Incident Diabetes among Older Asian, Native Hawaiian and Pacific Islander Women with Breast Cancer.

BACKGROUND: The risk of diabetes among Asian, Native Hawaiian and Pacific Islander (ANHPI) women after breast cancer is unclear. This study estimated the risk of incident type II diabetes in older ANHPI and older Non-Hispanic White (NHW) women with breast cancer from the US National Cancer Institute's Surveillance, Epidemiology and End Results (SEER) Medicare linked claims. METHODS: A matched cohort of 7,122 older ANHPI and 21,365 older NHW women with breast cancer were identified from the SEER-Medicare between 2000 and 2017. To assess the risk of incident type II diabetes after breast cancer, hazard ratios (HRs) and 95% confidence intervals (95%CI) were estimated using Cox proportional hazards model. RESULTS: During the mean 8 years of follow-up, 9.3% of older women with breast cancer developed incident type II diabetes. In comparison with NHW women, all older ANHPI women without known history of diabetes had an elevated risk of diabetes after breast cancer; with strong associations observed for Pacific Islander (HR = 3.09, 95%CI 1.43, 6.67), Vietnamese (HR = 2.12, 95%CI 1.33, 2.36), and Filipino (HR = 2.02, 95%CI 1.57, 2.59) women with breast cancer, adjusting for potential confounders. Among ANHPI women with breast cancer, more baseline comorbidities and obesity were risk factors for developing incident type II diabetes. CONCLUSION: ANHPI women diagnosed with breast cancer had an elevated risk of type II diabetes compared with older NHW women with breast cancer. Routine monitoring and management of diabetes are warranted in older ANHPI women with breast cancer.

Survival Outcomes of Limited-Stage Diffuse Large B-Cell Lymphoma Treated With Radiation Therapy.

BACKGROUND: Patients with favorable risk limited-stage (LS) diffuse large b-cell lymphoma (DLBCL) have shown excellent outcomes without radiotherapy (RT). However, the role of RT for the remainder of LS-DLBCL patients is less well defined. We aimed to investigate whether the addition of RT provided an overall survival (OS) benefit in a real-world cohort of LS-DLBCL patients based on primary site at presentation. MATERIALS AND METHODS: Retrospective data from 39,745 patients with stage I and II DLBCL treated with front-line combination chemotherapy alone or followed by RT were identified using the National Cancer Database from 2004 to 2015. RESULTS: The addition of RT was associated with improved 5-year OS for all LS patients as compared to those treated with chemotherapy alone (85% vs. 80%, P < .001). RT was associated with improved 5-year OS in both the nodal and extranodal disease patients (nodal: 85% vs. 80%, P < .001; extranodal: 83% vs. 79%; P < .001). Extranodal sites with prolonged OS from the addition of RT include skin and soft tissue, head and neck, testicular, and thyroid sites (all P < .02). Breast, bone, lung and gastrointestinal extranodal primary sites had no OS benefit from the inclusion of RT. In multivariate analysis, the addition of RT was an independent factor for improved survival for all LS patients ([HR] 0.84, 95% [CI] 0.81-0.88; P < .001). CONCLUSION: Though there is no consensus on optimal treatment indications for RT in LS-DLBCL, these data suggest certain subgroups may have benefit when RT is added to front-line chemotherapy.

Incident Cardiovascular Disease Risk among Older Asian, Native Hawaiian and Pacific Islander Breast Cancer Survivors.

BACKGROUND: Cardiotoxicity among breast cancer survivors is associated with chemotherapy and radiation therapy. The risk of cardiovascular disease (CVD) among Asian, Native Hawaiian and Pacific Islander (ANHPI) breast cancer survivors in the United States is unknown. METHODS: We used the SEER-Medicare linked database to estimate the risk of CVD among older breast cancer survivors. International Classification of Disease diagnosis codes were used to identify incident CVD outcomes. Cox proportional hazards models were used to estimate HRs and 95% confidence intervals (CI) comparing ANHPI with Non-Hispanic White (NHW) patients with breast cancer for CVD, and among ANHPI race and ethnicity groups. RESULTS: A total of 7,122 ANHPI breast cancer survivors and 21,365 NHW breast cancer survivors were identified. The risks of incident heart failure and ischemic heart disease were lower among ANHPI compared with NHW breast cancer survivors (HRheart failure, 0.72; 95% CI, 0.61-0.84; HRheart disease, 0.74; 95% CI, 0.63-0.88). Compared with Japanese patients with breast cancer, Filipino, Asian Indian and Pakistani, and Native Hawaiian breast cancer survivors had higher risks of heart failure. ischemic heart disease and death. Among ANHPI breast cancer survivors, risk factors for heart failure included older age, higher comorbidity score, distant cancer stage and chemotherapy. CONCLUSIONS: Our results support heterogeneity in CVD outcomes among breast cancer survivors among ANHPI race and ethnicity groups. Further research is needed to elucidate the disparities experienced among ANHPI breast cancer survivors. IMPACT: Filipino, Asian Indian and Pakistani, and Native Hawaiian patients with breast cancer had higher risks of heart failure, ischemic heart disease and death among ANHPI patients with breast cancer.

A systematic review and meta-analysis of pathologic complete response rates for patients with cholangiocarcinoma treated on liver transplant protocols.

BACKGROUND AND OBJECTIVES: Many heterogenous orthotopic liver transplant (OLT) protocols exist for patients with unresectable cholangiocarcinoma. Little is known about the incidence, predictors for, and the significance of achieving a pathologic complete response (pCR). METHODS: We performed a systematic review through September 2022 of the PubMed, Embase, and Web of Science databases. A random-effect meta-analysis was conducted to pool data across studies with reported pCR rates. Heterogeneity between treatment protocols was assessed via subgroup analysis. The pCR and 1-, 3-, and 5-year recurrence-free survival (RFS) and overall survival (OS) rates were extracted as outcomes of interest. RESULTS: A total of 15 studies reported pCR rates and were grouped by use of the Mayo protocol (4/15), stereotactic body radiation therapy (2/15), and an Other category (9/15). The pooled pCR rate among all studies was 32%. Both radiation technique and duration of CHT showed no significant association with pCR (p = 0.05 and 0.13, respectively). Pooled 1-year RFS and OS after any neoadjuvant therapy and OLT was 80% (95% confidence interval [CI], 0.61-0.91), and 91% (95% CI, 0.87-0.94), respectively. There was no 1-year OS difference detected among the three groups. pCR was not associated with OS in the meta-regression. Pooled 3- and 5-year OS among all studies was 72% and 61%, respectively. CONCLUSIONS: The pooled incidence of pCR was 32%. Differences in radiation technique did not appear to influence pCR rates and upon meta-regression, pCR was not a surrogate marker for survival.

Neoadjuvant Therapy Regimens for Hilar Cholangiocarcinoma Before Liver Transplant.

OBJECTIVES: Patients with unresectable hilar cholangiocarcinoma (hCCA) may be eligible for curative treatment through liver transplantation (LT). Neoadjuvant protocols often include radiotherapy (RT), however, there is no standard RT approach. The purpose of this study is to characterize practice patterns of RT use before transplantation for hCCA. METHODS: A survey was administered to radiation oncologists practicing at LT centers identified through the U.S. Organ Procurement and Transplant Network and the International Cholangiocarcinoma Research Network. The survey consisted of 13 questions regarding RT details as well as approaches to systemic therapy. For cross-regimen comparison, the cumulative RT tumor dose was standardized using the EQD2 method. RESULTS: Twenty-three centers utilizing neoadjuvant therapy for hCCA were identified. Most respondents (96%) use both chemotherapy and RT as part of their protocol. Elective nodal volumes commonly included the portal vein lymph nodes (91%) and celiac artery lymph nodes (70%). After an initial 45 Gy plan, a wide range of sequential boost regimens was used. The median cumulative dose including boosts to the gross disease was 58 Gy (EQD2) with a wide range of 40 to 110 Gy. Five (22%) include brachytherapy as part of their treatment plan. The majority (96%) used concurrent chemotherapy with fluoropyrimidines. CONCLUSIONS: These results suggest significant variability of neoadjuvant RT use for hCCA before LT. A wide range of doses and fractionation schemes are utilized with cumulative doses ranging from 40 to 110 Gy (EQD2). A further study evaluating the efficacy and toxicity of these various approaches is warranted to better inform best practices.

Secondary malignancies in non-Hodgkin lymphoma survivors: 40 years of follow-up assessed by treatment modality.

BACKGROUND: Survivors of non-Hodgkin lymphoma (NHL) have increased secondary malignancy (SM) risk. We quantified this risk by patient and treatment factors. METHODS: Standardized incidence ratios (SIR, observed-to-expected [O/E] ratio) were assessed in 142,637 NHL patients diagnosed from 1975 to 2016 in the National Cancer Institute's Surveillance, Epidemiology, and End Results Program. Comparisons were made between subgroups in terms of their SIRs relative to respective endemic populations. RESULTS: In total, 15,979 patients developed SM, more than the endemic rate (O/E 1.29; p < 0.05). Compared with white patients, relative to respective endemic populations, ethnic minorities had a higher risk of SM (white O/E 1.27, 95% CI 1.25-1.29; black O/E 1.40, 95% CI 1.31-1.48; other O/E 1.59, 95% CI 1.49-1.70). Relative to respective endemic populations, patients who received radiotherapy had similar SM rates to those who did not (O/E 1.29 each), but irradiated patients had increased breast cancer (p < 0.05). Patients who received chemotherapy had higher SM rates than those who did not (O/E 1.33 vs. 1.24, p < 0.05) including more leukemia, Kaposi sarcoma, kidney, pancreas, rectal, head and neck, and colon cancers (p < 0.05). CONCLUSIONS: This is the largest study to examine SM risk in NHL patients with the longest follow-up. Treatment with radiotherapy did not increase overall SM risk, while chemotherapy was associated with a higher overall risk. However, certain subsites were associated with a higher risk of SM, and they varied by treatment, age group, race and time since treatment. These findings are helpful for informing screening and long-term follow-up in NHL survivors.

The Implications of Treatment Delays in Adjuvant Therapy for Resected Cholangiocarcinoma Patients.

PURPOSE: The purpose of this study is to understand factors associated with timing of adjuvant therapy for cholangiocarcinoma and the impact of delays on overall survival (OS). METHODS: Data from the National Cancer Database (NCDB) for patients with non-metastatic bile duct cancer from 2004 to 2015 were analyzed. Patients were included only if they underwent surgery and adjuvant chemotherapy and/or radiotherapy (RT). Patients who underwent neoadjuvant or palliative treatments were excluded. Pearson's chi-squared test and multivariate logistic regression analyses were used to assess the distribution of demographic, clinical, and treatment factors. After propensity score matching with inverse probability of treatment weighting, OS was compared between patients initiating therapy past various time points using Kaplan Meier analyses and doubly robust estimation with multivariate Cox proportional hazards modeling. RESULTS: In total, 7,733 of 17,363 (45%) patients underwent adjuvant treatment. The median time to adjuvant therapy initiation was 59 days (interquartile range 45-78 days). Age over 65, black and Hispanic race, and treatment with RT alone were associated with later initiation of adjuvant treatment. Patients with larger tumors and high-grade disease were more likely to initiate treatment early. After propensity score weighting, there was an OS decrement to initiation of treatment beyond the median of 59 days after surgery. CONCLUSIONS: We identified characteristics that are related to the timing of adjuvant therapy in patients with biliary cancers. There was an OS decrement associated with delays beyond the median time point of 59 days. This finding may be especially relevant given the treatment delays seen as a result of COVID-19.

Evaluating patterns of care for early-stage low-grade follicular lymphoma in the rituximab era.

Radiotherapy (RT) utilization for early-stage, low-grade follicular lymphoma (FL) is low despite treatment guideline recommendations. We compare treatment trends for early-stage FL in the era of involved-site RT and rituximab. We identified 11,645 patients in the National Cancer Database (NCDB) with stage I-II, grade 1-2 nodal or extranodal FL diagnosed 2011-2017, with median follow-up of 44 months. From 2011 to 2017, RT utilization rates decreased from 33.4% to 22.4%, observation decreased from 65.3% to 49.7%, chemoimmunotherapy increased from 0.5% to 15.0%, immuno-monotherapy increased from 0.6% to 10.2%, and RT + systemic therapy increased from 0.6% to 2.5%. RT utilization remains low in the involved-site RT and rituximab era.

Second Primary Malignancies in Diffuse Large B-cell Lymphoma Survivors with 40 Years of Follow Up: Influence of Chemotherapy and Radiation Therapy.

Purpose: Previous studies have shown an increased risk of second primary malignancies (SPMs) in survivors of diffuse large B-cell lymphoma (DLBCL). Survivors live longer due to the intensification of and improvements in therapy; thus, we aimed to characterize SPM patterns in patients with DLBCL by treatment modality. Methods and Materials: Standardized incidence ratio and absolute excess risk of SPMs were assessed in patients with primary DLBCL from 1975 to 2016 in the National Cancer Institute's Surveillance, Epidemiology, and End Results Program. A subgroup analyses based on, sex, race, age at the time of diagnosis, latency, and treatment modality were performed. Propensity score-adjusted cumulative incidence curves were generated, stratified by treatment and accounting for death as a competing risk. Results: In total, 45,946 patients with DLBCL were identified with a mean follow up of 70 months. Overall, 9.2% of patients developed an SPM with a standardized incidence ratio of 1.23 (95% confidence interval, 1.20-1.27). There was no difference in SPM risk between men and women or Black and White patients. Patients age <25 years were particularly susceptible to the development of SPMs, with a risk 2.5 times greater than patients aged 50 to 74 years. Temporal patterns showed increasing risk of solid malignancies and decreasing risk of hematologic malignancies over time, with bladder cancer posing the greatest absolute excess risk of any cancer type after 15 years. Patients treated with radiation therapy (RT), chemotherapy (CT), and chemoradiation therapy (CRT) all had an increased risk of SPM development compared with the general population. The cumulative incidence of SPMs was the lowest in patients treated with RT and the highest when treated with CRT. In the modern treatment era, the cumulative incidence of SPM for patients treated with CT versus CRT was not significantly different. Conclusions: In this large population-based study, we demonstrate unique SPM risk patterns based on age, latency, and treatment modality that have important implications for the treatment and screening of patients diagnosed with DLBCL.

Mental health disorders are more common in patients with Hodgkin lymphoma and may negatively impact overall survival.

BACKGROUND: Long-term mental health outcomes were characterized in patients who were diagnosed with Hodgkin lymphoma (HL), and risk factors for the development of mental health disorders were identified. METHODS: Patients who were diagnosed with HL between 1997 and 2014 were identified in the Utah Cancer Registry. Each patient was matched with up to five individuals from a general population cohort identified within the Utah Population Database, a unique source of linked records that includes patient and demographic data. RESULTS: In total, 795 patients who had HL were matched with 3575 individuals from the general population. Compared with the general population, patients who had HL had a higher risk of any mental health diagnosis (hazard ratio, 1.77; 95% confidence interval, 1.57-2.00). Patients with HL had higher risks of anxiety, depression, substance-related disorders, and suicide and intentional self-inflicted injuries compared with the general population. The main risk factor associated with an increased risk of being diagnosed with mental health disorders was undergoing hematopoietic stem cell transplantation, with a hazard ratio of 2.06 (95% confidence interval, 1.53-2.76). The diagnosis of any mental health disorder among patients with HL was associated with a detrimental impact on overall survival; the 10-year overall survival rate was 70% in patients who had a mental health diagnosis compared with 86% in those patients without a mental health diagnosis (p < .0001). CONCLUSIONS: Patients who had HL had an increased risk of various mental health disorders compared with a matched general population. The current data illustrate the importance of attention to mental health in HL survivorship, particularly for patients who undergo therapy with hematopoietic stem cell transplantation.

Patterns of care and outcomes of early stage I-II Hodgkin lymphoma treated with or without radiation therapy.

Omission of radiotherapy in the upfront management of early-stage classic Hodgkin lymphoma (cHL) has become more common with time. We report patterns of care and outcomes of stage I-II cHL treated with chemotherapy (CT) only versus CT and radiotherapy (combined modality therapy, CMT). From the National Cancer Database, we identified 28,327 early-stage cHL patients treated with CT (n = 15,798) or CMT (n = 12,529) from 2004 to 2018. CMT utilization declined over the period from 58% to 34%. With median follow-up of 6.2 years, the 5- and 10-year overall survival for CT versus CMT was 93.3% versus 96.9% (p < 0.001) and 88.7% versus 93.5% (p < 0.001), respectively. On multivariable analysis, uninsured (OR 0.75, p < 0.001) and Black patients (OR 0.86, p = 0.02) were less likely to receive CMT, and treatment with CT was predictive of death (OR 2.0, p < 0.001). This report highlights real-world outcomes in early-stage cHL, with worse survival with CT and notable disparities in CMT utilization.

Improved overall survival over time in advanced stage mycosis fungoides: a cross-sectional study.

Mycosis Fungoides (MF) is a rare T-cell lymphoma and evidence on treatment practices, and outcomes are limited. We evaluated changes in practice patterns and corresponding effects on overall survival (OS) in MF using a cross-sectional study of patients diagnosed with MF from 2004 to 2016 in the National Cancer Database. Outcomes evaluated included patterns of care and OS across treatment eras. We found factors associated with chemotherapy use included male gender, treatment from 2004 to 2010 and stage III-IV disease. Factors associated with radiotherapy receipt included stage I-II disease, nonacademic treatment centers, male gender, non-black race, and Medicare status. Immunotherapy use was associated with treatment from 2004 to 2010 and stage III-IV disease. After propensity score matching, there was no OS difference among patients with stage I-II disease between 2004-2010 and 2011-2016. However, amongst patients with stage III-IV disease, OS was significantly improved in those treated from 2011 to 2016.

Feasibility and Clinical Utility of a Workflow Interfacing Radiation Oncology Lung Stereotactic Body Radiation Therapy Treatment Planning and Diagnostic Radiology.

Stereotactic body radiation therapy (SBRT) is commonly used to treat early-stage non-small cell lung cancer. Beam arrangements for SBRT include multiple entry and exit pathways resulting in irregular low-dose distributions within normal lung parenchyma. An improved understanding of posttreatment radiographic changes may improve the ability to predict clinical complications including radiation pneumonitis as well as assist in early detection of local failures. Radiation treatment planning is conducted using software systems separate from diagnostic radiology, often not accessible to the diagnostic radiologist. We developed a workflow for interfacing radiation dose information from lung SBRT treatments with a diagnostic radiology picture archiving and communication system (PACS). In an anonymized PACS study folder, SBRT dose maps depicting high-dose, low-dose, and nonirradiated lung volumes were viewable side by side with pretreatment and follow-up diagnostic computed tomography scans. Clinical utility was evaluated by 2 thoracic diagnostic radiologists reviewing posttreatment diagnostic follow-up scans in the PACS both with and without radiation dose maps available. The addition of the biologically effective dose map did not significantly change identification rates of radiation induced lung injury) (92% vs 95%; P = .32) but did significantly decrease radiologic suspicion for local recurrence (22% vs 8%; P = .003). The addition of biologically effective dose maps significantly increased confidence in identifying radiation induced lung injury (7.75 vs 8.82; P = .004) and local recurrence (5.5 vs 6.6; P = .005). The recommendation for additional workup was not significantly different (10% vs 7%; P = .41). We demonstrated the feasibility and clinical utility of a workflow generating simplified radiation dose maps that are viewable within a PACS for diagnostic radiology review.

NCCN Guidelines® Insights: Hodgkin Lymphoma, Version 2.2022.

Hodgkin lymphoma (HL) is an uncommon malignancy of B-cell origin. Classical HL (cHL) and nodular lymphocyte-predominant HL are the 2 main types of HL. The cure rates for HL have increased so markedly with the advent of modern treatment options that overriding treatment considerations often relate to long-term toxicity. These NCCN Guidelines Insights discuss the recent updates to the NCCN Guidelines for HL focusing on (1) radiation therapy dose constraints in the management of patients with HL, and (2) the management of advanced-stage and relapsed or refractory cHL.

Near Complete Response to Trametinib Treatment in Histiocytic Sarcoma Harboring a Somatic KRAS Mutation.

Survival outcomes of patients with histiocytic neoplasms are poor, with no standard-of-care treatments available for these malignancies. Recent characterization of the genomic landscape of various histiocytic neoplasms have shown a predominance of activating driver mutations within the MAPK/ERK pathway (ie, BRAF, MEK, KRAS, MAPK, and NRAS). Subsequently, successful treatment of these malignancies with BRAF and MEK inhibitors has been reported. This report presents the first patient with histiocytic sarcoma harboring a somatic KRAS Q61H mutation who was subsequently treated to a near complete response with the MEK inhibitor trametinib. Due to patient preference, lack of standard of care treatments, and associated morbidity from head and neck dissection, initial disease reduction provided by trametinib therapy allowed for a less morbid resection. This case report highlights the utility of up-front next-generation sequencing and the efficacy of MEK inhibition in patients with histiocytic sarcoma harboring activating KRAS mutations.

Screening and verification of potential gene targets in esophageal carcinoma by bioinformatics analysis and immunohistochemistry.

Background: To evaluate the potential of candidate proteins as diagnostic markers or drug targets in esophageal carcinoma (ESCA). Methods: GSE20347, GSE17351, and GSE45670 were downloaded from Gene Expression Omnibus (GEO). Differently expressed genes (DEGs) between ESCA and normal esophageal tissues from patients were obtained. Gene Ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were performed. The genes commonly featured in ESCA were screened by least absolute shrinkage and selection operator (LASSO) logistic regression and Boruta feature selection algorithm. The transcriptome data and corresponding clinical data of ESCA were downloaded from The Cancer Genome Atlas (TCGA) public database. Kaplan-Meier survival analysis was used to explore the core genes related to the prognosis of patients. A protein-protein interaction (PPI) network was generated by GeneMANIA to visualize the functional network between genes. Expressions of CRIP2, FOS, and HOXA10 genes in ESCA cells were verified by immunohistochemistry (IHC). Results: Out of 11,207 genes, 430 DEGs were identified, including 210 up-regulated genes and 220 down-regulated genes. After taking the intersection of LASSO regression and Boruta algorithm, 15 core genes were identified. Survival analyses demonstrated that low expression of CRIP2 (P=2.643e-02), as well as high expression of FOS (P=4.837e-02) and HOXA10 (P=4.97e-02), was significantly associated with the worse prognosis of ESCA patients. The 3 genes were strongly correlated with the content of immune cells and the stage of tumors. The expression of CRIP2 was correlated with the sensitivity of patients to dasatinib; FOS expression was correlated with the sensitivity of patients to erlotinib, and HOXA10 expression affected the sensitivity of patients to cisplatin, dasatinib, erlotinib, and gefitinib. The cBioportal database showed that 56 patients (31%) had the above core gene mutations: CRIP2 (8%), FOS (10%), and HOXA10 (17%). The IHC showed that there were differences in the expressions of these core genes between ESCA patients and the normal population (P<0.05), with ESCA patients showing higher expression. Conclusions: The low CRIP2 expression and high expressions of FOS and HOXA10 are associated with more advanced tumor stage, which may have the potential to be novel biomarkers for treatment selection in ESCA.

Factors associated with the refusal of surgery and the associated impact on survival in patients with rectal cancer using the National Cancer Database.

BACKGROUND: Surgical resection is an integral component of the curative-intent treatment for most patients with non-metastatic rectal cancer. However, some patients refuse surgery for a number of reasons. Utilizing the National Cancer Database (NCDB), we investigated the sociodemographic and clinical factors associated with patients who were coded as having been offered but refused surgery, and the factors affecting overall survival (OS) in these patients. METHODS: Adult patients with adenocarcinoma of the rectum (excluding T1N0M0 and M1 disease) diagnosed from 2004 to 2015 were analyzed in this retrospective cohort study. Logistic regression was performed to identify factors associated with refusal of surgery. OS of patients refusing surgery was compared using Kaplan-Meier estimate, log-rank test, propensity score matching, and proportional hazards regression. RESULTS: A total of 55,704 patients were identified: 54,266 received definitive surgery (97.4%) and 1,438 refused (2.6%). Of patients refusing surgery, 135 (9.4%) were stage I, 709 (49.3%) were stage II, and 594 (41.3%) were stage III. Patients were more likely to refuse surgery as the study period progressed (P<0.01). Factors associated with refusal of surgery on multivariate analysis include: age ≥70 years, Black race, non-private insurance, and tumor size greater than 2 cm (all values P≤0.01). The 5-year OS was 61.6% for the surgery cohort and 35.7% for the refusal cohort. In the propensity matched groups, median survival was 84.2 months in patients who received definitive surgery compared to 43.7 months in patients who refused surgery. As an index for comparison, patients who refused surgery but received both radiotherapy and chemotherapy had a median survival of 48.5 months. Among patients that refused surgery, those that received radiotherapy alone, chemotherapy alone, or radiotherapy and chemotherapy (compared to no treatment) experienced a survival benefit (all values P≤0.01). CONCLUSIONS: In patients with non-metastatic adenocarcinoma of the rectum reported in the NCDB, age, race, and insurance status were associated with refusal of surgery. Refusal of surgery was more common in the later years of the study. Survival is poor in patients who refused surgical resection.

Radiation-Associated Lymphopenia and Outcomes of Patients with Unresectable Hepatocellular Carcinoma Treated with Radiotherapy.

BACKGROUND: The immune system plays a crucial role in cancer surveillance. Previous studies have shown that lymphopenia associated with radiotherapy (RT) portends a poor prognosis. We sought to differentiate the effects of proton and photon RT on changes in absolute lymphocyte count (ALC) for patients with hepatocellular carcinoma (HCC). PATIENTS AND METHODS: Patients with HCC treated with definitive RT from 2006 to 2016 were studied. Serial ALCs were graded according to CTCAE v4.0. Overall survival (OS), disease-free survival, and distant metastasis-free survival were analyzed using the Kaplan-Meier method. Univariable and multivariable Cox-proportional hazards analyses were used to identify predictors of OS. A cohort analysis matched for treatment volume was performed to investigate differences in ALC dynamics between photon and proton therapy. RESULTS: Of 143 patients identified, the median age was 66 (range, 19-90) years. The treatment modality was photon in 103 (72%) and proton in 40 (28%). Median follow-up was 17 months (95% confidence interval, 13-25 months). The median time to ALC nadir after initiation of RT was 17 days with a median relative decrease of 67%. Those who received proton RT had a higher median ALC nadir (0.41 vs 0.32 k/µL, p=0.002) and longer median OS (33 vs 13 months, p=0.002) than those who received photon RT. Matched cohort analyses revealed a larger low-dose liver volume in the photon group, which correlated with lower ALC. On multivariable Cox analysis, Grade 3 or higher lymphopenia prior to or after RT, portal venous tumor thrombus, larger planning target volumes, Child-Pugh (CP) Class B, and increased CP score after RT were associated with a higher risk of death, whereas the use of proton therapy was associated with lower risk. CONCLUSION: Grade 3 or higher lymphopenia may be associated with poorer outcomes in patients receiving RT for HCC. Protons may mitigate lymphopenia compared with photons, potentially due to reduced dose exposure of sites of lymphopoiesis.