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1.
Ann Surg Oncol ; 31(1): 488-498, 2024 Jan.
Article in English | MEDLINE | ID: mdl-37782415

ABSTRACT

BACKGROUND: While lower socioeconomic status has been shown to correlate with worse outcomes in cancer care, data correlating neighborhood-level metrics with outcomes are scarce. We aim to explore the association between neighborhood disadvantage and both short- and long-term postoperative outcomes in patients undergoing pancreatectomy for pancreatic ductal adenocarcinoma (PDAC). PATIENTS AND METHODS: We retrospectively analyzed 243 patients who underwent resection for PDAC at a single institution between 1 January 2010 and 15 September 2021. To measure neighborhood disadvantage, the cohort was divided into tertiles by Area Deprivation Index (ADI). Short-term outcomes of interest were minor complications, major complications, unplanned readmission within 30 days, prolonged hospitalization, and delayed gastric emptying (DGE). The long-term outcome of interest was overall survival. Logistic regression was used to test short-term outcomes; Cox proportional hazards models and Kaplan-Meier method were used for long-term outcomes. RESULTS: The median ADI of the cohort was 49 (IQR 32-64.5). On adjusted analysis, the high-ADI group demonstrated greater odds of suffering a major complication (odds ratio [OR], 2.78; 95% confidence interval [CI], 1.26-6.40; p = 0.01) and of an unplanned readmission (OR, 3.09; 95% CI, 1.16-9.28; p = 0.03) compared with the low-ADI group. There were no significant differences between groups in the odds of minor complications, prolonged hospitalization, or DGE (all p > 0.05). High ADI did not confer an increased hazard of death (p = 0.63). CONCLUSIONS: We found that worse neighborhood disadvantage is associated with a higher risk of major complication and unplanned readmission after pancreatectomy for PDAC.


Subject(s)
Carcinoma, Pancreatic Ductal , Pancreatic Neoplasms , Humans , Pancreatectomy/adverse effects , Pancreatectomy/methods , Retrospective Studies , Pancreatic Neoplasms/pathology , Carcinoma, Pancreatic Ductal/pathology , Neighborhood Characteristics
2.
J Natl Compr Canc Netw ; 22(2D)2024 Jan 05.
Article in English | MEDLINE | ID: mdl-38181507

ABSTRACT

Ampullary carcinomas are rare but increasing in incidence. Ampullary cancers have molecular alterations that guide choice of therapy, particularly in nonresectable cases. These alterations can be more common by subtype (intestinal, pancreaticobiliary, or mixed), and next-generation sequencing is recommended for all patients who cannot undergo surgery. In this article, we review the approach to tissue acquisition and consideration for molecular testing. Common molecular targets of interest in ampullary cancer are also discussed in this review, including HER2/ERBB2, HER3, tumor mutational burden, microsatellite instability, KRAS, and germline BRCA and ATM mutations, along with emerging and rarer alterations.


Subject(s)
Ampulla of Vater , Common Bile Duct Neoplasms , Molecular Targeted Therapy , Humans , Ampulla of Vater/pathology , Molecular Targeted Therapy/methods , Common Bile Duct Neoplasms/therapy , Common Bile Duct Neoplasms/diagnosis , Common Bile Duct Neoplasms/genetics , Common Bile Duct Neoplasms/pathology , Mutation , Biomarkers, Tumor/genetics
3.
J Surg Res ; 299: 269-281, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38788463

ABSTRACT

INTRODUCTION: Colon cancer (CC) is one of the most common cancers among South Asian Americans (SAAs). The objective of this study was to measure differences in risk-adjusted survival among SAAs with CC compared to non-Hispanic Whites (NHWs) using a representative national dataset from the United States. METHODS: A retrospective analysis of patients with CC in the National Cancer Database (2004-2020) was performed. Differences in presentation, management, median overall survival (OS), three-year survival, and five-year survival between SAAs and NHWs were compared. Kaplan-Meier analysis and multivariable Cox regression were used to assess differences in survival outcomes, adjusting for demographics, presentation, and treatments received. RESULTS: Data from 2873 SAA and 639,488 NHW patients with CC were analyzed. SAAs were younger at diagnosis (62.2 versus 69.5 y, P < 0.001), higher stage (stage III [29.0% versus 26.2%, P = 0.001] or Stage IV [21.4% versus 20.0%, P = 0.001]), and experienced delays to first treatment (SAA 5.9% versus 4.9%, P = 0.003). SAAs with CC had higher OS (median not achieved versus 68.1 mo for NHWs), three-year survival (76.3% versus 63.4%), and five-year survival (69.1% versus 52.9%). On multivariable Cox regression, SAAs with CC had a lower risk of death across all stages (hazard ratio: 0.64, P < 0.001). CONCLUSIONS: In this national study, SAA patients with CC presented earlier in life with more advanced disease, and a higher proportion experienced treatment delay compared to NHW patients. Despite these differences, SAAs had better adjusted OS than NHW, warranting further exploration of tumor biology and socioeconomic determinants of cancer outcomes in SAAs.


Subject(s)
Asian , Colonic Neoplasms , Adult , Aged , Aged, 80 and over , Female , Humans , Male , Middle Aged , Asian/statistics & numerical data , Colonic Neoplasms/ethnology , Colonic Neoplasms/mortality , Cross-Sectional Studies , Databases, Factual , Kaplan-Meier Estimate , Neoplasm Staging , Retrospective Studies , United States/epidemiology , White/statistics & numerical data , Survival Analysis
4.
Cancer Causes Control ; 34(9): 777-784, 2023 Sep.
Article in English | MEDLINE | ID: mdl-37247136

ABSTRACT

PURPOSE: Partnerships between researchers and community members and organizations can offer multiple benefits for research relevance and dissemination. The goal of this project was to build infrastructure to create bidirectional relationships between University of Wisconsin Carbone Cancer Center (UWCCC) researchers and community educators in the Division of Extension, which connects the knowledge and resources of the university to communities across the state. METHODS: This project had three aims: (1) create linkages with Extension; (2) establish an in-reach program to educate and train researchers on the science of Community Outreach and Engagement (COE); and (3) identify and facilitate collaborative projects between scientists and communities. Survey and focus group-based needs assessments were completed with both researchers and Extension educators and program activity evaluations were conducted. RESULTS: Most Extension educators (71%) indicated a strong interest in partnering on COE projects. UWCCC faculty indicated interest in further disseminating their research, but also indicated barriers in connecting with communities. Outreach webinars were created and disseminated to community, a "COE in-reach toolkit" for faculty was created and a series of "speed networking" events were hosted to pair researchers and community. Evaluations indicated the acceptability and usefulness of these activities and supported continuation of collaborative efforts. CONCLUSION: Continued relationship and skill building, along with a sustainability plan, is critical to support the translation of basic, clinical, and population research to action in the community outreach and engagement context. Further incentives for faculty should be explored for the recruitment of basic scientists into community engagement work.


Subject(s)
Neoplasms , Research Personnel , Humans , Surveys and Questionnaires , Research Personnel/education , Community-Institutional Relations , Program Evaluation
5.
Cancer ; 127(5): 801-808, 2021 03 01.
Article in English | MEDLINE | ID: mdl-33231882

ABSTRACT

BACKGROUND: Postcancer work limitations may affect a substantial proportion of patients and contribute to the "financial toxicity" of cancer treatment. The degree and nature of work limitations and employment outcomes are poorly understood for cancer patients, particularly in the immediate period of transition after active treatment. We prospectively examined employment, work ability, and work limitations during and after treatment. METHODS: A total of 120 patients receiving curative therapy who were employed prior to their cancer diagnosis and who intended to work during or after end of treatment (EOT) completed surveys at baseline (pretreatment), EOT, and 3, 6, and 12 months after EOT. Surveys included measures of employment, work ability, and work limitations. Descriptive statistics (frequencies, percentages, means with standard deviations) were calculated. RESULTS: A total of 111 participants completed the baseline survey. On average, participants were 48 years of age and were mostly white (95%) and female (82%) with a diagnosis of breast cancer (69%). Full-time employment decreased during therapy (from 88% to 50%) and returned to near prediagnosis levels by 12-month follow-up (78%). Work-related productivity loss due to health was high during treatment. CONCLUSIONS: This study is the first to report the effects of curative intent cancer therapy on employment, work ability, and work limitations both during and after treatment. Perceived work ability was generally high overall 12 months after EOT, although a minority reported persistent difficulty. A prospective analysis of factors (eg, job type, education, symptoms) most associated with work limitations is underway to assist in identifying at-risk patients.


Subject(s)
Employment , Neoplasms/drug therapy , Adult , Female , Humans , Longitudinal Studies , Male , Middle Aged , Prospective Studies , Surveys and Questionnaires , Work Capacity Evaluation
6.
Invest New Drugs ; 38(5): 1520-1525, 2020 10.
Article in English | MEDLINE | ID: mdl-32253554

ABSTRACT

Neuroendocrine tumors (NETs) are understudied and have limited systemic treatment options. Prior studies for patients with advanced NETs have demonstrated promising results when antimetabolite agents, including fluoropyrimidines, were combined with temozolomide TMZ. TAS-102 (trifluridine/tipiracil) is an antineoplastic agent that is non-cross resistant with 5-fluorouracil and capecitabine and that has a different toxicity profile. This study evaluated the safety of TAS-102 in combination with TMZ in patients in neuroendocrine tumors. Escalating doses of TMZ (100, 150 and 200 mg/m2) on days 8-12 were given in combination with TAS-102 (35 mg/m2 twice a day) on days 1-5 and 8-12 of a 28 day cycle in subjects with advanced NETs. Primary endpoints were safety and determination of maximum tolerated dose (MTD). Growth factor support was mandated starting with level 2 to avoid treatment delays. Fifteen evaluable subjects were enrolled in the phase 1 study. No dose limiting toxicities (DLTs) were observed on level 1. One DLT was observed on level 2 (grade 3 fatigue and inability to resume treatment), and 1 on level 3 (grade 4 thrombocytopenia). The most common grade ≥ 3 adverse events included neutropenia (33%), lymphopenia (27%), and thrombocytopenia (27%). Disease control rate of 92% and partial response rate of 8% were observed in 13 evaluable subjects. This study established MTD of TAS-102 (35 mg/m2 twice daily) and TMZ (200 mg/m2 daily). This regimen was well tolerated. Early signs of clinically meaningful activity were observed. Further evaluation of the efficacy of this regimen is warranted.


Subject(s)
Antineoplastic Agents/administration & dosage , Antineoplastic Combined Chemotherapy Protocols/administration & dosage , Neuroendocrine Tumors/drug therapy , Pyrrolidines/administration & dosage , Temozolomide/administration & dosage , Thymine/administration & dosage , Trifluridine/administration & dosage , Adult , Aged , Antineoplastic Agents/adverse effects , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Drug Combinations , Female , Hematologic Diseases/chemically induced , Humans , Male , Maximum Tolerated Dose , Middle Aged , Pyrrolidines/adverse effects , Temozolomide/adverse effects , Thymine/adverse effects , Treatment Outcome , Trifluridine/adverse effects
7.
J Gen Intern Med ; 35(9): 2553-2559, 2020 09.
Article in English | MEDLINE | ID: mdl-32495085

ABSTRACT

BACKGROUND: Cancer screening is chiefly performed by primary care providers (PCPs) who rely on organizational screening guidelines. These guidelines provide evidence-based recommendations; however, they are often without unanimity leading to divergent screening recommendations. OBJECTIVE: Due to the high incidence of breast cancer, the availability of screening methods, and the presence of multiple incongruent guideline recommendations, we sought to understand breast cancer screening practices in Wisconsin to identify patterns that would allow us to improve evidence-based screening adherence. METHODS: A 46-question survey on breast cancer screening beliefs and practices for average-risk women was sent to healthcare providers in Wisconsin in 2018, who provided cancer screening services to women. Providers included physicians, nurse practitioners (NPs), physician assistants (PAs), and midwives. RESULTS: A total of 295 people responded to the survey, for a response rate of 28.6%. Most respondents were physicians (64.1%), followed by NPs (25.7%), PAs (5.3%), and midwives (1.5%). Of physicians, most practiced family medicine (65.3%), followed by internal medicine (25.3%) and gynecology (9.4%). The United States Preventive Services Task Force (USPSTF) was reported as being "very influential" for 60.5% of providers, followed by the American Cancer Society at 46.8%. For patients 40-49 years old, 75.6% of providers performed clinical breast exams and 58.5% recommended self-breast exams; these numbers increased for women 50+ years old to 78.7% and 61.2%, respectively. Mammography was more likely to be recommended annually for women aged 40-49 rather than biennially by non-physician clinicians compared to physicians (p < .001). CONCLUSIONS: PCPs in Wisconsin continue to overestimate the efficacy of clinical and self-breast exams as well as overuse these in clinical practice. Providers find multiple screening guidelines influential but favor the USPSTF; however, these guidelines are frequently not being followed. Further research needs to be done to investigate the lack of national guideline adherence by providers to improve compliance with evidence-based screening recommendations.


Subject(s)
Breast Neoplasms , Early Detection of Cancer , Adult , Breast Neoplasms/diagnosis , Breast Neoplasms/epidemiology , Female , Health Personnel , Humans , Mammography , Mass Screening , Middle Aged , Practice Patterns, Physicians' , Primary Health Care , Surveys and Questionnaires , United States , Wisconsin/epidemiology
8.
J Natl Compr Canc Netw ; 16(12): 1442-1450, 2018 12.
Article in English | MEDLINE | ID: mdl-30545991

ABSTRACT

Background: Molecular profiles guide the clinical management of metastatic colorectal cancer (mCRC), particularly related to the use of anti-epidermal growth factor receptor (EGFR) antibodies. Tumor sidedness has also been implicated in resistance to these therapies, but has largely been studied in the first-line setting. We examined the role of tumor sidedness and disease bulk in predicting clinical outcomes to anti-EGFR therapy in the treatment-refractory setting. Methods: We identified a retrospective cohort of 62 patients with KRAS wild-type mCRC who received anti-EGFR therapy in the late-line setting. Response was assessed per RECIST 1.1, with bulky disease defined as any single lesion >35 mm in longest cross-sectional diameter or nodal short axis. Primary sidedness was defined in relation to the splenic flexure. Results: Patients with right-sided primary tumors at time of late-line EGFR therapy presented with increased tumor bulk and worsened overall survival (OS) relative to left-sided primary tumors. Tumor bulk, defined as either a categorical or continuous variable, predicted worsened progression-free survival (PFS) and OS, which persisted when controlling for differences in the primary tumor location. Within the right-sided cohort, no objective responses were observed for bulky disease or during treatment with anti-EGFR monotherapy. The nonbulky cohort experienced clinical benefit with anti-EGFR monotherapy, showing similar PFS and an improved response rate compared with sequential chemotherapy. Conclusions: In an effort to expand understanding of the role of primary sidedness in clinical response to anti-EGFR therapy, we identified sidedness and tumor bulk as potential predictive biomarkers of clinical response in late-line mCRC. Future prospective studies of EGFR targeting should consider tumor bulk in addition to molecular profiling in the identification of populations most likely to achieve meaningful clinical benefit.


Subject(s)
Antineoplastic Agents, Immunological/therapeutic use , Colorectal Neoplasms/drug therapy , Aged , Aged, 80 and over , Antineoplastic Agents, Immunological/pharmacology , Cetuximab/pharmacology , Cetuximab/therapeutic use , Colorectal Neoplasms/genetics , Colorectal Neoplasms/mortality , Colorectal Neoplasms/pathology , Drug Resistance, Neoplasm/drug effects , Drug Resistance, Neoplasm/genetics , ErbB Receptors/antagonists & inhibitors , ErbB Receptors/genetics , ErbB Receptors/immunology , Female , Humans , Male , Middle Aged , Mutation , Panitumumab/pharmacology , Panitumumab/therapeutic use , Prognosis , Progression-Free Survival , Proto-Oncogene Proteins p21(ras)/genetics , Response Evaluation Criteria in Solid Tumors , Retrospective Studies
9.
Prev Chronic Dis ; 14: E85, 2017 09 28.
Article in English | MEDLINE | ID: mdl-28957034

ABSTRACT

INTRODUCTION: Infection with human papillomavirus (HPV) is common and can progress to various types of cancer. HPV infection can be prevented through vaccination; however, vaccination rates among adolescents are low. The objective of this study was to assess efforts among Wisconsin stakeholders in HPV vaccination and organizational capacity for future collaborative work. METHODS: We conducted a cross-sectional online survey of 277 stakeholders in HPV vaccination activities, from April 30, 2015, through June 30, 2015. Stakeholders were public health professionals, health care providers, educators, quality improvement professionals, researchers, and advocates identified as engaged in HPV vaccination work. RESULTS: Of the 277 invited stakeholders, 117 (42%) responded to the survey. Findings showed that most current HPV vaccination activities targeted 3 groups: adolescents and parents, clinical and health professionals, and communities and health systems. The main activities directed at these groups were providing printed educational materials, professional education, and media campaigns to raise awareness. Common barriers reported were lack of understanding about the link between HPV and cancer, requests to delay vaccination, difficulty completing the 3-dose vaccine series, and reluctance to discuss sexuality. CONCLUSION: HPV vaccination rates are far below those of other vaccinations administered to adolescents in Wisconsin. Our study showed that various local efforts were being made to increase HPV vaccination uptake; however, many barriers exist to initiation and completion of the vaccine series. Future interventions should address barriers and employ evidence-based strategies for increasing HPV vaccination rates.


Subject(s)
Health Promotion/methods , Papillomaviridae/immunology , Papillomavirus Infections/prevention & control , Papillomavirus Vaccines/immunology , Uterine Cervical Neoplasms/prevention & control , Adolescent , Cross-Sectional Studies , Female , Health Knowledge, Attitudes, Practice , Health Personnel , Humans , Immunization Schedule , Male , Papillomavirus Infections/epidemiology , Papillomavirus Vaccines/administration & dosage , Parents , Sexual Behavior , Stakeholder Participation , Surveys and Questionnaires , Uterine Cervical Neoplasms/epidemiology , Vaccination/statistics & numerical data , Wisconsin/epidemiology
10.
Health Promot Pract ; 18(5): 741-750, 2017 09.
Article in English | MEDLINE | ID: mdl-28812930

ABSTRACT

INTRODUCTION: Colorectal cancer is the second leading cause of cancer death in the United States. Black Americans suffer even higher incidence and death rates than the general population. Genetics and patient perceptions explain some of this difference, however, modifiable health care system factors such as lack of access to colon cancer screening also contribute. Partnering an academic health center with local community groups, we piloted a colorectal cancer screening program at a Federally Qualified Health Center (FQHC) serving predominately low socioeconomic status Black Americans. The program was designed to identify and remove barriers to screening and improve screening rates. METHOD: At a single center FQHC, we developed an outreach program centered around (1) patient and provider education, (2) immunochemical fecal occult blood test (iFOBT) distribution, and (3) patient navigation. We identified 402 eligible patients, of which 228 (56.7%) completed screening. RESULTS: Our 56.7% screening rate represented a twofold increase above prepilot levels at the clinic. Nine (4%) iFOBT returned positive. Three of these nine patients completed colonoscopy. Screening rates and follow through were higher under a single navigator model. CONCLUSIONS: Our academic-community partnership provided an effective, evidence based, and sustainable model for increasing colorectal cancer screening in a high risk, low resource community.


Subject(s)
Black or African American , Colorectal Neoplasms/diagnosis , Colorectal Neoplasms/ethnology , Early Detection of Cancer/methods , Patient Education as Topic/organization & administration , Patient Navigation/organization & administration , Community-Institutional Relations , Female , Humans , Male , Occult Blood , Poverty , Safety-net Providers/organization & administration , United States , Universities/organization & administration
11.
HPB (Oxford) ; 19(5): 465-472, 2017 05.
Article in English | MEDLINE | ID: mdl-28237627

ABSTRACT

BACKGROUND: Endoscopic ultrasound (EUS) is used for pancreatic adenocarcinoma staging and obtaining a tissue diagnosis. The objective was to determine patterns of preoperative EUS and the impact on downstream treatment. METHODS: The Surveillance, Epidemiology, and End Results (SEER) Medicare-linked database was used to identify patients with pancreatic adenocarcinoma. The staging period was the first staging procedure within 6 months of surgery until surgery. Logistic regression was used to determine factors associated with preoperative EUS. The main outcome was EUS in the staging period, with secondary outcomes including number of staging tests and time to surgery. RESULTS: 2782 patients were included, 56% were treated at an academic hospital (n = 1563). 1204 patients underwent EUS (43.3%). The factors most associated with receipt of EUS were: earlier year of diagnosis, SEER area, and a NCI or academic hospital (all p < 0.0001). EUS was associated with a longer time to surgery (17.8 days; p < 0.0001), and a higher number of staging tests (40 tests/100 patients; p < 0.0001). CONCLUSIONS: Factors most associated with receipt of EUS are geographic, temporal, and institutional, rather than clinical/disease factors. EUS is associated with a longer time to surgery and more preoperative testing, and additional study is needed to determine if EUS is overused.


Subject(s)
Adenocarcinoma/diagnostic imaging , Endosonography/statistics & numerical data , Neoplasm Staging/methods , Pancreatic Neoplasms/diagnostic imaging , Adenocarcinoma/pathology , Adenocarcinoma/surgery , Aged , Aged, 80 and over , Female , Humans , Linear Models , Logistic Models , Male , Multivariate Analysis , Odds Ratio , Pancreatectomy , Pancreatic Neoplasms/pathology , Pancreatic Neoplasms/surgery , Pancreaticoduodenectomy , Practice Patterns, Physicians' , Predictive Value of Tests , Retrospective Studies , SEER Program , Time Factors , Time-to-Treatment , United States
13.
Oncologist ; 21(7): 785-6, 2016 07.
Article in English | MEDLINE | ID: mdl-27261467

ABSTRACT

LESSONS LEARNED: Pancreatic neuroendocrine tumors versus carcinoid tumors should be examined separately in clinical trials.Progression-free survival is more clinically relevant as the primary endpoint (rather than response rate) in phase II trials for low-grade neuroendocrine tumors. BACKGROUND: The most common subtypes of neuroendocrine tumors (NETs) are pancreatic islet cell tumors and carcinoids, which represent only 2% of all gastrointestinal malignancies. Histone deacetylase (HDAC) inhibitors have already been shown to suppress tumor growth and induce apoptosis in various malignancies. In NET cells, HDAC inhibitors have resulted in increased Notch1 expression and subsequent inhibition of growth. We present here a phase II study of the novel HDAC inhibitor panobinostat in patients with low-grade NET. METHODS: Adult patients with histologically confirmed, metastatic, low-grade NETs and an Eastern Cooperative Oncology Group (ECOG) performance status of ≤2 were treated with oral panobinostat 20 mg once daily three times per week. Treatment was continued until patients experienced unacceptable toxicities or disease progression. The study was stopped at planned interim analysis based on a Simon two-stage design. RESULTS: Fifteen patients were accrued, and 13 were evaluable for response. No responses were seen, but the stable disease rate was 100%. The median progression-free survival (PFS) was 9.9 months, and the median overall survival was 47.3 months. Fatigue (27%), thrombocytopenia (20%), diarrhea (13%), and nausea (13%) were the most common related grade 3 toxicities. There was one grade 4 thrombocytopenia (7%). These results did not meet the prespecified criteria to open the study to full accrual. CONCLUSION: The HDAC inhibitor panobinostat has a high stable disease rate and reasonable PFS in low-grade NET, but has a low response rate.


Subject(s)
Histone Deacetylase Inhibitors/therapeutic use , Hydroxamic Acids/therapeutic use , Indoles/therapeutic use , Neuroendocrine Tumors/drug therapy , Adult , Aged , Aged, 80 and over , Female , Humans , Male , Middle Aged , Neuroendocrine Tumors/mortality , Panobinostat
14.
Ann Surg Oncol ; 23(9): 2788-94, 2016 09.
Article in English | MEDLINE | ID: mdl-27026436

ABSTRACT

BACKGROUND: Re-excision surgeries for the treatment of ductal carcinoma in situ (DCIS) put a strain on patients and healthcare resources; however, intraoperative pathologic assessment of DCIS may lead to a reduction in these additional surgeries. This study examined the relationship between intraoperative pathologic assessment and subsequent operations in patients with a diagnosis of DCIS. METHODS: Surveillance, Epidemiology, and End Results-Medicare patients diagnosed with DCIS from 1999 to 2007 who initially underwent partial mastectomy, without axillary surgery, were included in this study. Use of intraoperative frozen section or touch preparation during the initial surgery was assessed. Multivariable logistic regression was used to describe the relationship between the use of intraoperative pathologic assessment and any subsequent mastectomy or partial mastectomy within 90 days of the initial partial mastectomy. RESULTS: Of 8259 DCIS patients, 3509 (43 %) required a second surgery, and intraoperative pathologic assessment was performed for 2186 (26 %). Intraoperative pathologic assessment had no statistically significant effect on whether or not a subsequent breast surgery occurred (adjusted odds ratio 1.07, 95 % confidence interval 0.95-1.21; p = 0.293). Patient residence in a rural area, tumor size ≥2 cm, and poorly differentiated tumor grade were associated with a greater likelihood of subsequent surgery, while age 80 years and older was associated with a lower likelihood of subsequent surgery. CONCLUSIONS: The use of intraoperative frozen section or touch preparation during partial mastectomy from 1999 to 2007 was not associated with a reduction in subsequent breast operations in women with DCIS. These results highlight the need to identify cost-effective tools and strategies to reduce the need for additional surgery in patients with DCIS.


Subject(s)
Breast Neoplasms/pathology , Breast Neoplasms/surgery , Carcinoma, Intraductal, Noninfiltrating/pathology , Carcinoma, Intraductal, Noninfiltrating/surgery , Frozen Sections/statistics & numerical data , Reoperation/statistics & numerical data , Age Factors , Aged , Aged, 80 and over , Female , Humans , Intraoperative Period , Mastectomy, Segmental , Neoplasm Grading , Retrospective Studies , Rural Population/statistics & numerical data , SEER Program , Tumor Burden , Urban Population/statistics & numerical data
15.
Invest New Drugs ; 34(2): 168-75, 2016 Apr.
Article in English | MEDLINE | ID: mdl-26666244

ABSTRACT

BACKGROUND: KRAS mutations are clinically important predictors of resistance to EGFR-directed therapies in colorectal cancer (CRC). Oncogenic activation of the RAS/RAF/MEK/ERK signaling cascade mediates proliferation independent of growth factor signaling. We hypothesized that targeting MEK with selumetinib could overcome resistance to cetuximab in KRAS mutant CRC. METHODS: A phase I study (NCT01287130) was undertaken to determine the tolerability, and pharmacokinetic profiles of the combination of selumetinib and cetuximab, with an expanded cohort in KRAS-mutant CRC. RESULTS: 15 patients were treated in the dose escalation cohort and 18 patients were treated in the expansion cohort. Two dose-limiting toxicities were observed. One grade 3 acneiform rash and one grade 4 hypomagnesemia occurred. The most common grade 1 and 2 adverse events included rash, nausea/vomiting, diarrhea, and fatigue. The maximum tolerated dose was established at selumetinib 75 mg p.o. BID and cetuximab 250 mg/m(2) weekly following a 400 mg/m(2) load. Best clinical response in the dose escalation group included 1 unconfirmed partial response in a patient with CRC and stable disease (SD) in 5 patients (1 squamous cell carcinoma of the tonsil, 1 non-small cell lung cancer, and 3 CRC), and in the KRAS-mutant CRC dose expansion cohort, of the 14 patients who were evaluable for response, 5 patients had SD and 9 patients had progressive disease. CONCLUSIONS: The combination of selumetinib and cetuximab is safe and well tolerated. Minimal anti-tumor activity was observed in KRAS-mutant refractory metastatic CRC. Further investigations might be warranted in other cancer subtypes.


Subject(s)
Benzimidazoles/therapeutic use , Cetuximab/therapeutic use , Colorectal Neoplasms/drug therapy , Mitogen-Activated Protein Kinase Kinases/antagonists & inhibitors , Mutation/genetics , Protein Kinase Inhibitors/therapeutic use , Proto-Oncogene Proteins p21(ras)/genetics , Adult , Aged , Aged, 80 and over , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Antineoplastic Combined Chemotherapy Protocols/pharmacokinetics , Antineoplastic Combined Chemotherapy Protocols/pharmacology , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Benzimidazoles/adverse effects , Benzimidazoles/pharmacokinetics , Benzimidazoles/pharmacology , Cetuximab/adverse effects , Cetuximab/pharmacology , Colorectal Neoplasms/blood , Colorectal Neoplasms/genetics , Dose-Response Relationship, Drug , Female , Humans , Male , Maximum Tolerated Dose , Middle Aged , Mitogen-Activated Protein Kinase Kinases/metabolism , Protein Kinase Inhibitors/pharmacology , Treatment Outcome
16.
Clin Colon Rectal Surg ; 29(3): 232-8, 2016 Sep.
Article in English | MEDLINE | ID: mdl-27582648

ABSTRACT

As treatment strategies for patients with colorectal cancer advance, there has now become an ever-increasing need for multidisciplinary teams to care for these patients. Recent investigations into the timing and duration of perioperative therapy, as well as, the rise of molecular profiling have led to more systemic chemotherapeutic options. The most efficacious use, in terms of timing and patient selection, of these therapies in the setting of modern operative and radiotherapy techniques requires the generation of care teams discussing cases at multidisciplinary conferences. This review highlights the role of multidisciplinary team conferences, advances in perioperative chemotherapy, current clinical biomarkers, and emerging therapeutic agents for molecular subtypes of metastatic colon cancer. As our understanding of relevant molecular subtypes increases and as data becomes available on treatment response, the treatment of colorectal cancer will become more precise and effective.

18.
Invest New Drugs ; 33(1): 169-76, 2015 Feb.
Article in English | MEDLINE | ID: mdl-25318436

ABSTRACT

BACKGROUND: RO4929097 is an oral inhibitor of γ -secretase that results in Notch signaling inhibition. Prior work has demonstrated that Notch signaling inhibition enhances chemotherapy sensitivity of cancer cells. This phase I study was conducted to determine maximum tolerated dose (MTD), toxicities and efficacy of RO4929097 and capecitabine in advanced solid tumors. METHODS: Patients with refractory solid tumors received capecitabine at a fixed dose of 1,000 mg/m(2) twice daily with escalating doses of RO4929097 on a 21-day cycle in a 3 + 3 design. Capecitabine was administered for 14 days and the RO49029097 once daily, 3 days per week, both for a 21 day cycle. RESULTS: Thirty patients were treated on six dose levels (20 to 150 mg). The maximally tolerated dose was not reached. One dose limiting toxicity was observed at each level 3 through 6 (hypophosphatemia, fatigue, and nausea/vomiting). Three confirmed partial responses were observed: two patients with fluoropyrimide-refractory colon cancer and one patient with cervical cancer. Autoinduction of RO4929097 was demonstrated with increasing dose levels and duration. CONCLUSIONS: The recommended phase 2 dose is capecitabine 1,000 mg/m(2) orally twice daily on days 1 through 14 with RO4929097 20 mg orally once daily on days 1-3, 8-10 and 15-17 with a 21 day cycle. Clinical benefit was observed in cervical and colon cancer. Autoinduction of RO4929097 was seen both with increasing cycle number and increasing dose. Plasma concentrations of RO4929097 were above those needed for Notch inhibition.


Subject(s)
Amyloid Precursor Protein Secretases/antagonists & inhibitors , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Neoplasms/drug therapy , Aged , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Antineoplastic Combined Chemotherapy Protocols/blood , Antineoplastic Combined Chemotherapy Protocols/pharmacokinetics , Benzazepines/administration & dosage , Benzazepines/adverse effects , Benzazepines/blood , Benzazepines/pharmacokinetics , Capecitabine , Deoxycytidine/administration & dosage , Deoxycytidine/adverse effects , Deoxycytidine/analogs & derivatives , Female , Fluorouracil/administration & dosage , Fluorouracil/adverse effects , Fluorouracil/analogs & derivatives , Humans , Male , Maximum Tolerated Dose , Middle Aged , Neoplasms/metabolism , Prodrugs/administration & dosage , Prodrugs/adverse effects
19.
Ann Surg Oncol ; 21(6): 1781-91, 2014 Jun.
Article in English | MEDLINE | ID: mdl-24643898

ABSTRACT

BACKGROUND: Survival benefit from adjuvant chemotherapy is established for stage III colon cancer; however, uncertainty exists for stage II patients. Tumor heterogeneity, specifically microsatellite instability (MSI), which is more common in right-sided cancers, may be the reason for this observation. We examined the relationship between adjuvant chemotherapy and overall 5-year mortality for stage II colon cancer by location (right- vs left-side) as a surrogate for MSI. METHODS: Using Surveillance, Epidemiology, and End Results (SEER)-Medicare data, we identified Medicare beneficiaries from 1992 to 2005 with AJCC stage II (n = 23,578) and III (n = 17,148) primary adenocarcinoma of the colon who underwent surgery for curative intent. Overall 5-year mortality was examined with Kaplan-Meier survival analysis and Cox proportional hazards regression with propensity score weighting. RESULTS: It was found that 18 % of stage II patients (n = 2941) with right-sided cancer and 22 % (n = 1693) with left-sided cancer received adjuvant chemotherapy. After adjustment, overall 5-year survival benefit from chemotherapy was observed only for stage III patients (right-sided: hazard ratio [HR], 0.64; 95 % CI, 0.59-0.68; p < .001 and left-sided: HR, 0.61; 95 % CI, 0.56-0.68; p < .001). No survival benefit was observed for stage II patients with either right-sided (HR, 0.97; 95 % CI, 0.87-1.09; p = .64) or left-sided cancer (HR, 0.97; 95 % CI, 0.84-1.12; p = .68). CONCLUSIONS: Among Medicare patients with stage II colon cancer, a substantial number receive adjuvant chemotherapy. Adjuvant chemotherapy did not improve overall 5-year survival for either right- or left-sided colon cancers. Our results reinforce existing guidelines and should be considered in treatment algorithms for older adults with stage II colon cancer.


Subject(s)
Adenocarcinoma/drug therapy , Adenocarcinoma/pathology , Colonic Neoplasms/drug therapy , Colonic Neoplasms/pathology , Adenocarcinoma/mortality , Aged , Aged, 80 and over , Chemotherapy, Adjuvant , Colon, Ascending , Colon, Descending , Colon, Sigmoid , Colon, Transverse , Colonic Neoplasms/mortality , Female , Humans , Male , Medicare/statistics & numerical data , Neoplasm Staging , SEER Program/statistics & numerical data , Survival Rate , United States/epidemiology
20.
J Surg Oncol ; 109(8): 756-9, 2014 Jun.
Article in English | MEDLINE | ID: mdl-24643795

ABSTRACT

BACKGROUND: Use of sentinel lymph node biopsy (SLNB) is under-reported by cancer registries' "Scope of Regional Lymph Node Surgery" variable. In 2011, the Surveillance Epidemiology and End Results (SEER) Program recommended against its use to determine extent of axillary surgery, leaving a gap in the utilization of claims data for breast cancer research. The objective was to develop an algorithm using SEER registry and claims data to classify extent of axillary surgery for breast cancer. METHODS: We analyzed data for 24,534 breast cancer patients. CPT codes and number of examined lymph nodes classified the extent of axillary surgery. The final algorithm was validated by comparing the algorithm derived extent of axillary surgery to direct chart review for 100 breast cancer patients treated at our breast center. RESULTS: Using the algorithm, 13% had no axillary surgery, 56% SLNB and 31% axillary lymph node dissection (ALND). SLNB was performed in 77% of node negative patients and ALND in 72% of node positive. In our validation study, concordance between algorithm and direct chart review was 97%. CONCLUSIONS: Given recognized inaccuracies in cancer registries' "Scope of Regional Lymph Node Surgery" variable, these findings have high utility for health services researchers studying breast cancer treatment.


Subject(s)
Breast Neoplasms/surgery , Lymph Node Excision , Patient Selection , SEER Program , Algorithms , Axilla , Breast Neoplasms/epidemiology , Databases, Factual/statistics & numerical data , Female , Humans , Mastectomy , Medicare/statistics & numerical data , Prognosis , Sentinel Lymph Node Biopsy , United States/epidemiology
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