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1.
Acta Cytol ; 56(3): 285-8, 2012.
Article in English | MEDLINE | ID: mdl-22555531

ABSTRACT

BACKGROUND: Grading upper tract urothelial carcinomas (UTUC) in cell blocks with small distorted tissue fragments can be challenging; interobserver agreement is poor among pathologists. Mitotic figure (MF) counting along with nuclear features is important in grading these tumors. We evaluated the use of the mitotic-specific marker phosphohistone H3 (PHH3) as an adjunct to hematoxylin and eosin (H&E) stain for grading UTUC in cell blocks. METHODS: Formalin-fixed, paraffin-embedded tissues from the cell blocks of 61 UTUC were stained with H&E and PHH3 antibody. The grading of tumors was performed independently by 3 pathologists, on both H&E-stained and PHH3 plus H&E-stained slides. The grading system used was the 1973 WHO 3-point grading system. Gradings were compared by all the pathologists for H&E staining versus PHH3 plus H&E staining with the Stuart-Maxwell test of marginal homogeneity that accounts for the matched data. RESULTS: The average pairwise agreement by H&E alone was 55%, and 80% by PHH3 plus H&E. CONCLUSION: By adding PHH3 immunostain to the H&E, the agreement in grading the carcinomas among the 3 pathologists improved dramatically. PHH3 immunostain may play an important role in grading UTUC in small cell block samples.


Subject(s)
Biomarkers, Tumor/metabolism , Carcinoma/pathology , Histones/metabolism , Mitotic Index/methods , Neoplasm Grading/methods , Phosphoproteins/metabolism , Urinary Bladder Neoplasms/pathology , Urothelium/pathology , Carcinoma/metabolism , Humans , Phosphorylation/physiology , Predictive Value of Tests , Urinary Bladder Neoplasms/metabolism , Urinary Bladder Neoplasms/physiopathology , Urothelium/metabolism
2.
PLoS One ; 16(7): e0254337, 2021.
Article in English | MEDLINE | ID: mdl-34329299

ABSTRACT

Sentiment analysis is an evolving field of study that employs artificial intelligence techniques to identify the emotions and opinions expressed in a given text. Applying sentiment analysis to study the billions of messages that circulate in popular online social media platforms has raised numerous opportunities for exploring the emotional expressions of their users. In this paper we combine sentiment analysis with natural language processing and topic analysis techniques and conduct two different studies to examine whether engagement in entrepreneurship is associated with more positive emotions expressed on Twitter. In study 1, we investigate three samples with 6.717.308, 13.253.244, and 62.067.509 tweets respectively. We find that entrepreneurs express more positive emotions than non-entrepreneurs for most topics. We also find that social entrepreneurs express more positive emotions, and that serial entrepreneurs express less positive emotions than other entrepreneurs. In study 2, we use 21.491.962 tweets to explore 37.225 job-status changes by individuals who entered or quit entrepreneurship. We find that a job change to entrepreneurship is associated with a shift in the expression of emotions to more positive ones.


Subject(s)
Emotions , Entrepreneurship , Social Media , Humans , London , Los Angeles , Regression Analysis
3.
Breast Cancer Res Treat ; 121(2): 519-26, 2010 Jun.
Article in English | MEDLINE | ID: mdl-19768651

ABSTRACT

The aim of the study is to use the EQ-5D instrument to evaluate the long-term health states of women with early stage breast cancer treated by breast-conserving surgery and radiation. A total of 1,050 women treated with conservative surgery and radiation with or without systemic therapy completed 2,480 questionnaires during follow-up visits. The EQ-5D is a standardized and validated instrument for measuring quality of life outcomes. The descriptive system uses 5 dimensions of health with three possible levels of response that combine into 243 (3(5)) possible unique health states that are each assigned a values-based index score from 0 to 1. The visual analog scale (VAS) rates health on a simple vertical line from 0 to 100. Higher scores correspond to better health status. The mean index scores were 0.89 (95% CI: 0.87-0.91) at 5 years, 0.9 (95% CI: 0.86-0.94) at 10 years, and 0.9 (95% CI: 0.83-1.0) at 15 years. There were no significant differences in health states between patients by age when compared with U.S. controls. There was a statistically significant positive correlation between the results of the VAS and descriptive system. Significant trends in health dimensions over 15 years were increased problems with self-care and decreased problems with anxiety/depression, pain/discomfort, and performing usual activities. This study of EQ-5D is unique and demonstrates very high quality of life in patients long-term after breast-conserving surgery and radiation. These health states are comparable to the adult female U.S. population. These data will provide valuable patient utility information for informing decision analyses investigating new treatments in women with breast cancer.


Subject(s)
Breast Neoplasms , Health Status , Outcome Assessment, Health Care , Quality of Life , Activities of Daily Living , Adolescent , Adult , Aged , Breast Neoplasms/psychology , Breast Neoplasms/therapy , Female , Health Status Indicators , Humans , Mastectomy , Middle Aged , Radiotherapy , Young Adult
4.
5.
J Clin Oncol ; 23(10): 2145-54, 2005 Apr 01.
Article in English | MEDLINE | ID: mdl-15800308

ABSTRACT

PURPOSE: To test the ability of the cytoprotectant, amifostine, to reduce chemoradiotherapy-induced esophagitis and evaluate its influence on quality of life (QOL) and swallowing symptoms. PATIENTS AND METHODS: A total of 243 patients with stage II to IIIA/B non-small-cell lung cancer received induction paclitaxel 225 mg/m(2) intravenously (IV) days 1 and 22 and carboplatin area under the curve (AUC) days 1 and 22, followed by concurrent weekly paclitaxel (50 mg/m(2) IV) and carboplatin (AUC 2), and hyperfractionated radiation therapy (69.6 Gy at 1.2 Gy bid). Patients were randomly assigned at registration to amifostine (AM) 500 mg IV four times per week or no AM during chemoradiotherapy. Beyond standard toxicity end points, physician dysphagia logs (PDLs), daily patient swallowing diaries, and QOL (EORTC QLQ-C30/LC-13) were also collected. Swallowing AUC analyses were calculated from patient diaries and PDLs. RESULTS: A total of 120 patients were randomly assigned to receive AM, and 122, to receive no AM (one patient was ineligible); 72% received AM per protocol or with a minor deviation. AM was associated with higher rates of acute nausea (P = .03), vomiting (P = .007), cardiovascular toxicity (P = .0001), and infection or febrile neutropenia (P = .03). The rate of >/= grade 3 esophagitis was 30% with AM versus 34% without AM (P = .9). Patient diaries demonstrated lower swallowing dysfunction AUC with amifostine (z test P = .025). QOL was not significantly different between the two arms, except for pain, which showed more clinically meaningful improvement and less deterioration at 6 weeks follow-up (v pretreatment) in the AM arm (P = .003). The median survival rates for both arms were comparable (AM, 17.3 v no AM, 17.9 months; P = .87). CONCLUSION: AM did not significantly reduce esophagitis >/= grade 3 in patients receiving hyperfractionated radiation and chemotherapy. However, patient self-assessments suggested a possible advantage to AM that is being explored with modified dosing route strategies.


Subject(s)
Amifostine/therapeutic use , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Carcinoma, Non-Small-Cell Lung/drug therapy , Carcinoma, Non-Small-Cell Lung/radiotherapy , Deglutition Disorders/etiology , Deglutition Disorders/prevention & control , Esophagitis/etiology , Esophagitis/prevention & control , Lung Neoplasms/drug therapy , Lung Neoplasms/radiotherapy , Quality of Life , Radiation Injuries/prevention & control , Radiation-Protective Agents/therapeutic use , Aged , Carboplatin/administration & dosage , Combined Modality Therapy , Dose Fractionation, Radiation , Female , Humans , Infusions, Intravenous , Male , Middle Aged , Paclitaxel/administration & dosage , Survival Analysis , Treatment Outcome
6.
Int J Radiat Oncol Biol Phys ; 61(5): 1328-36, 2005 Apr 01.
Article in English | MEDLINE | ID: mdl-15817334

ABSTRACT

PURPOSE: Most recurrences in the breast after conservative surgery and whole-breast irradiation have been reported to occur within the same quadrant as the initial primary tumor. We analyzed the long-term risk of recurrence by area of the breast after whole-breast irradiation. MATERIALS AND METHODS: In all, 1,990 women with Stage 0-II breast cancer were treated with conservative surgery and whole-breast irradiation from 1970-1998. Stage was ductal carcinoma in situ in 237, T1 in 1273, and T2 in 480 patients. Of 120 local recurrences, 71 were classified as true local (confined to the original quadrant) and 49 as elsewhere (involving outside the original quadrant). Kaplan-Meier methodology was used to calculate 5-year, 10-year, and 15-year rates of recurrence (95% confidence intervals in parentheses). The median follow-up is 80 months. RESULTS: There was no apparent difference in the 15-year rate of true local vs. elsewhere recurrence, but the time to recurrence was different. The rate of true local recurrence was 2%, 5%, and 7% (5-9%) at 5, 10, and 15 years, respectively. The recurrences elsewhere in the breast were rare at 5 (1%) and 10 (2%) years, but increased to 6 (3-9%) at 15 years. This 15-year rate of elsewhere recurrence was half the rate of contralateral breast cancers of 13% (10-16%). CONCLUSIONS: Recurrence elsewhere in the breast is rare for the first 10 years, but by 15 years is nearly equal to true local recurrence even after whole-breast irradiation. The 15-year rate of elsewhere recurrence was half the rate of contralateral breast cancers. This may indicate a therapeutic effect of whole-breast radiation for other areas of the breast. Very long follow-up will be needed for partial breast irradiation with or without tamoxifen to show that the risk of elsewhere recurrence is not significantly different than after whole-breast irradiation.


Subject(s)
Breast Neoplasms/therapy , Carcinoma in Situ/therapy , Carcinoma, Ductal, Breast/therapy , Mastectomy, Segmental , Neoplasm Recurrence, Local , Adult , Aged , Aged, 80 and over , Antineoplastic Agents, Hormonal/therapeutic use , Breast Neoplasms/pathology , Breast Neoplasms/radiotherapy , Breast Neoplasms/surgery , Carcinoma in Situ/pathology , Carcinoma in Situ/radiotherapy , Carcinoma in Situ/surgery , Carcinoma, Ductal, Breast/pathology , Carcinoma, Ductal, Breast/radiotherapy , Carcinoma, Ductal, Breast/surgery , Female , Humans , Middle Aged , Neoplasm Recurrence, Local/pathology , Tamoxifen/therapeutic use
7.
J Invest Dermatol ; 121(6): 1522-30, 2003 Dec.
Article in English | MEDLINE | ID: mdl-14675205

ABSTRACT

The histologic diagnosis of cutaneous lymphoid lesions remains one of the most challenging areas of dermatopathology and is augmented by incorporation of immunophenotypic and genotypic data. To improve the analysis of surface Ig light chain expression and to increase the yield of immunophenotypic data obtained from skin biopsies, we evaluated the utility of flow cytometry in cutaneous lymphoid infiltrates. Flow cytometric immunophenotypic analyses were performed on skin specimens of 19 patients as a part of diagnostic procedures. We found that skin biopsy specimens, including a routine punch biopsy, yield sufficient material for diagnostic flow cytometry. One reactive lymphoid hyperplasia showed polyclonal B cells and no aberrant T cell populations. Ig light chain restriction was detected by flow cytometry and contributed to the diagnosis in 88% (15 of 17) of cutaneous primary or secondary B cell lymphomas, compared to 37% (three of eight) by immunohistochemistry. Nearly one-third of these cases were histologically suspicious but difficult lesions due to processing artifact, mixed cellular infiltrate, or paucity of abnormal cells. Additional markers (3-23) were analyzed by flow cytometry on 15 specimens, and contributed to subclassification of the lymphomas. Our experience demonstrates that flow cytometry can be successfully applied to routine skin biopsies and contributes to the diagnosis and subclassification of cutaneous lymphoid lesions.


Subject(s)
Flow Cytometry , Lymphoma, B-Cell/pathology , Lymphoma, Large B-Cell, Diffuse/pathology , Skin Neoplasms/pathology , Adult , Aged , Aged, 80 and over , Artifacts , Biopsy , Diagnosis, Differential , Female , Gene Rearrangement, T-Lymphocyte/genetics , Humans , Immunoglobulin Heavy Chains/genetics , Immunophenotyping , Lymphoma, B-Cell/genetics , Lymphoma, Large B-Cell, Diffuse/genetics , Male , Middle Aged , Skin Neoplasms/genetics
8.
Clin Breast Cancer ; 5(3): 225-31, 2004 Aug.
Article in English | MEDLINE | ID: mdl-15335456

ABSTRACT

A comparison was made of pretreatment characteristics and outcomes of patients with stage I/II breast cancer treated with breast-conserving therapy who had a history of parity with those who were nulliparous. From 1979 to 1996, 1358 women with stage I/II (T1/2 N0/1 M0) breast cancer underwent lumpectomy, axillary dissection, and radiation therapy with or without systemic therapy. Of the total population, 1162 patients (86%) were parous and 196 patients (14%) were nulliparous. The median follow-up was 87 months. The 2 groups were compared for clinical, pathologic, and treatment-related factors. Multivariate analysis was used to determine independent predictors of outcome. Outcome was also evaluated for patterns of failure including distant metastases (DM), cause-specific survival (CSS), and overall survival (OS). Significant differences between the 2 groups were observed for age > 60 years and median age. Multivariate analysis demonstrated that nulliparous status was an independent predictor of DM, CSS, and OS after adjusting for age. Multivariate analysis for DM, CSS, and OS for patients > 60 years of age demonstrated that parity was the most highly significant independent predictor of decreased DM and improved OS. Parity can be considered a prognostic factor in elderly patients with early-stage breast cancer, and therefore may be used as a tool for identifying patients who may benefit from a more aggressive treatment approach.


Subject(s)
Breast Neoplasms/pathology , Breast Neoplasms/therapy , Parity , Adult , Age Factors , Aged , Aged, 80 and over , Antineoplastic Agents/therapeutic use , Female , Follow-Up Studies , Humans , Mastectomy, Segmental , Middle Aged , Neoplasm Staging , Prognosis , Survival Rate
10.
Head Neck ; 33(2): 286-8, 2011 Feb.
Article in English | MEDLINE | ID: mdl-19953623

ABSTRACT

BACKGROUND: Head and neck cutaneous squamous cell carcinoma (SCC) metastatic to lymph nodes is commonly treated with surgery plus radiotherapy. METHODS: We present the case of a 92-year-old man with cutaneous SCC metastatic to the neck (7 cm) who was treated with primary cetuximab and has had a durable complete response for 7 months. Because of his age, comorbidities, and unresectable neck lymphadenopathy, he received primary cetuximab. He received a 400 mg/m(2) loading dose and a 250 mg/m(2) weekly dose for 3 months and then had to discontinue as a result of other unrelated medical issues. RESULTS: The patient had a complete response by 6 weeks. Seven months after discontinuing cetuximab, he continues to have a complete response. CONCLUSIONS: Primary cetuximab for cutaneous SCC metastatic to lymph nodes is an area that bears further investigation because of its apparent efficacy and excellent toxicity profile.


Subject(s)
Antibodies, Monoclonal/therapeutic use , Antineoplastic Agents/therapeutic use , Carcinoma, Squamous Cell/drug therapy , Head and Neck Neoplasms/drug therapy , Skin Neoplasms/drug therapy , Aged, 80 and over , Antibodies, Monoclonal, Humanized , Carcinoma, Squamous Cell/secondary , Cetuximab , Head and Neck Neoplasms/secondary , Humans , Lymphatic Metastasis , Male , Neoplasm Staging , Risk Factors , Skin Neoplasms/pathology , Treatment Outcome
11.
Head Neck ; 33(10): 1433-40, 2011 Oct.
Article in English | MEDLINE | ID: mdl-21928415

ABSTRACT

BACKGROUND: Oropharyngeal, laryngeal, and hypopharyngeal cancer treatment has changed at our institution, but survival outcomes have not been evaluated. METHODS: We approached the evaluation by a retrospective single-institution cohort study. RESULTS: Review of 180 patient records from 1993 to 2004 revealed that the number of patients with oropharyngeal cancer treated nearly doubled, whereas the number of patients with laryngeal and hypopharyngeal cancers declined (p = .006). Since 2000, concurrent chemotherapeutic regimens rather than radiation alone became the dominant treatment approach, with associated improvements in recurrence-free and overall survival (p = .009 and p = .006, respectively). Stratification by tumor site, however, revealed the survival of patients with oropharyngeal cancer improved markedly, whereas the survival of patients with laryngeal cancer did not change. In the multivariate analysis, T classification (p = .0001) and chemotherapy use (p = .0001) were associated with improved survival. The recurrence-free survival of nonsmokers was better than that for former or current smokers (p = .01), but was accounted for by earlier T classification on presentation in the multivariate analysis (p = .0001). The predominant initial site of failure remained at the primary site for oropharyngeal cancer (14 of 17 relapses or 82%), but not laryngeal cancer (3 of 7 relapses or 42%). As a result, an increasing number of patients with recurrent oropharyngeal cancer, and a decreasing number of recurrent laryngeal cancer patients were evaluated for salvage surgery. Patients with oropharyngeal recurrences, however, were less likely to undergo surgery with curative intent (p = .02) and were less likely to achieve locoregional control after disease recurrence. CONCLUSIONS: The survival of patients with oropharyngeal and hypopharyngeal cancers treated at our institution has improved over the last 15 years, which is likely related to changes in treatment and tumor biology. The improvement was not observed in patients with laryngeal cancer. A subset of patients with oropharyngeal cancer remain subject to local failure and disease-related death.


Subject(s)
Hypopharyngeal Neoplasms/mortality , Hypopharyngeal Neoplasms/therapy , Laryngeal Neoplasms/mortality , Laryngeal Neoplasms/therapy , Oropharyngeal Neoplasms/mortality , Oropharyngeal Neoplasms/therapy , Cancer Care Facilities , Carcinoma, Squamous Cell/mortality , Carcinoma, Squamous Cell/pathology , Carcinoma, Squamous Cell/therapy , Chemoradiotherapy, Adjuvant , Cohort Studies , Disease-Free Survival , Female , Humans , Hypopharyngeal Neoplasms/pathology , Laryngeal Neoplasms/pathology , Male , Middle Aged , Neoplasm Recurrence, Local/surgery , Oropharyngeal Neoplasms/pathology , Proportional Hazards Models , Radiotherapy, Conformal , Radiotherapy, Intensity-Modulated , Retrospective Studies , Salvage Therapy , Smoking/adverse effects
12.
Int J Radiat Oncol Biol Phys ; 79(1): 65-70, 2011 Jan 01.
Article in English | MEDLINE | ID: mdl-20385457

ABSTRACT

PURPOSE: To determine differences in clinical outcomes using intensity-modulated radiotherapy (IMRT) or a standard low neck field (LNF) to treat low neck. METHODS AND MATERIALS: This is a retrospective, single-institution study. Ninety-one patients with squamous cell carcinoma of the head and neck were treated with curative intent. According to physician preference, some patients were treated with LNF (Planning Target Volume 3) field using a single anterior photon field matched to the IMRT field. Field junctions were not feathered. The endpoints were time to failure and use of a percutaneous endoscopic gastrostomy (PEG) tube (as a surrogate of laryngeal edema causing aspiration), and analysis was done with χ(2) and log-rank tests. RESULTS: Median follow-up was 21 months (range, 2-89 months). Median age was 60 years. Thirty-seven patients (41%) were treated with LNF, 84% were Stage III or IV. A PEG tube was required in 30%, as opposed to 33% without the use of LNF. Node 2 or 3 neck disease was treated more commonly without LNF (38% vs. 24%, p = 0.009). Failures occurred in 12 patients (13%). Only 1 patient treated with LNF failed regionally, 4.5 cm above the match line. The 3-year disease-free survival rate was 87% and 79% with LNF and without LNF, respectively (p = 0.2), and the 3-year LR failure rate was 4% and 21%, respectively (p = 0.04). CONCLUSIONS: Using LNF to treat the low neck did not increase the risk of regional failure "in early T and early N diseases" or decrease PEG tube requirements.


Subject(s)
Carcinoma, Squamous Cell/radiotherapy , Head and Neck Neoplasms/radiotherapy , Radiotherapy, Intensity-Modulated/methods , Adult , Aged , Aged, 80 and over , Antineoplastic Agents/therapeutic use , Carcinoma, Squamous Cell/drug therapy , Carcinoma, Squamous Cell/pathology , Carcinoma, Squamous Cell/surgery , Chi-Square Distribution , Combined Modality Therapy/methods , Disease-Free Survival , Female , Follow-Up Studies , Gastrostomy/instrumentation , Gastrostomy/statistics & numerical data , Head and Neck Neoplasms/drug therapy , Head and Neck Neoplasms/pathology , Head and Neck Neoplasms/surgery , Humans , Linear Models , Lymph Node Excision , Male , Middle Aged , Radiotherapy Dosage , Radiotherapy, Intensity-Modulated/adverse effects , Retrospective Studies , Treatment Failure
13.
Int J Radiat Oncol Biol Phys ; 81(1): 69-76, 2011 Sep 01.
Article in English | MEDLINE | ID: mdl-20732766

ABSTRACT

PURPOSE: We examined the impact of radiation tumor bed boost parameters in early-stage breast cancer on local control and cosmetic outcomes. METHODS AND MATERIALS: A total of 3,186 women underwent postlumpectomy whole-breast radiation with a tumor bed boost for Tis to T2 breast cancer from 1970 to 2008. Boost parameters analyzed included size, energy, dose, and technique. Endpoints were local control, cosmesis, and fibrosis. The Kaplan-Meier method was used to estimate actuarial incidence, and a Cox proportional hazard model was used to determine independent predictors of outcomes on multivariate analysis (MVA). The median follow-up was 78 months (range, 1-305 months). RESULTS: The crude cosmetic results were excellent in 54%, good in 41%, and fair/poor in 5% of patients. The 10-year estimate of an excellent cosmesis was 66%. On MVA, independent predictors for excellent cosmesis were use of electron boost, lower electron energy, adjuvant systemic therapy, and whole-breast IMRT. Fibrosis was reported in 8.4% of patients. The actuarial incidence of fibrosis was 11% at 5 years and 17% at 10 years. On MVA, independent predictors of fibrosis were larger cup size and higher boost energy. The 10-year actuarial local failure was 6.3%. There was no significant difference in local control by boost method, cut-out size, dose, or energy. CONCLUSIONS: Likelihood of excellent cosmesis or fibrosis are associated with boost technique, electron energy, and cup size. However, because of high local control and rare incidence of fair/poor cosmesis with a boost, the anatomy of the patient and tumor cavity should ultimately determine the necessary boost parameters.


Subject(s)
Breast Neoplasms/radiotherapy , Breast Neoplasms/surgery , Adult , Aged , Aged, 80 and over , Analysis of Variance , Breast/pathology , Breast/radiation effects , Breast Neoplasms/pathology , Combined Modality Therapy/methods , Female , Fibrosis , Humans , Mastectomy, Segmental/methods , Middle Aged , Neoplasm Staging , Organ Size , Treatment Outcome , Tumor Burden , Young Adult
14.
J Appl Psychol ; 95(6): 1154-62, 2010 Nov.
Article in English | MEDLINE | ID: mdl-20718525

ABSTRACT

We applied multivariate genetics techniques to a sample of 3,412 monozygotic and dizygotic twins from the United Kingdom and 1,300 monozygotic and dizygotic twins from the United States to examine whether genetic factors account for part of the covariance between the Big Five personality characteristics and the tendency to be an entrepreneur. We found that common genes influenced the phenotypic correlations between only Extraversion and Openness to Experience and the tendency to be an entrepreneur. Although the phenotypic correlations between the personality characteristics and the tendency to be an entrepreneur were small in size, genetic factors accounted for most of them.


Subject(s)
Employment/psychology , Personality/genetics , Adult , Female , Humans , Male , Phenotype , United Kingdom , United States
15.
Head Neck ; 32(3): 341-7, 2010 Mar.
Article in English | MEDLINE | ID: mdl-19693946

ABSTRACT

BACKGROUND: The impact of posttreatment neck dissection on prolonged feeding tube dependence in patients with head and neck squamous cell cancer (HNSCC) treated with primary radiation or chemoradiation remains unknown. METHODS: We conducted a retrospective cohort study using propensity score adjustment to investigate the effect of neck dissection on prolonged feeding tube dependence. RESULTS: A review of 67 patients with node-positive HNSCC (T1-4N1-3), treated with primary radiation or chemoradiation, with no evidence of tumor recurrence and follow-up of at least 24 months, was performed. Following adjustment for covariates, the relative risk (RR) of feeding tube dependence at 18 months was significantly increased in patients treated with posttreatment neck dissection (RR 4.74, 95% confidence interval [CI] 2.07-10.89). At 24 months, the relative risk of feeding tube dependence in the patients having undergone neck dissection increased further (RR 7.66, 95% CI 2.07-10.89). Of patients with feeding tubes 2 years after completing treatment, 75% remained feeding tube dependent. CONCLUSION: Neck dissection may contribute to chronic oropharyngeal dysphagia in HNSCC patients treated with primary radiation or chemoradiation.


Subject(s)
Carcinoma, Squamous Cell/therapy , Deglutition Disorders/therapy , Enteral Nutrition , Head and Neck Neoplasms/therapy , Neck Dissection , Aged , Carcinoma, Squamous Cell/pathology , Chemotherapy, Adjuvant , Cohort Studies , Deglutition Disorders/etiology , Female , Head and Neck Neoplasms/pathology , Humans , Male , Middle Aged , Patient Selection , Radiotherapy, Adjuvant , Retrospective Studies , Risk Factors , Time Factors
16.
Int J Radiat Oncol Biol Phys ; 78(4): 1020-5, 2010 Nov 15.
Article in English | MEDLINE | ID: mdl-20231078

ABSTRACT

PURPOSE: To present the first report of a Phase I trial evaluating concurrent and maintenance erlotinib and reirradiation in patients with recurrent or secondary primary head-and-neck cancer (HNC). METHODS AND MATERIALS: Patients with recurrent or new primary HNC with an interval of at least 6 months since prior radiation were eligible. Patients were treated in 3 sequential cohorts: Cohort I, 100 mg of erlotinib daily with reirradiation at 61.6 Gy in 28 fractions; Cohort II, 150 mg of erlotinib with 61.6 Gy in 28 fractions; and Cohort III, 150 mg of erlotinib with 66 Gy in 30 fractions. Maintenance erlotinib started immediately after reirradiation at 150 mg daily and was continued for 2 years or until disease progression or dose-limiting toxicity. Dose-limiting toxicities were defined as any Grade 4 or 5 toxicity or a toxicity-related delay in radiation therapy of greater than 7 days. RESULTS: Fourteen patients were accrued, 3 to Cohort I, 4 to Cohort II, and 7 to Cohort III. Thirteen patients were evaluable for toxicity. Median follow-up was 8.4 months overall and 15.1 months for surviving patients. One patient had a dose-limiting toxicity in Cohort III. This patient declined initial percutaneous endoscopic gastrostomy tube placement, was hospitalized with Grade 3 dysphagia and aspiration, and required a delay in radiation therapy of greater than 7 days. No Grade 4 acute toxicity was observed. Acute Grade 3 toxicity occurred in 9 of 13 patients. No erlotinib-related toxicity of Grade 3 or greater was observed during maintenance therapy. One patient had Grade 5 carotid hemorrhage 6 months after reirradiation, and another patient had Grade 3 osteoradionecrosis. CONCLUSIONS: Reirradiation (66 Gy in 2.2 Gy fractions) with concurrent and maintenance erlotinib (150 mg daily) for recurrent or new primary HNC is feasible.


Subject(s)
Carcinoma, Squamous Cell , Head and Neck Neoplasms , Neoplasm Recurrence, Local , Protein Kinase Inhibitors/therapeutic use , Quinazolines/therapeutic use , Aged , Aged, 80 and over , Antibodies, Monoclonal/therapeutic use , Antibodies, Monoclonal, Humanized , Antineoplastic Agents/therapeutic use , Carcinoma, Squamous Cell/drug therapy , Carcinoma, Squamous Cell/mortality , Carcinoma, Squamous Cell/radiotherapy , Cetuximab , Combined Modality Therapy/methods , Drug Administration Schedule , Erlotinib Hydrochloride , Feasibility Studies , Female , Follow-Up Studies , Gastrostomy/methods , Head and Neck Neoplasms/drug therapy , Head and Neck Neoplasms/mortality , Head and Neck Neoplasms/radiotherapy , Humans , Male , Middle Aged , Neoplasm Recurrence, Local/drug therapy , Neoplasm Recurrence, Local/mortality , Neoplasm Recurrence, Local/radiotherapy , Protein Kinase Inhibitors/adverse effects , Quinazolines/adverse effects , Radiotherapy Dosage , Retreatment , Treatment Outcome
17.
Am J Clin Oncol ; 33(6): 599-603, 2010 Dec.
Article in English | MEDLINE | ID: mdl-21063195

ABSTRACT

PURPOSE: To determine the pattern of failures following intensity modulated radiation therapy for head and neck cancer. MATERIAL AND METHODS: A retrospective single institution study. Between May 2001 and June 2008, 176 patients with head and neck cancer were treated with intensity modulated radiation therapy at Fox Chase Cancer Center. Ninety-five (54%) were squamous cell carcinoma treated with curative intent. Tumor and nodal stage, tobacco history, definitive versus postoperative therapy (PORT), addition of chemotherapy and RT duration were analyzed for association with patterns of failure. In patients treated with definitive radiation, high-risk PTV (PTV1) was prescribed to 70 Gy and low-risk PTV (PTV2) to 56 Gy. In the PORT setting, PTV1 was prescribed to 60 to 66 Gy and PTV2 to 54 Gy. Patterns of failure were assessed. Local failure (LF) was defined as the persistence of disease or recurrence within PTV1, marginal failure as recurrence at the region of high-dose falloff, and regional failure as nodal recurrence within PTV2. RESULTS: Median follow-up was 20 months (range: 1-117). Median age was 60 years (range: 28-88), with 80% smokers and 81% stage III or IV. PORT was given to 29% and 71% were treated definitively, with concurrent Cisplatin used in the majority. Three-year local and locoregional (LR) failure rates were 9% and 16%, respectively. Failures occurred in 14 patients: 8 local, 3 regional, 1 LR, and 2 distant. Five of the 8 LF and all 3 marginal failures were observed in PORT cohort. On univariate analysis, the only predictor of LF was the use of PORT (P = 0.06). LR control was 66% for PORT versus 87%, 97% for definitive RT and chemoRT. CONCLUSIONS: Local, regional failures were more common following PORT related to an increased risk of marginal failures.


Subject(s)
Carcinoma, Squamous Cell/radiotherapy , Head and Neck Neoplasms/radiotherapy , Neoplasm Recurrence, Local/epidemiology , Radiotherapy, Intensity-Modulated/methods , Adult , Age Distribution , Aged , Aged, 80 and over , Carcinoma, Squamous Cell/mortality , Carcinoma, Squamous Cell/pathology , Carcinoma, Squamous Cell/surgery , Cohort Studies , Female , Head and Neck Neoplasms/mortality , Head and Neck Neoplasms/pathology , Head and Neck Neoplasms/surgery , Humans , Incidence , Male , Middle Aged , Neck Dissection , Neoplasm Recurrence, Local/pathology , Neoplasm Staging , Postoperative Care/methods , Postoperative Period , Prognosis , Radiotherapy Dosage , Radiotherapy, Intensity-Modulated/adverse effects , Retrospective Studies , Risk Assessment , Sex Distribution , Survival Analysis , Treatment Failure
18.
Cancer ; 115(5): 946-51, 2009 Mar 01.
Article in English | MEDLINE | ID: mdl-19156929

ABSTRACT

BACKGROUND: The results of radiation on the local control of triple receptor-negative breast cancer (negative estrogen [ER], progesterone [PR], and HER-2/neu receptors) was studied. METHODS: Conservative surgery and radiation were used in 753 patients with T1-T2 breast cancer. Three groups were defined by receptor status: Group 1: ER or PR (+); Group 2: ER and PR (-) but HER-2 (+); and Group 3: triple-negative (TN). Factors analyzed were age, menopausal status, race, stage, tumor size, lymph node status, presentation, grade, extensive in situ disease, margins, and systemic therapy. The primary endpoint was 5-year locoregional recurrence (LRR) isolated or total with distant metastases. RESULTS: ER- and PR-negative patients were statistically significantly more likely to be black, have T2 disease, have tumors detectable on both mammography and physical examination, have grade 3 tumors, and receive chemotherapy. There were no significant differences noted with regard to ER- and PR- patients by HER-2 status. There was a significant difference noted in rates of first distant metastases (3%, 12%, and 7% for Groups 1, 2, and 3, respectively; P = .009). However, the isolated 5-year LRR was not significantly different (2.3%, 4.6%, and 3.2%, respectively; P = .36) between the 3 groups. CONCLUSIONS: Patients with TN breast cancer do not appear to be at a significantly increased risk for isolated LRR at 5 years and therefore remain appropriate candidates for breast conservation.


Subject(s)
Breast Neoplasms/pathology , Mastectomy, Segmental , Neoplasm Recurrence, Local , Breast Neoplasms/radiotherapy , Breast Neoplasms/surgery , Combined Modality Therapy , Female , Humans , Middle Aged , Neoplasms, Hormone-Dependent/pathology , Progesterone/metabolism , Receptor, ErbB-2/metabolism , Receptors, Estrogen/metabolism
19.
Am J Clin Oncol ; 32(1): 30-3, 2009 Feb.
Article in English | MEDLINE | ID: mdl-19194121

ABSTRACT

OBJECTIVES: Inflammatory breast cancer (IBC) is a clinical staging based on history and physical findings. Dermal lymphatic invasion (DLI) can occur with or without IBC. We examine how these independently affect outcome in women treated with postmastectomy radiation. METHODS: Four hundred thirty-two patients treated with postmastectomy radiation for invasive mammary cancer were assessed. Kaplan-Meier methodology was used to calculate rates of locoregional recurrence (LRR), distant metastases (DM) and overall survival (OS). Variables entered into univariate and multivariate analysis included T stage, IBC, DLI, estrogen receptor/progesterone receptor status, HER-2/neu status, N stage, extracapsular node extension (ECE), and use of chemotherapy (CT). Median follow-up is 58 months. RESULTS: For all 432 patients, the rate of LRR was 3% and DM 28%. Seven percent are alive with disease (AWD) and 26% are dead of disease (DOD). Thirty-one patients had IBC without DLI, 21 had DLI without IBC, and 18 had both IBC and DLI. For DLI 10% developed LRR, 45% DM, 7.5% are AWD and 50% are DOD. Of patients with IBC, 8% developed LRR, 44% DM, 8% are AWD and 48% DOD. DLI was the only significant independent predictor for LRR (HR 4.8, P < 0.05). Predictors of DM and OS were IBC, > or =4 positive nodes, and CT. CONCLUSIONS: DLI and IBC are independent predictors of poor outcome after postmastectomy radiation. DLI is associated with an increased risk for LRR, and IBC with worse rates of DM and OS. Patients with both features have worse outcome than those with either alone.


Subject(s)
Breast Neoplasms/radiotherapy , Breast Neoplasms/surgery , Lymph Nodes/pathology , Mastectomy , Adult , Aged , Aged, 80 and over , Breast Neoplasms/pathology , Female , Humans , Inflammation , Lymphatic Metastasis , Middle Aged , Neoplasm Recurrence, Local/diagnosis , Neoplasm Recurrence, Local/etiology , Predictive Value of Tests , Prospective Studies , Skin , Survival Rate , Treatment Outcome , Young Adult
20.
Int J Radiat Oncol Biol Phys ; 74(1): 81-5, 2009 May 01.
Article in English | MEDLINE | ID: mdl-18823714

ABSTRACT

PURPOSE: The purpose of this study was to evaluate the likelihood of complications and cosmetic results among breast cancer patients who underwent modified radical mastectomy (MRM) and breast reconstruction followed by radiation therapy (RT) to either a temporary tissue expander (TTE) or permanent breast implant (PI). METHODS AND MATERIALS: Records were reviewed of 74 patients with breast cancer who underwent MRM followed by breast reconstruction and RT. Reconstruction consisted of a TTE usually followed by exchange to a PI. RT was delivered to the TTE in 62 patients and to the PI in 12 patients. Dose to the reconstructed chest wall was 50 Gy. Median follow-up was 48 months. The primary end point was the incidence of complications involving the reconstruction. RESULTS: There was no significant difference in the rate of major complications in the PI group (0%) vs. 4.8% in the TTE group. No patients lost the reconstruction in the PI group. Three patients lost the reconstruction in the TTE group. There were excellent/good cosmetic scores in 90% of the TTE group and 80% of the PI group (p = 0.22). On multivariate regression models, the type of reconstruction irradiated had no statistically significant impact on complication rates. CONCLUSIONS: Patients treated with breast reconstruction and RT can experience low rates of major complications. We demonstrate no significant difference in the overall rate of major or minor complications between the TTE and PI groups. Postmastectomy RT to either the TTE or the PI should be considered as acceptable treatment options in all eligible patients.


Subject(s)
Breast Implants , Breast Neoplasms/radiotherapy , Mammaplasty/adverse effects , Tissue Expansion Devices , Adult , Aged , Aged, 80 and over , Analysis of Variance , Breast Neoplasms/surgery , Esthetics , Female , Follow-Up Studies , Humans , Mammaplasty/methods , Mastectomy, Modified Radical/methods , Middle Aged , Postoperative Complications/etiology , Radiotherapy Dosage , Regression Analysis , Reoperation , Retrospective Studies , Thoracic Wall/radiation effects , Treatment Outcome
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