Single fraction stereotactic radiosurgery and fractionated stereotactic radiotherapy provide equal prognosis with overall survival in patients with brain metastases at diagnosis without surgery at primary site.

Background and purpose: Stereotactic radiosurgery (SRS) and fractionated stereotactic radiation therapy (SRT) are both treatments shown to be effective in treating brain metastases (BMs). However, it is unknown how these treatments compare in effectiveness and safety in cancer patients with BMs regardless of the primary cancer. The main objective of this study is to investigate the SRS and SRT treatments' associations with the overall survival (OS) of patients diagnosed with BMs using the National Cancer Database (NCDB). Materials and methods: Patients in the NCDB with breast cancer, non-small cell lung cancer, small cell lung cancer, other lung cancers, melanoma, colorectal cancer, or kidney cancer who had BMs at the time of their primary cancer diagnosis and received either SRS or SRT as treatment for their BMs were included in the study. We analyzed OS with a Cox proportional hazard analysis that adjusted variables associated with improved OS during univariable analysis. Results: Of the total 6,961 patients that fit the criteria for the study, 5,423 (77.9%) received SRS and 1,538 (22.1%) received SRT. Patients who received SRS treatment had a median survival time of 10.9 (95% CI [10.5-11.3]), and those who received SRT treatment had a median survival time of 11.3 (95% CI [10.4-12.3]) months. This difference was not found to be significant (Log-rank P = 0.31). Multivariable Cox proportional hazard analysis did not yield a significant difference between the treatments' associations with OS (Hazard Ratio: 0.942, CI 95% [0.882-1.006]; P = .08) or SRS vs. SRT. Conclusions: In this analysis, SRS and SRT did not show a significant difference in their associations with OS. Future studies investigating the neurotoxicity risks of SRS as compared to SRT are warranted.

Sociodemographic disparities in targeted therapy in ovarian cancer in a national sample.

Background: The treatment landscape for ovarian cancer has changed in recent years with the introduction of targeted therapies to treat patients with advanced disease. We investigated patient demographic and clinical factors associated with use of targeted therapies as a part of the first-line treatment for ovarian cancer. Methods: This study included patients diagnosed with stage I-IV ovarian cancer between 2012 and 2019 from the National Cancer Database. Information on demographic and clinical characteristics were collected and described using frequency and percent across receipt of targeted therapy. Logistic regression was used to compute the odds ratios (ORs) and 95% confidence intervals (CI) associating patient demographic and clinical factors with receipt of targeted therapy. Results: Among 99,286 ovarian cancer patients (mean age 62 years), 4.1% received targeted therapy. The rate of targeted therapy receipt across racial and ethnic groups over the study period was fairly similar; however, non-Hispanic Black women were less likely to receive targeted therapy than their non-Hispanic White counterparts (OR=0.87, 95% CI: 0.76-1.00). Patients who received neoadjuvant chemotherapy were more likely to receive targeted therapy than those who received adjuvant chemotherapy (OR=1.26; 95% CI: 1.15-1.38). Moreover, among patients who received targeted therapy, 28% received neoadjuvant targeted therapy, with non-Hispanic Black women being most likely to receive neoadjuvant targeted therapy (34%) compared with other racial and ethnic groups. Conclusions: We observed differences in receipt of targeted therapy by factors such as age at diagnosis, stage, and comorbidities present at diagnosis, as well as factors related to healthcare access-including neighborhood education level and health insurance status. Approximately 28% of patients received targeted therapy in the neoadjuvant setting, which could negatively impact treatment outcomes and survival due to the increased risk of complications associated with targeted therapies that may delay or prevent surgery. These results warrant further evaluation in a cohort of patients with more comprehensive treatment information.

Immunotherapy plus stereotactic body radiation therapy or whole-brain radiation therapy in brain metastases.

Aim: To investigate the association of stereotactic radiation therapy (SRT) or whole-brain radiation therapy (WBRT) plus immunotherapy with the overall survival (OS) of cancer patients with brain metastases (BMs) regardless of the primary cancer. Patients & methods: Patients diagnosed with BMs were identified from the National Cancer Database. Results: A total of 34,286 patients were included. SRT plus immunotherapy was associated with improved OS compared with SRT without immunotherapy (hazard ratio: 0.774; 95% CI: 0.687-0.872; p < 0.001), and WBRT plus immunotherapy was associated with improved OS compared with WBRT without immunotherapy (hazard ratio: 0.724; 95% CI; 0.673-0.779; p < 0.001). Conclusion: SRT plus immunotherapy was associated with improved OS compared with SRT. WBRT plus immunotherapy was associated with improved OS compared with WBRT in cancer patients who had BMs at the time of primary cancer diagnosis.

Aim: The purpose of this study was to examine if adding immunotherapy to the two types of brain radiation therapy (stereotactic radiation therapy [SRT] or whole-brain radiation therapy [WBRT]) will improve the overall survival of cancer patients with brain metastases (BMs). Patients & methods: Patients diagnosed with BMs were identified from the National Cancer Database. Results: This study included 34,286 patients. Patients who received SRT plus immunotherapy or WBRT plus immunotherapy were on average 23% and 28% less likely to die of any cause compared with patients who received SRT or WBRT without immunotherapy (hazard ratio: 0.774; 95% CI: 0.687­0.872; p < 0.001 and hazard ratio: 0.724; 95% CI: 0.673­0.779; p < 0.001, respectively). Conclusion: BMs patients who received SRT plus immunotherapy or WBRT plus immunotherapy had better overall survival compared with patients who received SRT or WBRT without immunotherapy.

Association of Cigarette Smoking and Alcohol Consumption With Subsequent Mortality Among Black Breast Cancer Survivors in New Jersey.

Importance: There are limited data about how lifestyle factors are associated with breast cancer prognosis among Black or African American women because most of the evidence is based on studies of White breast cancer survivors. Objective: To examine the association of prediagnostic cigarette smoking and alcohol consumption with all-cause mortality and breast cancer-specific mortality in a cohort of Black breast cancer survivors. Design, Setting, and Participants: This population-based cohort study included 1926 Black or African American breast cancer survivors who received a diagnosis from June 6, 2005, to May 21, 2019, identified in 10 counties in New Jersey through rapid case ascertainment by the New Jersey State Cancer Registry. Statistical analysis was conducted from January 1, 2021, to August 1, 2022. Exposures: Information on prediagnostic cigarette smoking, alcohol consumption, and additional covariates was collected during in-person interviews. The covariates examined included smoking status at the time of breast cancer diagnosis (currently smoking at the time of breast cancer diagnosis, formerly smoking, or never smoking), smoking duration (number of years smoking), smoking intensity (cigarettes smoked per day), number of pack-years of smoking, and regular alcohol consumption the year before diagnosis (categorized as nondrinkers, ≤3 drinks per week, or >3 drinks per week). Main Outcomes and Measures: Primary outcomes included breast cancer-specific mortality and all-cause mortality. Results: Among the 1926 women in the study, the mean (SD) age at breast cancer diagnosis was 54.4 (10.8) years. During 13 464 person-years of follow-up (median follow-up, 6.7 years [range, 0.5-16.0 years]), there were 337 deaths, of which 187 (55.5%) were breast cancer related. Compared with never smokers, current smokers at the time of breast cancer diagnosis had a 52% increased risk for all-cause mortality (hazard ratio [HR], 1.52; 95% CI, 1.15-2.02), which was most pronounced for those with 10 or more pack-years of smoking (HR, 1.84; 95% CI, 1.34-2.53). Similar findings were observed for breast cancer-specific mortality (current smokers vs never smokers: HR, 1.27; 95% CI, 0.87-1.85), although they were not statistically significant. There was no statistically significant association between alcohol consumption and all-cause mortality (>3 drinks per week vs nondrinkers: HR, 1.05; 95% CI, 0.73-1.51) or breast cancer-specific mortality (>3 drinks per week vs nondrinkers: HR, 1.06; 95% CI, 0.67-1.67). Conclusions and Relevance: This population-based cohort study of Black breast cancer survivors suggests that current smoking at the time of diagnosis was associated with an increased risk of all-cause mortality, particularly among women with greater pack-years of smoking.

Neoadjuvant Chemotherapy in Ovarian Cancer: Are There Racial Disparities in Use and Survival?

BACKGROUND: We investigated racial and ethnic disparities in treatment sequence [i.e., neoadjuvant chemotherapy (NACT) plus interval debulking surgery (IDS) versus primary debulking surgery (PDS) plus adjuvant chemotherapy] among patients with ovarian cancer and its contribution to disparities in mortality. METHODS: Study included 37,566 women ages ≥18 years, diagnosed with stage III/IV ovarian cancer from the National Cancer Database (2004-2017). Logistic regression was used to compute ORs and 95% confidence intervals (CI) for racial and ethnic disparities in treatment sequence. Cox proportional hazards regression was used to estimate HRs and 95% CI for racial and ethnic disparities in all-cause mortality. RESULTS: Non-Hispanic Black (NHB) and Asian women were more likely to receive NACT plus IDS relative to PDS plus adjuvant chemotherapy than non-Hispanic White (NHW) women (OR: 1.12; 95% CI: 1.02-1.22 and OR: 1.12; 95% CI: 0.99-1.28, respectively). Compared with NHW women, NHB women had increased hazard of all-cause mortality (HR: 1.14; 95% CI: 1.09-1.20), whereas Asian and Hispanic women had a lower hazard of all-cause mortality (HR: 0.81; 95% CI: 0.74-0.88 and HR: 0.83; 95% CI: 0.77-0.88, respectively), which did not change after accounting for treatment sequence. CONCLUSIONS: NHB women were more likely to receive NACT plus IDS and experience a higher all-cause mortality rates than NHW women. IMPACT: Differences in treatment sequence did not explain racial disparities in all-cause mortality. Further evaluation of racial and ethnic differences in treatment and survival in a cohort of patients with detailed treatment information is warranted.

The Association of Immunotherapy With the Overall Survival of Inoperable Stage III Non-small Cell Lung Cancer Patients Who Do Not Receive Chemoradiation.

Immunotherapy has been approved for stage III non-small cell lung cancer (NSCLC) as consolidation therapy after chemoradiation in patients whose disease does not progress after chemoradiation. However, many patients do not receive chemoradiation due to either the drugs' side effects or poor performance status. This study's objective is to investigate the association of immunotherapy combined with chemotherapy or Radiotherapy (RT) with the overall survival (OS) of stage III NSCLC patients who do not receive chemoradiation. Patients with stage III NSCLC who received either chemotherapy or RT with or without immunotherapy were identified from NCDB. The Cox proportional hazard regression analysis was implied to assess the effect of immunotherapy on survival after adjusting the model for age at diagnosis, race, sex, education, treatment facility type, insurance status, comorbidity score, histology year of diagnosis, and treatment types, such as chemotherapy and radiation therapy. The final analysis included 32,328 patients, among whom 3,205 (9.9%) received immunotherapy. In the multivariable analysis adjusted for all the factors previously mentioned, immunotherapy was associated with significantly improved OS (HR: 0.76, CI: 0.71-0.81) compared with no immunotherapy. Treatment with chemotherapy plus immunotherapy was significantly associated with improved OS (HR: 0.83, CI: 0.77-0.90) compared with chemotherapy without immunotherapy. Further, RT plus immunotherapy was associated with significantly improved OS (HR: 0.62, CI: 0.54-0.70) compared with RT alone. In this comprehensive analysis, the addition of immunotherapy to chemotherapy or radiotherapy was associated with improved OS compared with chemotherapy or radiation therapy without immunotherapy in stage III NSCLC patients.

Association of facility type with overall survival in patients with nonsurgically managed pancreatic cancer.

Aim: To investigate the association between receiving treatment at academic centers and overall survival in pancreatic ductal adenocarcinoma patients who do not receive definitive surgery of the pancreatic tumor. Methods: Using the National Cancer Database, patients who were diagnosed with pancreatic ductal adenocarcinoma between 2004 to 2016 were identified. Results: Of 262,209 patients, 101,003 (38.5%) received treatment at academic centers. In the multivariable Cox regression analysis, patients who received treatment at a nonacademic facility had significantly worse overall survival compared with patients who were treated at an academic center (hazard ratio: 1.279; 95% CI: 1.268-1.290; p = 0.001). Conclusion: Compared with treatment at academic centers, treatment at nonacademic centers was associated with significantly worse overall survival in patients with nonsurgically managed pancreatic ductal adenocarcinoma.

The aim of this study is to examine the association between receiving treatment at academic hospitals and overall survival in patients diagnosed with pancreatic cancer who do not receive definitive surgery of the pancreatic tumor. The authors used the National Cancer Database to identify patients who were diagnosed with pancreatic cancer between 2004 and 2016. The authors' study included 262,209 patients. The authors found that patients who received treatment at nonacademic hospitals were on average 28% more likely to die of any cause compared with patients who were treated at academic centers (hazard ratio: 1.279; 95% CI: 1.268­1.290; p < 0.001). Patients who received treatment at nonacademic hospitals were more likely to die of any cause compared with patients who received treatment at academic hospitals.

The association of health insurance with the survival of cancer patients with brain metastases at diagnosis.

BACKGROUND: Synchronous brain metastases (SBMs) are a presentation of stage IV cancers with limited treatment options. This study examines the association between health insurance status and overall survival (OS) of patients with SBMs using the National Cancer Database (NCBD). METHODS: We queried the NCDB for patients with SBMs from 2010 to 2015. Included cases were from seven primary cancers. Patients were grouped based on their insurance status. We assessed the association of insurance with OS using a Cox proportional hazards model adjusted for age at diagnosis, sex, race, education level, income level, residential area, treatment facility type, Charlson-Deyo comorbidity status, year of diagnosis, primary tumor type, and receipt of chemotherapy, radiation therapy (RT), immunotherapy, and primary site surgery. RESULTS: Of 97,659 patients included, those who had Medicaid, Medicare, or without health insurance were less likely to receive brain RT, chemotherapy, and/or surgery of the primary cancer site compared to privately insured patients. In multivariable COX analysis, patients with Medicare (HR = 1.11, 95% CI: 1.09-1.14, P < 0.001), Medicaid (HR = 1.11, 95% CI: 1.09-1.13, P < 0.001), or no insurance (HR = 1.18, 95% CI: 1.14-1.22, P < 0.001) were associated with decreased OS compared to private insurance. CONCLUSION: After retrospective analysis, Medicaid, Medicare, and no insurance were all associated with worse OS compared to private insurance. Future studies can focus on determining the factors associated with insurance status and factors contributing to improved OS stratified by insurance status.

The impact of treatment facility type on the survival of brain metastases patients regardless of the primary cancer type.

BACKGROUND: Cancer patients with brain metastases (BMs) require multidisciplinary care, and treatment facility may play a role. This study aimed to investigate the impact of receiving treatment at academic centers on the overall survival (OS) of cancer patients with brain metastases (BMs) regardless of the primary cancer site. METHODS: This retrospective analysis of the National Cancer Database (NCDB) included patients diagnosed with non-small cell lung cancer, small-cell lung cancer, other types of lung cancer, breast cancer, melanoma, colorectal cancer, and kidney cancer and had brain metastases at the time of diagnosis. The data were extracted from the de-identified file of the NCDB, a joint program of the Commission on Cancer of the American College of Surgeons and the American Cancer Society. The Cox proportional hazard model adjusted for age at diagnosis, race, sex, place of living, income, education, primary tumor type, year of diagnosis, chemotherapy, radiation therapy (RT), and surgery of the primary cancer site was used to determine treatment facility-associated hazard ratios (HR) for survival. Overall survival was the primary outcome, which was analyzed with multivariable Cox proportional hazards regression modeling. RESULTS: A total of 93,633 patients were analyzed, among whom 31,579/93,633 (34.09%) were treated at academic centers. Based on the log-rank analysis, patients who received treatment at an academic facility had significantly improved OS (median OS: 6.18, CI: 6.05-6.31 vs. 4.57, CI: 4.50-4.63 months; p < 0.001) compared to patients who were treated at non-academic facilities. In the multivariable Cox regression analysis, receiving treatment at an academic facility was associated with significantly improved OS (HR: 0.85, CI: 0.84-0.87; p < 0.001) compared to non-academic facility. CONCLUSIONS: In this extensive analysis of the NCDB, receiving treatment at academic centers was associated with significantly improved OS compared to treatment at non-academic centers.

The impact of stereotactic body radiation therapy on the overall survival of patients diagnosed with early-stage non-small cell lung cancer.

BACKGROUND AND PURPOSE: Stereotactic Body Radiotherapy (SBRT) has emerged as a standard treatment for inoperable early-stage non-small cell lung cancer (NSCLC) with remarkable local control. However, it is not clear if this local control translates to overall survival (OS). The objective of this study is to investigate the impact of SBRT on the OS of early-stage NSCLC patients and examine if the extent of this impact changes with the era of diagnosis, T stage, age, and comorbidity status. MATERIALS AND METHODS: Using the National Cancer Database, we compared the OS of cT1-3 cN0 cM0 NSCLC patients with SBRT or observation. Multivariable analyses were adjusted for age, race, sex, income, education, place of living, hospital type, insurance status, comorbidity score, histology types, and diagnosis year. RESULTS: Among 50,819 patients, 27,027 (53.18%) received SBRT and 23,792 (46.82%) were observed. Multivariable Cox Proportional-Hazards analysis demonstrated SBRT was associated with an improved OS compared to observation (HR:0.56, p < 0.001). Subset multivariable Cox Proportional-Hazards analyses stratified by T stage, year of diagnosis, age, or Charlson Score revealed that HRs of SBRT vs. observation decrease from cT1 to cT3 (0.73-0.68), from 2004 to 2015 (0.65-0.51), from <50 to ≥80 years old (1.04-0.58) and from a Charlson Score 0 to 2 (0.69-0.58). CONCLUSION: SBRT was associated with improved OS compared to no treatment in early-stage NSCLC. The magnitude of the impact of SBRT on OS increases in patients with advanced age, higher T stages, higher comorbidity scores and more recent treatment eras.

The Association of the Sequence of Immunotherapy With the Survival of Unresectable Pancreatic Adenocarcinoma Patients: A Retrospective Analysis of the National Cancer Database.

Background: Immunotherapy has shown great success in various malignancies. However, its efficacy in pancreatic ductal adenocarcinoma (PDAC) remains a challenge, and the lack of understanding about the appropriate timing of immunotherapy with other standard-of-care cancer treatments may be one of the causes. The objective of the current study is to investigate the impact of the timing of immunotherapy with chemotherapy and radiation therapy (RT) on the overall survival (OS) of PDAC patients who did not receive surgical resection of the pancreatic tumor. Materials and Methods: Patients with pancreatic adenocarcinoma who did not receive surgical resection of the pancreatic tumor were identified from the National Cancer Database (NCDB). Cox proportional hazard models were employed to compare the OS between patients who received immunotherapy with chemotherapy or RT with a different sequence of treatment. The multivariable analysis was adjusted for age of diagnosis, race, sex, place of living, income, education, treatment facility type, insurance status, and year of diagnosis. Results: In total, 705 patients received chemotherapy and immunotherapy, while 226 received radiation therapy and immunotherapy. In the multivariable analysis, there was no significant difference in the OS of patients who started immunotherapy 31-90 days before the start of chemotherapy with a hazard ratio (HR) of [HR:1.057 (CI: 0.716-1.56; p < 0.781)] and patients who started immunotherapy 91-180 days before the start of chemotherapy [HR: 0.900 (CI: 0.584-1.388; p < 0.635)] compared to patients who started chemotherapy and immunotherapy within 30 days of each other. There was also no significant difference in the OS of patients who started RT> 30 days before the start of immunotherapy [HR: 0.636 (CI: 0.346-1.171; p < 0.146)] and patients who started immunotherapy > 30 days before the start of RT [HR: 0.660 (CI: 0.328-1.329; p < 0.246)] compared to patients who started RT and immunotherapy within 30 days of each other. Conclusion: The sequence of immunotherapy with chemotherapy or RT was not associated with improved OS. Future studies with a larger subgroup sample size investigating the impact of the timing of immunotherapy with chemotherapy and RT on the OS of PDAC patients who do not receive surgical resection of the pancreatic tumor are needed.

Association of Immunotherapy With Survival Among Patients With Brain Metastases Whose Cancer Was Managed With Definitive Surgery of the Primary Tumor.

Importance: Immunotherapy has shown significant control of intracranial metastases in patients with melanoma. However, the association of immunotherapy combined with other cancer treatments and overall survival (OS) of patients with brain metastases, regardless of primary tumor site, is unknown. Objective: To explore the association of immunotherapy with OS in patients with cancer and brain metastases who received definitive surgery of the primary site. Design, Setting, and Participants: This comparative effectiveness study included 3112 adult patients in the National Cancer Database from 2010 to 2016 with non-small cell lung cancer, breast cancer, melanoma, colorectal cancer, or kidney cancer and brain metastases at the time of diagnosis and who received definitive surgery of the primary site. Data analysis was conducted from March to April 2020. Exposures: Treatment groups were stratified as follows: (1) any treatment with or without immunotherapy, (2) chemotherapy with or without immunotherapy, (3) radiotherapy (RT) with or without immunotherapy, and (4) chemoradiation with or without immunotherapy. Main Outcomes and Measures: The association of immunotherapy with OS was assessed with Cox proportional hazards regression, adjusted for age at diagnosis, race, sex, place of living, income, education, treatment facility type, primary tumor type, and year of diagnosis. Results: Of 3112 patients, 1436 (46.14%) were men, 2714 (87.72%) were White individuals, 257 (8.31%) were Black individuals, and 123 (3.98%) belonged to other racial and ethnic groups. The median (range) age at diagnosis was 61 (19-90) years. Overall, 183 (5.88%) received immunotherapy, 318 (10.22%) received chemotherapy alone, 788 (25.32%) received RT alone, and 1393 (44.76%) received chemoradiation alone; 22 (6.47%) received chemotherapy plus immunotherapy, 72 (8.37%) received RT plus immunotherapy, and 76 (5.17%) received chemoradiation plus immunotherapy. In the multivariable analysis, patients who received immunotherapy had significantly improved OS compared with no immunotherapy (hazard ratio, 0.62; 95% CI, 0.51-0.76; P < .001). Treatment with RT plus immunotherapy was associated with significantly improved OS compared with RT alone (hazard ratio, 0.59; 95% CI, 0.42-0.84; P = .003). Chemotherapy plus immunotherapy or chemoradiation plus immunotherapy were not associated with improved OS in the multivariable analysis. Conclusions and Relevance: In this study, the addition of immunotherapy to RT was associated with improved OS compared with radiotherapy alone in patients with brain metastases who received definitive surgery of the primary tumor site.

The impact of immunotherapy on the survival of pancreatic adenocarcinoma patients who do not receive definitive surgery of the tumor.

BACKGROUND AND PURPOSE: Immunotherapy has shown great efficacy in many cancers, but its role in pancreatic ductal adenocarcinoma (PDAC) remains unclear. The objective of this study was to investigate the impact of immunotherapy on the overall survival of PDAC patients who did not receive definitive surgery of the pancreatic primary tumor site using the National Cancer Database (NCDB). MATERIALS AND METHODS: Patients with pancreatic adenocarcinoma who did not receive surgery were identified from NCDB. Cox proportional hazard models were employed to assess the impact of immunotherapy on survival after adjusting for age at diagnosis, race, sex, place of living, income, education, treatment facility type, insurance status, year of diagnosis, and treatment types such as chemotherapy and radiation therapy. RESULTS: Of 263,886 patients who were analyzed, 911 (0.35%) received immunotherapy. Among patients who received chemotherapy (101,546), and chemoradiation (30,226) therapy, 555/101,546 (0.55%) received chemotherapy plus immunotherapy, and 299/3,022 (9.9%) received chemoradiation plus immunotherapy. In a multivariable analysis adjusted for the factors mentioned above, immunotherapy was associated with significantly improved OS (HR: 0.866 (0.800-0.937); P < 0.001) compared to no immunotherapy. Chemotherapy plus immunotherapy was significantly associated with improved OS (HR: 0.848 (0.766-0.938); P < 0.001) compared to chemotherapy without immunotherapy. Further, chemoradiation plus immunotherapy was associated with significantly improved OS (HR: 0.813 (0.707-0.936); P < 0.001) compared to chemoradiation alone. CONCLUSION: In this study, the addition of immunotherapy to chemotherapy and chemoradiation therapy was associated with significantly improved OS in PDAC patients without definitive surgery. The study warrants future clinical trials of immunotherapy in PDAC.

The impact of immunotherapy on the survival of pancreatic adenocarcinoma patients who received definitive surgery of the pancreatic tumor: a retrospective analysis of the National Cancer Database.

BACKGROUND: Immunotherapy has paved the way for new therapeutic opportunities in cancer but has failed to show any efficacy in Pancreatic Adenocarcinoma (PDAC), and its therapeutic role remains unclear. The objective of this study is to examine the impact of immunotherapy in combination with chemotherapy, RT, and chemoradiation on the overall survival (OS) of PDAC patients who received definitive surgery of the tumor using the National Cancer Database (NCDB). METHODS: Patients with PDAC who received definitive surgery of the pancreatic tumor and were diagnosed between 2004 and 2016 from the NCDB were identified. Cox proportional hazard analysis was used to assess the survival difference between patients who received chemotherapy plus immunotherapy and chemoradiation therapy plus immunotherapy and their counterparts who only receive these treatments without immunotherapy. The multivariable analysis was adjusted for age of diagnosis, race, sex, place of living, income, education, treatment facility type, insurance status, year of diagnosis, and treatment types such as chemotherapy and radiation therapy. RESULTS: In total, 63,154 PDAC patients who received definitive surgery of the tumor were included in the analysis. Among the 63,154 patients, 636 (1.01%) received immunotherapy. Among patients who received chemotherapy (21,355), and chemoradiation (21,875), 157/21,355 (0.74%) received chemotherapy plus immunotherapy, and 451/21,875 (2.06%) received chemoradiation plus immunotherapy. Patients who received chemoradiation plus immunotherapy had significantly improved median OS compared to patients who only received chemoradiation with an absolute median OS benefit of 5.7 [29.31 vs. 23.66, p < 0.0001] months. In the multivariable analysis, patients who received immunotherapy had significantly improved OS compared to patients who did not receive immunotherapy (HR: 0.900; CI: 0.814-0.995; P < 0.039). Patients who received chemoradiation plus immunotherapy had significantly improved OS compared to their counterparts who only received chemoradiation without immunotherapy (HR: 0.852 CI: 0.757-0.958; P < 0.008). CONCLUSIONS: In this study, the addition of immunotherapy to chemoradiation therapy was associated with significantly improved OS in PDAC patients who received definitive surgery. The study warrants further future clinical trials of immunotherapy in PDAC.

The impact of neoadjuvant and adjuvant immunotherapy on the survival of pancreatic cancer patients: a retrospective analysis.

BACKGROUND: Immunotherapy has become an essential part of cancer treatment after showing great efficacy in various malignancies. However, its effectiveness in pancreatic ductal adenocarcinoma (PDAC), especially in resectable pancreatic cancer, has not been studied. The primary objective of this study is to compare the OS impact of immunotherapy between PDAC patients who receive neoadjuvant immunotherapy and patients who receive adjuvant immunotherapy. The secondary objective is to investigate the impact of neoadjuvant and adjuvant immunotherapy in combination with chemotherapy and chemoradiation by performing subset analyses of these two groups. METHODS: Patients diagnosed with PDAC between 2004 and 2016 were identified from the National Cancer Database (NCDB). Multivariable Cox proportional hazard analysis was performed to examine the effect of neoadjuvant and adjuvant immunotherapy in combination with chemotherapy and chemoradiation on the OS of the patients. The multivariable analysis was adjusted for essential factors such as the age at diagnosis, sex, race, education, income, place of living insurance status, hospital type, comorbidity score, and year of diagnosis. RESULTS: Overall, 526 patients received immunotherapy. Among whom, 408/526 (77.57%) received neoadjuvant immunotherapy, and the remaining 118/526 (22.43%) received adjuvant immunotherapy. There was no significant difference in OS between neoadjuvant and adjuvant immunotherapy (HR: 1.06, CI: 0.79-1.41; p < 0.714) in the multivariable analysis. In the univariate neoadjuvant treatment subset analysis, immunotherapy was associated with significantly improved OS compared to no immunotherapy (HR: 0.88, CI: 0.78-0.98; p < 0.026). This benefit disappeared in the multivariable analysis. However, after patients were stratified by educational level, the multivariable Cox regression analysis revealed that neoadjuvant immunotherapy was associated with significantly improved OS (HR: 0.86, CI: 0.74-0.99; p < 0.04) compared to no immunotherapy only in patients with high-level of education, but not in patients with low-level of education. CONCLUSION: In this study, no difference in the OS between patients who received neoadjuvant immunotherapy and patients who received adjuvant immunotherapy was noticed. Future studies comparing neoadjuvant adjuvant immunotherapy combined with chemotherapy, radiation therapy, and chemoradiation are needed.