Unadjusted Overall Survival Research Articles

Breast cancer staging for patients with “low risk” disease: Are they all the same?

6584 Background: Studies have shown that a low (<11) Oncotype DX recurrence score (RS) is associated with better survival outcomes. RS is currently included in the AJCC prognostic staging criteria. Not all patients with a low RS are downstaged. It has been suggested that a low RS should further downstage patients regardless of other disease factors. We explored survival outcomes for patients with a low RS to assess if additional patients should be downstaged. Methods: Using the National Cancer Database, female patients ages 18-75 with invasive unilateral pT1-3, pN0-1, M0 hormone receptor positive (ER+ and/or PR+), HER2- breast cancer and a RS <11, diagnosed 2010-2018 were identified. Patients who received neoadjuvant treatment were excluded. Patients were grouped based on the AJCC 8th edition prognostic stage (IA, IB, IIA, IIB, IIIA). Variables were summarized, and unadjusted overall survival (OS) was estimated using the Kaplan-Meier method. Cox proportional hazards models were used to estimate the association of stage with OS after adjustment for available covariates. Results: Of the 54,961 patients with a RS <11, median follow-up was 57.7 months (95% CI 57.3-58.1), and median age was 61yo (IQR 52-67). Most tumors were grade 1 (37.6%) or 2 (56.9%) with ductal histology (75.3%). The median tumor size was 1.5 cm (IQR 1-2), and most were pN0 (83.3%). Although most patients with a RS <11 were stage IA (94.2%), some had a higher stage assignment (5.1% stage IB, 0.6% IIA, 0.1% IIB, <0.01% IIIA). Most patients (93.4%) received endocrine therapy (ET), and few (3%) received chemotherapy. Patients treated with chemotherapy more often had younger age, lobular histology, higher grade, larger tumor size, and/or pN+ disease (all p<0.001). Unadjusted OS was reduced with higher stage (log-rank p<0.001), and this remained true when limited to only those who received ET without chemotherapy (log-rank p<0.001). After adjustment for relevant covariates including treatment, higher stage remained associated with worse OS [stage IA: ref; IB: HR 1.66 (95% CI 1.34-2.05); IIA: HR 2.29 (95% CI 1.44-3.65); IIB: HR 2.48 (95% CI 1.03-5.95); overall p<0.001]. Conclusions: For patients with a low RS, survival outcomes vary with current AJCC prognostic disease stage, suggesting that not all patients with a RS <11 should be downstaged based on RS alone. Anatomic and other non-genomic factors remain relevant when assessing prognosis. [Table: see text]

Association of venetoclax-based therapy with increased survival in multiple myeloma (MM) harboring t(11;14): A single-center experience.

e20055 Background: The BCL-2 inhibitor venetoclax (Ven) has shown activity in MM with t(11;14). However, a randomized trial comparing bortezomib and dexamethasone ± Ven in unselected MM patients was notable for decreased overall survival (OS) in the non-t(11;14) population treated with Ven despite improved progression free survival (PFS). In a subgroup analysis of 35 t(11;14) patients, those randomized to the Ven arm had superior OS (HR, 0.61 [95% CI, 0.16-2.32]) but this did not reach statistical significance (Kumar et al, Blood 2021). We sought to investigate the real-world impact of Ven-based therapy in t(11;14) MM and to explore patient and disease-related factors impacting response and durability. Methods: We retrospectively identified all t(11;14) MM patients treated at Moffitt Cancer Center between 2000-2022. The primary endpoint was OS measured from the time of MM diagnosis compared between Ven-treated patients and those who did not receive Ven. Secondary endpoints were ≥VGPR rate, PFS, and key toxicities. The era of MM diagnosis (5-year intervals) was included in analyses to account for novel therapies. Kaplan-Meier estimates and Cox regression were employed. Results: 262 MM patients were included. Median age was 64 years (interquartile range [IQR], 56-71 years); 61% were male; 87% were White. Ven was used in 78 patients (30%) on median in the 5th line (IQR, 4-7) and most commonly in combination with anti-CD38 antibodies (42%) or proteasome inhibitor (32%). Most patients (77%) initiated treatment at 400 mg daily and 25% required dose reduction. At a median follow-up of 52 months, 18 (23%) patients died in the Ven group as compared to 87 (47%) in the non-Ven group. Median unadjusted OS was longer in the Ven group (206 months [95% CI, 112-249 months] vs 75 months [95% CI, 65-97 months]; p < 0.01). In multivariable analysis accounting for demographics, high-risk cytogenetics, time of diagnosis, penta-exposed status, autologous stem cell transplant and BCMA-directed therapy, Ven was associated with a reduced risk of death (HR, 0.26; 95% CI, 0.15-0.47). Of 73/78 with available response data, 38% achieved ≥VGPR with Ven-based therapy. Median PFS was 27 months (95% CI, 13-39 months). In univariable analyses, 1q amplification/gain was associated with inferior PFS (13 months [95% CI, 6.5-28 months]) vs 33 months [95% CI, 23 months-not reached/NR]; p = 0.04). Median PFS was longer anti-CD38 antibody (33 months [95% CI, 13 months-NR]) compared to proteasome inhibitor combinations (11 months [95% CI, 7 months-NR]), but this difference was not statistically significant (p = 0.1). No grade 3/4 infections or deaths were directly attributable to Ven. Conclusions: In this real world dataset, MM patients with t(11;14) treated with Ven-based combinations exhibited superior survival. The response to Ven may be impacted by the partner agent and concurrent cytogenetic abnormalities.

Impact of the treatment crossover design on comparative efficacy in EMPOWER-Lung 1: Cemiplimab monotherapy as first-line treatment of advanced non-small cell lung cancer.

In randomized-controlled crossover design trials, overall survival (OS) treatment effect estimates are often confounded by the control group benefiting from treatment received post-progression. We estimated the adjusted OS treatment effect in EMPOWER-Lung 1 (NCT03088540) by accounting for the potential impact of crossover to cemiplimab among controls and continued cemiplimab treatment post-progression. Patients were randomly assigned 1:1 to cemiplimab 350 mg every 3 weeks (Q3W) or platinum-doublet chemotherapy. Patients with disease progression while on or after chemotherapy could receive cemiplimab 350 mg Q3W for ≤108 weeks. Those who experienced progression on cemiplimab could continue cemiplimab at 350 mg Q3W for ≤108 additional weeks with four chemotherapy cycles added. Three adjustment methods accounted for crossover and/or continued treatment: simplified two-stage correction (with or without recensoring), inverse probability of censoring weighting (IPCW), and rank-preserving structural failure time model (RPSFT; with or without recensoring). In the programmed cell death-ligand 1 ≥50% population (N=563; median 10.8-month follow-up), 38.2% (n=107/280) crossed over from chemotherapy to cemiplimab (71.3%, n=107/150, among those with confirmed progression) and 16.3% (n=46/283) received cemiplimab treatment after progression with the addition of histology-specific chemotherapy (38.7%, n=46/119, among those with confirmed progression). The unadjusted OS hazard ratio (HR) with cemiplimab versus chemotherapy was 0.566 (95% confidence interval [CI]: 0.418, 0.767). Simplified two-stage correction-the most suitable method based on published guidelines and trial characteristics-produced an OS HR of 0.490 (95% CI: 0.365, 0.654) without recensoring and 0.493 (95% CI: 0.361, 0.674) with recensoring. The IPCW and RPSFT methods produced estimates generally consistent with simplified two-stage correction. After adjusting for treatment crossover and continued cemiplimab treatment after progression with the addition of histology-specific chemotherapy observed in EMPOWER-Lung 1, cemiplimab continued to demonstrate a clinically important and statistically significant OS benefit versus chemotherapy, consistent with the primary analysis.

Novel Prognostic Staging System for Patients With De Novo Metastatic Breast Cancer.

Given the heterogeneity and improvement in outcomes for metastatic breast cancer (MBC), we developed a staging system that refines prognostic estimates for patients with metastatic cancer at the time of initial diagnosis, de novo MBC (dnMBC), on the basis of survival outcomes and disease-related variables. Patients with dnMBC (2010-2016) were selected from the National Cancer Database (NCDB). Recursive partitioning analysis (RPA) was used to group patients with similar overall survival (OS) on the basis of clinical T category, grade, estrogen receptor (ER), progesterone receptor, human epidermal growth factor receptor 2, histology, organ system site of metastases (bone-only, brain-only, visceral), and number of organ systems involved. Three-year OS rates were used to assign a final stage: IVA: >70%, IVB: 50%-70%, IVC: 25 to <50%, and IVD: <25%. Bootstrapping was applied with 1,000 iterations, and final stage assignments were made based on the most commonly occurring assignment. Unadjusted OS was estimated. Validation analyses were conducted using SEER and NCDB. At a median follow-up of 52.9 months, the median OS of the original cohort (N = 42,467) was 35.4 months (95% CI, 34.8 to 35.9). RPA stratified patients into 53 groups with 3-year OS rates ranging from 73.5% to 5.7%; these groups were amalgamated into four stage groups: 3-year OS, A = 73.2%, B = 61.9%, C = 40.1%, and D = 17% (log-rank P < .001). After bootstrapping, the survival outcomes for the four stages remained significantly different (log-rank P < .001). This staging system was then validated using SEER data (N = 20,469) and a separate cohort from the NCDB (N = 7,645) (both log-rank P < .001). Our findings regarding the heterogeneity in outcomes for patients with dnMBC could guide future revisions of the current American Joint Committee on Cancer staging guidelines for patients with newly diagnosed stage IV disease. Our findings should be independently confirmed.

Abstract P1-06-02: The effect of race on pathologic complete response rates and overall survival in patients with triple negative breast cancer

Abstract Introduction: Despite the recent overall improvement in survival for patients with breast cancer, racial disparities in outcomes persist. While studies have demonstrated that socioeconomic factors and access to treatment play a role, differences in tumor biology may also contribute. Black women are significantly more likely to develop triple negative breast cancer (TNBC), the deadliest of the breast cancer subtypes, with more TNBC patients progressing to incurable, metastatic disease than patients with any other breast cancer subtype. Studies have demonstrated that TNBC patients who achieve a pathologic complete response (pCR), defined as no residual invasive cancer in the breast or lymph nodes after neoadjuvant chemotherapy (NAC), have improved survival. We hypothesize that rates of pCR and overall survival (OS) in patients with TNBC may differ by race/ethnicity, which may account in part for the disparities in outcomes observed. Methods: Adult female patients with stage I-III TNBC diagnosed in 2010-2019 who received NAC followed by surgery were identified from the National Cancer Database (NCDB). Race/ethnicity was defined as Hispanic (H), Non-Hispanic White (NHW), Non-Hispanic Black (NHB), Non-Hispanic Asian (NHA), and Non-Hispanic Other (NHO). pCR was defined as no invasive cancer in either the breast or axilla (ypT0/is,N0) at surgery. Logistic regression was used to estimate the association of race/ethnicity with achievement of pCR after adjustment for covariates. Unadjusted OS was estimated using the Kaplan-Meier method, and the log-rank test was used to compare groups. Cox Proportional Hazards models were used to estimate the association of race/ethnicity and achievement of pCR with OS after adjustment for covariates. Additional interaction and subgroup analyses were also conducted. Results: Of the 40,890 patients identified, 29.8% (n=12,173) demonstrated pCR after NAC. The unadjusted 5-year OS rates for those who achieved pCR were significantly higher compared to patients with no pCR (0.917, 95% CI 0.911-0.923 vs 0.667, 95% CI 0.661-0.673, log-rank p&amp;lt; 0.001). Hispanic patients were more likely to achieve pCR (OR 1.19, 95% CI 1.08-1.31, p=0.001), and NHB patients were less likely to achieve pCR (OR 0.89, 95% CI 0.83-0.95, p=0.001) compared to NHW, even after adjustment. Unadjusted OS was also notably lower for NHB patients compared to every other race group (5-year OS rate: NHB 0.709 vs NHW 0.746 vs NHO 0.771 vs H 0.772 vs NHA 0.816, log-rank p&amp;lt; 0.001); however, this difference did not persist after adjustment for patient and disease factors, including achievement of pCR. Interval from diagnosis to start of chemotherapy (OR 0.95, 95% CI 0.94-0.96, p&amp;lt; 0.001) and duration after chemotherapy start to surgery (OR 1.02, 95% CI 1.02-1.03, p&amp;lt; 0.001) were associated with the odds of achieving pCR. Overall, the effect of achieving pCR on OS did not differ by race/ethnicity (interaction p=0.10). Discussion: Achieving pCR after NAC in patients with TNBC is associated with a significant improvement in OS. Yet, rates of pCR appear to differ based on race/ethnicity, with NHB patients demonstrating significantly lower rates of pCR than NHW patients, which may contribute to the disparities in survival outcomes observed. In addition to addressing socioeconomic factors and access to treatment, further research examining whether biological differences exist based on race that influence response of TNBC to current standard therapies is essential for improving survival outcomes for this disproportionately affected patient population. Citation Format: Hannah E. Woriax, Samantha M. Thomas, Jennifer K. Plichta, Laura H. Rosenberger, Astrid Botty van de bruele, Akiko Chiba, Gayle DiLalla, Carolyn Menendez, E Shelley Hwang, Maggie L. DiNome. The effect of race on pathologic complete response rates and overall survival in patients with triple negative 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 P1-06-02.

Racial differences in survival and healthcare resource utilization among Medicaid-insured adults with metastatic castration-sensitive prostate cancer.

26 Background: Racial inequalities in healthcare have long existed in the United States, with Black or African American (BAA) men having higher overall cancer death rates compared to other racial or ethnic groups. One of the greatest disparities is in prostate cancer (PC), which disproportionately affects BAA men, though when matched for stage, whether outcomes differ by race is controversial. This study assessed differences in overall survival (OS) and healthcare resource utilization (HRU) by race in Medicaid-insured patients with metastatic castration-sensitive prostate cancer (mCSPC). Methods: This retrospective longitudinal cohort study evaluated de-identified administrative claims data from the Centers for Medicare and Medicaid Services 100% Medicaid data files, from 01/01/2010 - 12/31/2018. The study included adult patients with a diagnosis for PC, ≥1 claim for androgen deprivation therapy (ADT), diagnosis of metastasis before or within 90 days after ADT, and continuous eligibility for ≥6 months pre-index (defined baseline period) and ≥3 months post-index. The date of first receipt of ADT or first receipt of novel hormonal therapy or docetaxel if initiated within 30 days before ADT defined the index date. OS and HRU were assessed from the index date to the earliest of end of continuous eligibility, data availability, or death. A multivariable Cox proportional hazards model of OS and a multivariable Poisson model of HRU were implemented and controlled for age, plan type, region, median state income, residence in a state with Medicaid expansion, index year, Charlson comorbidity index (CCI), baseline HRU, and clinical characteristics. Results: The study included 1,488 patients with mCSPC (467 [31%] BAA, 446 [30%] White [W], 219 [15%] Hispanic [H], 356 [24%] Other races [O]). H were the oldest (mean age 68 years), followed by O (67 years), W (64 years), and BAA (63 years). BAA and H had the highest CCI (0.6), followed by O (0.5), and W (0.4). Median unadjusted OS was 71.3 months in H, 57.1 months in O, 52.1 months in BAA, and 44.9 months in W. After adjustment, H had significantly lower risk of death compared to W (hazard ratio [95% confidence interval (CI)]: 0.65 [0.43, 0.96]) and BAA patients had comparable survival to W (0.91 [0.69, 1.22]). Adjusted incidence rate ratios (IRR) showed significantly lower incidence of PC-related outpatient (OP) visits for BAA as compared to W (IRR [95% CI]: 0.71 [0.55, 0.99]), per patient per year. The remaining HRU endpoints were not significantly different among racial groups. Conclusions: Among Medicaid-insured adult patients with mCSPC, H were more likely to live longer than W patients. BAA patients had similar survival and lower rates of PC-related OP visits as compared with W, which shows differential use of PC-related healthcare resources between BAA and W.

Effects of losartan and vitamin D on outcomes in metastatic pancreatic adenocarcinoma.

723 Background: Active modification of surrounding stroma is a critical mechanism of tumor cell growth in pancreatic ductal adenocarcinoma (PDAC). There is some early translational evidence that losartan (L) and vitamin D (D) may affect the tumor microenvironment and supportive stroma in PDAC to help restore a physically and biologically tumor-suppressive stroma. These effects of potentially stroma-modifying drugs have not been established in the clinical management of metastatic PDAC (mPDAC), where there have been limited advances in treatment and prognosis remains poor. Methods: This is a single center, retrospective analysis of patients with mPDAC treated at Fox Chase Cancer Center from 2010 to 2019. All data including L and D use were extracted from the medical record. Patient characteristics were compared across subgroups using Chi-square tests, Fisher’s exact tests, and Wilcoxon rank sum tests. The primary outcome was overall survival (OS) from the time of metastatic diagnosis. Kaplan-Meier curves and log-rank tests were used to compare unadjusted OS across subgroups. Cox proportional hazards models were used to characterize OS adjusted for age at metastatic diagnosis, sex, initial stage at diagnosis, performance status, Charlson Comorbidity Index (CCI), hypertension, and renal disease. Results: 518 patients were included; a majority were male (54.1%), White (82.4%), and diagnosed with de novo mPDAC (54.6%). About half of patients had hypertension (53.5%) and few had renal dysfunction (5.6%). 153 (29.5%) patients were taking D and 41 (8%) patients were taking L. Women were more likely to take D than men (p &lt; 0.001) and White patients were more likely to take L than other races/ethnicities (p = 0.006). Median OS since metastatic diagnosis for patients taking L was 11.4 months compared to 9.6 months for patients not taking L (p = 0.07). Median OS for patients taking D was 11.3 months compared to 8.7 months for those not taking D (p = 0.10). A Cox proportional hazards model adjusting for confounders, however, showed that both L (HR 0.66, p = 0.02) and D (HR 0.81, p = 0.04) were significantly associated with improved OS from time of metastatic diagnosis. Conclusions: This large retrospective study demonstrates potential clinical and survival benefit of L and D in conjunction with mPDAC treatment. L and D are safe, well tolerated, and widely used in general medical practice. These results support further investigation of the stroma-modifying potential of L and D, as well as conducting prospective trials with these agents to further validate these findings.

Real-world adjuvant chemotherapy patterns and outcomes among elderly patients with resected early non-small-cell lung cancer in the USA.

Background: This study investigated real-world treatment patterns and overall survival (OS) in early non-small-cell lung cancer patients and the association between OS and time to adjuvant treatment. Materials & methods: This retrospective study using Surveillance, Epidemiology, and End Results data linked with Medicare claims included resected early non-small-cell lung cancer patients between 2010 and 2015. Unadjusted OS analyses used Kaplan-Meier curves; adjusted OS analyses used extended Cox proportional hazards models. Results: Only 54-71% of stage II-IIIA patients received any adjuvant treatment. Adjusted risk of death was higher when starting treatment outside 6-8weeks after surgery (p<0.05). Conclusion: Improved systemic therapy in the adjuvant chemotherapy setting is needed.

Survival After Breast-Conserving Surgery Compared with that After Mastectomy in Breast Cancer Patients Receiving Neoadjuvant Chemotherapy.

Breast-conserving surgery (BCS) plus radiotherapy (BCS + RT) has been shown to improve survival compared with mastectomy in patients with early breast cancer; however, whether this superiority is maintained in breast cancer patients receiving neoadjuvant chemotherapy (NCT) is unclear. We evaluated and compared the survival outcomes after BCS + RT and mastectomy in Korean women with breast cancer treated with NCT. We evaluated 1641 patients who received NCT before surgery (BCS or mastectomy). We performed propensity score matching to minimize potential bias due to factors other than the surgical method and compared the 5-year, disease-free survival (DFS), distant metastasis-free survival (DMFS), and overall survival (OS) rates before and after exact matching. Among the 1641 patients, 839 (51.1%) underwent BCS + RT and 802 (48.9%) underwent mastectomy. Patients who underwent mastectomy had larger tumors and more frequently had positive nodes. For BCS+RT and mastectomy, the unadjusted 5-year DFS, 5-year DMFS, and 5-year OS rates were 87.0% and 73.1%, 89.5% and 77.0%, and 91.8% and 81.0%, respectively (all p < 0.05 = 0.000). After PSM, 5-year DFS, 5-year DMFS, and 5-year OS rates for BCS + RT and mastectomy were 87.6% and 69.1%, 89.7% and 76.0%, and 89.1% and 75.7%, respectively (all p < 0.05). In both unadjusted and adjusted analyses accounting for various confounding factors, BCS + RT was significantly associated with improved DFS (p < 0.05), DMFS (p < 0.05), and OS (p < 0.05) rates compared with mastectomy. BCS + RT does not impair DFS and OS in patients treated with NCT. Tumor biology and treatment response are significant prognostic indicators. Our results suggest that BCS + RT may be preferred in most breast cancer patients when both BCS and mastectomy are suitable.

African American Race Is a Potential Favorable Biologic Factor That Impacts Clinical Outcome for Patients with Multiple Myeloma

Multiple myeloma (MM) remains an incurable malignancy characterized by plasma cells that are nurtured and proliferate within the permissive bone marrow milieu. It has a greater incidence in African Americans (AA) compared to whites (13.8 vs. 6.5/100,000). The five-year age adjusted mortality rate, according to SEER database, is greater in AA compared to white Pts (5.8 vs. 2.9/100,000), which is likely explained by a greater incidence in the AA population. However, recent reports have also shown that AAs with equal access to care have an even better survival than their white counterparts [Fiala et al. Cancer. 2017]. Conversely, results from the CoMMpass registry database showed that OS was shorter for AA compared with Whites (age-adjusted hazard ratio (HR) 1.7, 95% confidence interval 1.2-2.4, P = 0.003) [Derman et al. Blood Cancer J. 2020]. Here, we report the interplay of race and other dimensions of MM care using the National Cancer Database (NCDB). Methods: NCDB is the largest cancer database in the US including >70% of all newly diagnosed cancer patients. The International Classification of Diseases for Oncology (ICD-O) code of 9732 was used. OS was calculated from the date of MM diagnosis. Given that Smoldering MM (SMM) does not have specific ICD code, we defined patients who did not receive any treatment within 3 months after the diagnosis as SMM, similar to other authors (Ravindran et al. Blood Cancer J. 2016). Initiation of systemic treatment was considered as a surrogate of progression to symptomatic MM. Overall survival (OS) of SMM patients was calculated from initiation of systemic treatment after they progressed to MM, estimated by the Kaplan-Meier method, and compared with the log-rank test. Cumulative incidence of progression from SM to MM was calculated with death as a competing risk and compared with the Gray's test. Multivariable Cox and logistic regression analysis were performed to identify independent predictors of OS and progression to MM, respectively. Results: We identified 56,021 patients with MM and 11,485 with SMM between 2010 to 2014 in this database. Among MM patients, 42,836 (76%) were white and 11,255 (20%) self-identified as AA. For AA patients, there was a lower proportion of Medicare (46 vs. 56%), and private insurance (35 vs. 36%) and a higher percentage of Medicaid (11 vs. 5%) and uninsured Pts (6 vs. 3%) compared to Pts that self-identified as white. A larger proportion of AAs had a Charlson score ≥1 (30 vs. 24%, p<0.001). The percentage of Pts who underwent radiation was higher among whites compared to AA (23 vs 8%). However, unadjusted OS was greater for AA compared to white Pts, 55 vs. 48 months, respectively (P < 0.0001). Among SMM patients, 8,324 (72%) were white and 2,756 (24%) were AA. SMM was diagnosed in AA patients at a median of 3.7 years younger than in white patients. Similar socioeconomic disparities were observed in SMM as in MM cohort. The time from diagnosis of SMM to first therapy which is indicative of progression from SMM to MM is the same among AA and white (median time in days 136 vs 135 days, p=0.672) with comparable OS. Multivariable Cox and logistic regression analysis showed that lower age, AA race, Female gender, ASCT, living in a higher income area and having Medicare or Private insurance compared to no insurance were independent predictors for better OS in MM. Although other predictive factors persisted for patients with SMM, race did not reach statistical significance. Conclusion: Taken together, our results utilizing one of the largest available datasets in the US, reflect a similar outcome for AA and white patients with MM despite a clear disparity in healthcare access and SES. This finding might suggest a more favorable biology of the disease among AA Pts. The lower rate of radiation among AA is also an indirect measure of bone complications. AA enjoy less bone loss and fractures under physiologic and pathologic conditions. Further studies to elucidate the role of bony compartment of the MM microenvironment at the cellular and molecular levels might be able to explain this disparity and help advance a more personalized treatment options to improve outcomes. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Outcomes of Newly Diagnosed Therapy-Related AML and AML with Myelodysplasia-Related Changes Treated with 7+3, Hypomethylating Agents with or without Venetoclax and CPX-351: A Retrospective Cohort Study

Introduction Therapy-related acute myeloid leukemia (t-AML) and AML with myelodysplasia-related changes (AML-MRC) are associated with poor outcomes due to older age at diagnosis and adverse-risk cytogenetics and molecular features and, therefore, treatment of these groups of patients remain a challenge. There is a paucity of real-world data on outcomes of t-AML and AML-MRC treated with 7+3, hypomethylating agents (HMA) with or without venetoclax (VEN) or CPX-351 (Vyxeos). Methods We conducted a single-center retrospective cohort study to compare overall survival (OS), event-free survival (EFS), and composite complete response (CCR) of patients with t-AML or AML-MRC treated with first-line 7+3, HMA, HMA+VEN or Vyxeos. Therapy-related myelodysplastic syndrome were not included. OS was defined from day 1 of initial chemotherapy until death from any cause. Patients were not censored at the time of allogeneic transplant. Sixty and 90-day treatment-related mortality were estimated as surrogates for treatment toxicity. Propensity score modeling was used to adjust for baseline characteristics (age, AML subtype, comorbidities, performance status, cardiac ejection fraction, cytogenetics, and mutations). Results Of 488 consecutive AML patients treated at the University of Maryland between 2013-2021, 136 patients had t-AML or AML-MRC and received one of the above therapies. 40% were female. The median age of the cohort was 67.5 [IQR: 60.9-73.2]. The median age of patients who received 7+3 (n=34) was 63.4 years, HMA (n=61) 70.3 years, HMA+VEN (n=27) 72.6 years, and Vyxeos (n=14) 62.2 years (age P-value= 0.1). 42 and 17 patients received decitabine in the HMA and HMA+VEN arms, respectively. None of the patients treated with 7+3 or Vyxeos received HMA prior to AML diagnosis. However, 3 and 6 patients received HMA in the HMA and HMA+VEN arms prior to AML diagnosis, respectively. Both 7+3 and HMA were given mostly before 2019 (7+3: 88%; HMA: 81%) compared to HMA+VEN and Vyxeos, which were given mostly in years 2019 and after (HMA+VEN: 74%; Vyxeos: 71%) (P<0.01). The median follow-up was 73.5 months (mo). Table 1 demonstrates unadjusted outcomes. Figure 1 demonstrates the unadjusted OS of treated groups. Using propensity score for adjustment, there was no difference in median OS or CCR in patients treated with 7+3 vs. HMA (11.2 vs. 10.6 mo, P=0.63; 42% vs. 31%, P=0.38). However, patients treated with HMA+VEN had worse adjusted m-OS than patients treated with 7+3 (5.3 vs. 20.2 mo, P=0.02) or HMA alone (5.3 vs. 10.1 mo, P=0.02). Patients treated with Vyxeos had a statistically similar adjusted-median OS to those treated with 7+3 (5.1 vs. 15.4 mo, P=0.34) and a trend toward a worse outcome than those treated with HMA alone (5.3 vs. 10.1 mo, P=0.07). Conclusion The outcomes of t-AML and AML-MRC remains poor. In t-AML and AML-MRC, using 7+3 and HMA resulted in similar OS; however, improved outcomes compared to HMA+VEN. Almost 50% of patients treated with HMA+VEN died in the first 90 days, possibly related to treatment toxicity. Further studies are needed to determine the role of VEN combination with HMA in t-AML and AML-MRC. Moreover, further real-world, multi-institutional data are needed to evaluate the effectiveness of Vyxeos in t-AML and AML-MRC. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Survival and prognosis analysis of patients with Hodgkin lymphoma treated with standard treatment paradigm

Objective: To analyze the survival and prognosis of Hodgkin lymphoma (HL) patients receiving standard first-line therapy. Methods: Data of clinical characteristics and treatment outcomes of patients with HL diagnosed in Cancer Hospital Chinese Academy of Medical Sciences (CHCAMS) from January 1st, 2000 to December 31st, 2018 who received standard first-line treatment were retrospectively analyzed and compared with that of HL patients who received treatment in the Surveillance, Epidemiology and End Results (SEER) database in the United States during the same period. Factors associated with freedom from progression (FFP) of patients in CHCAMS were analyzed. Treatment and survival data of patients with relapsed/refractory HL (r/rHL) who had failed the standard first-line treatment during the corresponding period in CHCAMS were collected to analyze the outcomes of salvage therapy. Results: A total of 764 HL patients in CHCAMS were included in this study. The median age was 30 years (range, 14-83 years), with 424 males and 340 females. By February 26th, 2022, the patients were followed-up for a median time of 111 months(range, 0.3-262.0 months). Lymphoma-specific survival (LSS) rate and overall survival (OS) rate at 10 years for HL patients in CHCAMS was 91.7% (95%CI: 89.5%-93.9%) and 87.1% (95%CI: 84.5%-89.8%), respectively. LSS and OS rate at 10 years for HL patients from SEER database was 86.8% (95%CI: 86.3%-87.2%) and 79.0% (95%CI: 78.5%-79.5%), respectively. The unadjusted LSS and OS rate for patients in CHCAMS were higher than those for patients from SEER database (both P<0.001). No significant difference was observed in LSS and OS rate (both P>0.05) between the two groups after adjustment. European Organization for Research and Treatment of Cancer staging system (early-stage unfavorable: HR=2.35, 95%CI: 1.13-4.89, P=0.023; advanced stage: HR=5.44, 95%CI: 2.62-11.30, P<0.001) and serum β2 microglobulin (HR=1.67, 95%CI: 1.08-2.58, P=0.021) were influencing factors of FFP for patients in CHCAMS. The complete remission rate, median progression-free survival (PFS), 5-year PFS rate and 5-year OS rate for the 116 patients with r/rHL was 37.9% (95%CI: 29.6%-47.0%), 15.0 months (95%CI: 9.9-20.1 months), 29.9% (95%CI: 20.9%-38.9%) and 62.9% (95%CI: 54.1%-71.7%), respectively. Conclusions: The outcomes of HL patients receiving standard first-line treatment are excellent. However, the therapeutic effect of HL patients who incurrs disease progression or relapse after standard first-line treatment is not satisfying.

Implications of missing data on reported breast cancer mortality.

National cancer registries are valuable tools to analyze patterns of care and clinical outcomes; yet, missing data may impact the accuracy and generalizability of these data. We sought to evaluate the association between missing data and overall survival (OS). Using the NCDB (National Cancer Database) and SEER (Surveillance, Epidemiology, End Results Program), we assessed data missingness among patients diagnosed with invasive breast cancer from 2010 to 2014. Key variables included demographic (age, race, ethnicity, insurance, education, income), tumor (grade, ER, PR, HER2, TNM stages), and treatment (surgery in both databases; chemotherapy and radiation in NCDB). OS was compared between those with and without missing data using Cox proportional hazards models. Overall, 775,996 patients in the NCDB and 263,016 in SEER were identified; missing at least 1 key variable occurred for 29% and 13%, respectively. Of those, the overwhelming majority (NCDB 80%; SEER 88%) were missing tumor variables. When compared to patients with complete data, missingness was associated with a greater risk of death: NCDB HR 1.23 (99% CI 1.21-1.25) and SEER HR 2.11 (99% CI 2.05-2.18). Patients with complete tumor data had higher unadjusted OS estimates than that of the entire sample: NCDB 82.7% vs 81.8% and SEER 83.5% vs 81.7% for 5-year OS. Missingness of select variables is not uncommon within large national cancer registries and is associated with a worse OS. Exclusion of patients with missing variables may introduce unintended bias into analyses and result in findings that underestimate breast cancer mortality.

Outcomes Following SBRT vs. IMRT and 3DCRT for Older Patients with Stage IIA Node-Negative Non-Small Cell Lung Cancer > 5 cm

BackgroundTo describe outcomes and compare the effectiveness of stereotactic body radiotherapy (SBRT) versus 3-dimensional conformal radiotherapy (3DCRT) or intensity-modulated radiotherapy (IMRT) in patients with stage IIA lymph node-negative (N0) non-small cell lung cancer (NSCLC) tumors > 5 cm. MethodsWe used the SEER-Medicare database (2005-2015) to identify patients > 65 years with stage IIA (AJCC TNM7) N0 NSCLC > 5 cm tumors who were treated with SBRT, IMRT, and 3DCRT. We used propensity score methods with inverse probability weighting to compare lung cancer-specific survival (LCSS), overall survival (OS), and toxicity. ResultsOf 584 patients, 88 (15%), 140 (24%), and 356 (61%) underwent SBRT, IMRT, and 3DCRT, respectively. The SBRT group was older (P = .004), had more comorbidities (P = .02), smaller tumors (P = .03), and more adenocarcinomas (P < .0001). We found a trend towards higher median unadjusted OS with SBRT compared to IMRT and 3DCRT (19 vs. 13 and 14 months, respectively, P = .37). In our propensity score-adjusted analyses, SBRT was significantly associated with better OS and LCSS compared to IMRT (HROS: 0.78, 95% CI: 0.68-0.89, HRLCSS: 0.70, 95% CI: 0.60-0.81) and 3DCRT (HROS: 0.81, 95% CI: 0.72-0.93, HRLCSS: 0.80, 95% CI: 0.68-0.93). SBRT-treated patients also had lower overall adjusted complication rates compared to IMRT (OR: 0.74, 95% CI: 0.55-0.99) and 3DCRT (OR: 0.53, 95% CI: 0.40-0.71). ConclusionFor patients with NSCLC tumors > 5 cm, SBRT trends towards fewer toxicities and improved survival compared to other forms of radiotherapy. Our findings support SBRT as an appropriate treatment strategy for older patients with larger inoperable NSCLC tumors.

The role of tumor phenotype in the surgical treatment of early-stage breast cancer

BackgroundWe investigated whether tumor phenotype influences surgical decision-making, and how that may impact overall survival (OS) for early-stage breast cancer. MethodsWomen aged 18–69 with cT0-2/cN0/cM0 breast cancer in the National Cancer Database (2010–2017) were included. A generalized logistic model was used to identify factors associated with surgery type. A Kaplan-Meier curve was used to visualize unadjusted OS, and the log-rank test was used to test for differences in OS between surgery types. ResultsOf 597,149 patients, 58% underwent lumpectomy with radiation (BCT), 25% unilateral mastectomy (UM), and 17% bilateral mastectomy (BM). After adjustment, HER2+ and triple-negative (TN) tumors were less likely to undergo UM than BCT, versus hormone receptor-positive tumors (OR = 0.881, 95% CI = 0.860–0.903; OR = 0.485, 95% CI = 0.470–0.501). UM and BM had worse 5-year OS versus BCT (UM: 0.926, vs BM: 0.952, vs BCT: 0.960). ConclusionsBCT is increasingly used to treat HER2+ and TN tumors. More extensive surgery is not associated with better survival outcomes, regardless of tumor phenotype.

Examining the role of wide excision margins in pediatric melanoma: A National Cancer Database analysis.

Although adult guidelines are often applied to children, age-specific surgical margins have not been defined for pediatric melanoma. Patients &lt;20years of age with invasive, cutaneous melanoma were identified using the 2004-2016 National Cancer Database and categorized as undergoing wide (&gt;1cm) or narrow (≤1cm) excision. Unadjusted overall survival (OS) was compared using the Kaplan-Meier method and log-rank test. Multivariable Cox proportional hazard models were used to estimate the effect of excision margin on OS after adjustment for available covariates. In total, 2081 patients met study criteria: 1338 (64.3%) patients underwent wide excision whereas 743 (35.7%) underwent narrow excision. Unadjusted OS was improved in the narrow-excision group (log-rank p=.01), which was consistent among patients with thicker (&gt;1mm) and thinner (≤1mm) tumors. After adjustment for patient and tumor characteristics, we found no evidence of a difference in OS for patients who underwent narrow excision compared to patients who underwent wide excision (adjusted hazard ratio 0.57, 95% confidence interval 0.32-1.01, p=.053). There was no interaction between excision margin width and Breslow depth (p=.85), indicating that the effect of excision margin width on OS does not differ based on Breslow depth. In this analysis, wide excision (&gt;1cm) does not appear to be associated with improved survival in children with melanoma regardless of tumor characteristics. Although further studies are needed to define optimal excision margins in pediatric melanoma, this study suggests that more narrow margins (≤1cm) may be acceptable.

Major surgical postoperative complications and survival in breast cancer: Swedish population-based register study in 57 152 women.

Postoperative complications may activate prometastatic systemic pathways through tissue damage, wound healing, infection, and inflammation. Postoperative complications are associated with inferior survival in several types of cancer. The aim was to determine the association between postoperative complications and survival in breast cancer. This population-based cohort included women operated for T1-3 N0-3 M0 invasive breast cancer in Sweden from 2008 to 2017. Only major surgical postoperative complications leading to readmission and/or reoperation within 30 days were considered. Main outcomes were overall survival (OS) and breast cancer-specific survival (BCSS). Prospectively collected nationwide register data were used. Multivariable Cox models were adjusted for clinical and socioeconomic confounders and co-morbidity. Among 57 152 women, major surgical postoperative complications were registered for 1854 patients. Median follow-up was 6.22 (0.09-11.70) years. Overall, 9163 patients died, and 3472 died from breast cancer. Major surgical postoperative complications were more common after mastectomy with or without immediate reconstruction (7.3 and 4.3 per cent respectively) than after breast-conserving surgery (2.3 per cent). Unadjusted 5-year OS and BCSS rates were 82.6 (95 per cent c.i. 80.8 to 84.5) and 92.1 (90.8 to 93.5) per cent respectively for women with a major surgical postoperative complication, and 88.8 (88.6 to 89.1) and 95.0 (94.8 to 95.2) per cent for those without a complication (P < 0.001). After adjustment, all-cause and breast cancer mortality rates remained higher after a major surgical postoperative complication (OS: HR 1.32, 95 per cent c.i. 1.15 to 1.51; BCSS: HR 1.31, 1.04 to 1.65). After stratification for type of breast surgery, this association remained significant only for women who had mastectomy without reconstruction (OS: HR 1.41, 1.20 to 1.66; BCSS: HR 1.36, 1.03 to 1.79). Major surgical postoperative complications are associated with inferior survival, especially after mastectomy. These results underline the importance of surgical de-escalation.

Outcome of Patients with High-Risk Endometrial Cancer Undergoing Sentinel Lymph Node Assessment versus Full Lymphadenectomy (070)

Objectives: Sentinel lymph node mapping and dissection (SLN) is endorsed by the National Comprehensive Cancer Network as a recommended surgical staging approach in patients diagnosed with apparent uterine-confined endometrial cancer (EC) of all histologies. While SLN has been validated for use in patients with high-risk histologies, data regarding the oncologic safety of SLN in the management of high-risk EC is limited and inconclusive. The objective of this study was to determine the 3-year progression-free survival (PFS) and overall survival (OS) in patients with high-risk EC who underwent SLN compared to patients who underwent pelvic ± para-aortic lymphadenectomy (LND). Methods: All patients in our healthcare system diagnosed with EC with no radiologic evidence of extra-uterine disease who underwent surgical management between January 1, 2014, and September 1, 2020, were identified, and follow-up data were recorded. SLN was performed in accordance with evidence-based practice, and an SLN algorithm was used. High-risk EC was classified based on hysterectomy specimen pathology demonstrating non-endometrioid histology or FIGO grade 3 endometrioid histology. Patients were excluded if they had more than one primary cancer at the time of diagnosis or if no follow-up records were available. Patients were categorized based on intention to treat. All statistical analyses were performed using SAS version 9.4. Conclusions: Patients with high-risk EC who underwent SLN had no difference in 3-year survival relative to LND; however, the SLN group experienced shorter unadjusted OS. When adjusting for age, adjuvant therapy, and surgical approach, the two methods were found to be similar, with a trend towards worse OS for those who underwent SLN. A randomized control trial comparing SLN versus LND with long-term follow-up for patients with EC of high-risk histologies is necessary. Objectives: Sentinel lymph node mapping and dissection (SLN) is endorsed by the National Comprehensive Cancer Network as a recommended surgical staging approach in patients diagnosed with apparent uterine-confined endometrial cancer (EC) of all histologies. While SLN has been validated for use in patients with high-risk histologies, data regarding the oncologic safety of SLN in the management of high-risk EC is limited and inconclusive. The objective of this study was to determine the 3-year progression-free survival (PFS) and overall survival (OS) in patients with high-risk EC who underwent SLN compared to patients who underwent pelvic ± para-aortic lymphadenectomy (LND). Methods: All patients in our healthcare system diagnosed with EC with no radiologic evidence of extra-uterine disease who underwent surgical management between January 1, 2014, and September 1, 2020, were identified, and follow-up data were recorded. SLN was performed in accordance with evidence-based practice, and an SLN algorithm was used. High-risk EC was classified based on hysterectomy specimen pathology demonstrating non-endometrioid histology or FIGO grade 3 endometrioid histology. Patients were excluded if they had more than one primary cancer at the time of diagnosis or if no follow-up records were available. Patients were categorized based on intention to treat. All statistical analyses were performed using SAS version 9.4. Conclusions: Patients with high-risk EC who underwent SLN had no difference in 3-year survival relative to LND; however, the SLN group experienced shorter unadjusted OS. When adjusting for age, adjuvant therapy, and surgical approach, the two methods were found to be similar, with a trend towards worse OS for those who underwent SLN. A randomized control trial comparing SLN versus LND with long-term follow-up for patients with EC of high-risk histologies is necessary.

Segmental Ureterectomy Versus Radical Nephroureterectomy in Older Patients Treated for Upper Tract Urothelial Carcinoma.

The world population is ageing and surgical procedures for older patients are associated with higher perioperative morbidity and mortality rates than in younger patients. Segmental ureterectomy (SU) has been proposed as an alternative to radical nephroureterectomy (RNU) for selected upper tract urothelial carcinomas (UTUC), to reduce post-operative morbidity, and preserve renal function. The aim of this study was to compare RNU and SU in terms of post-operative complications, functional outcomes, and overall survival (OS) in older patients treated for UTUC. Data of patients aged 75 years or older and treated for UTUC were included. The primary outcome was to compare RNU versus SU according to post-operative complications, the estimated glomerular filtration rate (eGFR) variation, and OS. Complications were defined according to the Clavien-Dindo classification. eGFR was calculated according to the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) formula. Un-adjusted OS curves were plotted using the Kaplan-Meier method. Overall, 177 patients (150 RNU and 27 SU) were eligible for the analysis. Pre- and post-operative characteristics were similar between the 2 groups. RNU patients showed higher incidence of post-operative complications (34.0% vs. 7.4%, P=.011). The mean post-operative serum creatinine was lower in SU patients in comparison with the RNU ones (1.23 vs. 1.69 mg/dL, P=.046), but no differences were found in terms of eGFR variation (P=.258). At 3 years of follow-up, the OS was comparable between the two surgical techniques (P=.129). In older patients diagnosed with UTUC, SU could offer lower rates of post-operative complications without affecting survival.

Durvalumab After Chemoradiation for Unresectable Stage III Non-Small Cell Lung Cancer: Inferior Outcomes and Lack of Health Equity in Hispanic Patients Treated With PACIFIC Protocol (LA1-CLICaP).

ObjectivesTo compare the rate disparity between outcomes (overall survival (OS), progression-free survival (PFS), and safety) of concurrent chemoradiation (cCRT) followed by durvalumab in two patient cohorts with locally advanced (LA) stage III non-small cell lung cancer (NSCLC), one non-Hispanic White (NHW), and the other Latin-American.MethodsA multicenter retrospective study was performed, including 80 Hispanic and 45 NHW LA stage III NSCLC patients treated with cCRT followed by durvalumab. Both cohorts were analyzed in terms of main outcomes (OS, PFS, and safety) and compared between them and with the PACIFIC trial population outcomes. The efficacy-effectiveness gap was assessed using an efficacy-effectiveness (EE) factor that was calculated by dividing each cohort median overall survival by the corresponding reference OS from the PACIFIC trial. In both cohorts, results of PD-L1 testing were recorded, and the main outcomes were compared according to PD-1 expression levels (≥50%, 1–49%, and <1%).ResultsFor the entire population (N=125), the overall response rate (ORR) was 57.6% (N=72), and 18.4% (N=25) achieved stable disease. OS was 26.3 months (95%CI 23.9-28.6), and PFS was 20.5 months (95%CI 18.0-23.0). PFS assessed by ethnicity showed a median for the Hispanic population of 19.4 months (95%CI 16.4-22.5) and 21.2 months (95%CI 17.2-23.3; p=0.76) for the NHW group. OS by race showed a significant difference in favor of the NHW group, with a median OS of 27.7 months (95%CI 24.6-30.9) vs. 20.0 months (95%CI 16.4-23.5) for Hispanics. (P=0.032). Unadjusted 12-month and 24-month OS was 86.6% (95%CI 79.9–88.0) and 46.6% (95%CI 40.2–48.3) for NHW compared to 82.5% (95%CI 77.1–84.2) and 17.5% (95%CI 15.6-24.5) in Hispanics. NHW had an EE factor of 0.78 and Hispanics had 0.58, showing a reduction in survival versus NHW and PACIFIC of 20% and 42%, respectively. HR for the OS among NHWs and Hispanics was 1.53 (95%CI 1.12-1.71; P=0.052) and 2.31 (95%CI 1.76-2.49; P=0.004). Fifty-six patients (44.8%) had some degree of pneumonitis due to cCRT plus durvalumab. There was no difference in the proportion of pneumonitis according to race (P=0.95), and the severity of pneumonitis was not significantly different between Hispanics and NHWs (P=0.41).ConclusionsAmong patients with LA stage III NSCLC, NHW had better survival outcomes when compared to Hispanics, with an OS that seems to favor the NHW population and with an EE factor that shows a shorter survival in Hispanics compared with NHW and with the PACIFIC trial group.