Similar Disease-free Survival Research Articles

RET Fusion-Positive Papillary Thyroid Cancers are Associated with a More Aggressive Phenotype.

It is unclear if different genetic drivers in papillary thyroid cancer (PTC) confer different phenotypic tumor behavior leading to more aggressive disease. We hypothesized that RET-driven cancers are more aggressive. We reviewed records of consecutive patients treated for newly diagnosed PTC at this single institution from 2015 to 2016. Tumor samples from these patients were genotyped to identify RET-translocated, BRAFV600E mutant, and HRAS, KRAS, and NRAS mutant tumors. Patient demographic, clinicopathologic, and outcomes data were compared to identify genotype-specific patterns of disease. Of the 327 patients who underwent initial surgery for PTC during the study period, 192 (58.7%) had BRAFV600E mutant tumors (BRAF), 14 (4.3%) had RET-rearranged tumors (RET), 46 (14.1%) had RAS mutant tumors (RAS), and 75 (22.9%) had BRAF, RET, and RAS wildtype tumors. RET-driven tumors were more likely to have extrathyroidal extension (50.0% versus 27.0% for BRAF and 2.2% for RAS, P < 0.001), multifocal disease (85.7% versus 60.3%, and 44.4%, respectively, P = 0.017), and distant metastases (14.3% versus 1.1%, and 0%, respectively, P = 0.019). RET and BRAF patients also had worse disease-free survival than RAS patients (Kaplan-Meier log rank, P = 0.027). Patients with RET-driven PTCs had higher rates of extrathyroidal extension, multifocal disease, and distant metastases than patients whose tumors had BRAFV600E or RAS mutations. Patients with RET-rearranged tumors had similar disease-free survival to patients with BRAFV600E mutant tumors. RET rearrangement may confer an aggressive phenotype in PTC.

Abstract P3-18-03: Long-term outcomes for breast conservation plus radiotherapy versus mastectomy in early breast cancer after neoadjuvant systemic therapy: Results from the Swedish national breast cancer register (NKBC)

Abstract Background: Population-based studies have consistently shown improved long-term outcomes with breast conserving surgery (BCS) plus radiotherapy (RT) vs. mastectomy in primarily operated breast cancer (BC) patients. However, the survival impact of type of local therapy following modern neoadjuvant systemic therapy (NST) is unclear. Methods: The population-based Swedish National Breast Cancer Register (NKBC), a prospectively collected population-based cohort, was used to identify female BC patients who were diagnosed from January, 2007 until December, 2017 and received NST in the Stockholm region. Patients were divided into BCS+RT and mastectomy groups, and the prognostic factors reflecting the response to NST like pathologic complete response (pCR) and Neo-bioscore calculated by pre/postoperative TNM stage, nuclear grade, and receptors status, were used for stratification. Disease-free survival (DFS), locoregional recurrence-free survival (LRFS), distant metastasis-free survival (DMFS) and overall survival (OS) were evaluated using inverse probability of treatment weighted (IPTW) Cox proportional hazards model, which enables covariates like age, St Gallen subtypes, cTNM and ypTNM stages to be balanced between the two groups. Results: Among 1,409 eligible women, 456 (32.4%) were treated with BCS+RT, and 953 (67.6%) with mastectomy. Overall, 87 (6.2%) local recurrences, 256 (18.2%) distant metastases, and 282 (20.0%) deaths occurred over a median follow-up of 61 months. Patients diagnosed during later years, younger patients, patients with earlier stage and higher-grade tumors were more likely to receive BCS+RT. After adjusting for age at diagnosis, Neo-bioscore, adjuvant chemotherapy and radiotherapy, significant improvements for BCS+RT compared with mastectomy were observed in DFS (weighted-multivariate hazard ratio (HR), 0.51; 95%CI, 0.28-0.93; median 5-year DFS: 79.1% vs 73.6%) and DMFS (HR, 0.44; 95%CI, 0.23-0.82; median 5-year DMFS: 83.7% vs 74.8%), but no difference was identified in LRFS (HR, 0.94; 95%CI, 0.29-3.07; median 5-year LRFS: 89.9% vs 92.0%) or OS (HR, 0.7; 95%CI, 0.34-1.45; median 5-year OS: 88.4% vs 81.2%). The DFS benefit was observed regardless of pCR status, but varied by Neo-bioscore. Patients with Neo-bioscore 4-7 treated with BCS+RT had better DFS (HR, 0.31; 95%CI, 0.12-0.81) compared with those undergoing mastectomy, whereas low-risk patients with Neo-bioscore 0-3 had similar DFS between the two groups. Both triple negative (N=252; HR for DFS, 0.26; 95%CI, 0.07-0.97) and HER2-positive (N=533; HR for DFS, 0.24, 95%CI, 0.09-0.68) BC patients benefited from BCS+RT, but not patients with luminal tumors (N=589; HR for DFS, 0.82, 95%CI, 0.31-2.18). Similarly, superior DFS with BCS+RT was also seen in patients with neoadjuvant anti-HER2 targeted therapy (N=505; HR, 0.19; 95%CI, 0.05-0.75) or neoadjuvant chemotherapy alone (N=594; HR, 0.47; 95%CI, 0.21-1.06), but not among those receiving neoadjuvant endocrine therapy (N=162; HR, 0.53; 95%CI, 0. 1-2.85). Conclusion: After adjusting for response to NST and other confounders, BCS+RT was associated with reduced risks of tumor recurrence or metastasis compared with mastectomy. This benefit was more pronounced in patients with high Neo-bioscore, indicating that Neo-bioscore rather than pCR status has the potential to tailor breast surgery after NST. Further studies with larger sample size or prospective randomized clinical trials are warranted to confirm our findings. Citation Format: Kang Wang, Aafke Duinmeijer, Alexios Matikas, Renske Altena, Hemming Johansson, Hanna Fredholm, Theodoros Foukakis. Long-term outcomes for breast conservation plus radiotherapy versus mastectomy in early breast cancer after neoadjuvant systemic therapy: Results from the Swedish national breast cancer register (NKBC) [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P3-18-03.

BRAF V600E mutation in papillary thyroid carcinoma: it's relation to clinical features and oncologic outcomes in a single cancer centre experience.

PurposeThis study focuses on the oncologic influence of BRAF V600E mutations in a cohort of Middle Eastern papillary thyroid carcinoma (PTC) patients treated at a single centre. We tested the association of BRAF V600E mutation with papillary thyroid carcinoma at King Hussein Cancer Center.Methods Patients with histologically confirmed PTC who underwent surgical treatment between 2006 and 2015 were included in this study. Oncological outcomes, both short- and long-termed, were collected.Results A total of 128 patients (68% females) were included in this study with a mean age of 38 years (±13.8). The median follow-up period was 50 months. The BRAF V600E mutation was found in 71% of patients. The tumour size for patients with a negative BRAF V600E mutation was significantly larger in comparison to patients who tested positive for the mutation (3.47 cm vs 2.31 cm, respectively, P = 0.009). The two groups showed similar disease-free survival (DFS) rates; positive = 75% (median 43 months (0–168)) compared to 78% for the negative BRAF V600E mutation (median 38 months (3–142)) (P = 0.162, HR = 0.731) Furthermore, both groups showed similar overall survival rates, positive = 94.5% (median 56 months (0–228)) compared to 94.6% for the negative BRAF V600E mutation (median 43 months (3–157)) (P = 0.941, HR = 0.940).Conclusion BRAF V600E mutation had no effect on loco-regional recurrence, distant metastasis, overall survival, or DFS. These findings may be attributed to geographic variations or reflect that BRAF V600E may only serve as an indicator of poor prognosis in high-risk group as such.

Impact of Adjuvant Treatment in pN3 Penile Cancer

AimsDue to the lack of high-quality evidence and consensus on adjuvant treatment for locoregionally advanced penile cancer, we reviewed the outcomes of pN3 patients to determine the suitable adjuvant treatment options. Patients and methodsAll consecutive pN3 penile cancer patients treated at our institution between January 2010 and December 2018 were reviewed to assess the impact of demographical, pathological and treatment factors on disease-free survival (DFS) and overall survival. The DFS and overall survival were estimated using the Kaplan–Meier method and association was tested using the Cox regression model (two-sided test with P < 0.05 considered significant). ResultsOf 128 patients, 31 (24%) had pelvic nodal involvement. Twenty-six patients (20.3%) received no adjuvant treatment, 40 (31.3%) received single modality adjuvant treatment and 62 (48.4%) received multimodality adjuvant treatment (a combination of chemotherapy and radiotherapy). At a median follow-up of 22 months, the DFS and overall survival were 55.4 and 62%, respectively. The best DFS and overall survival was noted with chemotherapy followed by concurrent chemoradiation (C-CTRT; 93% each). On multivariate analysis, both DFS and overall survival were worse with pelvic node involvement (2.2 [1.3–4], P = 0.027 and 2.2 [1.3–4], P = 0.027, respectively) and better with any adjuvant treatment (single modality: 3 [1.5–5.5], P < 0.001; multimodality: 3.1 [1.6–6], P < 0.001). C-CTRT was associated with improved DFS over chemotherapy alone (0.17 [0.4–0.78], P = 0.02) but not over radiotherapy alone (0.35 [0.07–1.6], P = 0.19). In patients with no pelvic nodes involved, chemotherapy and radiotherapy as single modalities were associated with similar DFS and overall survival. In patients with pelvic nodes, multimodality treatment was associated with better DFS than single modality treatment (0.3 [0.1–1], P = 0.05).Conclusion: pN3 penile cancer is a diverse prognostic group with poorer outcomes associated with pelvic nodes. Single modality adjuvant treatment may be adequate in inguinal nodes with extranodal extension, but multimodality treatment should be given in patients with pelvic nodal involvement.

Long-Term Survival Following Definitive Radiation Therapy for Oligometastases in Gynecological Malignancies: A Landmark Analysis

Radiation therapy (RT) has been shown to prolong survival for patients with select oligometastatic cancers. Limited long-term follow-up data exist to determine if the prolonged survival correlates with cure versus a delayed relapse. To investigate this, we evaluated the clinical and disease characteristics of long-term survivors treated with definitive RT for oligometastatic gynecological cancer at our institution.We performed a landmark analysis in patients with oligometastatic gynecological cancer (OMGC) who survived for at least 5 years following treatment of their metastasis. OMGC was defined as metastasis (maximum of 5 total and 3 per site) present at a distant site at time of diagnosis or at a regional or distant site at time of recurrence. All patients received definitive RT between 2000 and 2015. Demographic and clinical variables were extracted from the medical record. Disease-free survival (DFS) after treatment of the first ROMGC was modeled using Kaplan Meier curves.48 patients with OMGC were analyzed; 20 (41.7%) had ovarian cancer, 16 (33.3%) had uterine cancer, 11 (22.9%) had cervical cancer, 1 (2.1%) had vaginal cancer. Median age was 52 years. A majority (45.8%) were stage III at primary diagnosis. The most common histology was adenocarcinoma (35.4%). The most common site of OMGC was in the pelvic lymph nodes (LN) (40.7%), with the following other sites: para-aortic LN (38.9%), supraclavicular LN (7.4%), lung (5.6%), mediastinal LN (3.7%), and axillary LN (3.7%). The median size was 2 cm. The median [interquartile range (IQR)] total RT dose and fractionation was 62.1 [52.5-64.5] Gy and 2.1 [2-2.2] Gy/fraction. The majority (70.8%) were treated with intensity-modulated RT. 25 (52.1%) patients received concurrent chemoRT (CRT) for their OMGC. After a median follow-up of 9.9 years after OMGC treatment, median [range] DFS for all patients was 73 [4-212] months (mo). 5-year DFS for cervical, uterine, and ovarian cancers was 82% (95% confidence interval [CI], 45-95%), 69% (CI, 41-86%), and 35% (CI, 16-55%), respectively. Patients who received CRT had better median DFS than those treated with RT alone (103 vs. 65 mo, P = 0.18). Patients with nodal OMGC had similar median DFS as those with non-nodal OMGC (73 vs. 66 mo, P = 0.86). During the first OMGC course, patients treated for 1 site had worse median DFS than those treated for 2+ sites (65 vs. 103 mo, P = 0.61). Of all 48 patients, 8 (16.7%) died of gynecologic cancer, 11 (22.9%) died of other causes, 3 (6.3%) had progression of disease. The remaining 26 (54.2%) patients were disease free at long-term follow up.Cure is possible for patients treated definitively for OMGC. Patients with cervical cancer, a greater number of treated OMGC sites, and treated with CRT had the longest DFS among this selected cohort. A randomized trial in oligometastatic gynecologic cancer is needed to determine if RT increases overall survival.K.L. Corrigan: None. A.K. Yoder: None. L.L. Lin: Employee; VA Hospital. Research Grant; Astra Zeneca. Travel Expenses; Astra Zeneca. A. Jhingran; American Board of Radiology. M.M. Joyner: Consultation with executive management and participation in board meetings; Frontline Bioenergy. P.J. Eifel: Travel Expenses; National Cancer Center Network. Stock; Apple Computer. L. Colbert: None. K.H. Lu: None. A.H. Klopp: Research Grant; MD Anderson Cancer Center SPORE Grant.

The choice of a neoadjuvant chemotherapy cycle for breast cancer has significance in clinical practice: results from a population-based, real world study.

Objective:Neoadjuvant chemotherapy (NAC) is currently used in both early stage and locally advanced breast cancers. The survival benefits of standard vs. non-standard NAC cycles are still unclear. This study aimed to investigate the relationship between NAC cycles and survival based on real world data.Methods:We identified patients diagnosed with invasive primary breast cancers who underwent NAC followed by surgery. Patients who received at least 4 NAC cycles were defined as having received standard cycles, while patients who received less than 4 NAC cycles were defined as having received non-standard cycles. Kaplan-Meier curves and Cox proportional hazard models were used to estimate the disease-free survival (DFS) and overall survival (OS).Results:Of the 1,024 included patients, 700 patients received standard NAC cycles and 324 patients received non-standard NAC cycles. The DFS estimates were 87.1% and 81.0% (P = 0.007) and the OS estimates were 90.0% and 82.6% (P = 0.001) in the standard and non-standard groups, respectively. Using multivariate analyses, patients treated with standard NAC cycles showed significant survival benefits in both DFS [hazard ratio (HR): 0.62, 95% confidence interval (CI): 0.44–0.88] and OS (HR: 0.54, 95% CI: 0.37–0.79). Using stratified analyses, standard NAC cycles were associated with improved DFS (HR: 0.59, 95% CI: 0.36–0.96) and OS (HR: 0.49, 95% CI: 0.28–0.86) in the HER2 positive group. Similar DFS (HR: 0.50, 95% CI: 0.25–0.98) and OS (HR: 0.45, 95% CI: 0.22–0.91) benefits were shown for the triple negative group.Conclusions:Standard NAC cycles were associated with a significant survival benefit, especially in patients with HER2 positive or triple negative breast cancer.

Simple Hysterectomy for Patients with Stage IA2 Cervical Cancer: A Retrospective Cohort Study.

ObjectiveThe purpose of this study was to compare long-term survival outcomes of simple hysterectomy versus radical hysterectomy in stage IA2 cervical cancer.MethodsA total of 440 patients who underwent simple hysterectomy (SH group) or radical hysterectomy (RH group) between 2014 and 2019 were included in this study. Overall survival (OS) and disease-free survival (DFS) were analyzed using the Kaplan–Meier method and compared by the Log rank test. The Cox proportional hazards regression model was employed to control for confounders.ResultsThere were 258 patients in the RH group and 182 patients in the SH group. The two groups had similar 5-year DFS rate (89.25% vs 91.14%, P=0.562) and 5-year OS rate (95.71% vs 94.76%, P=0.482). Multivariable analysis showed that simple hysterectomy was not independently associated with poorer DFS (aHR, 1.608; 95% CI, 0.640–4.041; P=0.312) and OS (aHR, 1.122; 95% CI, 0.319–3.493; P=0.858) than radical hysterectomy for women with stage IA2 cervical cancer.ConclusionFor stage IA2 cervical cancer, a simple hysterectomy is safe and effective. Further studies are needed to testify against our findings.

Association of RAD51 with homologous recombination deficiency (HRD) and clinical outcomes in untreated triple-negative breast cancer (TNBC): analysis of the GeparSixto randomized clinical trial

Current genetic and genomic tests measuring homologous recombination deficiency (HRD) show limited predictive value. This study compares the performance of an immunohistology-based RAD51 test with genetic/genomic tests to identify patients with HRD primary triple-negative breast cancer (TNBC) and evaluates its accuracy to select patients sensitive to platinum-based neoadjuvant chemotherapy (NACT).This is a retrospective, blinded, biomarker analysis from the GeparSixto randomized clinical trial. TNBC patients received neoadjuvant paclitaxel plus Myocet®-nonpegylated liposomal doxorubicin (PM) or PM plus carboplatin (PMCb), both arms including bevacizumab. Formalin-fixed paraffin-embedded (FFPE) tumor samples were laid on tissue microarrays. RAD51, BRCA1 and γH2AX were quantified using an immunofluorescence assay. The predictive value of RAD51 was assessed by regression models. Concordance analyses were carried out between RAD51 score and tumor BRCA (tBRCA) status or genomic HRD score (Myriad myChoice®). Associations with pathological complete response (pCR) and survival were studied. Functional HRD was predefined as a RAD51 score ≤10% (RAD51-low).Functional HRD by RAD51-low was evidenced in 81/133 tumors (61%). RAD51 identified 93% tBRCA-mutated tumors and 45% non-tBRCA mutant cases as functional HRD. The concordance between RAD51 and genomic HRD was 87% [95% confidence interval (CI) 79% to 93%]. In patients with RAD51-high tumors, pCR was similar between treatment arms [PMCb 31% versus PM 39%, odds ratio (OR) 0.71, 0.23-2.24, P = 0.56]. Patients with RAD51-low tumors benefited from PMCb (pCR 66% versus 33%, OR 3.96, 1.56-10.05, P = 0.004; interaction test P = 0.02). This benefit maintained statistical significance in the multivariate analysis. Carboplatin addition showed similar disease-free survival in the RAD51-high [hazard ratio (HR) 0.40, log-rank P = 0.11] and RAD51-low (0.45, P = 0.11) groups.The RAD51 test identifies tumors with functional HRD and is highly concordant with tBRCA mutation and genomic HRD. RAD51 independently predicts clinical benefit from adding Cb to NACT in TNBC. Our results support further development to incorporate RAD51 testing in clinical decision-making.

Características y resultados oncológicos del carcinoma epidermoide de ano: análisis comparativo entre los pacientes inmunocompetentes y los inmunodeprimidos

ObjectiveMost evidence, including recent randomized controlled trials, analysing anal squamous cell carcinoma (SCC) do not consider immunocompromise patient population. The aim of this study was to compare clinical and oncological outcomes among immunocompetent and immunocompromised patients with anal squamous cell carcinoma. MethodMulticentric retrospective comparative study including 2 cohorts of consecutive patients, immunocompetent and immunocompromised, diagnosed with anal SCC. This study evaluated clinical characteristics, clinical response to radical chemoradiotherapy (CRT) and long-term oncological results including both local and distant recurrence, overall survival (OS) and disease-free survival (DFS). ResultsA total of 84 patients, 47 (55.6%) female, diagnosed with anal SCC from January 2012 to December 2017 were included, 22 (26%) and 62 (74%) patients in immunocompromised and immunocompetent groups respectively. Patients in immunocompromised group were significantly younger (53 vs. 61 years; P=0.001), with smaller tumoral size (P=0.044) and reported higher rates of substance abuse.including tobacco use (P=0.034) and parenteral drug consumption (P=0.001). No differences were found in administered therapies (P=301) neither in clinical response to chemoradiotherapy (83 vs. 100%). Moreover, similar 5-year OS (60 vs. 64%; P=0.756) and DFS (65 vs. 68%; P=0.338) were observed. ConclusionThe present study shows no significant differences in long-term oncological results among immunocompetent and immunocompromised patients diagnosed with anal SCC, with a similar oncologic treatment. This evidence might be explained due to the close monitoring and adequate therapeutic control of HIV positive patients.

Challenges and Controversies in the Surgical Treatment of Cervical Cancer: Open Radical Hysterectomy versus Minimally Invasive Radical Hysterectomy.

Objective: The aim of the study was to perform a systematic assessment of disease-free survival (DFS), overall survival, and morbidity rates after open radical hysterectomy (ORH) and minimally invasive surgery (MIS) for early-stage cervical cancer and discuss with experts the consequences of the LACC trial (published by Ramirez et al. in 2018) on clinical routine. Methods: A total of 5428 records were retrieved. After exclusion based on text screening, four records were identified for inclusion. Five experts from three independent large-volume medical centers in Europe were interviewed for their interpretation of the LACC trial. Results: The LACC trial showed a significantly higher risk of disease progression with MIS compared to ORH (HR 3.74, 95% CI 1.63 to 8.58). This was not seen in one epidemiological study and was contradicted by one prospective cohort study reported by Greggi et al. A systematic review by Zhang et al. mentioned a similar DFS for robot-assisted radical hysterectomy (RRH) and LRH. Recurrence rates were significantly higher with MIS compared to ORH in the LACC trial (HR 4.26, 95% CI 1.44 to 12.60). In contrast, four studies presented by Greggi reported no significant difference in recurrence rates between LRH/RRH and ORH, which concurred with the systematic reviews of Zhang and Zhao. The experts mentioned various limitations of the LACC trial and stated that clinicians were obliged to provide patients with detailed information and ensure a shared decision-making process. Conclusions: The surgical treatment of early-stage cervical cancer remains a debated issue. More randomized controlled trials (RCT) will be needed to establish the most suitable treatment for this condition.

Comparison between laparoscopic and abdominal radical hysterectomy for low-risk cervical cancer: a multicentre retrospective study.

To compare oncological outcomes of laparoscopic radical hysterectomy (LRH) and abdominal radical hysterectomy (ARH) for low-risk cervical cancer. We retrospectively compared the 3-year overall survival (OS) and 3-year disease-free survival (DFS) of 1269 low-risk cervical cancer patients with FIGO 2009 stage IA2, IB1 and IIA1 with a tumour size < 2cm, no lymphovascular space invasion (LVSI), superficial stromal invasion and no lymph node involvement on imaging, and who received LRH (n = 672) and ARH (n = 597) between 2009 and 2018 at 47 hospitals. In the total study population, LRH and ARH showed similar 3-year OS (98.6% vs. 98.9%, P = 0.850) and DFS rates (95.7% vs. 96.4%, P = 0.285). LRH was not associated with worse 3-year OS (HR 0.897, 95% CI 0.287-2.808, P = 0.852) or DFS (HR 0.692, 95% CI 0.379-1.263, P = 0.230) as determined by multivariable analysis. After propensity score matching in 1269 patients, LRH (n = 551) and ARH (n = 551) still showed similar 3-year OS (98.4% vs. 98.8%, P = 0.704) and DFS rates (95.5% vs. 96.3%, P = 0.249). LRH was still not associated with worse 3-year OS (HR 0.816, 95% CI 0.262-2.541, P = 0.725) or DFS (HR 0.694, 95% CI 0.371-1.296, P = 0.251). Among patients with low-risk cervical cancers < 2cm, no LVSI, superficial stromal invasion, and no lymph node involvement on imaging, no significant differences were observed in 3-year OS or DFS rates between LRH and ARH.

From conventional two-stage hepatectomy to ALPPS: Fifteen years of experience in a hepatobiliary surgery unit

BackgroundHepatectomy in patients with large tumor load may result in postoperative liver failure and associated complications due to excessive liver parenchyma removal. Conventional two-stage hepatectomy (TSH) and associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) technique are possible solutions to this problem. Colorectal liver metastases (CRLM) is the most frequent indication, and there is a need to assess outcomes for both techniques to improve surgical and long-term oncological outcomes in these patients. MethodsA single-center retrospective study was designed to compare TSH with ALPPS in patients with initially unresectable bilateral liver tumors between January 2005 and January 2020. ALPPS was performed from January 2012 onwards as the technique of choice. Long-term overall survival (OS) and disease-free survival (DFS) were evaluated as primary outcome in CRLM patients. Postoperative morbidity, mortality and liver growth in all patients were also evaluated. ResultsA total of 38 staged hepatectomies were performed: 17 TSH and 21 ALPPS. Complete resection rate was 76.5% (n = 13) in the TSH group and 85.7% (n = 18) in the ALPPS group (P = 0.426). Overall major morbidity (Clavien-Dindo ≥ 3a) (stage 1 + stage 2) was 41.2% (n = 7) in TSH and 33.3% (n = 7) in ALPPS patients (P = 0.389), and perioperative 90-day mortalities were 11.8% (n = 2) vs. 19.0% (n = 4) in each group, respectively (P = 0.654). Intention-to-treat OS rates at 1 and 5 years in CRLM patients for TSH (n = 15) were 80% and 33%, and for ALPPS (n = 17) 76% and 35%, respectively. DFS rates at 1 and 5 years were 36% and 27% in the TSH group vs. 33% and 27% in the ALPPS group, respectively. ConclusionsALPPS is an effective alternative to TSH in bilateral affecting liver tumors, allowing higher resection rate, but patients must be carefully selected. In CRLM patients similar long-term OS and DFS can be achieved with both techniques.

Continuous versus intermittent extended adjuvant letrozole for breast cancer: final results of randomized phase III SOLE (Study of Letrozole Extension) and SOLE Estrogen Substudy

Late recurrences in postmenopausal women with hormone receptor-positive breast cancers remain an important challenge. Avoidance or delayed development of resistance represents the main objective in extended endocrine therapy (ET). In animal models, resistance was reversed with restoration of circulating estrogen levels during interruption of letrozole treatment. This phase III, randomized, open-label Study of Letrozole Extension (SOLE) studied the effect of extended intermittent letrozole treatment in comparison with continuous letrozole. In parallel, the SOLE estrogen substudy (SOLE-EST) analyzed the levels of estrogen during the interruption of treatment. SOLE enrolled 4884 postmenopausal women with hormone receptor-positive, lymph node-positive, operable breast cancer between December 2007 and October 2012 and among them, 104 patients were enrolled in SOLE-EST. They must have undergone local treatment and have completed 4-6 years of adjuvant ET. Patients were randomized between continuous letrozole (2.5 mg/day orally for 5 years) and intermittent letrozole treatment (2.5 mg/day for 9 months followed by a 3-month interruption in years 1-4 and then 2.5 mg/day during all of year 5). Intention-to-treat population included 4851 women in SOLE (n= 2425 in the intermittent and n= 2426 in the continuous letrozole groups) and 103 women in SOLE-EST (n= 78 in the intermittent and n= 25 in the continuous letrozole groups). After a median follow-up of 84 months, 7-year disease-free survival (DFS) was 81.4% in the intermittent group and 81.5% in the continuous group (hazard ratio: 1.03, 95% confidence interval: 0.91-1.17). Reported adverse events were similar in both groups. Circulating estrogen recovery was demonstrated within 6 weeks after the stop of letrozole treatment. Extended adjuvant ET by intermittent administration of letrozole did not improve DFS compared with continuous use, despite the recovery of circulating estrogen levels. The similar DFS coupled with previously reported quality-of-life advantages suggest intermittent extended treatment is a valid option for patients who require or prefer a treatment interruption.

ADV score is a quantifiable prognostic prediction model for surgical resection of hepatocellular carcinoma: A Korea-Japan collaborative validation study with 10,606 patients

We previously demonstrated that multiplication of α-fetoprotein (AFP), des-γ-carboxy prothrombin (DCP) and tumor volume (TV) (ADV score, expressed in log10) is an integrated surrogate marker of post-resection prognosis for hepatocellular carcinoma (HCC). This study aimed to validate the ADV score as a quantifiable biomarker for oncological aggressiveness of HCC on its prognostic impact following resection of HCC. A multicenter validation cohort with 10,606 patients (4,900 [46.2%] from Korea and 5,706 [53.8%] from Japan) was established through the Korea-Japan collaboration study groups managed by the Korea and Japan Society of Hepatobiliary Pancreatic Surgery. In the Korean cohort, disease-free survival (DFS) and overall survival (OS) rate at 5 years were 66.7% and 93.0% in ADV score < 2log; 56.0% and 84.1% in ADV score 2.0-2.9log; 51.0% and 79.7% in ADV score 3.0-3.9log; 45.7% and 75.3% in ADV score 4.0-4.9log; 44.4% and 69.4% in ADV score 5.0-5.9log; 38.4% and 64.3% in ADV score 6.0-6.9log; 32.6% and 62.9% in ADV score 7.0-7.9log; 28.7% and 53.2% in ADV score 8.0-8.9log; 30.4% and 46.5% in ADV score 9.0-9.9log; 30.5% and 47.7% in ADV score 10.0-10.9log; 22.5% and 35.7% in ADV score 11.0-11.9log; and 18.1% and 33.8% in ADV score ≥ 12log, respectively (both p < 0.001). The ADV-score dependent DFS and OS rates in the Japanese cohort were very similar with those of the Korean cohort. Consequently, the overall study cohort also revealed similar ADV-score dependent DFS and OS rates. Multiplication of AFP and DCP (AD score) and TV were independent risk factors for DSF and OS. The 5-year DFS and OS rates were visualized according to AD score and TV as like weather prediction diagrams. This high-volume international validation study revealed that the preoperative ADV score is a reliable surrogate biomarker for quantifiable prediction of post-resection prognosis in the Korean and Japanese patients with HCC.

Managing HER2-Positive Breast Cancer Amid COVID-19

Managing HER2-Positive Breast Cancer Amid COVID-19

52P Adjuvant endocrine therapy in HER2-positive breast cancer patients: Systematic review and meta-analysis

Approximately 50% of HER2-positive breast cancer lesions express hormone receptors. These tumors present a unique therapeutic challenge, and the optimal endocrine therapeutic approach remains controversial. We aimed to study the optimal adjuvant endocrine therapy in this setting in order to better establish the bases for clinical recommendations in HER2-positive disease. We conducted a literature search up to May 2020 in which we identified randomized controlled trials (RCTs) that investigated the efficacy of various adjuvant hormonal therapies among premenopausal and postmenopausal patients with hormone receptor (HR)-positive HER2-positive early breast cancer. Disease-free survival (DFS) was calculated with the random effect model and hazard ratios (HRs) with 95% confidence intervals (CI). Six RCTs (n=5,390 patients) were included in the final analysis. There was no significant difference in DFS between adjuvant treatment with aromatase inhibitors and tamoxifen (HR 0.99, 95% CI 0.68-1.44, P=0.96). After omitting the ALTTO trial because it did not randomize patients to hormonal therapy, no significant difference was observed between the two protocols (HR 1.06, 95% CI 0.65-1.73, P=0.81). Our study demonstrates similar DFS with tamoxifen and aromatase inhibitors as adjuvant endocrine treatment in HER2-positive HR-positive early breast cancer patients. Future larger prospective studies focusing on the various contemporary endocrine regimens are warranted to validate our findings.

Prognostic value of the number of the metastatic lymph nodes in locally early-stage cervical cancer: squamous cell carcinoma versus non-squamous cell carcinoma

To clarify the prognostic value of the number of metastatic lymph nodes (mLNs) in squamous and non-squamous histologies among women with node-positive cervical cancer. One hundred ninety-one node-positive cervical cancer patients who had undergone radical hysterectomy plus systematic pelvic and para-aortic lymphadenectomy followed by concurrent radiochemotherapy were retrospectively reviewed. The prognostic value of the number of mLNs was investigated in squamous cell carcinoma (SCC) v (n = 148) and non-SCC (n = 43) histologies separately with univariate log-rank test and multivariate Cox regression analyses. In SCC cohort, mLNs > 2 was significantly associated with decreased 5-year disease-free survival (DFS) [hazard ratio (HR) = 2.06; 95% confidence interval (CI) 1.03-4.09; p = 0.03) and overall survival (OS) (HR = 2.35, 95% CI 1.11-4.99; p = 0.02). However mLNs > 2 had no significant impact on 5-year DFS and 5-year OS rates in non-SCC cohort (p = 0.94 and p = 0.94, respectively). We stratified the entire study population as SCC with mLNs ≤ 2, SCC with mLNs > 2, and non-SCC groups. Thereafter, we compared survival outcomes. The non-SCC group had worse 5-year OS (46.8% vs. 85.3%, respectively; p < 0.001) and 5-year DFS rates (31.6% vs. 82.2%, respectively; p < 0.001) when compared to those of the SCC group with mLNs ≤ 2. However, the non-SCC group and the SCC group with mLNs > 2 had similar 5-year OS (46.8% vs. 65.5%, respectively; p = 0.16) and 5-year DFS rates (31.6% vs. 57.5%, respectively; p = 0.06). Node-positive cervical cancer patients who have non-SCC histology as well as those who have SCC histology with mLNs > 2 seem to have worse survival outcomes when compared to women who have SCC histology with mLNs ≤ 2.

P04.01 Adjuvant Chemotherapy is not Associated with Worse Disease-Free Survival in the Elderly Population.

Adjuvant chemotherapy after complete surgical resection is currently the standard of care for patients with stage IB-IIIA (7th Ed. TNM) non-small-cell lung cancer. The applicability of this treatment to the elderly population however is not completely established. This retrospective study evaluated the indication of adjuvant treatment and the influence of age on survival in patients over 65 years with stage I-III non-small-cell lung cancer. We analyzed 177 patients with resectable stage I-III non-small-cell lung cancer who underwent standard lung cancer surgery between 2005 and 2019 at A. C. Camargo Cancer Center, São Paulo, Brazil. Patients were divided in two age groups: <65 years-old and ≥65 years-old years. Indication of chemotherapy by age group and the influence of age on survival were studied. We used descriptive statistics (median and frequencies) to characterize the population. Frequencies were compared by the Pearson’s Chi-squared or Fisher’s exact test. Kaplan-Meier method was used to calculate survival curves. Overall survival (OS) was defined as the time in months from the date of surgery to the date of death by any cause. Survival curves were compared by the log-rank test. Disease-free survival (DFS) was defined as the time in months from the date of surgery to the date of disease relapse, diagnosis of second neoplasia or death by any cause. A p-value<0.05 was considered statistically significant for all tests. 40.7% patients were older than 65 years. Median age at diagnosis was 72 years among the elderly and 55 years in the younger group. 15.8% were stage IB, 23.7% stage II and 21.5% stage IIIA. The majority of patients (55.9%) had ECOG 0 and 65% had a Charlson’s comorbidity score of 3 to 5. The elderly had statistically more comorbidities when compared to the young group (40.1% x 64.2%, p=0.0005). 38.4% of patients received adjuvant chemotherapy after surgery with no statistical difference between the two groups (53.1% x 41.9%, p=0.12). With a medium follow-up of 48.13 months, OS was significantly shorter in the elderly population (55.5mo x 39.2mo; 95%CI 41.09-55.16; p=0.002), nevertheless DFS did not differ significantly between groups (15.6mo x 15.3mo; 95%CI 12.7-17.8; p=0.93). Furthermore, when analyzed according to number of comorbidities, OS was significantly shorter in the group with ≥2 comorbidities (p=0.04). Age was not employed as the sole criteria to withheld adjuvant chemotherapy in our center. Most of patients had multiple comorbidities and the elderly had considerably more. Despite the lower OS among the elderly, our data showed similar DFS, suggesting there is an excess of death in this group due to non-cancer related causes.

Abstract PS15-01: Radiation therapy improves survival in early-stage HER2-positive breast cancer with high-level of tumor infiltrating lymphocytes

Abstract Background: Scientific evidence strongly indicates that locoregional control in early-stage breast cancer (BC) by lumpectomy with radiation therapy or by mastectomy yields similar disease-free survival (DFS) and overall survival (OS). A recent retrospective review of a Danish prospective database demonstrated strong favorable interaction between radiotherapy (RT) and all BC subtypes that contain high amount of tumor infiltrating lymphocytes (TILs). Objective: We aim to compare DFS and OS in patients with early-stage HER2-positive BC, whose tumors demonstrate high involvement by TILs after locoregional treatment by either mastectomy or lumpectomy and whole breast radiotherapy. Methods: We retrospectively reviewed the charts and histopathology slides of patients with HER2-positive BC with clinical stage T1-T2 N0, who were treated in our center between January 2009 and December 2018. Locoregional management included either mastectomy (no radiation group) or lumpectomy with whole breast irradiation (radiation group). Stromal TILs were estimated using hematoxylin-eosin staining, according to the recommendations of the TILs working group 2014. This was performed by 3 independent pathologists who were blinded to the clinical course of the patients. A competing risk model, Kaplan-Meier analysis and multivariate Cox regression analysis were used to estimate correlations between TILs and clinical outcomes. Results: A total of 110 charts were reviewed and 99 were included in the final analysis. Patients were dichotomized into groups of “low-TILs” and “high-TILs” using a 40% cut off. Approximately 25% of patients (26/99) were “high-TILs” and around 50% of the “high-TILs” and “low-TILs” patients received RT. In all groups, around 90% of patients received chemotherapy and anti-HER2 therapy. All hormone receptor-positive patients received adjuvant endocrine therapy. While RT did not result in significant DFS or OS advantage in the low-TILs group, patients with high-TILs had significant improvement of DFS and OS with the addition of RT. Table 1 depict the 5-year DFS and 5-year OS in "high-TILs" and "low-TILs" groups in relation to RT, respectively. Conclusion: In this retrospective analysis, our findings indicate that in high-TILs early-stage HER2-positive BC, RT was associated with significant improvement of 5-year DFS and OS. The exact mechanism is not well understood. However, this observation is important and warrants confirmation in prospective clinical trials. 5-year DFS5-year OSHigh TILsLow TILsHigh TILsLow TILsRT group100%90%100%83%No RT group65%90%72%93%p-value0.0270.960.0250.184 Citation Format: Jason A Mouabbi, Momal Chand, Ramen Sakhi, Ishaq A Asghar, Daniel Ockner, Tarik Hadid, Carrie L Dul, Mothaffar F Rimawi, Amer Aref. Radiation therapy improves survival in early-stage HER2-positive breast cancer with high-level of tumor infiltrating lymphocytes [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 PS15-01.

Clinicopathological characteristics and impact on efficacy of three versus six months of adjuvant chemotherapy in early-onset colon cancer: ACHIEVE and ACHIEVE-2 trials.

60 Background: Colorectal cancer (CRC) incidence and mortality have decreased since the 1970s but several data such as the SEER CRC registry show that the incidence of early onset colon cancer (eoCC, age 20-49) and RC keep increasing. There is limited results suggesting eoCC may have different behaviors compared to traditional CC (tCC, age ≥ 50). Methods: Individual patient data of 1,805 high-risk stage II/III colon cancer (CC) patients (pts) as the modified ITT population in ACHIEVE and ACHIEVE-2 trials were investigated. Clinicopathological features and treatment-related data were assessed by age group. Disease-free survival (DFS) was assessed by Kaplan-Meier curves and Cox multivariable models adjusted by trials, regimen, T and N. Results: Of the 1,805 pts, eoCC were 155 pts (8.6%). Using 5% difference between age groups as clinically meaningful cutoff, eoCC had similar gender (female, 52 vs 48%), PS (PS = 1, 1 vs 4%), risk group (high-risk, 43 vs 42%) and T stage (T4, 30 vs 30%) as tCC, while eoCC were less likely right-sided colon primary (32 vs 39%), had N1 disease (48 vs 54%), and treated by FOLFOX (16 vs 23%). Overall, eoCC significantly had a worse DFS than tCC (3y-DFS, 75 vs 82%; Adjusted Hazard Ratio = 1.40: 95% Confidence Interval, 1.00-1.95: p= 0.0478); in addition, similar DFS were observed among tCC pts (age 50-69 vs &gt;70). eoCC experienced less neutropenia, thrombocytopenia and stomatitis, but had more diarrhea, nausea and/or vomiting. There were 38 and 297 pts with an initial relapse in eoCC and tCC, respectively. Of those, peritoneal metastases were more frequently seen in eoCC (n = 13, 34%) than in tCC (n = 63, 21%) (p = 0.097), whereas liver and lung metastases were similar between the two groups. Impact on DFS of 3 versus 6 months of adjuvant chemotherapy in eoCC (3y-DFS, 75% vs 76%) is similar to that in tCC (83% vs 81%). Conclusions: eoCC had unique characteristics; the difference in DFS between eoCC and tCC were potentially due to a different metastatic spread. eoCC had a different adverse event profile compared to tCC. No impact on DFS of treatment duration in eoCC was suggested. Clinical trial information: UMIN000013036.