ABSTRACT
BACKGROUND: National cancer registries are valuable tools to analyze patterns of care and clinical outcomes; yet, missing data may impact the accuracy and generalizability of these data. We sought to evaluate the association between missing data and overall survival (OS). METHODS: Using the NCDB (National Cancer Database) and SEER (Surveillance, Epidemiology, End Results Program), we assessed data missingness among patients diagnosed with invasive breast cancer from 2010 to 2014. Key variables included demographic (age, race, ethnicity, insurance, education, income), tumor (grade, ER, PR, HER2, TNM stages), and treatment (surgery in both databases; chemotherapy and radiation in NCDB). OS was compared between those with and without missing data using Cox proportional hazards models. RESULTS: Overall, 775,996 patients in the NCDB and 263,016 in SEER were identified; missing at least 1 key variable occurred for 29% and 13%, respectively. Of those, the overwhelming majority (NCDB 80%; SEER 88%) were missing tumor variables. When compared to patients with complete data, missingness was associated with a greater risk of death: NCDB HR 1.23 (99% CI 1.21-1.25) and SEER HR 2.11 (99% CI 2.05-2.18). Patients with complete tumor data had higher unadjusted OS estimates than that of the entire sample: NCDB 82.7% vs 81.8% and SEER 83.5% vs 81.7% for 5-year OS. CONCLUSIONS: Missingness of select variables is not uncommon within large national cancer registries and is associated with a worse OS. Exclusion of patients with missing variables may introduce unintended bias into analyses and result in findings that underestimate breast cancer mortality.
Subject(s)
Breast Neoplasms , Humans , Female , Breast Neoplasms/epidemiology , Breast Neoplasms/therapy , SEER Program , Registries , Ethnicity , Proportional Hazards ModelsABSTRACT
Background Guidelines recommend annual surveillance imaging after diagnosis of ductal carcinoma in situ (DCIS). Guideline adherence has not been characterized in a contemporary cohort. Purpose To identify uptake and determinants of surveillance imaging in women who underwent treatment for DCIS. Materials and Methods A stratified random sample of women who underwent breast-conserving surgery for primary DCIS between 2008 and 2014 was retrospectively selected from 1330 facilities in the United States. Imaging examinations were recorded from date of diagnosis until first distant recurrence, death, loss to follow-up, or end of study (November 2018). Imaging after treatment was categorized into 10 12-month periods starting 6 months after diagnosis. Primary outcome was per-period receipt of asymptomatic surveillance imaging (mammography, MRI, or US). Secondary outcome was diagnosis of ipsilateral invasive breast cancer. Multivariable logistic regression with repeated measures and generalized estimating equations was used to model receipt of imaging. Rates of diagnosis with ipsilateral invasive breast cancer were compared between women who did and those who did not undergo imaging in the 6-18-month period after diagnosis using inverse probability-weighted Kaplan-Meier estimators. Results A total of 12 559 women (median age, 60 years; IQR, 52-69 years) were evaluated. Uptake of surveillance imaging was 75% in the first period and decreased over time (P < .001). Across the first 5 years after treatment, 52% of women participated in consistent annual surveillance. Surveillance was lower in Black (adjusted odds ratio [OR], 0.80; 95% CI: 0.74, 0.88; P < .001) and Hispanic (OR, 0.82; 95% CI: 0.72, 0.94; P = .004) women than in White women. Women who underwent surveillance in the first period had a higher 6-year rate of diagnosis of invasive cancer (1.6%; 95% CI: 1.3, 1.9) than those who did not (1.1%; 95% CI: 0.7, 1.4; difference: 0.5%; 95% CI: 0.1, 1.0; P = .03). Conclusion Half of women did not consistently adhere to imaging surveillance guidelines across the first 5 years after treatment, with racial disparities in adherence rates. © RSNA, 2023 Supplemental material is available for this article. See also the editorial by Rahbar and Dontchos in this issue.
Subject(s)
Breast Neoplasms , Carcinoma, Ductal, Breast , Carcinoma, Intraductal, Noninfiltrating , Female , Humans , United States , Middle Aged , Carcinoma, Intraductal, Noninfiltrating/pathology , Retrospective Studies , Breast Neoplasms/pathology , Mammography/methods , Mastectomy, Segmental , Carcinoma, Ductal, Breast/surgeryABSTRACT
LESSONS LEARNED: Antitumor activity was observed in the study population. Dose modifications of cabozantinib improve long-term tolerability. Biomarkers are needed to identify patient populations most likely to benefit. Further study of cabozantinib with or without panitumumab in patients with metastatic colorectal cancer is warranted. BACKGROUND: The epidermal growth factor receptor (EGFR) antibody panitumumab is active in patients with RAS wild-type (WT) metastatic colorectal cancer (mCRC), but nearly all patients experience resistance. MET amplification is a driver of panitumumab resistance. Cabozantinib is an inhibitor of multiple kinases, including vascular endothelial growth factor receptor 2 (VEGFR2) and c-MET, and may delay or reverse anti-EGFR resistance. METHODS: In this phase Ib clinical trial, we established the maximum tolerated dose (MTD) and recommended phase II dose (RP2D) of cabozantinib and panitumumab. We then treated an expansion cohort to further describe the tolerability and clinical activity of the RP2D. Eligibility included patients with KRAS WT mCRC (later amended to include only RAS WT mCRC) who had received prior treatment with a fluoropyrimidine, oxaliplatin, irinotecan, and bevacizumab. RESULTS: Twenty-five patients were enrolled and treated. The MTD/RP2D was cabozantinib 60 mg p.o. daily and panitumumab 6 mg/kg I.V. every 2 weeks. The objective response rate (ORR) was 16%. Median progression free survival (PFS) was 3.7 months (90% confidence interval [CI], 2.3-7.1). Median overall survival (OS) was 12.1 months (90% CI, 7.5-14.3). Five patients (20%) discontinued treatment due to toxicity, and 18 patients (72%) required a dose reduction of cabozantinib. CONCLUSION: The combination of cabozantinib and panitumumab has activity. Dose reductions of cabozantinib improve tolerability.
Subject(s)
Colorectal Neoplasms , Vascular Endothelial Growth Factor A , Anilides , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Colorectal Neoplasms/drug therapy , Colorectal Neoplasms/genetics , Humans , Panitumumab/pharmacology , Panitumumab/therapeutic use , Proto-Oncogene Proteins p21(ras) , PyridinesABSTRACT
BACKGROUND: Although the management of localized anal canal squamous cell carcinomas is well established, the role of pelvic chemoradiation (CRT) in the treatment of patients presenting with synchronous metastatic (stage IV) disease is poorly defined. This study used a national cancer database to compare the overall survival (OS) rates of patients with synchronous metastatic disease receiving CRT to the pelvis and patients treated with chemotherapy (CT) alone. METHODS: This study included adult patients with anal canal squamous cell carcinomas presenting with synchronous metastases diagnosed from 2004 to 2012. Multiple imputation and 2:1 propensity score matching were used to create a matched data set for testing. The proportional hazards model was used to estimate the hazard ratio (HR) for the effect of the treatment group on OS. With only patients in the matched data set, the OS of the treatment groups was estimated with the Kaplan-Meier method by treatment group. RESULTS: This study started with an unmatched data set of 978 patients, and 582 patients were selected for the matched data set: 388 in the CRT group and 194 in the CT-alone group. The HR for the group effect was 0.75 (95% confidence interval [CI], 0.61-0.92; P = .006). The median OS was 21.1 months in the CRT group (95% CI, 17.4-24.0 months) and 14.6 months in the CT group (95% CI, 12.2-18.4 months). The corresponding 5-year OS rates were 23% (95% CI, 18%-28%) and 14% (95% CI, 7%-21%), respectively. CONCLUSIONS: In this large series analyzing OS in patients with stage IV anal cancer, CRT was associated with improved OS in comparison with CT alone. Because of the lack of prospective data in this setting, this evidence will help to guide treatment approaches in this group of patients.
Subject(s)
Anus Neoplasms/therapy , Carcinoma, Squamous Cell/therapy , Chemoradiotherapy/mortality , Pelvic Neoplasms/therapy , Adult , Aged , Aged, 80 and over , Anus Neoplasms/pathology , Carcinoma, Squamous Cell/pathology , Cohort Studies , Female , Follow-Up Studies , Humans , Lymphatic Metastasis , Male , Middle Aged , Pelvic Neoplasms/secondary , Prognosis , Survival Rate , Young AdultABSTRACT
BACKGROUND: Cancer treatment costs are not routinely addressed in shared decisions for breast cancer surgery. Thus, we sought to characterize cost awareness and communication among surgeons treating breast cancer. METHODS: We conducted a self-administered, confidential electronic survey among members of the American Society of Breast Surgeons from 1 July to 15 September 2018. Questions were based on previously published or validated survey items, and assessed surgeon demographics, cost sensitivity, and communication. Descriptive summaries and cross-tabulations with Chi-square statistics were used, with exact tests where warranted, to assess findings. RESULTS: Of those surveyed (N = 2293), 598 (25%) responded. Surgeons reported that 'risk of recurrence' (70%), 'appearance of the breast' (50%), and 'risks of surgery' (47%) were the most influential on patients' decisions for breast cancer surgery; 6% cited out-of-pocket costs as significant. Over half (53%) of the surgeons agreed that doctors should consider patient costs when choosing cancer treatment, yet the majority of surgeons (58%) reported 'infrequently' (43%) or 'never' (15%) considering patient costs in medical recommendations. The overwhelming majority (87%) of surgeons believed that patients should have access to the costs of their treatment before making medical decisions. Surgeons treating a higher percentage of Medicaid or uninsured patients were more likely to consistently consider costs (p < 0.001). Participants reported that insufficient knowledge or resources (61%), a perceived inability to help with costs (24%), and inadequate time (22%) impeded cost discussions. Notably, 20% of participants believed that discussing costs might impact the quality of care patients receive. CONCLUSIONS: Cost transparency remains rare, however in shared decisions for breast cancer surgery, improved cost awareness by surgeons has the potential to reduce financial hardship.
Subject(s)
Breast Neoplasms/economics , Communication , Cost of Illness , Drug Costs/statistics & numerical data , Health Care Costs/statistics & numerical data , Surgeons/psychology , Breast Neoplasms/therapy , Female , Humans , Male , Middle Aged , Societies, Medical , Surgeons/statistics & numerical dataABSTRACT
BACKGROUND: Patients with chemotherapy refractory metastatic colorectal cancer (CRC) have a poor prognosis and limited therapeutic options. In this phase Ib/II clinical trial, we established the maximum tolerated dose (MTD) and recommended phase II dose (RPTD) for the combination of capecitabine and ziv-aflibercept, and then we evaluated the efficacy of the combination in patients with chemotherapy refractory metastatic CRC. METHODS: All patients were required to have a Karnofsky Performance Status > 70% and adequate organ function. The phase Ib dose escalation cohort included patients with advanced solid tumors who had progressed on all standard therapies. Using a standard 3 + 3 design, we identified the MTD and RPTD for the combination. Fifty patients with metastatic CRC who had progressed on or were intolerant of a fluoropyrimidine, oxaliplatin, irinotecan, and bevacizumab were then enrolled in a single-arm phase II expansion cohort, and were treated at the RPTD. Prior EGFR antibody therapy was required for subjects with RAS wildtype tumors. The primary endpoint for the expansion cohort was progression-free survival (PFS) at two months. Secondary endpoints included objective response rate (ORR) and overall survival (OS). RESULTS: A total of 63 patients were enrolled and evaluable for toxicity (13 dose escalation; 50 expansion). The MTD and RPTD were: capecitabine 850 mg/m2, P.O. bid, days 1-14, and ziv-aflibercept 6 mg/kg I.V., day 1, of each 21-day cycle. In the expansion cohort, 72% of patients were progression-free at two months (95% confidence interval [CI], 60-84%). Median PFS and OS were 3.9 months (95% CI, 2.3-4.5) and 7.1 months (95% CI: 5.8-10.0), respectively. Among all patients evaluable for toxicity, the most common treatment related adverse events (all grade [%]; grade ≥ 3 [%]) included palmar-plantar erythrodysesthesia (41%; 6%), hypertension (33%; 22%), and mucositis (19%; 5%). RNA was isolated from archived tumor specimens and gene expression analyses revealed no association between angiogenic biomarkers and clinical outcomes. CONCLUSION: The combination of capecitabine and ziv-aflibercept at the RPTD demonstrated acceptable safety and tolerability. PFS at 2 months in patients with chemotherapy refractory metastatic CRC was significantly greater than that in historical controls, indicating that this combination warrants further study. TRIAL REGISTRATION: This clinical trial was registered in the www.clinicaltrials.gov system as NCT01661972 on July 31, 2012.
Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Capecitabine/therapeutic use , Colorectal Neoplasms/drug therapy , Receptors, Vascular Endothelial Growth Factor/therapeutic use , Recombinant Fusion Proteins/therapeutic use , Adult , Aged , Aged, 80 and over , Cohort Studies , Colorectal Neoplasms/mortality , Colorectal Neoplasms/pathology , Drug Resistance, Neoplasm , Female , Humans , Male , Maximum Tolerated Dose , Middle Aged , Neoplasm Metastasis , Neoplasm Staging , Survival Analysis , Treatment OutcomeABSTRACT
BACKGROUND: Recruitment into clinical trials for retroperitoneal sarcoma has been challenging, resulting in termination of the only randomised multicentre trial in the USA investigating perioperative radiotherapy. Nonetheless, use of radiotherapy for retroperitoneal sarcoma has increased over the past decade, substantiated primarily by its established role in extremity sarcoma. In this study, we used a nationwide clinical oncology database to separately compare overall survival for patients with retroperitoneal sarcoma who had surgery and preoperative radiotherapy or surgery and postoperative radiotherapy versus surgery alone. METHODS: We did two case-control, propensity score-matched analyses of the National Cancer Data Base, which included adult patients with retroperitoneal sarcoma who were diagnosed from 2003 to 2011. Patients were included if they had localised, primary retroperitoneal sarcoma. Patients were classified into three groups based on use of radiotherapy: preoperative radiotherapy, postoperative radiotherapy, and no radiotherapy (surgery alone). Patients were excluded if they received both preoperative radiotherapy and postoperative radiotherapy, or if they received intraoperative radiotherapy. Parallel propensity score-matched datasets were created for patients who received preoperative radiotherapy versus those who received no radiotherapy and for patients who received postoperative therapy versus those who received no radiotherapy. Propensity scores were calculated with logistic regression, with multiple imputation and backwards elimination, with a significance level to stay of 0·05. Matching was done with a nearest-neighbour algorithm and matched 1:2 for the preoperative radiotherapy dataset and 1:1 for the postoperative radiotherapy dataset. The primary objective of interest was overall survival for patients who received preoperative radiotherapy or postoperative radiotherapy compared with those who received no radiotherapy within the propensity score-matched datasets. FINDINGS: 9068 patients were included in this analysis: 563 in the preoperative radiotherapy group, 2215 in the postoperative radiotherapy group, and 6290 in the no radiotherapy group. Matching resulted in two comparison groups (preoperative radiotherapy vs no radiotherapy, and postoperative radiotherapy vs no radiotherapy) with negligible differences in all demographic, clinicopathological, and treatment-level variables. In the matched case-control analysis for preoperative radiotherapy median follow-up time was 42 months (IQR 27-70) for the preoperative radiotherapy group versus 43 months (25-64) for the no radiotherapy group; median overall survival was 110 months (95% CI 75-not estimable) versus 66 months (61-76), respectively. In the matched case-control analysis for postoperative radiotherapy median follow-up time was 54 months (IQR 32-79) for patients in the postoperative radiotherapy group and 47 months (26-72) for patients in the no radiotherapy group; median overall survival was 89 months (95% CI 79-100) versus 64 months (59-69), respectively. Both preoperative radiotherapy (HR 0·70, 95% CI 0·59-0·82; p<0·0001) and postoperative radiotherapy (HR 0·78, 0·71-0·85; p<0·0001) were significantly associated with improved overall survival compared with surgery alone. INTERPRETATION: To the best of our knowledge, this is the largest study to date of the effect of radiotherapy on overall survival in patients with retroperitoneal sarcoma. Radiotherapy was associated with improved overall survival compared with surgery alone when delivered as either preoperative radiotherapy or postoperative radiotherapy. Together with the results from the ongoing randomised EORTC trial (62092-22092; NCT01344018) investigating preoperative radiotherapy for retroperitoneal sarcoma pending, these data might provide additional support for the increasing use of radiotherapy for patients with retroperitoneal sarcoma undergoing surgical resection. FUNDING: Department of Surgery, Duke University School of Medicine.
Subject(s)
Neoplasm Recurrence, Local/diagnosis , Postoperative Complications/radiotherapy , Propensity Score , Retroperitoneal Neoplasms/radiotherapy , Retroperitoneal Neoplasms/surgery , Sarcoma/radiotherapy , Sarcoma/surgery , Case-Control Studies , Databases, Factual , Female , Follow-Up Studies , Humans , Male , Medical Oncology , Middle Aged , Neoplasm Grading , Neoplasm Staging , Preoperative Care , Prognosis , Radiotherapy, Adjuvant , Retroperitoneal Neoplasms/pathology , Sarcoma/pathology , Survival RateABSTRACT
PURPOSE: Women with early-stage breast cancer face the complex decision to undergo one of three equally effective oncologic surgical strategies: breast-conservation surgery with radiation (BCS), mastectomy, or mastectomy with breast reconstruction. With comparable oncologic outcomes and survival rates, evaluations of satisfaction with these procedures are needed to facilitate the decision-making process and to optimize long-term health. METHODS: Women recruited from the Army of Women with a history of breast cancer surgery took electronically administered surgery-specific surveys, including the BREAST-Q© and a background survey evaluating patient-, disease-, and procedure-specific factors. Descriptive statistics and regression analysis were used to evaluate the effect of procedure type on breast satisfaction scores. RESULTS: Overall, 7,619 women completed the questionnaires. Linear regression revealed that women who underwent abdominal flap, or buttock or thigh flap reconstruction reported the highest breast satisfaction score, scoring an average of 5.6 points and 14.4 points higher than BCS, respectively (p < 0.0001 and p = 0.027, respectively). No difference in satisfaction was observed in women who underwent latissimus dorsi flap reconstruction compared with those who underwent BCS. Women who underwent implant reconstruction reported scores 8.6 points lower than BCS (p < 0.0001). Those with mastectomies without reconstruction or complex surgical histories scored, on average, 10 points lower than BCS (p < 0.0001). CONCLUSION: Women who underwent autologous tissue reconstruction reported the highest breast satisfaction, while women undergoing mastectomy without reconstruction reported the lowest satisfaction. These findings emphasize the value of patient-reported outcome measures as an important guide to decision making in breast surgery and underscore the importance of multidisciplinary participation early in the surgical decision-making process.
Subject(s)
Breast Neoplasms/surgery , Mammaplasty , Mastectomy , Patient Satisfaction , Breast Implantation , Breast Neoplasms/radiotherapy , Decision Making , Female , Humans , Linear Models , Mastectomy, Segmental , Middle AgedABSTRACT
PURPOSE: Patients with advanced non-small cell lung cancer (aNSCLC) face a significant symptom burden. Little is known about the frequency and severity of symptoms over time, so we longitudinally characterized patients' symptoms using the Patient Care Monitor (PCM) version 2.0, an electronic symptom-assessment tool. METHODS: Ninety-seven patients with aNSCLC completed the PCM at up to four clinic visits. We analyzed symptom data by incidence, severity, type (functional vs. nonfunctional), proximity to death, and cancer anorexia-cachexia syndrome status (CACS). RESULTS: Functional concerns predominated, even in the non-CACS group. Average severity among the top 5 symptoms was worse for functional than nonfunctional items (mean difference 0.62, 95% CI 0.22-1.01, P = 0.003). Severe dyspnea and fatigue were the most prevalent nonfunctional symptoms; moderate/severe dyspnea was reported by at least 29% of patients, and fatigue by over 50%. Depression was reported infrequently, with over half of patients at each visit reporting "none"; moderate or severe depression was reported in only 2.5-9.3 and 3.4-6.2% of patients, respectively. The average number of moderate/severe symptoms increased with proximity to death; 84% reported moderate/severe fatigue in the last 3 months of life, compared to 48% at ≥ 12 months from death (P = 0.007). CONCLUSIONS: Patients with aNSCLC face a significant symptom burden, which increases with proximity to death. Symptom type and severity vary by proximity to death, but even patients without overt CACS report significant functional symptoms throughout. We recommend an individualized approach to palliative symptom intervention in advanced lung cancer, based on detailed symptom assessment and tracking.
Subject(s)
Carcinoma, Non-Small-Cell Lung/epidemiology , Carcinoma, Non-Small-Cell Lung/psychology , Lung Neoplasms/epidemiology , Lung Neoplasms/psychology , Symptom Assessment/methods , Aged , Aged, 80 and over , Carcinoma, Non-Small-Cell Lung/pathology , Carcinoma, Non-Small-Cell Lung/therapy , Disease Progression , Female , Humans , Internet , Longitudinal Studies , Lung Neoplasms/pathology , Lung Neoplasms/therapy , Male , Middle Aged , Patient Outcome Assessment , Prevalence , Quality of Life , Self ReportABSTRACT
BACKGROUND: Quality measurement has become a priority for national healthcare reform, and valid measures are necessary to discriminate hospital performance and support value-based healthcare delivery. The Commission on Cancer (CoC) is the largest cancer-specific accreditor of hospital quality in the United States and has implemented Quality of Care Measures to evaluate cancer care delivery. However, none has been formally tested as a valid metric for assessing hospital performance based on actual patient outcomes. METHODS: Eligibility and compliance with the Quality of Care Measures are reported within the National Cancer Database, which also captures data for robust patient-level risk adjustment. Hospital-level compliance was calculated for the core measures, and the association with patient survival was tested using Cox regression. RESULTS: Seven hundred sixty-eight thousand nine hundred sixty-nine unique cancer cases were included from 1323 facilities. Increasing hospital-level compliance was associated with improved survival for only two measures, including a 35% reduced risk of mortality for the gastric cancer measure G15RLN (HR 0.65, 95% CI 0.58-0.72) and a 19% reduced risk of mortality for the colon cancer measure 12RLN (HR 0.81, 95% CI 0.77-0.85). For the lung cancer measure LNoSurg, increasing compliance was paradoxically associated with an increased risk of mortality (HR 1.14, 95% CI 1.08-1.20). For the remaining measures, hospital-level compliance demonstrated no consistent association with patient survival. CONCLUSION: Hospital-level compliance with the CoC's Quality of Care Measures is not uniformly aligned with patient survival. In their current form, these measures do not reliably discriminate hospital performance and are limited as a tool for value-based healthcare delivery.
Subject(s)
Hospitals/standards , Neoplasms/mortality , Neoplasms/therapy , Quality of Health Care , Accreditation , Breast Neoplasms/mortality , Breast Neoplasms/therapy , Carcinoma, Non-Small-Cell Lung/mortality , Carcinoma, Non-Small-Cell Lung/therapy , Colonic Neoplasms/mortality , Colonic Neoplasms/therapy , Databases, Factual , Female , Hospitals/statistics & numerical data , Humans , Kaplan-Meier Estimate , Lung Neoplasms/mortality , Lung Neoplasms/therapy , Male , Neoplasms/epidemiology , Proportional Hazards Models , Quality Improvement , Rectal Neoplasms/mortality , Rectal Neoplasms/therapy , Stomach Neoplasms/mortality , Stomach Neoplasms/therapy , United States/epidemiologyABSTRACT
PURPOSE: In this prospective trial, we sought to assess the feasibility of concurrent administration of ipilimumab and radiation as adjuvant, neoadjuvant, or definitive therapy in patients with regionally advanced melanoma. PATIENTS AND METHODS: Twenty-four patients in two cohorts were enrolled and received ipilimumab at 3 mg/kg every 3 weeks for four doses in conjunction with radiation; median dose was 4,000 cGy (interquartile range, 3,550-4,800 cGy). Patients in cohort 1 were treated adjuvantly; patients in cohort 2 were treated either neoadjuvantly or as definitive therapy. RESULTS: Adverse event profiles were consistent with those previously reported with checkpoint inhibition and radiation. For the neoadjuvant/definitive cohort, the objective response rate was 64% (80% confidence interval, 40%-83%), with 4 of 10 evaluable patients achieving a radiographic complete response. An additional 3 patients in this cohort had a partial response and went on to surgical resection. With 2 years of follow-up, the 6-, 12-, and 24-month relapse-free survival for the adjuvant cohort was 85%, 69%, and 62%, respectively. At 2 years, all patients in the neoadjuvant/definitive cohort and 10/13 patients in the adjuvant cohort were still alive. Correlative studies suggested that response in some patients were associated with specific CD4+ T-cell subsets. CONCLUSIONS: Overall, concurrent administration of ipilimumab and radiation was feasible, and resulted in a high response rate, converting some patients with unresectable disease into surgical candidates. Additional studies to investigate the combination of radiation and checkpoint inhibitor therapy are warranted.
Subject(s)
Chemoradiotherapy, Adjuvant/mortality , Ipilimumab/therapeutic use , Melanoma/therapy , Neoadjuvant Therapy/mortality , Neoplasm Recurrence, Local/therapy , Adult , Aged , Aged, 80 and over , Antineoplastic Agents, Immunological/therapeutic use , Feasibility Studies , Female , Follow-Up Studies , Humans , Male , Melanoma/pathology , Middle Aged , Neoplasm Recurrence, Local/pathology , Prognosis , Prospective Studies , Radiotherapy Dosage , Survival Rate , Young AdultABSTRACT
The human hepatoma cell lines HepG2 and Huh7 have been used extensively to study hepatitis B virus (HBV) transcription and replication. Both cell lines support transcription of the 3.5-kb viral pregenomic RNA and subsequent viral DNA synthesis by reverse transcription. The effects of the coactivator peroxisome proliferator-activated receptor gamma coactivator 1alpha (PGC1alpha) and corepressor small heterodimer partner (SHP) on HBV transcription and replication mediated by nuclear receptors were examined in the context of individual nuclear receptors in nonhepatoma cells and in hepatoma cells in an attempt to determine the relative contribution of the various nuclear receptors to viral biosynthesis in the hepatoma cells. PGC1alpha and SHP modulated viral biosynthesis differently in the human hepatoma cell lines HepG2 and Huh7, indicating distinct modes of transcriptional regulation. Consistent with this suggestion, it appears that retinoid X receptor alpha/farnesoid X receptor alpha and liver receptor homolog 1 or estrogen-related receptor beta (ERRbeta) may contribute to the majority of the viral replication observed in HepG2 cells, whereas ERRalpha and ERRgamma are probably responsible for the majority of viral biosynthesis in Huh7 cells. Therefore, this approach indicates that the transcriptional regulation of HBV biosynthesis in HepG2 and Huh7 cells is primarily controlled by different transcription factors.
Subject(s)
Heat-Shock Proteins/metabolism , Hepatitis B virus/physiology , Host-Pathogen Interactions , Receptors, Cytoplasmic and Nuclear/metabolism , Transcription Factors/metabolism , Virus Replication , Cell Line , Humans , Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha , RNA, Viral/biosynthesis , Transcription, GeneticABSTRACT
Hepatitis B virus (HBV) biosynthesis involves the transcription of the 3.5-kb viral pregenomic RNA, followed by its reverse transcription into viral DNA. Consequently, the modulation of viral transcription influences the level of virus production. Nuclear receptors are the only transcription factors known to support viral pregenomic RNA transcription and replication. The coactivator peroxisome proliferator-activated receptor gamma coactivator 1alpha (PGC1alpha) and corepressor small heterodimer partner (SHP) have central roles in regulating energy homeostasis in the liver by modulating the transcriptional activities of nuclear receptors. Therefore, the effect of PGC1alpha and SHP on HBV transcription and replication mediated by nuclear receptors was examined in the context of individual nuclear receptors in nonhepatoma cells and in hepatoma cells. This analysis indicated that viral replication mediated by hepatocyte nuclear factor 4alpha, retinoid X receptor alpha (RXRalpha) plus peroxisome proliferator-activated receptor alpha (PPARalpha), and estrogen-related receptor (ERR) displayed differential sensitivity to PGC1alpha activation and SHP inhibition. The effects of PGC1alpha and SHP on viral biosynthesis in the human hepatoma cell line Huh7 were similar to those observed in the nonhepatoma cells expressing ERRalpha and ERRgamma. This suggests that these nuclear receptors, potentially in combination with RXRalpha plus PPARalpha, may have a major role in governing HBV transcription and replication in this cell line. Additionally, this functional approach may help to distinguish the transcription factors in various liver cells governing viral biosynthesis under a variety of physiologically relevant conditions.
Subject(s)
Heat-Shock Proteins/metabolism , Hepatitis B virus/physiology , Host-Pathogen Interactions , Receptors, Cytoplasmic and Nuclear/metabolism , Transcription Factors/metabolism , Virus Replication , Cell Line , Humans , Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha , RNA, Viral/biosynthesis , Transcription, GeneticABSTRACT
BACKGROUND: Breast cancer survival continues to improve, with women living longer after treatment. It is not well understood how long-term satisfaction and well-being differ following treatment or how types of reconstruction differ when compared to the norm. METHODS: In a propensity-matched sample, the authors compared patient-reported outcomes in breast cancer patients at various time intervals from surgery with normative BREAST-Q data. All data were obtained using the Army of Women, an online community fostering breast cancer research. Breast cancer patients were stratified by surgical treatment and reconstruction type. Regression lines were estimated and differences in slope tested between cancer patients and noncancer controls. RESULTS: The authors compared normative (n = 922) and breast cancer (n = 4343) cohorts in a propensity-matched analysis. Among the breast cancer patients, 49.4 percent underwent lumpectomy, 17.0 percent underwent mastectomy, 21.7 percent underwent implant reconstruction, and 11.9 percent underwent autologous reconstruction. Median time since surgery was 4.7 years, with 21.1 percent more than 10 years after surgery. At the time of survey, breast cancer patients reported higher Satisfaction with Breasts and Psychosocial Well-being scores compared to noncancer controls (p < 0.01), with the cohorts undergoing lumpectomy and autologous reconstruction both reporting higher scores than the normative controls. After mastectomy, scores averaged lower than the noncancer controls, but improved over time. However, all breast cancer groups reported significantly lower Physical Well-being scores than the noncancer cohort (all p < 0.01). CONCLUSIONS: Breast cancer patients undergoing lumpectomy or autologous reconstruction reported higher psychosocial well-being compared to noncancer controls. These differences were influenced both by time since treatment and by choice of surgical procedure.
Subject(s)
Breast Neoplasms/surgery , Mammaplasty/psychology , Mastectomy/adverse effects , Patient Reported Outcome Measures , Patient Satisfaction , Quality of Life , Adult , Aged , Aged, 80 and over , Breast/surgery , Breast Neoplasms/psychology , Cross-Sectional Studies , Datasets as Topic , Female , Follow-Up Studies , Humans , Mastectomy/methods , Middle Aged , Propensity Score , Time Factors , Treatment OutcomeABSTRACT
PURPOSE: Early indication of treatment outcome may guide therapeutic de-escalation strategies in patients with human papillomavirus (HPV)-related oropharyngeal cancer (OPC). This study investigated the relationships between tumor volume and 18F-fluorodeoxyglucose positron emission tomography (PET) parameters before and during definitive radiation therapy with treatment outcomes. METHODS AND MATERIALS: Patients undergoing definitive (chemo)radiation for HPV-related/p16-positive OPC were prospectively enrolled on an institutional review board-approved study. 18F-fluorodeoxyglucose PET/computed tomography scans were performed at simulation and after 2 weeks at a dose of â¼20 Gy. Tumor volume and standardized uptake value (SUV) characteristics were measured. SUV was normalized to blood pool uptake. Tumor volume and PET parameters associated with recurrence were identified through recursive partitioning (RPART). Recurrence-free survival (RFS) and overall survival (OS) curves between RPART-identified cohorts were estimated using the Kaplan-Meier method, and Cox models were used to estimate the hazard ratios (HRs). RESULTS: From 2012 to 2016, 62 patients with HPV-related OPC were enrolled. Median follow-up was 4.4 years. RPART identified patients with intratreatment SUVmax (normalized to blood pool SUVmean) <6.7 or SUVmax (normalized to blood pool SUVmean) ≥6.7 with intratreatment SUV40% ≥2.75 as less likely to recur. For identified subgroups, results of Cox models showed unadjusted HRs for RFS and OS (more likely to recur vs less likely) of 7.33 (90% confidence interval [CI], 2.97-18.12) and 6.09 (90% CI, 2.22-16.71), respectively, and adjusted HRs of 6.57 (90% CI, 2.53-17.05) and 5.61 (90% CI, 1.90-16.54) for RFS and OS, respectively. CONCLUSIONS: PET parameters after 2 weeks of definitive radiation therapy for HPV-related OPC are associated with RFS and OS, thus potentially informing an adaptive treatment approach.
Subject(s)
Neoplasm Recurrence, Local , Oropharyngeal Neoplasms/radiotherapy , Papillomavirus Infections/complications , Positron Emission Tomography Computed Tomography/methods , Analysis of Variance , Antineoplastic Agents/administration & dosage , Cisplatin/administration & dosage , Docetaxel/administration & dosage , Female , Fluorodeoxyglucose F18 , Human papillomavirus 16 , Humans , Kaplan-Meier Estimate , Male , Middle Aged , Neoplasm Recurrence, Local/diagnostic imaging , Oropharyngeal Neoplasms/diagnostic imaging , Oropharyngeal Neoplasms/pathology , Oropharyngeal Neoplasms/virology , Proportional Hazards Models , Prospective Studies , Radiopharmaceuticals , Treatment Outcome , Tumor BurdenABSTRACT
BACKGROUND: This study aimed to identify differences in patient-reported abdominal well-being, satisfaction, and quality of life in women with muscle-preserving free abdominal versus pedicle transverse rectus abdominis musculocutaneous (TRAM) flap for breast reconstruction. METHODS: Women with a history of breast cancer surgery were recruited from the Army of Women foundation to take the BREAST-Q and a background questionnaire. Descriptive statistics and regression analyses were used to compare abdominal physical well-being, breast satisfaction, chest physical, psychosocial well-being, and sexual well-being in women undergoing free versus pedicle TRAM flaps. RESULTS: Of 657 women, 273 (41 percent) underwent free flap surgery and 384 (58 percent) underwent pedicle TRAM flap surgery. Compared with unilateral pedicle TRAM flaps, those with unilateral free flaps scored an average of 9.5 points higher (95 percent CI, 5.4 to 13.6; p < 0.0001) and those with bilateral free flaps reported no difference in physical well-being of the abdomen. Compared with bilateral pedicle TRAM flaps, the following groups scored higher in physical well-being of the abdomen: unilateral free flaps, an average of 17.4 (95 percent CI, 11.5 to 23.3; p < 0.0001); bilateral free flaps, an average of 6.8 (95 percent CI, 0.3 to 13.3; p = 0.04); and unilateral pedicle TRAM flaps, an average of 7.9 (95 percent CI, 2.4 to 13.4; p = 0.005) higher. Women with bilateral pedicle flaps reported sexual well-being scores 7.4 (95 percent CI, 0.6 to 14.3; p = 0.03) and 6.8 (95 percent CI, 0.3 to 13.2; p = 0.04) points lower than those with unilateral free and unilateral pedicle flaps. CONCLUSIONS: Muscle-preserving techniques result in improved abdominal wall function and decreased morbidity compared with pedicle TRAM flap reconstruction. These data highlight the importance of offering patients the option of microsurgical techniques.
Subject(s)
Free Tissue Flaps/transplantation , Mammaplasty/methods , Myocutaneous Flap/transplantation , Patient Reported Outcome Measures , Transplant Donor Site/physiopathology , Abdominal Wall/physiopathology , Abdominal Wall/surgery , Aged , Breast Neoplasms/surgery , Cohort Studies , Female , Free Tissue Flaps/adverse effects , Humans , Mammaplasty/adverse effects , Mastectomy/adverse effects , Microsurgery/adverse effects , Microsurgery/methods , Middle Aged , Myocutaneous Flap/adverse effects , Organ Sparing Treatments/adverse effects , Organ Sparing Treatments/methods , Patient Selection , Quality of Life , Rectus Abdominis/transplantation , Transplantation, Autologous/adverse effects , Transplantation, Autologous/methodsABSTRACT
BACKGROUND: Evidence increasingly supports the integration of specialist palliative care (PC) into routine cancer care. A novel, fully integrated PC and medical oncology inpatient service was developed at Duke University Hospital in 2011. OBJECTIVE: To assess the impact of PC integration on health care utilization among hospitalized cancer patients before hospice enrollment. METHODS: Retrospective cohort study. Patients in the solid tumor inpatient unit who were discharged to hospice between September 1, 2009, and June 30, 2010 (pre-PC integration), and September 1, 2011, to June 30, 2012 (postintegration). Cohorts were compared on the following outcomes from their final hospitalization before hospice enrollment: intensive care unit days, invasive procedures, subspecialty consultations, radiographic studies, hospital length of stay, and use of chemotherapy or radiation. Cohort differences were examined with descriptive statistics and nonparametric tests. RESULTS: Two hundred ninety-six patients were included in the analysis (133 pre-PC integration; 163 post-PC integration). Patient characteristics were similar between cohorts. Health care utilization was relatively low in both groups, although 26% and 24% were receiving chemotherapy at the time of admission or during hospitalization in the pre- and post-PC integration cohorts, respectively, and 6.8% in each cohort spent time in an intensive care unit. We found no significant differences in utilization between cohorts. DISCUSSION: PC integration into an inpatient solid tumor service may not impact health care utilization during the final hospitalization before discharge to hospice. This likely reflects the greater benefits of integrating PC farther upstream from the terminal hospitalization, if one hopes to meaningfully impact utilization near the end of life.
Subject(s)
Delivery of Health Care, Integrated/organization & administration , Hospice and Palliative Care Nursing/organization & administration , Medical Oncology/organization & administration , Neoplasms/nursing , Patient Acceptance of Health Care/statistics & numerical data , Adult , Aged , Aged, 80 and over , Cohort Studies , Female , Humans , Male , Middle Aged , North Carolina , Retrospective StudiesABSTRACT
BACKGROUND: Controversy exists over the use of adjuvant chemotherapy for locally advanced (stages II-III) rectal cancer (LARC) patients who demonstrate pathologic complete response (pCR) following neoadjuvant chemoradiation. We conducted a retrospective analysis to determine whether adjuvant chemotherapy imparts survival benefit among this population. METHODS: The National Cancer Database (NCDB) was queried to identify LARC patients with pCR following neoadjuvant chemoradiation. The cohort was stratified by receipt of adjuvant chemotherapy. Multiple imputation and a Cox proportional hazards model were employed to estimate the effect of adjuvant chemotherapy on overall survival. RESULTS: There were 24,418 patients identified in the NCDB with clinically staged II or III rectal cancer who received neoadjuvant chemoradiation. Of these, 5606 (23.0%) had pCR. Among patients with pCR, 1401 (25%) received adjuvant chemotherapy and 4205 (75%) did not. Patients who received adjuvant chemotherapy were slightly younger, more likely to have private insurance, and more likely to have clinically staged III disease, but did not differ significantly in comparison to patients who did not receive adjuvant chemotherapy with respect to race, sex, facility type, Charlson comorbidity score, histologic tumor grade, procedure type, length of stay, or rate of 30-day readmission following surgery. On adjusted analysis, receipt of adjuvant chemotherapy was associated with a lower risk of death at a given time compared to patients who did not receive adjuvant chemotherapy (HR 0.808; 95% CI 0.679-0.961; p = 0.016). CONCLUSION: Supporting existing NCCN guidelines, the findings from this study suggest that adjuvant chemotherapy improves survival for LARC with pCR following neoadjuvant chemoradiation.
Subject(s)
Neoplasm Staging , Proctectomy/methods , Rectal Neoplasms/therapy , Chemoradiotherapy/methods , Chemotherapy, Adjuvant , Female , Humans , Male , Middle Aged , Neoadjuvant Therapy/methods , Prognosis , Rectal Neoplasms/diagnosis , Rectal Neoplasms/mortality , Retrospective Studies , Survival Rate/trends , United States/epidemiologyABSTRACT
PURPOSE: Follow-up imaging after stereotactic radiosurgery (SRS) is crucial to identify salvageable brain metastases (BM) recurrence. As optimal imaging intervals are poorly understood, we sought to build a predictive model for time to intracranial progression. METHODS: Consecutive patients treated with SRS for BM at three institutions from January 1, 2002 to June 30, 2017 were retrospectively reviewed. We developed a model using stepwise regression that identified four prognostic factors and built a predictive nomogram. RESULTS: We identified 755 patients with primarily non-small cell lung, breast, and melanoma BMs. Factors such as number of BMs, histology, history of prior whole-brain radiation, and time interval from initial cancer diagnosis to metastases were prognostic for intracranial progression. Per our nomogram, risk of intracranial progression by 3 months post-SRS in the high-risk group was 21% compared to 11% in the low-risk group; at 6 months, it was 43% versus 27%. CONCLUSION: We present a nomogram estimating time to BM progression following SRS to potentially personalize surveillance imaging.