Cancer-specific Survival Research Articles

Use of nucleotyping and tumor stroma ratio to predict prognosis in patients with resected intestinal-type gastric cancer.

483 Background: Heterogeneity exists in recurrence and survival among patients with intestinal-type gastric cancer (IGC). Nucleotyping is the alterations in chromatin organization. We sought to identify the prognostic utility of nucleotyping, tumor stroma ratio (TSR) and DNA ploidy in these patients. Methods: Radical resection of gastric carcinoma (> 15 LNs removed) was performed in 283 patients (stage I, n=73; stage II, n=102; stage III, n=108) at our university hospital between 2010 and 2018. Automated image cytometry tools were used to quantitatively measure nucleotyping, TSR and DNA ploidy. Cutpoints of nucleotyping and TSR were 0.044 and 50%, respectively. Associations of these features with clinicopathological characteristics, time-to-recurrence (TTR) and cancer specific survival (CSS) were analyzed by univariate and multivariate analysis. Results: Among 283 patients, chromatin heterogeneity, high TSR and non-diploid were significantly associated with larger tumor size, higher T and N stage, and poorer TTR and CSS at 5 years. In a Cox multivariable analysis, nucleotyping and TSR were independently associated with TTR and CSS (P＜0.05) (Table). The top three contributors to TTR were N stage (33.9%), nucleotying (29.7%) and TSR (25.5%). The top three contributors to CSS were N stage (35.6%), nucleotying (29.7%) and TSR (18.0%). As a combined variable, the percent relative contribution of nucleotyping and TSR ranked first for TTR and CSS (56.0%, 50.0%), ahead of N stage (33.4%, 34.6%) and TILs (8.4%, 10.6%). Conclusions: Nucleotyping and TSR were each significantly and independently associated with TTR and CSS, and their combined variable was more strongly prognostic than either alone. Cox multivariable analysis of TTR and CSS. Features TTR HR (95%CI) TTR P value CSS HR (95%CI) CSS P value Tumor size (>3cm vs ≤3cm) 1.10 (0.48-2.54) 0.83 0.77 (0.35-1.70) 0.56 T stage (T3-T4 vs T1-T2) 1.07 (0.46-2.49) 0.87 1.41 (0.53-3.76) 0.49 N stage (N2N3 vs N0N1) 2.84 (1.39-5.78) <0.01 7.69 (3.37-17.55) <0.01 Adjuvant Therapy (with vs without) 1.32 (0.72-2.40) 0.37 0.85 (0.48-1.52) 0.59 TB (high vs low) 1.29 (0.62-2.69) 0.50 1.61 (0.85-3.07) 0.15 TILs（low vs high） 1.73 (0.96-3.13) 0.07 1.90 (1.06-3.40) 0.03 Nucleotyping (Chromatin heterogeneous vs Chromatin homogeneous) 2.19 (1.21-3.99) 0.01 3.44 (1.96-6.03) <0.01 TSR (high vs low) 2.12 (1.16-3.82) 0.01 2.51 (1.43-4.41) <0.01 DNA ploidy (Non-diploid vs Diploid) 1.20 (0.55-2.63) 0.65 0.98 (0.44-2.15) 0.95 1 TTR, time-to-recurrence; 2 CSS, cancer specific survival.

Surgery versus radiotherapy for older patients (aged≥65 years) with stage I-II laryngeal cancer: an investigational study from the SEER database

ABSTRACT Background Currently, the choice between radiotherapy and surgery for treating older patients with early laryngeal cancer remains unclear. The aim of this retrospective study is to investigate the therapeutic patterns and survival outcomes for a cohort of older patients with early laryngeal cancer who received radiation therapy (RT) or surgery. Methods Clinical records of 1833 patients aged 65+ with stage I/II laryngeal cancer from the SEER registry (2010-2015) were assessed. Of these, 1319 underwent RT and 514 had surgery alone. Kaplan-Meier analysis assessed overall survival (OS) and cancer-specific survival (CSS), with Log-rank tests for comparison. Results The 5-year OS and CSS rates were 61.1% and 80.6%, respectively. Univariate analysis showed age, gender, T stage, histology, and treatment as prognostic factors for OS and CSS. Multivariate analysis linked age, T stage, and treatment to OS, and gender, histology, T stage, and treatment to CSS. Surgery improved OS and CSS for most early-stage patients, except those with grade III cancer. Conclusion Among early-stage laryngeal cancer patients aged 65 years or older reported in the SEER database, those treated with surgery experienced longer OS and CSS compared to those treated with RT, except for patients with grade III.

Effectiveness of anti-epidermal growth factor receptor agents in elderly patients (age ≥ 70 years) with RAS wild-type metastatic colorectal cancer: Nationwide real-world data.

57 Background: This study investigated the efficacy and safety of anti-epidermal growth factor receptor (EGFR) agents plus chemotherapy for elderly patients (aged > or = 70 years) with RAS wild-type metastatic colorectal cancer (mCRC) from nationwide data in Taiwan. Methods: Total 756 patients with RAS wild-type mCRC who received first-line therapy with anti-EGFR agents (Cetuximab) plus chemotherapy at nationwide multiple institutions from November 2016 to January 2021. The study explored the prognostic impact between two age groups (≥70 vs <70). Progression-free survival (PFS) and cancer-specific survival (CSS) were compared. Additionally, severe adverse events (SAEs) were also compared between two age groups. Results: The median PFS and CSS were comparable between the two age groups (14.0 vs 14.0 months, p = 0.098; 32.0 vs 35.0 months, p = 0.226, respectively). Moreover, subgroup analysis revealed similar PFS and CSS between two age groups in patients with synchronous or metachronous mCRC and left-sided or right-sided tumors (all p > 0.05). Regarding hematologic SAEs, a significant higher incidence of grade ≥ 3 anemia was found in elderly patient group (13.3% vs 5.0%, p = 0.003). However, no significant difference was observed in the incidence of non-hematologic SAEs (all p > 0.05). Conclusions: According to this nationwide real-world data, for patients carrying RAS wild-type mCRC treated with cetuximab plus chemotherapy, elderly patients could have comparable benefit as younger ones. Except for grade ≥ 3 anemia, other hematologic SAEs and non-hematologic SAEs revealed no significant difference between two age groups.

Adjuvant cytokine-induced killer cell immunotherapy in hepatocellular carcinoma: Extended follow-up of a randomized controlled trial and post-treatment immune cell profiling.

518 Background: Notwithstanding the pressing need for adjuvant therapy for hepatocellular carcinoma (HCC), most adjuvant therapies, including atezolizumab/bevacizumab, have failed. Meanwhile, adjuvant immunotherapy utilizing autologous cytokine-induced killer (CIK) cells for HCC improved recurrence-free survival (RFS) in a previously reported randomized controlled trial (RCT) and real-world data. This study aimed to assess the longer-term outcomes of the RCT and elucidate the underlying mechanisms of sustained effects of CIK cell treatment. Methods: This study comprised two parts: a long-term follow-up of the preceding RCT and an analysis of immune cells in patients who received adjuvant CIK cell treatment. In the original RCT, 226 patients who underwent curative treatment for stage I or II HCC were randomly allocated to either the CIK (n=114, 16 injections of 6.4×10 9 CIK cells over an 11-month period) or control group (n=112). The follow-up period was extended to 9 years after the enrollment of the last patient. The primary endpoint was recurrence-free survival (RFS). The secondary endpoints included cancer-specific survival (CSS) and overall survival (OS). Parallelly, a prospective study was conducted to investigate post-treatment changes of immune cells in peripheral blood of 7 patients, who received repeated transfer of CIK cells after curative treatment for HCC, using flow cytometry. Results: In the extended follow-up of the RCT (median follow-up=115.7 months, interquartile range=74.2–130.5 months), the CIK group sustained a significantly prolonged RFS (median=43.5 vs 27.4 months; hazard ratio [HR]=0.74, 95% confidence interval [CI]=0.55–0.99, P =0.045) and CSS (median=unreached; HR=0.49, 95% CI=0.25–0.95, P=0.04) compared to the control group. Adjuvant CIK cell therapy reduced the risk of overall death by 30%, although it did not achieve statistical significance (median=unreached; HR=0.70, 95% CI=0.44–1.11, P=0.1). A preliminary analysis of peripheral blood immune cells revealed that the CIK cell treatment tended to increase the frequencies of CD8 + and CD4 + classical memory cells. Conclusions: Adjuvant CIK cell treatment demonstrated significantly enhanced RFS and CSS in the prolonged follow-up of the RCT extending to 9 years in patients who received curative treatment for HCC. The CIK group also demonstrated a consistent trend of improved OS. The increase in memory T cell populations might be linked to the sustained off-treatment anti-tumor efficacy of CIK cell treatment.

Prognostic factors in T1 high-grade urothelial carcinoma of the bladder with lymphovascular invasion: a retrospective cohort study.

To evaluate the long-term treatment outcomes of T1 high-grade (T1HG) urothelial carcinoma (UCB) with lymphovascular invasion (LVI). We retrospectively analyzed the data of 70 patients of T1HG UCB with LVI who were treated at the Second Hospital of Tianjin Medical University between 2009 and 2019. The log rank test and Cox regression analyses were performed to identify factors that predict the recurrence and survival of these "highest risk" group of non-muscle invasive bladder cancer (NMIBC). With a median follow-up of 46.0months (range 2-151), the 5-year overall survival (OS), cancer-specific survival (CSS), recurrence-free survival (RFS) and progression-free survival (PFS) rates were 65%, 78%, 28% and 56% after trans-urethral resection of bladder tumor (TURBT), and 35%, 48%, 35% and 35% after radical cystectomy (RC), respectively. Treatment modality (tumor burden) was and independent predictor of OS (Hazard ratios (HRs) 2.176, 95% confidence intervals (CIs) 1.021-4.637, p = 0.044) and CSS (HRs 3.675, CIs 1.311-10.297, p = 0.013), and was weakly associated with RFS (HRs 0.560, CIs 0.281-1.114, p = 0.099). A history of urothelial carcinoma of the bladder (H.UCB) was an independent predictor of RFS (HRs 2.246, CIs 1.102-4.579, p = 0.026) and PFS (HRs 2.259, CIs 1.036-4.927, p = 0.041). Tumor size was an independent predictor of RFS (HRs 2.093, CIs 1.054-4.159, p = 0.035). In T1HG UCB with LVI, tumor burden was a significant predictor of survival. Radical cystectomy should be individualized and not universally recommended. Recurrent T1HG UCB with LVI potentially represents a sign of progression, and RC regardless of tumor burden might be a reasonable alternative for this subgroup of patients.

Histopathological growth patterns of gastric cancer liver metastasis and their association with patient prognosis.

484 Background: The histopathological growth patterns (HGPs) of liver metastasis reflect the complicated and varied interactions between tumor cells and the host microenvironment. We studied HGPs of gastric cancer liver metastasis (GCLM) and sought to predict them using radiomic and clinical variables. Methods: Hepatectomy was performed in 62 patients with GCLM at our university hospital between 2011 and 2021. HGPs were evaluated according to international consensus guidelines, and were classified as either desmoplastic HGP (dHGP) or non-dHGP. CD4, CD8, VEGF and CD31 were analyzed by immunohistochemistry. Eight hundred and fifty-one radiomics features were extracted from CT portal venous phase images and the optimal radiomics signature was determined by univariate analysis and LASSO regression. Multivariable regression analyses and ROC curves were used to assess the predictive performance of HGPs with a radiomic and clinical combined model. Results: Among 62 patients, 14 were categorized as dHGP, and 48 as non-dHGP. Non-dHGP vs. d-HGP was associated with higher tumor N stage and CEA level, and with decreased CD8 + T cells, and lower VEGF and CD31 expression. HGP status was independently associated with patient cancer-specific survival (CSS) (P＜0.05) multivariately.Analysis of percent relative contribution revealed that HGP ranked first for CSS (35.9%), ahead of T (28.9%) and N (28.9%) stage. A model with combined radiomic and clinical features demonstrated robust performance with area under the curve (AUC) values of 0.993 and 0.933 in the training and validation sets, respectively. Conclusions: Non-invasive determination of radiomic and clinical features was shown to predict HGPs types. Compared to dHGP, GCLM with non-dHGP exhibited significantly lower immune cell infiltration and decreased angiogenesis. Among features examined in GCLM, HGP was the most robust for prognostication. Univariate and multivariate analysis of prognostic factors for cancer-specific survival. Characteristics Univariate analysis Multivariate rergression analysis HR (95%CI) P HR (95%CI) P Gender ( Women vs Men ) 1.13(0.61-2.09) 0.71 Age ( >60years vs ≤60years) 1.08(0.60-1.70) 0.98 HGP ( non-desmoplastic HGP vs desmoplastic HGP ) 3.63(1.78-7.41) 0.00 3.48(1.37-8.88) 0.01 T stage ( T3-T4 vs T1-T2 ) 2.03(1.08-3.80) 0.03 2.29(1.15-4.58) 0.02 N stage ( N1-N3 vs N0 ) 3.46(1.66-7.23) 0.00 2.54(1.17-5.56) 0.02 CEA ( >5ng/ml vs ≤5ng/ml ) 2.37(1.25-4.48) 0.01 1.56(0.70-3.48) 0.27

Effect of adjuvant radiotherapy after endoscopic resection of early esophagus cancer to prevent new intraluminal mucosal recurrence.

381 Background: Endoscopic resection (ER) is effective for treating T1a early esophageal squamous cell carcinoma (ESCC). Occasional distant metastasis and recurrence are inevitable invasion in depth of muscularis mucosa(MM). Additional surgical resection is an effective means for cure and prevent recurrence, but it imposes a heavy physical burden. Chemoradiation therapy (CRT) is a comparable alternative to surgery. Not all patients will want those additional treatment. Another problem is the occurrence of new esophagus intraluminal mucosal recurrence. After endoscopic treatment, there is an increased risk of scarring and deformity. But there are few reports of the effectiveness of additional RT in suppressing new lesions. This study was designed to verify the efficacy of not only curability but also suppressive effect the occurrence of new lesions additional treatment of T1a(MM) ESCC. Methods: This study was a retrospective study. We reviewed 71 consecutive patients who underwent ER followed by clinical stage I (T1a: MM) ESCC. We compared patients in the radiotherapy group or non-radiotherapy group after ER. Patients of radiotherapy group received radiation within 3 months after ER. All patients underwent regular follow-up. Recurrence, recurrence-free survival, cancer-specific survival, overall survival, and complications were evaluated. Results: There were 34 cases of radiotherapy group and 37 cases of non-radiotherapy group. 3 patients (8.9 %) in the radiotherapy group experienced intraluminal mucosal recurrence, and 2 patients (6.6 %) experienced local recurrence. On the other hand, in the non-radiotherapy group, 9 patients (24.3 %) experienced intraluminal mucosal recurrence, and 7 patients (18.9 %) experienced local recurrence (intraluminal mucosal recurrence: p< 0.05, local recurrence p=0.14). The recurrent group received chemotherapy. The 3-year cumulative recurrence-free survival was 97 % in the radiotherapy group and 83.7 % in the non-radiotherapy group (p< 0.05). No severe radiation toxicities were recorded. Conclusions: The radiotherapy after ESD reduced the risk of lymph nodes recurrence not only local lymph node recurrence but also new intraluminal mucosal recurrence, and safe and effective therapeutic strategy.

The TAB-EOAO study: Trends in use and benefit of adjuvant chemotherapy between early onset and average onset locally advanced colon cancer.

105 Background: Despite the declining incidence rates (IR) in average onset colon cancer (AO-CC), IR for early onset colon cancer (EO-CC), defined as patients (pts) younger than 50-years-old at diagnosis, has been increasing. Treatment for high risk locally advanced colon cancer (CC) is surgical resection followed by adjuvant chemotherapy (AC). Data indicates a more permissive chemotherapy use in EO-CC. There is limited data about treatment and survival trends in EO-CC. Thus, we aimed to assess the use and benefit of AC between in EO vs AO CC in locally advanced disease. Methods: CC diagnosed between 2000-2020 were identified in the Surveillance, Epidemiology, and End Results Program (SEER) Database. Eligible pts were adults (≥18), Stage II or III at diagnosis. Stage II disease was further stratified as low risk (pT1-3) and high risk (pT4). Logistic regression methods were used to assess Odds Ratio (OR) of AC between EO-CC and AO-CC; Cox models were used to compare overall survival (OS) and Cancer-specific survival (CSS) between both groups during 2000-2010 and 2011-2020. Results: Our study included 136,676 pts (AO-CC= 121,606; EO-CC =15,070). The median age for EO-CC was 44 years versus 71 years for AO-CC population. The use of AC increased over time for both the EO-CC (63% vs 66%) and AO-CC (33% vs 40%). Moreover, pts with AO-CC received less AC than EO-CC in the entire study time (see table). In pts with AO-CC, AC improved CSS (HR=0.69 for 2000-2010, HR=0.50 2011-2020). However, among those with EO-CC, AC improved CSS in 2011-2020 (HR=0.76) but did not improve CSS in 2000-2010 (HR=1.02). Conclusions: Over the past 20 years EO-CC has been managed aggressively, especially for stage II low risk patients where current guidelines do not support the use of AC. In this real world data set we show that for EO-CC AC did not improve CSS in the decade 2000- 2010 but did improve CSS in the 2011- 2020 period. Further analysis may clarify stage specific benefits of AC. There clearly remains a need for better risk stratification, including the use of ctDNA, to identify the subpopulations of EO-CC patients that will best benefit from AC. Multivariable logistic regression model of chemotherapy by timeframe with interaction term: Age* stage. 2000-2010 2011-2020 AO-CC vs EO-CC OR 95% CI OR 95% CI Stage II low risk 0.23 (0.21, 0.26) 0.28 (0.24, 0.32) Stage II high risk 0.28 (0.22, 0.36) 0.28 (0.21, 0.36) Stage III 0.36 (0.32, 0.4) 0.30 (0.26, 0.34)

Annual versus less frequent mammographic surveillance in people with breast cancer aged 50 years and older in the UK (Mammo-50): a multicentre, randomised, phase 3, non-inferiority trial.

The frequency of mammographic surveillance for women after diagnosis of breast cancer varies globally. The aim of this study was to evaluate whether less than annual mammography was non-inferior in terms of breast cancer-specific survival in women aged 50 years or older. Mammo-50 was a multicentre, randomised, phase 3 trial of annual versus less frequent mammography (2-yearly after conservation surgery; 3-yearly after a mastectomy) for women aged 50 years or older at initial diagnosis of invasive or non-invasive breast cancer and who were recurrence free 3 years post curative surgery. The trial was conducted at 114 National Health Service hospitals in the UK. Participants were randomly assigned (1:1) to annual or less frequent mammograms at 3 years post curative surgery and were followed up for 6 years. The co-primary outcomes were breast cancer-specific survival and cost-effectiveness. The cost-effectiveness analysis will be reported elsewhere. Breast cancer-specific survival was assessed in the intention-to-treat population. Secondary outcomes were recurrence-free interval, overall survival, and referrals back to the hospital system. 5000 women provided 90% power to detect a 3% absolute non-inferiority margin for breast cancer-specific survival with 2·5% one-sided significance. The trial was registered with the ISRCTN registry, ISRCTN48534559; recruitment is complete but longer-term follow-up is ongoing. Between April 22, 2014, and Sept 28, 2018, 5235 women were randomly assigned to annual mammography (n=2618) or less frequent mammography (n=2617). 3858 (73·6%) women were aged 60 years or older, 4202 (80·3%) had undergone conservation surgery, 4576 (87·4%) had invasive disease, 1159 (22·1%) had node positive disease, and 4330 (82·7%) had oestrogen receptor-positive tumours. With a median of 5·7 years follow-up (IQR 5·0-6·0; 8·7 years post curative surgery), 343 women died, including 116 who died of breast cancer (61 in the annual mammography group and 55 in the less frequent mammography group). 5-year breast cancer-specific survival was 98·1% (95% CI 97·5-98·6) in the annual mammography group and 98·3% (97·8-98·8) in the less frequent mammography group (hazard ratio 0·92, 95% CI 0·64-1·32), demonstrating non-inferiority of less frequent mammography at the pre-specified 3% margin (non-inferiority p<0·0001). 5-year recurrence-free interval was 94·1% (95% CI 93·1-94·9) in the annual mammography group and 94·5% (93·5-95·3) in the less frequent mammography group. Overall survival at 5 years was 94·7% (95% CI 93·8-95·5%) and 94·5% (93·5-95·3), respectively. 224 (64·9%) of 345 breast cancer events were detected from emergency admissions or symptomatic referrals back to the hospital system, including 108 (61·7%) of 175 in the annual mammography group and 116 (68·2%) of 170 in the less frequent mammography group. For patients aged 50 years or older and at 3 years post diagnosis, less frequent mammograms were non-inferior compared with annual mammograms for breast cancer-specific survival, recurrence-free interval, and overall survival, and should be considered for this population. National Institute for Health Research Health Technology Assessment programme.

Real-world outcomes for high-risk non-muscle-invasive bladder cancer: screened patients for the BRAVO trial.

To report real-world outcomes for high-risk non-muscle-invasive bladder cancer (HRNMIBC), including bacillus Calmette-Guérin (BCG) and radical cystectomy (RC), as randomised comparisons of these have not been possible. We detail consecutive participants screened for the BRAVO randomised controlled trial comparing RC with BCG (International Standard Randomised Controlled Trial Number [ISRCTN]12509361). Patients were prospectively registered and case-note review used for outcomes. The primary outcome was overall survival. Secondary outcomes included recurrence, progression, metastasis, and bladder cancer-specific survival. A total of 193 patients were screened, including 106 (54.9%) who received BCG, 43 (22.3%) primary RC, 37 (19.2%) 'other' treatment and seven (3.6%) hyperthermic intravesical mitomycin C. All-cause death occurred in 55 (28.5%) patients at median (interquartile range [IQR]) of 29.0 (19.5-42.0) months. In multivariable analysis, overall mortality was more common in older patients (hazard ratio [HR] 2.63, 95% confidence interval [CI] 1.35-5.13; Cox P = 0.004 for age >70 years), those recruited from district hospitals (HR 0.53, 95% CI 0.3-0.95; P = 0.032) and those who did not undergo RC as their first treatment (HR 2.16, 95% CI 1.17-3.99; P = 0.014). In all, 17 (8.8%) patients died from bladder cancer (BC) at median (IQR) of 22.5 (19-36.25) months. In multivariable analysis, BC-specific mortality was more common in older patients (HR 4.87, 95% CI 1.1-21.6; P = 0.037) and those with Tis/T1 disease (HR 2.26, 95% CI 1.23-4.16; P = 0.008) but did not vary with initial treatment. Patients with HRNMIBC are at high-risk of mortality. Those choosing RC as their initial treatment have lower risks of mortality than others, although this may reflect fitness and selection.

Association between surgery and increased survival in primary central nervous system lymphoma: a retrospective cohort study

This study investigated the effect of surgery on the prognosis of patients with primary central nervous system lymphoma (PCNSL) using data from the surveillance, epidemiology, and end results (SEER) database. A cohort of 5932 patients was analyzed, with 1466 undergoing surgical intervention (780 subtotal resection (STR), 686 gross total resection (GTR)) and 4466 receiving no surgery or biopsy only. The median age of the study population was 61.5 years. The median survival was 24.0 months for STR, 30.0 months for GTR, and 18.0 months for non-surgical patients (P < 0.001). Multivariate Cox regression analyses showed that the adjusted hazard ratio (HR) for STR was 0.77 (95% CI 0.70–0.85, P < 0.001) for overall survival (OS) and 0.74 (95% CI 0.66–0.83, P < 0.001) for cancer-specific survival (CSS). For GTR, the adjusted HR was 0.73 (95% CI 0.65–0.80, P < 0.001) for OS and 0.73 (95% CI 0.65–0.82, P < 0.001) for CSS. These results remained robust even after subgroup analyses, sensitivity analyses and propensity score matching (PSM). No significant interactions were observed in any subgroup. These findings indicate that surgery may improve the survival of patients with PCNSL, though further research is needed to confirm these findings. A key limitation is the inability to stratify patients by performance status and lesion number, critical for assessing resective surgery suitability.

Outcomes and treatment patterns for stage I human epidermal growth factor receptor 2-positive breast cancer in the Surveillance, Epidemiology, and End Results database, 2010-2019.

The risk of recurrence in patients with small, lymph node-negative, human epidermal growth factor receptor 2 (HER2)-positive breast cancers untreated with adjuvant chemotherapy/HER2-directed therapy is uncertain. To investigate this, the authors conducted a retrospective, population-based study of chemotherapy use and breast cancer-specific survival (BCSS) among patients with stage IA HER2-positive breast cancer. The authors analyzed Surveillance, Epidemiology, and End Results data from patients diagnosed with stage IA HER2-positive breast cancer from 2010 to 2019. They examined the frequency of chemotherapy use by tumor size and hormone receptor (HR) status and applied multivariate logistic regression to assess the factors associated with receipt of chemotherapy. BCSS was evaluated and performed multivariable Cox regression was performed to evaluate the association between chemotherapy receipt and BCSS. Among 12,896 patients, 74.0% had HR-positive/HER2-positive breast cancer, and 26.0% had HR-negative/HER2-positive breast cancer. Adjuvant chemotherapy was received by to 58.9% of patients, with lower utilization for those who were older, Hispanic or Asian/Pacific Islander, separated/divorced/widowed, or had a lower median household income. The median follow-up was 46 months. Among the patients who had pathologic T1 (pT1) microscopic, pT1a, or pT1b tumors, the 5-year BCSS rate was 97.6%-99.6% in those who had no evidence of chemotherapy receipt in the medical record versus 98.4%-100.0% in those who did receive chemotherapy. Among patients who had pT1c tumors and had no evidence of chemotherapy receipt, the 5-year BCSS rate was 92.1% for those with HR-negative/HER2-positive breast cancer and 96.0% for those with HR-positive/HER2-positive breast cancer. Patients who had pT1c tumors and received chemotherapy had a 5-year BCSS rate of 96.7% in those with HR-negative/HER2-positive breast cancer and 98.7% in those with HR-positive/HER2-positive breast cancer. In this large, population-based study of patients with stage IA HER2-positive breast cancer, patients who had tumors ≤1 cm had excellent outcomes with or without chemotherapy. Patients with pT1c tumors had a greater increase in BCSS with the receipt chemotherapy.

Machine learning based predictive model and genetic mutation landscape for high-grade colorectal neuroendocrine carcinoma: a SEER database analysis with external validation

BackgroundHigh-grade colorectal neuroendocrine carcinoma (HCNEC) is a rare but aggressive subset of neuroendocrine tumors. This study was designed to construct a risk model based on comprehensive clinical and mutational genomics data to facilitate clinical decision making.MethodsA retrospective analysis was conducted using data from the Surveillance, Epidemiology, and End Results (SEER) database, spanning 2000 to 2019. The external validation cohort was sourced from two tertiary hospitals in Southwest China. Independent factors influencing both overall survival (OS) and cancer-specific survival (CSS) were identified using LASSO, Random Forest, and XGBoost regression techniques. Molecular data with the most common mutations in CNEC were extracted from the Catalogue of Somatic Mutations in Cancer (COSMIC) database.ResultsIn this prognostic analysis, the data from 714 participants with HCNEC were evaluated. The median OS for the cohort was 10 months, whereas CSS was 11 months. Six variables (M stage, LODDS, Nodes positive, Surgery, Radiotherapy, and Chemotherapy) were screened as key prognostic indicators. The machine learning model showed reliable performance across multiple evaluation dimensions. The most common mutations of CNEC identified in the COSMIC database were TP53, KRAS, and APC.ConclusionsIn this study, a refined machine learning predictive model was developed to assess the prognosis of HCNEC accurately and we briefly analyzed its genomic features, which might offer a valuable tool to address existing clinical challenges.

Segmental Resection with Ureteral Reimplantation vs Radical Nephroureterectomy with Bladder Cuff Removal for Urothelial Carcinoma of Distal Ureter: A Propensity Score Matching Study in a Large Chinese Center.

Purpose: We aim to compare the clinical outcomes of radical nephroureterectomy with bladder cuff removal (RNU) and segmental resection with ureteral reimplantation (RR) in Chinese patients with distal ureteral urothelial carcinoma. Materials and Methods: A retrospective analysis of medical records was performed for 922 patients found to have distal ureteral cancer, defined as below the level of the iliac vessels, with 747 patients who underwent RNU and 175 who underwent RR included in the final analysis. The primary endpoints included clinical outcomes and changes in the estimated glomerular filtration rate (eGFR). Survival analysis was conducted using the Kaplan-Meier method, and propensity score matching (PSM) was utilized to mitigate selection bias between the two surgical approaches. Results: After PSM, the Kaplan-Meier survival curves demonstrated significant associations between surgical approach and both local recurrence-free survival (LRFS) and bladder recurrence-free survival (BRFS), but no significant differences were found in cancer-specific survival (CSS) and overall survival (OS). There were no significant differences in metastasis-free survival and contralateral recurrence-free survival between the two groups. Multivariate Cox regression analysis identified RR as an independent predictor of poorer outcomes for LRFS and BRFS. In addition, a significant increase in eGFR was observed following RR, whereas a significant decrease was noted after RNU. Conclusion: RR is associated with equivalent CSS and OS compared with RNU, even in the context of high-risk distal ureteral cancer, and results in improved postoperative eGFR, whereas the potential of RR to increase the risk of local tumor recurrence and intravesical recurrence requires clinical consideration.

Long-term survival from a randomized controlled trial of lobectomy by video-assisted thoracoscopic surgery versus thoracotomy for early-stage lung cancer.

We previously did a randomized clinical trial of lobectomy by VATS or thoracotomy for early-stage lung cancer and found that patients who underwent VATS had less postoperative pain and better quality of life compared with thoracotomy. VATS has since been regarded the preferred surgical method for early-stage lung cancer. It is assumed that long-term survival is not influenced by surgical approach, but this assumption primarily rests on non-randomized comparative studies. We decided to do a long-term follow-up of patients who entered our previous randomized trial. Between 2008 and 2014 we randomly assigned 206 patients to VATS (n = 103) or anterolateral thoracotomy (n = 103) for proven or suspected early-stage NSCLC. Records from patients with NSCLC on final pathology were identified in the national electronic patient-record system and the Danish Lung Cancer Registry. Overall, disease-free, and cancer-specific survival were estimated using the Kaplan-Meier method and log-rank test was used to compare the two interventions. A total of 196 patients had NSCLC on final histopathology. Four patients were lost to follow-up and the remaining 192 were included in this follow-up study with 128 events used for overall survival analysis, 100 events for disease-free survival analysis and 79 events for cancer-specific survival analysis. VATS was used in 99 patients versus 93 by thoracotomy. Median age at time of surgery was 66 years (range 41-85 years). After a median follow-up time of 12.8 years (range 9.9-15.8 years), 33% of patients were alive. Overall, disease-free, and cancer-specific survival were not significantly different between VATS and thoracotomy: Overall survival (p = 0.29), disease-free survival (p = 0.17) and cancer-specific survival (p = 0.31). We did not find any statistically significant differences in overall, disease-free, or cancer-specific survival between VATS and thoracotomy. However, larger trials with better power for survival analysis are needed to fully explore if there are differences. Alternatively, differences in survival between thoracotomy and VATS for early-stage NSCLC could be investigated by pooling survival data from two similar randomized trials that have since been published.

Impact of chemoradiotherapy for first primary lung cancer on the prognosis and re-chemoradiotherapy sensitivity of second primary lung cancer

BackgroundDespite undergoing surgery and chemoradiotherapy, patients with first primary lung cancer (FPLC) remain at risk for second primary lung cancer (SPLC), which is associated with a poor prognosis. The effects of FPLC chemoradiotherapy on SPLC prognosis and its sensitivity to re-chemoradiotherapy have not been adequately investigated.MethodsThis cohort study analyzed data from 23,827 patients who underwent FPLC surgery during 1973–2021, drawn from the Surveillance, Epidemiology, and End Results database. Among these, 5,302 FPLC patients developed SPLC within 5 years of their initial diagnosis. We employed the Fine-Gray competitive risk model, Cox proportional hazards model, and restricted mean survival time analysis to assess the effects of FPLC radiotherapy and chemotherapy on SPLC risk and survival differences.ResultsThe competitive risk model indicated that FPLC radiotherapy and chemotherapy did not significantly change the risk of developing SPLC. However, the Cox proportional hazards model revealed that FPLC radiotherapy was associated with decreased overall survival (OS; HR=1.251, P&amp;lt;0.001) and cancer-specific survival (CSS; HR=1.228, P=0.001) in patients with SPLC. Conversely, FPLC chemotherapy was linked to improved OS (HR=0.881, P=0.012) in this population. Patients with SPLC who received combined chemoradiotherapy for FPLC exhibited significantly reduced survival times (OS: HR=1.157, P=0.030; CSS: HR=1.198, P=0.018), a finding confirmed across multiple models. For SPLC patients with prior FPLC chemoradiotherapy, subsequent SPLC radiotherapy significantly improved prognosis. Notably, this benefit is even more pronounced in patients who have not received prior chemoradiotherapy. While SPLC chemotherapy enhanced OS for patients who did not receive FPLC chemotherapy, it was associated with reduced CSS for those who had.ConclusionsOverall, FPLC chemoradiotherapy influences SPLC prognosis and influences sensitivity to treatment. Tailoring SPLC management to FPLC treatment regimens may improve survival outcomes.

“Modernized” en Bloc Radical Cystectomy Versus Standard Radical Cystectomy: A Nationwide Multi-Institutional Propensity Score Matched Analysis

Background: Pelvic lymph node dissection during standard radical cystectomy (stdRC) for muscle invasive bladder cancer is performed as separate templates. In the modernized en bloc radical cystectomy (mEbRC), the bladder is removed together with all its associated lymphatic tissue as one specimen. Our aim was to evaluate the oncological and surgical outcomes of mEbRC with a propensity-matched national cohort of stdRC cases. Methods: 935 patients (mEbRC: 214 and stdRC: 721) were eligible for analysis, and 1:2 propensity score matching was performed regressing mEbRC treatment on the variables age, gender, neoadjuvant chemotherapy, Charlson Comorbidity Index, lymph node metastases at final pathology, carcinoma in situ, and pT-stage. The primary outcome was recurrence-free survival (RFS). Secondary endpoints were overall survival (OS) and cancer-specific survival (CSS), survival for female patients. and perioperative measures. Results: There were no significant differences between the groups regarding complications, 30-day readmission rates, and 30- and 90-day mortality rates. In the propensity score matched groups, the 5-year RFS was 83% in the mEbRC group vs. 67% in the stdRC group (p &lt; 0.001), the CSS was 89% and 78% (p ≤ 0.001), and OS 81% vs. 68% (p &lt; 0.001) in the same groups, respectively. The results were confirmed by Cox regression analyses with hazard ratios ranging from 0.41 to 0.50 and p-values ≤ 0.001, favoring mEbRC. The 5-year OS for female patients was 86% for mEbRC and 60% for stdRC (p = 0.022). Conclusions: Performing mEbRC over stdRC might yield significantly better oncological outcomes, with equal survival rates for both genders.

The association between radiotherapy and the prognosis of follicular lymphoma patients with different characteristics in the rituximab era: a cohort study based on Surveillance, Epidemiology and End Results.

This retrospective cohort study examined the association between radiotherapy and prognosis in follicular lymphoma (FL) patients, with stratification by age, Ann Arbor stage, primary tumor site, surgical status, and grade. Using data from the SEER database, we employed Cox proportional hazards and competing risk models to assess the impact of radiotherapy on overall survival (OS) and cancer-specific survival (CSS) in 7,551 FL patients. The association between radiotherapy and second primary cancer (SPC) was explored using Logistic regression model. At the end of the 60-month follow-up, 6,053 patients were alive, while 1,498 had died. The overall result showed that radiotherapy was associated with the better OS [hazard ratio (HR): 0.70, 95% confidence interval (95%CI): 0.59-0.83, P < 0.001] and CSS (HR: 0.67, 95% CI: 0.52-0.87, P = 0.002)) in FL patients. Radiotherapy was associated with improved OS and CSS in patients aged ≥ 60 years [OS: HR: 0.65, CI: 0.53-0.79; CSS: HR: 0.63, CI: 0.52-0.77], early Ann Arbor stage (OS HR: 0.51, CI: 0.40-0.65; CSS HR: 0.51, CI: 0.40-0.65), primary sites at lymph nodes (OS HR: 0.76, CI: 0.62-0.93; CSS HR: 0.76, CI: 0.62-0.93) and skin/soft tissue (OS HR: 0.35, CI: 0.16-0.81; CSS HR: 0.36, CI: 0.16-0.82), and in both surgical (OS HR: 0.70, CI: 0.52-0.93; CSS HR: 0.70, CI: 0.52-0.93) and non-surgical patients (OS HR: 0.71, CI: 0.56-0.89; CSS HR: 0.69, CI: 0.55-0.87). Radiotherapy showed no significant association with second primary cancer (SPC) risk. These findings suggest radiotherapy improves 5-year survival outcomes in FL patients during the rituximab era.

Adjuvant radiation improves survival outcomes in adrenocortical carcinoma: A population-based study.

The aim of this study was to evaluate the clinical benefits and outcomes of adjuvant radiation therapy on adrenocortical carcinoma (ACC) patients. All patients with ACC that were reported between 2010 and 2015 were identified from the Surveillance, Epidemiology, and End Results database. A forward-stepwise Cox proportional hazards regression was used to identify independent risk factors. A new nomogram was created to predict overall and cancer-free survival probabilities at 1, 3, and 5 years for ACC patients. The concordance index, the area under the receiver operating characteristic curve, calibration curves, and decision curve analysis were used to validate the accuracy and reliability of the model. A total of 426 ACC patients were enrolled in this study, of which 84 (19.7%) cases underwent adjuvant radiation therapy (RT). Six factors (age, T stage, type of surgery, radiation, and bone and liver metastases) were significantly related to overall survival (OS) (P < .05). Five factors (T stage, type of surgery, radiation, and bone and liver metastases) were significantly related to cancer-specific survival (CSS) (P < .05). A nomogram for OS and CSS was constructed. The area under the receiver operating characteristic curve values for 1-, 3-, and 5-year OS were 0.85, 0.818, and 0.814, respectively, and for CSS, they were 0.839, 0.803, and 0.796, respectively. C-indices were 0.756 and 0.749 for OS and CSS, respectively, indicating that the nomograms for OS and CSS had satisfactory discriminative power. A good consistency between the observed and the predicted survival was found in the calibration curves, and the nomogram has a good net clinical benefit, which is presented in the decision curve analysis curves. Our study demonstrates that adjuvant RT can produce a significant improvement in survival outcomes for ACC patients and suggests that adjuvant RT should routinely be applied in ACC patients.

Primary tumor resection might improve outcomes in metastatic thoracic esophageal cancer

The study aims to evaluate the survival impact of primary tumor resection (PTR) on thoracic esophageal cancer with distant metastasis(TECDM). Data of patients with TECDM was collected from the Surveillance, Epidemiology, and End Results database(SEER) from 2010 to 2020. A 1:1 propensity-score matching(PSM) analysis was employed to minimize heterogeneity between the groups. Total 7733 patients with TECDM were included in the analysis, of which 121 underwent primary tumor resection and 7612 did not. Patients who underwent primary tumor resection exhibited better median overall survival(OS) and median cancer-specific survival(CSS) compared to those who did not, in both the overall and PSM cohort. In the PSM cohort, the median OS was 11 months (95% CI, 9 to 13 months) for TECDM patients who underwent PTR, compared to 7 months (95% CI, 5 to 9 months) for those who did not. Furthermore, Cox proportional hazards models indicated that PTR was a significantly protective factor for TECDM patients in OS (HR: 0.5529; 95% CI, 0.5196 to 0.7730, P < 0.001) and CSS (HR:0.5869 ; 95% CI, 0.479 to 0.7192, P < 0.001). In conclusion, primary tumor resection is associated with improved overall survival and cancer-specific survival in thoracic esophageal cancer patients with distant metastasis.