1% (95% CI, 86.6-95.8) and 90.3% (95% CI, 87.9-92.8), respectively ( p = 0.930). The lack of differences in IDFS by chemotherapy was consistent across subgroups including pre-/postmenopausal patients, grade 1-2/3 tumors, and ER-negative diseases. Conclusions: In HER2-positive MIBC, a clinically meaningful proportion of patients experience IDFS events with long-term follow-up. The role of modern adjuvant chemotherapy regimens, as well as the role of adjuvant trastuzumab, should be further explored in this early-stage patient population.

Is Robotic Surgery Beneficial for Rectal Cancer Patients with Unfavorable Characteristic After Neoadjuvant Chemoradiotherapy?

The objective of this study was to compare long-term oncologic outcomes of robot and laparoscopic surgeries for patients with advanced rectal cancer who underwent neoadjuvant chemoradiotherapy (nCRT) followed by radical resection. This study analyzed 3240 rectal cancer patients who underwent radical surgery from 2008 to 2019. Among them, 1204 patients who received nCRT (robotic, n = 316; laparoscopic, n = 888) were analyzed. The oncological outcome according to the number of unfavorable factors (male, body mass index ≥ 25, receiving CCRT) present in patients also was analyzed. We used 1:1 propensity score matching (PSM) to adjust for potential baseline confounders between groups. After PSM, two groups showed similar demographics and pathological results. After PSM analysis, the robotic group showed higher 5-year disease-free survival (DFS) and local recurrence-free survival rates than the laparoscopic group, whereas 5-year overall survival and distant recurrence-free survival rates were similar between the two groups. In addition, by comparing survival rates for each yp stage, it was found 5-year DFS and local recurrence-free survival of the robotic group in yp stage III were significantly higher than those of the laparoscopic group. Five-year DFS was conducted according to the number of unfavorable factors (male, body mass index ≥ 25 kg/m2, and undergoing nCRT) as a subgroup analysis. In patients with all three unfavorable factors, the robotic group showed significantly higher DFS than the laparoscopic group. Robotic approach for rectal cancer after nCRT, especially for patients with yp stage III and unfavorable factors, have the advantage of improving oncologic outcomes even for surgeons specializing in colorectal cancer.

Race, Gene Expression Signatures, and Clinical Outcomes of Patients With High-Risk Early Breast Cancer

There has been little consideration of genomic risk of recurrence by breast cancer subtype despite evidence of racial disparities in breast cancer outcomes. To evaluate associations between clinical trial end points, namely pathologic complete response (pCR) and distant recurrence-free survival (DRFS), and race and examine whether gene expression signatures are associated with outcomes by race. This retrospective cohort study used data from the Investigation of Serial Studies to Predict Your Therapeutic Response With Imaging and Molecular Analysis 2 (I-SPY 2) multicenter clinical trial of neoadjuvant chemotherapy with novel agents and combinations for patients with previously untreated stage II/III breast cancer. Analyses were conducted of associations between race and short- and long-term outcomes, overall and by receptor subtypes, and their association with 28 expression biomarkers. The trial enrolled 990 female patients between March 30, 2010, and November 5, 2016, with a primary tumor size of 2.5 cm or greater and clinical or molecular high risk based on MammaPrint or hormone receptor (HR)-negative/ERBB2 (formerly HER2 or HER2/neu)-positive subtyping across 9 arms. This data analysis was performed between June 10, 2021, and October 20, 2022. Race, tumor receptor subtypes, and genomic biomarker expression of early breast cancer. The primary outcomes were pCR and DRFS assessed by race, overall, and by tumor subtype using logistic regression and Cox proportional hazards regression models. The interaction between 28 expression biomarkers and race, considering pCR and DRFS overall and within subtypes, was also evaluated. The analytic sample included 974 participants (excluding 16 self-reporting as American Indian or Alaska Native, Native Hawaiian or Other Pacific Islander, or multiple races due to small sample sizes), including 68 Asian (7%), 120 Black (12%), and 786 White (81%) patients. Median (range) age at diagnosis was 47 (25-71) years for Asian, 49 (25-77) for Black, and 49 (23-73) years for White patients. The pCR rates were 32% (n = 22) for Asian, 30% for Black (n = 36), and 32% for White (n = 255) patients (P = .87). Black patients with HR-positive/ERBB2-negative tumors not achieving pCR had significantly worse DRFS than their White counterparts (hazard ratio, 2.28; 95% CI, 1.24-4.21; P = .01), with 5-year DRFS rates of 55% (n = 32) and 77% (n = 247), respectively. Black patients with HR-positive/ERBB2-negative tumors, compared with White patients, had higher expression of an interferon signature (mean [SD], 0.39 [0.87] and -0.10 [0.99]; P = .007) and, compared with Asian patients, had a higher mitotic score (mean [SD], 0.07 [1.08] and -0.69 [1.06]; P = .01) and lower estrogen receptor/progesterone receptor signature (mean [SD], 0.31 [0.90] and 1.08 [0.95]; P = .008). A transforming growth factor β signature had a significant association with race relative to pCR and DRFS, with a higher signature associated with lower pCR and worse DRFS outcomes among Black patients only. The findings show that women with early high-risk breast cancer who achieve pCR have similarly good outcomes regardless of race, but Black women with HR-positive/ERBB2-negative tumors without pCR may have worse DRFS than White women, highlighting the need to develop and test novel biomarker-informed therapies in diverse populations.

Subpopulation treatment effect pattern plot analysis: a prognostic model for distant recurrence-free survival to estimate delayed adjuvant chemotherapy initiation effect in triple-negative breast cancer.

Triple-negative breast cancer (TNBC) is a heterogeneous disease associated with a poor prognosis. Delaying in time to start adjuvant chemotherapy (TTC) has been related to an increased risk of distant recurrence-free survival (DRFS). We aimed to develop a prognostic model to estimate the effects of delayed TTC among TNBC risk subgroups. We analyzed 687 TNBC patients who received adjuvant chemotherapy at the Instituto Nacional de Enfermedades Neoplasicas (Lima, Peru). Database was randomly divided to create a discovery set (n=344) and a validation set (n=343). Univariate and multivariate Cox regression models were performed to identify prognostic factors for DRFS. Risk stratification was implemented through two models developed based on proportional hazard ratios from significant clinicopathological characteristics. Subpopulation treatment effect pattern plot (STEPP) analysis was performed to determine the best prognostic cut-off points for stratifying TNBC subgroups according to risk scores and estimate Kaplan-Meier differences in 10-year DRFS comparing TTC (≤30 vs.>30 days). In univariate analysis, patients aged ≥70 years (HR=4.65; 95% CI: 2.32-9.34; p=<0.001), those at stages pT3-T4 (HR=3.28; 95% CI: 1.57-6.83; p=0.002), and pN2-N3 (HR=3.00; 95% CI: 1.90-4.76; p=<0.001) were notably associated with higher risk. STEPP analysis defined three risk subgroups for each model. Model N°01 categorized patients into low (score: 0-31), intermediate (score:32-64), and high-risk (score: 65-100) cohorts; meanwhile, Model N°02: low (score: 0-26), intermediate (score: 27-55), and high (score: 56-100). Kaplan-Meier plots showed that in the discovery set, patients with TTC>30 days experienced a 17.5% decrease in 10-year DRFS rate (95%CI=6.7-28.3), and the impact was more remarkable in patients who belong to the high-risk subgroup (53.3% decrease in 10 years-DRFS rate). Similar results were found in the validation set. We developed two prognostic models based on age, pT, and pN to select the best one to classify TNBC. For Model N°02, delayed adjuvant chemotherapy conferred a higher risk of relapse in patients ≥70 years and who were characterized by pT3/T4 and pN2/N3. Thus, more efforts should be considered to avoid delayed TTC in TNBC patients, especially those in high-risk subgroups.

A comprehensive analysis of Fanconi anemia genes in Chinese patients with high-risk hereditary breast cancer

BackgroundFour Fanconi anemia (FA) genes (BRCA1, BRCA2, PALB2 and RAD51C) are defined as breast cancer (BC) susceptibility genes. Other FA genes have been inconsistently associated with BC. Thus, the role of other FA genes in BC should be explored in specific populations.MethodsMutations in 16 FA genes were screened with a 98-gene panel sequencing assay in a cohort of 1481 Chinese patients with high-risk hereditary BC. The association between mutations and clinicopathological characteristics as well as prognosis was analyzed. The risk of BC in carriers of FA gene mutations was assessed in the Genome Aggregation Database and the Westlake Biobank for Chinese cohort.ResultsA total of 2.57% (38/1481) BC patients were identified who had 12 other FA gene germline mutations. Among them, the most frequently mutated gene was FANCA (8/1481, 0.54%). These 38 patients carried 35 distinct pathogenic/likely pathogenic variants, of which 21 were novel. We found one rare FANCB deleterious variant (c.1327-3dupT) in our cohort. There was a statistically significant difference in lymph node status between FA gene mutation carriers and non-carriers (p = 0.041). We observed a trend that mutation carriers had larger tumor sizes, lower estrogen receptor (ER) and progesterone receptor (PR) positivity rates, and lower 3.5-year invasive disease-free survival (iDFS) and distant recurrence-free survival (DRFS) rates than non-carriers (tumor size > 2 cm: 51.43% vs. 45.63%; ER positivity rates: 51.43% vs. 60.81%; PR positivity rates: 48.57% vs. 55.16%; 3.5-year iDFS rates: 58.8% vs. 66.7%; 3.5-year DRFS rates: 58.8% vs. 68.8%). The frequency of the mutations in FANCD2, FANCM and BRIP1 trended to be higher among BC cases than that in controls (p = 0.055, 0.08 and 0.08, respectively).ConclusionThis study comprehensively estimated the prevalence, clinicopathological characteristics, prognosis and risk of BC associated with deleterious variants in FA genes in Chinese high-risk hereditary BC patients. It enriches our understanding of the role of FA genes with BC.

Retrospective Study of Treatment Patterns and Natural History of Patients with T1a/b N0 Triple-Negative Breast Cancers: A Single-Institution Experience

Introduction: T1a/b, node-negative (node−), triple-negative breast cancers (TNBCs) are underrepresented in randomized drug-approving clinical trials. Given their low incidence, the clinicopathological features, natural history, and treatment patterns of these tumors remain insufficiently understood. Methods: We conducted a single-institution retrospective cohort study of patients with T1a/b, N0, M0 TNBCs. Deidentified patient- and tumor-related data were collected and summarized. Kruskal-Wallis, χ2, or Fisher exact tests were used to evaluate associations of interest. Kaplan-Meier methods, log-rank tests, and Cox’s proportional hazards models were applied for survival analyses. Results: Of 108 cases of node– TNBCs measuring ≤2 cm, 34 node– T1a/b tumors were included in our analysis. All cases had an intermediate to high histological grade, and most had a Ki-67 score of ≥20%. All patients received adjuvant chemotherapy, and many underwent mastectomy (47%). Docetaxel combined with cyclophosphamide was the most common adjuvant chemotherapy regimen (75%). We did not observe significant associations between improved outcomes and treatment with anthracycline-containing regimens. Among patients with node– pT1a/b tumors, the estimated 3-year recurrence-free survival (RFS) and distant RFS rates were both 96.3% (95% CI: 76.5–99.5), and the overall survival rate was estimated to be 100% (95% CI: 100–100). There were no cases of local recurrences observed. Conclusions: In our cohort, all patients with T1a/b node– TNBCs were treated with adjuvant chemotherapy and had favorable outcomes even when treated with anthracycline-sparing regimens.

Abstract P6-01-37: Tumor microenvironment subtype influence the response of neoadjuvant chemotherapy in breast cancer

Abstract Introduction Recent transcriptome analysis developed a holistic tumor microenvironment (TME) classification platform based on immune and fibrotic markers. This TME classification had four categories, immune enriched, fibrotic (IE/F); immune enriched, non-fibrotic (IE); Fibrotic (F); and Immune Desert (D). And these four TME subtypes are a predictive biomarker to immunotherapy in multiple cancer and four subtypes have been changed during treatment. Previously our study suggested baseline immune features and dynamic immune response on-treatment were predictive of treatment outcome in BC with neoadjuvant chemotherapy (NAC). In this study, we evaluated the impact of TME classification and dynamic change of TME classification on treatment outcome in BC with NAC. Methods Early and locally advanced BCs which would be planned to receive standard NAC (four cycles of anthracycline plus cyclophosphamide and four cycles of docetaxel or docetaxel plus trastuzumab for human epidermal growth factor receptor 2[HER2+] disease or six cycles of docetaxel, carboplatin, trastuzumab and pertuzumab for HER2+ disease) followed by curative surgery. We prospectively collected tumor tissue and matched blood three times for each patients: at BC diagnosis (T1), three weeks after the first cycle of NAC (T2), and curative surgery (T3). RNASeq was performed to classify TME subtype. In terms of clinical variables, clinical stage and IHC subtype at diagnosis, pathologic complete response (pCR), distant recurrence free survival (DRFS) and overall survival (OS) were used. Generalized logistic regression was used for predicting RCB class and pCR with clinical and genomic characteristics at T1. Kaplan-Meier analysis were performed to analysis DRFS and OS. Results In total, 210 patients who were treated with scheduled NAC were enrolled. Finally, RNASeq in 240 BC tissues (T1:119, T2:91 and T3:30) were conducted from 142 patients. In 119 BCs which was performed RNASeq at T1, hormone receptor(HR)+, HER2- BC was 32 (26.9%), 29 of HR+HER2+ BC (24.4%), 18 of HR-HER2+ BC (15.1%) and 44 of triple negative BC (TNBC) (37.0%). In TME classification, immune desert (D) was most frequently observed (45.3%), followed by IE (35.3%), F (10.1%) and IE/F (9.2%). The association between BC subtype and TME subtype suggested that HR+HER2- BC was frequently categorized into D (22 of 32, 68.8%) whereas TNBC was into IE (24 of 44, 54.5%) (p&amp;lt; 0.001). TME subtype has been dynamically changed during NAC. At T2, IE subtype was most frequently observed (27.5%) followed by D (25.3%), IE/F (24.2%) and F (23.1%). The inclination of TME change were different according to NAC response. In BC achieved pCR, IE/F subtype had increased (4 at T1 and 10 at T2) and decrease of D subtype (15 at T1 and 3 at T2). In BC with non-pCR, IE/F subtype had slightly increased at T2 (7 at T1 and 12 at T2) but there was no IE/F subtype at T3 point. Contrarily, D subtype had decreased at T2 but increased at T3 (39 at T1, 20 at T2 and 24 at T3). The impact of TME subtype was different according to pCR status. In BC with pCR, F subtype had poor prognosis in DRFS and OS compared to other subtype ([5year DRFS rate for F vs. others: 66.7% vs. 93.2%, p=0.028], [5year OS rate for F vs. others: 70.7% vs. 100%, p&amp;lt; 0.001]). In BC without pCR, there was no different DRFS and OS according to TME subtypes. Conclusion Our data suggested that TME subtype has been changed during NAC and the subtype switching was affected by the NAC response. Moreover, TME subtype may have prognostic role in DRFS and OS according to pCR status. Citation Format: ji-Yeon Kim, Kyunghee Park, woong-Yang Park, Jeong Eon Lee, Seok Won Kim, Seok Jin Nam, Se Kyung Lee, Yeon Hee Park. Tumor microenvironment subtype influence the response of neoadjuvant chemotherapy in breast cancer [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P6-01-37.

RecurIndex assay as an aid for adjuvant chemotherapy decisions in HR-positive HER2-negative breast cancer patients.

Adjuvant chemotherapy is a major adjuvant treatment modality for hormonal receptor (HR)-positive and HER2-negative early breast cancer, but only 2%-20% of patients derive practical benefits. How to balance its potential benefits and risks becomes a challenging clinical problem. The purpose of this study was to assess whether RecurIndex assay could serve as an aid for adjuvant chemotherapy decisions in Chinese patients with HR-positive HER2-negative early breast cancer. The tissue samples of pT1-2N0 HR-positive HER2-negative breast cancer from multiple centers were detected using RecurIndex assay, based on which the patients were assigned into low- and high-risk groups. The survival outcomes of low- and high-risk patients including those with and without adjuvant chemotherapy were compared, and the risk factors for recurrence and metastasis were identified. Totally 445 patients were eligible for analysis. By contrast to high-risk patients, low-risk patients represented better 7-year recurrence-free survival (RFS), distant recurrence-free survival (DRFS) and local recurrence-free survival (LRFS) rates. For low-risk patients, no significant differences were shown between those with and without adjuvant chemotherapy in 7-year RFS, DRFS and LRFS rates. These differences were also inapparent between high-risk patients with and without adjuvant chemotherapy. The multivariate model revealed high-risk patients had a significantly elevated risk of recurrence and metastasis than those at low risk. HR-positive HER2-negative early breast cancer patients at low risk stratified by RecurIndex assay might be exempt from adjuvant chemotherapy. Whether adjuvant chemotherapy may derive survival benefits for high-risk patients still needs larger cohorts to verify.

Subpopulation analysis of survival in high-risk T1 colorectal cancer: surgery versus endoscopic resection only

This study aimed to assess the long-term survival of patients with T1 colorectal cancer (CRC) after local or surgical resection considering the type and number of risk factors for lymph node metastasis. This study included patients with high-risk T1 CRC who underwent therapeutic resection at the National Cancer Center, Korea between January 2001 and December 2014. Risk factors included positive resection margin, high-grade histology, deep submucosal invasion, vascular invasion, budding, and no background adenoma (BGA). We statistically divided the population into favorable or unfavorable subpopulations. The favorable subpopulation included the following 5 combinations of risk factors: positive margin only or unconditional for margin status, deep submucosal invasion only, budding only, no BGA only, and budding+ no BGA. We analyzed the survival rate according to the resection type (local or surgical) in the total cohort and in each subpopulation. Eighty-one and 466 patients underwent local and surgical resections, respectively. The distant recurrence-free survival (DRFS) and overall survival (OS) rates were significantly high in the surgical group (hazard ratio [HR], .20; 95% confidence interval [CI], .06-.61; P= .0045 and HR, .41; 95% CI, .25-.70; P= .0010, respectively). In the favorable subpopulation, both DRFS and OS rates were not significantly different between the surgical and local groups (HR, .26; 95% CI, .02-4.19; P= .3431 and HR, .58; 95% CI, .27-1.23; P= .1534, respectively). Intensive surveillance without additional surgery may be another option in selected cases after of high-risk T1 CRC endoscopic resection.

Real World Evidence of Neoadjuvant Docetaxel/Carboplatin/Trastuzumab/Pertuzumab (TCHP) in Patients with HER2-Positive Early or Locally Advanced Breast Cancer: A Single-Institutional Clinical Experience.

PurposeDocetaxel/carboplatin/trastuzumab/pertuzumab (TCHP) regimen is frequently used to treat early and locally advanced human epidermal growth factor receptor 2 (HER2)–positive breast cancer (BC) in neoadjuvant setting. However, large-scaled real-world evidence did not exist.Materials and MethodsWe retrospectively reviewed medical records of patients with early or locally advanced HER2-positive BC who underwent neoadjuvant TCHP followed by curative surgery at Samsung Medical Center between January 2016 and August 2020.ResultsOf 447 patients, 316 (70.7%) received breast-conserving surgery and 131 (29.3%) received total mastectomy. In terms of neoadjuvant chemotherapy response, pathologic complete response (pCR) and residual cancer burden (RCB) score were analyzed. The rate of pCR was 64% a class of RCB 0 was observed in 65% of cases, RCB class I in 12%, RCB class II in 14%, and RCB class III in 2%. The 3-year event-free survival rate was 90.6%, BC with pCR occurred in 92.8%, and BC with non-pCR in 86.3% (p=0.016). In terms of distant metastasis, the 3-year distant recurrence-free survival rate was 93.5%; BC with pCR occurred in 95.9% and BC with non-pCR in 89.2% (p=0.013). Mucositis (85.2%), pain (83.2%), and diarrhea (70.5%) were the most common non-hematologic adverse events. In terms of hematologic adverse events, anemia (89.9%) was the most commonly observed adverse events followed by thrombocytopenia (29.8%).ConclusionNeoadjuvant TCHP therapy had a pCR rate of 64% and a 3-year event-free survival of 90% in real world experience. In terms of toxicity profile, anemia was frequently observed and adequate management including occasional transfusion was required.

Prognostic factors for follicular thyroid carcinoma: the importance of vascular invasion.

The World Health Organization (WHO) classifies follicular thyroid carcinoma (FTC) into three categories: minimally invasive (mFTC), encapsulated angioinvasive (eaFTC), and widely invasive (wFTC). This study investigated whether this classification is appropriate. We enrolled 523 patients who underwent initial surgery at Kuma Hospital between 1998 and 2015 and were diagnosed with FTC. Capsular invasion (CI) was classified as none, minimal (microscopic), or wide (macroscopic) invasion. Vascular invasion (VI) was divided according to the number of invasive foci into three degrees: VI(-), VI(1+), and VI(2+). For 507 M0 patients, age ≥55 years (p = 0.004), non-oxyphilic histology (p = 0.043), and male sex (p < 0.001) predicted poor distant recurrence-free survival (DR-FS) on univariate analysis; however, tumor size >4 cm and wide CI did not. The DR-FS rates significantly decreased from VI(-) to VI(2+) in a step-by-step fashion, including VI(-) vs. VI(1+) (p = 0.011) and VI(1+) vs. VI(2+) (p = 0.014). Multivariate analysis revealed that older age (p = 0.0004), non-oxyphilic histology (p = 0.041), male sex (p = 0.0052), VI(1+) (p = 0.017), and VI(2+) (p < 0.001) independently predicted distant recurrence. The DR-FS rates did not significantly differ among mFTC, wFTC/VI(-), and eaFTC/VI(1+). The DR-FS rate of eaFTC/VI(2+) was worse than that of eaFTC/VI(1+) (p = 0.042), but did not differ from that of wFTC/VI(1+/2+). Our findings suggest that subclassifying eaFTC according to the degree of VI and restricting wFTC to VI-positive cases would be better in the WHO classification. Revising the definition for wide CI is recommended.

Clinicopathological features and outcomes of intrathyroidal thymic carcinoma: a single institution study.

Intrathyroidal thymic carcinoma (ITTC) is a rare malignancy of the thyroid. It is thought to originate from ectopic thymic tissue or embryonic thymic rest, in, or adjacent to, the thyroid. We analyzed the backgrounds, clinicopathological features, and prognosis of 20 patients with ITTC, treated at our hospital. Thirteen of the 15 patients (86%) who underwent ultrasonography were diagnosed as malignant, based on imaging findings. 16 of the 17 patients (93%) who underwent cytology, were diagnosed or suspected to be malignant. Locally curative surgery (thyroidectomy and lymph node dissection) was performed for 19 patients. Large tumor size (>4 cm) was positively related to pathological node metastasis (p = 0.0389). Fourteen patients, including nine Ex-positive patients, underwent adjuvant external beam radiotherapy (EBRT) of the neck after surgery. Two patients showed recurrence of thyroid bed after and neither of them underwent adjuvant EBRT after surgery. Two patients who underwent EBRT showed recurrences of the lateral nodes (level V and level II), but they were easily dissected by re-operation. Ten- and 20-year local recurrence-free survival rates were 84.9% and 60.6%, respectively. To date, four patients showed distant recurrence, and 10- and 20-year distant recurrence-free survival rates were 75.0% and 75.0%, respectively. Our findings indicate that 1) the prognosis of ITTC is generally favorable, and 2) large tumor size is significantly related to lymph node metastasis. Two patients showing recurrence of the central region did not undergo EBRT; thus, further comparative studies are desirable to elucidate whether EBRT can prevent significant local recurrence.

Outcomes in Exceptionally Poor-Responders to Neoadjuvant Chemotherapy

<h3>Purpose/Objective(s)</h3> The use of neoadjuvant chemotherapy (NAC) in patients with operable breast cancer allows for assessment of treatment response, and subsequent tailoring of adjuvant therapy. While there is robust evidence demonstrating worse prognosis with residual disease versus path CR after NAC, there is little data regarding outcomes among patients with a heavy residual tumor burden after NAC. We report outcomes in patients who have exceptionally poor responses to NAC—those with > 9 nodes after NAC or with 5 cm or more of residual disease in the breast. <h3>Materials/Methods</h3> Between 06/2014 and 04/2020, 1511 patients received NAC followed by surgery at our institution. Poor responders, defined as those with positive nodes or residual tumor in the breast, were identified for analysis. Those with 1-3 positive nodes after NAC were used as a comparison cohort. Recurrence and survival outcomes were compared based on residual disease burden after NAC. Clinicopathologic parameters were summarized with descriptive statistics. Overall survival and recurrence-free survival estimates were calculated using Kaplan Meier methodology. <h3>Results</h3> Among 517 poor-responders, 315 patients had 1-3 positive nodes (N1a), 108 had 4-9 positive nodes (N2a), and 62 had > 9 positive nodes (high-volume residual, HVR); 32 patients with > 5cm of residual tumor in the breast were categorized as HVR. With a median follow-up of 39 months (IQR 27-50), the 5-year overall survival rate was 90% among N1a, 72% among N2a, and 78% among HVR patients (<i>P</i> = 0.003). The 5-year distant recurrence-free survival and local recurrence-free survival rates were 87%/87% among N1a vs. 59%/71% among N2a vs. 68%/75% among HVR (<i>P</i> < 0.001 and <i>P</i> = 0.009), respectively. 5-year local-regional and distant recurrence cumulative incidence rates, stratified by residual disease burden and by breast cancer subtype, are shown in Table 1. <h3>Conclusion</h3> Our work confirms that patients with high-volume residual are at high risk for LR and distant recurrence as well as death, despite best available standard-of-care treatment. ypN2a patients appear to perform as bad as HVR patients in terms of DM and death, but better in terms of local-regional recurrence. Triple-negative patients with residual disease had high rates of recurrence and death compared to other subtypes. Treatment intensification efforts are urgently needed.

Maxillary Sinus Floor Infiltration: Results From a Series of 118 Maxillary Sinus Cancers

Maxillary cancers are rare and aggressive tumors, which can spread beyond the sinus bony walls. Preoperative assessment of infiltration of maxillary sinus floor (MSF) is paramount for surgical planning, as palatomaxillary demolition significantly impacts patients' quality of life. This study investigates the challenges involved in the preoperative and intraoperative evaluation of MSF infiltration and analyzes its prognostic relevance. Retrospective case series. A retrospective review of patients treated for sinonasal malignancies at a single Institution was performed. Patients receiving surgical-based treatment with curative intent for primary maxillary sinus cancers, between January 2000 and November 2019, were included. A cohort of 118 patients was analyzed. By comparing intraoperative findings (endoscopic assessment and frozen sections) with preoperative radiological assessment, diagnostic changes with regard to MSF infiltration were found in 27.1% (32/118 cases). MSF infiltration negatively affected the prognosis in both univariate and multivariate analyses in the overall population. In the subgroup ofpT1-T3 tumors, MSF infiltration was significantly associated with reduced overall (P=.012), disease-free (P=.011), and distant recurrence-free (P=.002) survival rates. Conversely, pT classification was not able to stratify patients according to prognosis, mainly because early-staged cancers (pT1-T2) with MSF infiltration showed reduced survival rates, similar to those observed in pT3 cancers. Preoperative imaging should be integrated with intraoperative findings based on endoscopic inspection and frozen sections. Future studies are required to investigate the opportunity to incorporate MSF infiltration in the TNM staging system, considering its crucial role in defining the extent of surgery and its potential as prognosticator. 4 Laryngoscope, 132:26-35, 2022.

Oncologic and survival outcomes in elderly patients with locally advanced rectal cancer receiving neoadjuvant chemoradiotherapy and total mesorectal excision.

The efficacy of the addition of neoadjuvant chemotherapy to neoadjuvant chemoradiotherapy and total mesorectal excision for locally advanced rectal cancer in elderly patients has not been established. A total of 3096 locally advanced rectal cancer patients who received neoadjuvant chemotherapy, along with neoadjuvant chemoradiotherapy and total mesorectal excision, with or without adjuvant chemotherapy, between January 2010 and December 2018, were studied retrospectively. Patients were divided into elderly (>75years) and younger (≤75years) groups, and propensity score matching was used to balance a potentially confounding clinical bias. Overall survival, cancer-specific survival, disease-free survival, distant metastasis-free survival and local recurrence-free survival rates for the two groups were compared. Hazard ratios (HR) with 95% confidence intervals (CI) for different clinicopathological variables were calculated to determine predictors of 3-year overall survival. Mean follow-up was 39.0 (range, 5-140) months. The overall 3-year overall survival, cancer-specific survival, disease-free survival, distant metastasis-free survival and locoregional relapse-free survival rates were 86.1, 87.6, 80.0, 82.4 and 95.4%, respectively. Only 3-year overall survival rates differed significantly between the elderly (77.2%) and younger (88.9%) groups (P=0.01). Cancer-specific survival, disease-free survival, distant metastasis-free survival and locoregional relapse-free survival rates did not differ significantly between the two groups. Significant negative independent prognostic factors for 3-year overall survival were age>75years (HR=2.016, 95% CI 1.157-23.511, P=0.01) and high pathologic TNM stage (yp stage III, P<0.001). For elderly locally advanced rectal cancer patients who have good health and performance status, the addition of neoadjuvant chemotherapy to neoadjuvant chemoradiotherapy and total mesorectal excision can result in disease-related survival rates and oncological outcomes similar to those experienced by younger patients. The decision to use this treatment approach in elderly patients should not be based solely on chronological age.

Randomized controlled study to examine the efficacy of hepatic arterial infusion chemotherapy with cisplatin before radiofrequency ablation for hepatocellular carcinoma.

Hepatic arterial infusion chemotherapy (HAIC) with cisplatin is beneficial to patients with advanced hepatocellular carcinoma (HCC) treated with sorafenib. This study aimed to examine the effect of HAIC with cisplatin before radiofrequency ablation (RFA) in patients with HCC. This was a multicenter, single-blinded, randomized controlled study (UMIN000007267). Early-stage HCC patients were randomly assigned (1:1) to receive HAIC with cisplatin before RFA therapy (HAIC group) or RFA monotherapy (non-HAIC group). The primary end-point was recurrence-free survival. Efficacy analysis and safety analysis followed the intention-to-treat principle. Between August 2012 and July 2016, 74 patients were recruited. A total of 70 eligible patients were randomly assigned to the HAIC group (n=35) and non-HAIC group (n=35). Recurrence-free survival rates at 1 (3)year in the HAIC group and non-HAIC group were 82.9% (54.3%) and 74.3% (34.3%), respectively (hazard ratio [HR], 0.597; 95% confidence interval [CI], 0.320-1.091; p=0.094]. Subgroup analysis showed that the beneficial effect of HAIC was observed in patients with a single nodule and Child-Pugh score 5. Intrahepatic distant recurrence-free survival rate in the HAIC group was significantly better than that in the non-HAIC group (HR, 0.468; 95% CI, 0.235-0.896; p=0.022). Adverse events were observed in just two patients in the HAIC group (6%) - grade2 cholecystitis and grade2 hyperkalemia. HAIC with cisplatin before RFA did not significantly decrease recurrence in patients with early-stage HCC. However, it might be effective in preventing intrahepatic distant recurrence.

Abstract PD9-02: Personalized ctDNA as a predictive biomarker in high-risk early stage breast cancer (EBC) treated with neoadjuvant chemotherapy (NAC) with or without pembrolizumab (P)

Abstract Background: In the I-SPY 2 TRIAL, the addition of P to standard NAC resulted in more than doubling of the pathologic complete response (pCR) rates for both hormone receptor-positive (HR+)/HER2- and triple-negative (TN) early breast cancer (EBC) patients (pts) compared to NAC only (Nanda et al, JAMA Oncol, 2020). At 3 years, distant recurrence-free survival (DRFS) rates in pts with pCR following NAC+P was &amp;gt;95%. We hypothesized that ctDNA can serve as a predictive biomarker of response and survival in pts treated with NAC. Methods: A personalized ctDNA test (Signatera) was performed on 511 serial plasma samples from 138 pts with high-risk HR+/HER2- (n=77) or TN (n=61) stage II/III EBC. Pts received P with paclitaxel (Tx) followed by AC (P arm, n=42) or standard NAC only (n=96), an exploratory subset of pts evaluated for P efficacy. Plasma was collected; pretreatment (T0), 3 weeks after treatment initiation (T1), between Tx+/-P and AC regimens (T2), and prior to surgery (T3). ctDNA was deemed positive with a minimum of 2 of the pt specific tumor mutation fragments detected in cfDNA. Association of ctDNA with response and survival was analyzed using logistic and Cox regressions with pCR and DRFS as endpoints. Median follow-up was 2.8 years. Results: Detection of ctDNA decreased over time (P arm: T0-81%, T1-50%, T2-19%, T3-3%) and NAC only: T0-82%, T1-65%, T2-26%, T3-10%). ctDNA data at T0 and T1 was available for 96% (132/138) of pts in P arm or NAC only (Table). Among ctDNA+ patients at baseline, clearance at T1 was significantly associated with pCR (OR=1.92, ctDNA+/-; OR=0.27, ctDNA+/+; LR p&amp;lt;0.001). This association remained significant after adjustment for HR status and treatment (LR p&amp;lt;0.001) and P arm or NAC only (P: LR p=0.03; NAC: LR p=0.01). ctDNA data at T0, T1, and T2 was available for 86% (118/138) pts. (Table). Among all ctDNA+ pts at baseline, dynamics through T2 was associated with pCR (OR=1.44, ctDNA+/-/-; OR=0.33, ctDNA+/+/-, OR=0.12, ctDNA+/+/+; LR p=0.0011). This association remained significant when adjusted for HR status and treatment (LR p&amp;lt;0.001). Analysis within individual treatments showed significant association for NAC (LR p=0.040) and a non-significant trend in NAC+P (LR p=0.063), likely due to smaller sample size. All pts who achieved pCR were ctDNA- at T3 (n=34). Among those who failed to achieve pCR (n=81), DRFS was significantly better in ctDNA- (n=72/81; 20 in P and 52 in NAC) versus ctDNA+ pts (n=9/81; 1 in P and 8 in NAC) (adjusted HR 0.13; 95% CI 0.05-0.37). Conclusions: These exploratory results align with our previous findings that early clearance of ctDNA during NAC treatment was significantly associated with increased likelihood of achieving pCR. Additionally, we show that ctDNA clearance can be an early surrogate marker for therapy response assessment. Residual ctDNA after neoadjuvant treatment was a significant predictor of metastatic recurrence and death. Personalized monitoring of ctDNA during the course of NAC is feasible and provides information that can be combined with imaging and pathology, and may help to optimize decision making for de-escalation or escalation of therapy. Larger studies are ongoing. ctDNA dynamics and pCRctDNA status at T0 and T1 (n=132)ctDNA status at T0, T1, and T2 (n=118)ctDNA-/-ctDNA+/-ctDNA+/+ctDNA-/-/-ctDNA+/-/-ctDNA+/+/-ctDNA+/+/+Total, n (%)24 (18)28 (21)80 (61)22 (19)24 (20)43 (36)27 (23)pCR, n (%)9 (38)15 (54)11 (14)9 (41)12 (50)8 (19)2 (7)No pCR, n (%)15 (63)13 (46)69 (86)13 (59)12 (50)35 (81)25 (93) Citation Format: Mark Jesus M Magbanua, Denise Wolf, Derrick Renner, Svetlana Shchegrova, Lamorna Brown Swigart, Christina Yau, Gillian Hirst, Hsin-Ta Wu, Ekaterina Kalashnikova, Antony Tin, Amy Delson, Douglas Yee, Angela DeMichele, Raheleh Salari, Angel Rodriguez, Bernhard Zimmermann, Himanshu Sethi, Alexey Aleshin, Paul Billings, Laura Esserman, Minetta Liu, Rita Nanda, Laura van ‘t Veer, I-SPY 2 Investigators. Personalized ctDNA as a predictive biomarker in high-risk early stage breast cancer (EBC) treated with neoadjuvant chemotherapy (NAC) with or without pembrolizumab (P) [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PD9-02.

Operabilni invazivni karcinom dojke u eri konzervativne kirurgije; retrospektivna analiza 5-godišnjeg preživljenja i kontrole bolesti

Background: Following breast cancer treatment recommendations, the conservative approach is accepted and highly respected in the Clinical Hospital Center (CHC) Rijeka. However, we have found that institutional follow-up data are lacking. This retrospective analysis aims to update institutional data on survival and disease control rates. Methods: From 2011 till 2014, 915 breast cancer patients underwent surgery at CHC Rijeka, and 615 were included in this analysis. The Institutional Ethics Committee approved the analysis. Results: All patients were female, and the average age was 59 years. In the 5-year postoperative period, local, regional, and distant recurrence-free survival rates and overall survival and disease-free survival were calculated. All rates negatively correlate with a higher T and N status and a higher stage of the disease. The analysis has also demonstrated that in the pT1-3 pN0-1 subgroup, sentinel lymph node biopsy (SLNB) was not inferior to axillary lymph node dissection (ALND) in terms of locoregional control of disease and overall survival. Conclusion: Besides updating institutional data, the analysis confirmed that overall survival and locoregional control of the disease in the upfront-surgery patients are similar between pN0 and pN1 subpopulations and between pN2 and pN3, but statistically significantly different between pN0-1 and pN2-3. Currently ongoing, prospective observational multicenter clinical trial aims to translate the significance of these results into the neoadjuvant era.

Patterns of recurrence in patients with curative resected rectal cancer according to different chemoradiotherapy strategies: Does preoperative chemoradiotherapy lower the risk of peritoneal recurrence?

The present study aimed to compare the pattern of distant recurrence between patients with non-metastatic rectal cancer treated with pre-operative (OP) and those treated with post-operative (post-OP) chemoradiotherapy (CRT). A total of 631 patients with newly diagnosed non-metastatic rectal cancer who had received pre-OP or post-OP CRT with curative intent surgery between August 2008 and April 2015 were identified. Inverse probability of treatment weighting (IPTW) was performed to account for baseline differences between the two arms. Overall, 449 and 182 patients were treated with pre-OP and post-OP CRT, respectively. Sex, tumor location, clinical tumor stage, CRT regimen and adjuvant chemotherapy regimen were significantly different between the two arms. The median follow-up duration was 55.4 months (range, 53.7-57.1). The 5-year distant recurrence-free survival (RFS) rates and 5-year overall survival (OS) rates were not significantly different between the pre-OP and post-OP CRT arms (RFS, 67.5 vs. 71.6%, P=0.595 and OS, 81.9 vs. 77.0%, P=0.449), and no difference was observed in the distant recurrence patterns. Following IPTW, there was still no difference in distant RFS (pre-OP vs. post-OP CRT; hazard ratio (HR)=0.62; P=0.911), but pre-OP CRT was significantly associated with lower peritoneal recurrence (pre-OP vs. post-OP CRT; HR, 0.13; P=0.032). In addition, there was no significant difference in OS between the two arms (pre-OP vs. post-OP CRT; HR, 0.85; P=0.665). In conclusion, although distant RFS was not significantly different between the two arms, pre-OP CRT was significantly associated with a lower risk of peritoneal recurrence than post-OP CRT in patients non-metastatic rectal cancer.