Difference In 10-year Overall Survival Research Articles

Abstract PO1-15-04: Young Black Women With Triple-Negative Breast Cancer Molecular Subtypes: Population-Specific Patterns and Batch Effect Considerations

Abstract Introduction: While triple-negative breast cancer (TNBC) molecular subtypes have been associated with biological differences and clinical outcomes, studies have overwhelmingly been conducted in populations of European or Asian ancestry. Data collected across diverse populations is required to better leverage clinical directions from translational studies in TNBC. Through females recruited through the Black Women: Etiology and Survival of Triple-Negative Breast Cancers (BEST) study, we sought to characterize subtypes and explore associations. Methods: Our study included Black women diagnosed with early-stage (I-III) invasive TNBC at < = age 50 from 2005 to 2016, with recruitment from Florida and Tennessee state cancer registries. Germline DNA, tumor RNA, clinical outcomes, and risk factor data were collected. TNBC status in the BEST study was based on immunohistochemistry from pathology reports, cancer registry data, and self-reported data. Analyses on banked tumor samples, extracted at multiple time points, were conducted through PAM50 (Nanostring) and whole-transcriptome RNA-seq. TNBC subtype was assessed using TNBCtype-4 (Lehmann et al. 2016). Sources of batch effect were evaluated using PCA and corrected via limma. Genetic ancestry based on OncoArray or MEGA genotyping data was inferred using 1000Genomes continental reference samples. Immune cell characterization was performed via CIBERSORT and ESTIMATE. Statistical significance in comparing differences across subtypes was assessed via Chi-square test. Kaplan-Meier estimates and log-rank test were used for survival analysis. Results: RNA-seq from 114 self-reported Black females with TNBC was analyzed. TNBC subtype distribution in the BEST study cohort included 31.6% basal-like 1 (BL1), 28.9% basal-like 2 (BL2), 16.7% luminal androgen receptor (LAR), and 21.9% mesenchymal (M). While results were largely consistent with prior studies in patients of European or East Asian ancestry, a higher percentage of BL2 subtype was observed (28.9% vs. 21.0%, p=0.053). Based on PAM50 subtyping, 100% of tumors with BL1 and M were basal, whereas 68.8% of LAR and 86.7% of BL2 subtypes were basal. Tumors without subtype decreased from 9.8% to 1.1% after batch correcting for location at which RNA was extracted (Moffitt vs. Vanderbilt) and time between RNA banking and sequencing. All TNBC subtypes in this population demonstrated monocyte/activated dendritic cell predominance, with no significant subtype-specific associations with immune cell patterns. A lower relative proportion of M subtype was found in tumors from BRCA1/2 carriers, but this was not statistically significant due to the small number of carriers (8% vs. 18%; p=0.22). With a median follow-up time of 9 years, there was no significant difference in 10-year overall survival by TNBC subtype (p=0.18). However, patients with M subtype appeared to have worse survival relative to other subtypes combined (p=0.036). Conclusion: Our study is among the largest to date that interrogates TNBC subtypes and associated molecular/clinical data in self-reported Black females with invasive breast cancer. Our findings suggest that established TNBC subtyping can be applied in patients of African ancestry. Furthermore, data to correct for lab-based confounders remains critical; in this study, it enabled us to use many samples that could not be subtyped initially. Several population-specific patterns were observed, including no difference in 10-year overall survival across TNBC subtypes (consistent with prior data), but worse initial outcomes in M subtype; a preliminary association between BRCA1/2 carriers and non-M subtypes (in contrast to prior data); and no significant difference in immune cell distributions (in contrast to prior data mainly from patients of European ancestry). Studies of associations between TNBC subtypes, additional clinical data, and treatment data (type and response rates) are ongoing. Citation Format: Padma Rajagopal, Sonya Reid, Run Fan, Lindsay Venton, Anne Weidner, Mya Roberson, Susan Vadaparampil, Xuefeng Wang, Sean Yoder, Marilin Rosa, Jibril Hirbo, Jennifer Whisenant, Jennifer Pietenpol, Fei Ye, Tuya Pal, Brian Lehmann. Young Black Women With Triple-Negative Breast Cancer Molecular Subtypes: Population-Specific Patterns and Batch Effect Considerations [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO1-15-04.

Survival assessment of nephron-sparing surgery or radical nephrectomy in children with unilateral Wilms tumor receiving adjuvant chemotherapy: a retrospective cross-sectional study.

Surgical treatment of unilateral Wilms tumor (WT) in children is controversial. In this study, we aimed to evaluate the survival and prognosis of radical nephrectomy (RN) and nephron-sparing surgery (NSS) in children with unilateral WT receiving adjuvant chemotherapy. Data on pediatric patients with WT were collected from the Surveillance, Epidemiology, and End Results (SEER) database from 2000 to 2019. Multivariate logistic regression was used to analyze factors influencing the choice of surgical strategy. Cox proportional hazard models were used to assess factors associated with overall survival. We included 1,825 patients with unilateral WT (<14 years) who received adjuvant chemotherapy and surgery. Between 2000 and 2019, the percentage of patients treated with NSS increased from 4% in 2000 to 8% in 2019. There was no significant difference in 10-year overall survival between the two surgical strategies [NSS vs. RN, 93.26% (95% CI, 86.88%-100%) vs. 92.17% (95% CI, 90.75%-93.61%), p=0.98]. Patients with unilateral WTs ≤4 cm were more likely to be treated with NSS. There was no survival benefit for patients treated with RN compared with that for those treated with NSS (HR, 0.74; 95% CI, 0.29-1.86; p=0.5). The use of NSS in children with unilateral WT has increased over the last two decades. Tumor size is an important influencing factor for the surgical application of NSS. Patients who underwent NSS had an equivalent OS compared with the overall group of patients with unilateral tumors who received RN.

Surgical management of T1/T2 node-negative papillary thyroid cancer with tall cell histology: Is lobectomy enough?

BackgroundThe tall cell variant of papillary thyroid carcinoma has traditionally been treated more aggressively than classic papillary thyroid carcinoma. However, this may not be justified in patients with T1/T2 tall cell variant node-negative tumors. MethodsWe evaluated well-differentiated thyroid cancers treated surgically between 1985 and 2015 at our institution. We compared patients undergoing lobectomy for node-negative T1/T2 tall cell variant tumors with the same cohort with classic papillary thyroid carcinoma. Patients who underwent early planned completion thyroidectomy were excluded. Tall cell variant tumors were defined as those with ≥30% tall cells. Survival and recurrence outcomes were determined by the Kaplan-Meier method and groups compared using the log-rank test. ResultsThyroid lobectomy was performed for T1/T2 N0X disease in 70 (15%) tall cell cases and 429 (23%) classic papillary thyroid carcinoma cases. There was no significant difference in 10-year overall survival (P = .56) or locoregional recurrence-free probability (P = .52). Disease-specific survival and local or central nodal recurrence-free probability were 100% in both groups. In 9 papillary thyroid carcinoma cases, subsequent contralateral lobe tumors developed, and in 5, lateral neck metastases developed. No recurrences were seen in the tall cell group. ConclusionT1 node-negative tumors with tall cell histology can be satisfactorily managed with thyroid lobectomy, with equivalent oncological outcomes to classic papillary thyroid carcinoma.

Treatment and Prognosis of Resectable Cervical Esophageal Cancer: A Population-Based Study

BackgroundThe optimal treatment strategy for resectable cervical esophageal cancer remains controversial. This study aimed to explore prognostic factors and optimal treatment strategies in the context of staging. MethodsIn this population-based study, 1371 patients with resectable cervical esophageal cancer were identified in the Surveillance, Epidemiology, and End Results database. Univariate analysis and multivariable Cox regression model were performed to evaluate factors related to overall survival (OS). Subgroup analysis based on staging was performed to assess the effect of treatments on survival and propensity score matching was conducted to adjust confounding factors. ResultsUnivariate and multivariable analyses revealed that age, sex, year of diagnosis, histological type, tumor size, cN stage, surgery, radiotherapy, and chemotherapy are independent prognostic factors. After propensity score matching, patients with local disease (cT1-2N0M0) who received surgery alone had a higher 10-year OS rate than those received chemoradiotherapy (CRT) (20.7% vs 11.4%, P = .023). Compared with CRT, surgery-based multimodal therapy did not increase the OS rate of patients (14.8% vs 11.1%, P = .084). For regional disease (cT3-4aN0M0/cT1-4aN1-3M0), although surgery alone did not improve the OS rate of patients compared with CRT (7.3% vs 8.2%, P = .18), we observed a significant difference in 10-year OS among patients who underwent surgery-based multimodal therapy vs those who underwent CRT (20.4% vs 9.0%, P = .031). ConclusionsCompared with CRT, surgery alone improves the long-term survival of patients with localized disease, and surgery-based multimodal therapy increases the survival rate of patients with regional disease. Further studies are required to confirm our findings.

Tumor Maximum Area May Determine the Survival Outcomes of Patients with Thymic Epithelial Tumors.

The tumor maximum area (TMA) of thymic epithelial tumors (TETs) is not mentioned in current staging systems. This study aimed to assess whether TMA is of prognostic significance in TETs. Patients who underwent extended thymectomy for TETs from 2001 to 2019 at our institute were retrospectively reviewed. TMA was examined by computed tomography imaging prior to surgery. Time-dependent receiver operating characteristic (ROC) curves were used to divide the cohort into two groups. The relationships between the TMA and clinicopathological characteristics or survival outcomes were assessed. Cox proportional hazards models were used to identify independent prognostic factors. A total of 122 TET patients were included for evaluation, with a median age of 61years (range 27-83). The time-dependent ROC curve indicated that the difference in 10-year overall survival (OS) was most significant for a TMA of 1392mm2 (area under the curve 0.793); therefore, the two groups of larger (n = 40) and smaller (n = 82) TMAs were divided. The differences in adjuvant therapy, TNM stage, and disease progression between the two groups were significant (p < 0.05). Kaplan-Meier curves indicated that TET patients with a larger TMA had worse survival outcomes, including OS, progression-free survival (PFS) and disease-free survival (DFS) [p < 0.05]. TMA was demonstrated to be an independent prognostic factor of all of the above survival outcomes in multivariate analysis (p < 0.05). A larger TMA is associated with a more advanced TNM stage and disease progression in TET patients and may indicate worse survival outcomes, even if more patients receive adjuvant therapy.

Abstract P2-14-07: Association between initiation of adjuvant chemotherapy beyond 30 days following surgery and overall survival among patients with triple-negative breast cancer

Abstract Background: The optimal time between surgery and initiation of adjuvant chemotherapy is unknown, though delayed time to chemotherapy (TTC) is associated with decreased outcomes of breast cancer patients. Recently, studies have suggested that the association might be subtype-dependent and that TTC within 30 days should be warranted particularly in high-risk triple-negative breast cancer (TNBC) patients. Objective: To determine the extent to which TTC beyond 30 days is associated with reduced overall survival (OS) in TNBC patients. Methods: Using the population-based nationwide Netherlands Cancer Registry we identified TNBC patients diagnosed between 2006 and 2014 who received adjuvant chemotherapy. We distinguished between patients who underwent breast-conserving surgery (BCS) versus mastectomy given the difference in preoperative characteristics and outcomes. Median (95% confidence interval) follow-up was 82.9 (80.5-86.5) and 81.4 (79.5-83.9) months, respectively. Main outcomes and measures: The association between TTC beyond 30 days and OS was estimated with hazard ratios (HR) using propensity-score matched Cox proportional hazard analyses separately for patients who underwent BCS and mastectomy. Results: In total, 3016 patients were included, of whom 1079 (35.8%) underwent BCS and 1937 (64.2%) underwent a mastectomy. In matched patients who underwent BCS, 10-year OS was significantly better for patients with TTC within 30 days compared to patients with TTC beyond 30 days (84.4% vs. 76.9%, P=0.001). Patients with TTC beyond 30 days were more likely than those with TTC within 30 days to die within 10 years after surgery (HR 1.69 (95% CI 1.22-2.34), P=0.002). In matched patients who underwent mastectomy, there was no difference in 10-year OS between those with TTC within or beyond 30 days (74.5% vs. 74.7%, P=0.716), nor an increased risk of death for those with TTC beyond 30 days (HR 1.04 (95%-CI 0.84-1.28), P=0.716). In both populations, the associations were independent of adjuvant radiotherapy. Conclusions: The current results suggest that initiation of chemotherapy beyond 30 days is associated with decreased OS in TNBC patients who underwent BCS; no association was observed for patients who underwent a mastectomy. Therefore, timelier initiation of chemotherapy in TNBC patients undergoing BCS seems warranted. Citation Format: Erik Heeg, Perla J. Marang-van de Mheen, Marissa C. Van Maaren, Kay Schreuder, Rob A.E.M. Tollenaar, Sabine Siesling, Monique E.M.M. Bos, Marie-Jeanne T.F.D. Vrancken Peeters. Association between initiation of adjuvant chemotherapy beyond 30 days following surgery and overall survival among patients with triple-negative breast cancer [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 P2-14-07.

Ten-year survival outcomes for patients with early stage classical Hodgkin lymphoma: An analysis from Kentucky Cancer Registry

Objective/BackgroundEarly stage classical Hodgkin lymphoma (cHL) has an excellent outcome. Recent studies focus on decreasing toxicity related to the addition of radiation along with chemotherapy. Real-life reporting of the addition of radiation to chemotherapy is lacking. This study investigates the outcomes obtained from a statewide cancer registry for early stage cHL patients treated with chemotherapy alone (CT) versus patients treated with the combined modality of chemotherapy and radiation (CMT). MethodsA retrospective study of cHL patients diagnosed and treated was identified using a statewide cancer registry from 2005 to 2014. Patients with early stage disease (I, II) were then grouped on the basis of the presence of B symptoms into favorable and unfavorable groups. Baseline characteristics (age, gender, extranodal involvement, and histology) as well as overall survival were compared for both groups depending on whether they received CT or CMT as first line therapy for their cHL. ResultsA total of 961 patients were identified; of those, 127 were excluded as they received only radiation or another form of treatment. Of the remaining patients, 293 were categorized as early stage favorable cHL (Group 1) and 130 adults were in the unfavorable cHL (Group 2). There were 335 patients with advanced stage cHL (Group 3) and 76 patients in an unknown stage. The 10-year overall survival for Group 1 was 81.3% versus 76.3% for Group 2 and 52.7% for Group 3. For Group 1, 10-year overall survival was 86.7% with CMT versus 75.1% for those receiving CT only (p = .004). For Group 2, there was no difference in 10-year overall survival between the CMT group (80.0%) and CT (72.5%) (p = .73). ConclusionWhile radiation therapy might increase long-term toxicity in cHL, in our large data cohort, radiotherapy consolidation as part of the initial therapy for early stage disease provides superior survival at 10 years, especially in favorable risk cHL.

Prognostic Value of Tumor Size in T2 Glottic Laryngeal Cancer Staging

We report on the largest detailed analysis of T2 glottic laryngeal cancer using the National Cancer Database (NCDB) and identify patient subsets within the current T2 stage grouping with significantly different overall survival (OS). Adults with glottic laryngeal squamous cell carcinoma were identified in the 2004-2015 NCDB, grouped according to AJCC 8 staging as T2N0M0, classified by supra/sub-glottic extension (SGE) vs. impaired vocal cord mobility (VCM), stratified by tumor size and analyzed according to demographics, HPV status, disease extent and treatment received. Patients with missing data and non-squamous histologies were excluded. Propensity score-matched analysis (PSM) was utilized to create balanced cohorts between SGE and impaired VCM subgroups. Additionally, a second PSM was performed to create balanced cohorts between tumor size subgroups (≤ 2cm vs. >2cm). Kaplan-Meier statistics and Cox proportional hazards regression modeling were used for these two sets of matched cohorts. Of 11,375 patients identified, 4,679 met inclusion criteria; 3,862 (82.5%) male and 817 (17.5%) female. Median age 66 years (range, 20-90 years). Median follow-up 3.8 years (range, 0.02-12.8 years). Tumor size was documented in 1,213 cases (26%), with the majority (75%) of tumors ≤ 2cm. In propensity score matched analysis comparing T2N0 glottic cancers with impaired VCM (n=965) and those with SGE (n=965), no significant difference in 10-year OS was found (36% vs 37%, log-rank test, P= .93; HR, 1.03; 95% CI, 0.89-1.18; P= .72), while tumor size >2cm was a predictor for poorer OS at 10-years (HR, 2.11; 95% CI, 1.59-2.80; P< .001). 10-year OS remained statistically significant after PSM between tumor size ≤ 2cm and >2cm, favoring ≤ 2cm (38% vs 22%, log-rank test, P< .001; HR, 1.65; 95% CI, 1.29-2.11; P= .01). In T2N0 glottic laryngeal cancer, 10-year OS is superior with tumors ≤ 2cm compared to those >2cm. These results suggest that current AJCC grouping of these two subsets of patients into a single T2 stage group may obscure the more favorable prognosis of patients with smaller tumors. Our findings support the consideration of T2a and T2b subdivisions for glottic cancers based on tumor size in future staging iterations.

Clinical features and prognosis of children with acute lymphoblastic leukemia and different platelet levels

To study the association of platelet level at diagnosis with prognosis in children with acute lymphoblastic leukemia (ALL). A total of 892 children with ALL who underwent chemotherapy with the CCLG-ALL 2008 regimen were enrolled. According to the platelet count at diagnosis, these children were divided into normal platelet count group (platelet count ≥100×109/L; n=263) and thrombocytopenia group (platelet count <100×109/L; n=629). The thrombocytopenia group was further divided into (50- <100)×109/L (n=243), (20- <50)×109/L (n=263), and <20×109/L (n=123) subgroups. The association of clinical features (sex, age, immunophenotype, and molecular biology) with event-free survival (EFS) and overall survival (OS) was analyzed. Compared with the thrombocytopenia group, the normal platelet count group had significantly lower positive rate of MLL gene rearrangement and recurrence rate (P<0.05), as well as a significantly higher 10-year EFS rate (P<0.05). There was no significant difference in 10-year OS between the two groups (P>0.05). The normal platelet count group still had a significantly higher 10-year EFS rate than the thrombocytopenia group after the children with MLL gene rearrangement were excluded (P<0.05), and there was still no significant difference in 10-year OS between the two groups (P>0.05). The <20×109/L subgroup had significantly lower 10-year EFS and OS rates than the normal platelet count group, the (50- <100)×109/L subgroup, and the (20- <50)×109/L subgroup (P<0.05). After the children with MLL gene rearrangement were excluded, the <20×109/L subgroup still had significantly lower 10-year EFS and OS rates than the normal platelet count group, the (50-<100)×109/L subgroup, and the (20- <50)×109/L subgroup (P<0.05). ALL children with MLL gene rearrangement often have the clinical manifestation of thrombocytopenia. Platelet level at diagnosis is associated with the prognosis of ALL children. The children with normal platelet count have a low recurrence rate and good prognosis, and those with a platelet count of <20×109/L have the worst prognosis.

National trends, outcomes, and costs of radiation therapy in the management of low- and high-intermediate risk endometrial cancer

ObjectiveTo assess treatment patterns, outcomes, and costs for women with low-(LIR) and high-intermediate risk endometrial cancer (HIR) who are treated with and without adjuvant radiotherapy. MethodsAll patients with stage I endometrioid endometrial cancer who underwent surgery from 2000 to 2011 were identified from the SEER-Medicare database. LIR was defined as G1–2 tumors with <50% myometrial invasion or G3 with no invasion. HIR was defined as G1–2 tumors with ≥50% or G3 with <50% invasion. Patients were categorized according to whether they received adjuvant radiotherapy (vaginal brachytherapy [VBT], external beam radiotherapy [EBRT], or both) or no radiotherapy. Outcomes were analyzed and compared (primary outcome was overall survival). Results10,842 patients met inclusion criteria. In the LIR group (n = 7609), there was no difference in 10-year overall survival between patients who received radiotherapy and those who did not (67% vs 65%, adjusted HR 0.95, 95% CI 0.81–1.11). In the HIR group (n = 3233), patients who underwent radiotherapy had a significant increase in survival (60% vs 47%, aHR 0.75, 95% CI 0.67–0.85). Radiotherapy was associated with increased costs compared to surgery alone ($26,585 vs $16,712, p < .001). Costs for patients receiving VBT, EBRT, and concurrent VBT/EBRT were $24,044, $27,512, and $31,564, respectively (p < .001). Radiotherapy was associated with an increased risk of gastrointestinal (7 vs 4%), genitourinary (2 vs 1%), and hematologic (16 vs 12%) complications (p < .001). ConclusionsRadiotherapy was associated with improved survival in women with HIR, but not in LIR. It also had increased costs and a higher morbidity risk. Consideration of observation without radiotherapy in LIR may be reasonable.

National trends, outcomes, and costs of radiation therapy in the management of low- and high-intermediate risk endometrial carcinoma.

9 Background: Our objective was to assess treatment patterns, outcomes, and costs for women with low- (LIR) and high-intermediate risk endometrial cancer (HIR) who are treated with and without adjuvant radiotherapy (RT). Methods: All pts with endometrioid endometrial cancer who underwent surgery from 2000 – 2011 were identified from the SEER – Medicare database. LIR was defined as G1-2 tumors with &lt;50% myometrial invasion or G3 with no invasion. HIR was defined as G1-2 tumors with ≥50% or G3 with &lt;50% invasion. Pts were categorized according to whether they received adjuvant RT (vaginal brachytherapy [VBT], external beam radiotherapy [EBRT], or both) or no RT. All costs incurred up to 6 months postoperatively were analyzed. Outcomes were compared using the χ2test and a Cox PH regression model. Multivariate analyses were performed on both survival and costs. Results: 10,842 pts were included, of which 70% were LIR and 30% were HIR. 9% of pts with LIR had RT, compared to 46% of those with HIR. Among all pts who underwent RT, the use of VBT increased from 25% in 2000 to 71% in 2011, while EBRT use declined from 41% to 18%, and concurrent VBT/EBRT declined from 34% to 11% (p&lt;0.001). In the LIR group, there was no difference in 10-year overall survival (OS) between pts who had RT and those who did not (67% vs. 65%, multivariate HR 0.95, 95% CI 0.81 – 1.11). In the HIR group, pts who underwent RT had a significant increase in 10-year OS (60% vs. 47%, multivariate HR 0.75, 95% CI 0.67 – 0.85). Similar outcomes were noted on subgroup analysis stratifying by RT modality. RT was associated with an increased risk of gastrointestinal (7% vs. 4%, p&lt;0.001), genitourinary (2% vs. 1%, p&lt;0.001), and hematologic (16% vs. 12%, p&lt;0.001) 2-year complications. Compared to pts who only had surgery, RT was associated with increased mean adjusted costs ($22.5k vs. $14.4k, p&lt;0.001). Costs for pts receiving VBT, EBRT, and concurrent VBT/EBRT were $20.6k, $23.3k, and $26.5, respectively (p&lt;0.001). Conclusions: RT was associated with improved OS in women with HIR, but not in the LIR cohort. RT also had significantly increased costs and a higher morbidity risk. In the absence of other risk factors, consideration of observation without RT in LIR may be reasonable.

Long-term Outcomes for Stage I–II Aggressive Non-Hodgkin Lymphoma of Waldeyer's Ring

To determine the long-term outcome of patients treated at the University of Florida for aggressive non-Hodgkin lymphoma (NHL) of Waldeyer's ring. Forty-six patients treated with radiotherapy (RT) at the University of Florida from 1964 to 2006 for biopsy-proven aggressive NHL of Waldeyer's ring were included in this study. Of this group, 20 patients were treated with RT alone and 26 with combined-modality therapy (CMT) with the addition of chemotherapy: 24 patients with induction and 2 with concurrent or adjuvant chemotherapy. The 5-year and 10-year in-field control rates were 95% and 85%, respectively, and the out-of-field control rates were 67% and 63%, respectively. The 10-year disease-free survival (DFS), cause-specific survival, and overall survival (OS) rates were 47%, 50%, and 37%, respectively. The CMT group had superior 10-year DFS compared with the RT-alone group (57% vs. 37%), but this difference was not statistically significant. No difference in 10-year OS was seen between the CMT group and the RT-alone group. Similar to other sites, out-of-field recurrences are the primary pattern of failure for NHL of Waldeyer's ring. DFS was superior with CMT compared with RT alone and remains the standard of care.