Image guided volumetric response during chemoradiotherapy for head and neck squamous cell carcinoma as a predictor of disease outcomes.

PURPOSE: The goal of this study was to correlate volumetric image guided disease response to clinical outcomes in patients receiving chemoradiation therapy (CRT) for locally advanced head and neck squamous cell carcinoma (HNSCC). MATERIALS AND METHODS: Thirty four patients completing definitive CRT for locally advanced HNSCC with megavoltage computed tomography (MVCT) guided tomotherapy IMRT were retrospectively reviewed for volumetric response. Grossly identifiable primary tumor (PT) and nodal disease (ND) response was evaluated by weekly MVCT regression. Percent end-of-treatment (EOT) residual volumes and regression rates were correlated with risk of local failure (LF), progression free survival (PFS), and overall survival (OS). RESULTS: A total of 7 LFs were identified in 6 patients at a median follow-up of 8months. The mean percent EOT residual volumes for PT and ND in patients with and without LF were 20% vs. 5% (p=0.005) and 47% vs. 6% (p=0.0001), respectively. The PT and ND volume regression rates for patients with and without LF were 12.7% per week vs. 15.9% per week (p=0.04) and 3.4% per week vs. 10.5% per week (p<0.001), respectively. Utilizing an EOT cut-off value of 25% residual volume, the relative risks of LF for PT and ND were 14.7 (p=0.03) and 25 (p=0.001), respectively. Patients found with PT and/or ND residual volumes <25% at EOT had longer 2year OS of 100% vs. 67% (p=0.0023) and PFS of 87% vs. 17% (p<0.001) compared with patients with residual volumes >/= 25% at EOT. CONCLUSION: Patients with locally advanced HNSCC who have significant MVCT volume reduction over the course of definitive CRT tend to have favorable clinical outcomes.

Electronic brachytherapy for treatment of non-melanoma skin cancers: clinical results and toxicities.

PURPOSE: Although surgical approaches are standard for most non-melanomatous skin cancers, some patients are not candidates due to medical co-morbidities or functional or cosmetic or lesion location. High-dose-rate electronic brachytherapy (HDR-EBT) may be an alternative treatment modality. MATERIAL AND METHODS: A retrospective chart review was conducted from April 2011 to April 2013. All lesions were pathologically confirmed as malignant basal cell or squamous cell carcinoma. A HDR-EBT system delivered a median biological equivalent dose of 50 Gy total to a depth of 0.1-0.5 cm using various sizes of applicators. Treatment feasibility, acute and late toxicity, cosmetic outcomes, and local recurrence were assessed. RESULTS: Thirty-three patients with a mean age of 76 years with 50 cutaneous lesions were treated. Locations included 17 extremity lesions and 33 head and neck lesions. After treatments, acute grade 3 moist desquamation developed in 9 of the lesions (18%). Acute grade 4 ulceration developed in 3 lesions in the lower extremity (6%) and 1 upper lip lesion (2%). These toxicities were improved after a median of 20 days. Amongst the 4 lesions with grade 4 toxicities, a greater proportion were in lower extremity lesions compared to head and neck lesions (75% vs. 25%). There was no difference in the rate of grade 3 and 4 toxicities between patients aged ≤ 75 years and aged > 75 years (p = 0.082). With a mean long-term follow-up of 45.6 months, there was 1 local recurrence treated with surgery and no reported late toxicities. CONCLUSIONS: Our experience with HDR-EBT for non-melanomatous skin cancers is encouraging in terms of efficacy and convenience for patients. Our long-term follow-up shows a good response in all treated sites. Caution should be used for extremity sites, and more fractionated regimens should be considered to avoid severe acute toxicities.

Feedback from artificial intelligence improved the learning of junior endoscopists on histology prediction of gastric lesions.

Background and study aims Artificial intelligence (AI)-assisted image classification has been shown to have high accuracy on endoscopic diagnosis. We evaluated the potential effects of use of an AI-assisted image classifier on training of junior endoscopists for histological prediction of gastric lesions. Methods An AI image classifier was built on a convolutional neural network with five convolutional layers and three fully connected layers A Resnet backbone was trained by 2,000 non-magnified endoscopic gastric images. The independent validation set consisted of another 1,000 endoscopic images from 100 gastric lesions. The first part of the validation set was reviewed by six junior endoscopists and the prediction of AI was then disclosed to three of them (Group A) while the remaining three (Group B) were not provided this information. All endoscopists reviewed the second part of the validation set independently. Results The overall accuracy of AI was 91.0 % (95 % CI: 89.2-92.7 %) with 97.1 % sensitivity (95 % CI: 95.6-98.7%), 85.9 % specificity (95 % CI: 83.0-88.4 %) and 0.91 area under the ROC (AUROC) (95 % CI: 0.89-0.93). AI was superior to all junior endoscopists in accuracy and AUROC in both validation sets. The performance of Group A endoscopists but not Group B endoscopists improved on the second validation set (accuracy 69.3 % to 74.7 %; P  = 0.003). Conclusion The trained AI image classifier can accurately predict presence of neoplastic component of gastric lesions. Feedback from the AI image classifier can also hasten the learning curve of junior endoscopists in predicting histology of gastric lesions.

Prognostic factors and risk of extrauterine metastases in 3867 women with grade 1 endometrioid corpus cancer.

OBJECTIVE: The purpose of this study was to evaluate the role of surgical staging in patients with grade 1 endometrioid uterine cancer. STUDY DESIGN: Data were extracted from Surveillance, Epidemiology, and End Results Program from 1988 to 2001. Kaplan-Meier and Cox proportional hazards analyses were used to determine predictors for disease-specific survival. RESULTS: Twelve thousand seven hundred and twelve women were reported with endometrioid carcinoma, including 3867 with grade 1 disease, of which 25.5% had stage IC or more advanced disease, 15.4% with disease extending beyond the uterine corpus, 7.3% with extrauterine metastases, and 3.3% with lymph node metastases. On multivariate analysis, younger age and earlier stage remained as significant prognostic factors for improved survival. CONCLUSION: Since grade 1 endometrioid uterine cancers have a 15.4% risk of extrauterine spread, a complete surgical staging procedure is recommended when clinically feasible. Younger age and earlier stage are significant prognostic factors for improved survival.

Trends in demographic and clinical characteristics in women diagnosed with corpus cancer and their potential impact on the increasing number of deaths.

OBJECTIVE: The purpose of this study was to determine factors responsible for the increasing number of deaths from corpus cancer over three time periods. STUDY DESIGN: Data were collected from the Surveillance, Epidemiology and End Results database from 1988-2001. Kaplan-Meier and Cox proportional hazards regression analyses were performed. RESULTS: Of 48,510 women with corpus cancer, there was an increase in the proportion of patients dying from advanced cancers (52.1% to 56.0% to 68.8%; P < .001), grade 3 disease (47.5% to 53.3% to 60.6%; P < .001), serous tumors (14.3% to 18.4% to 16.6%; P < .001), and sarcomas (19.1% to 20.4% to 27.2%; P < .001) over time. On multivariate analysis, older age, African American race, lack of primary staging procedures, advanced-stage, high-grade, and non-endometrioid histology were independent prognostic factors for worse survival. CONCLUSION: Our data suggest that the increase in mortality in women with corpus cancer over the last 14 years may be related to an increased rate of advanced-stage cancers and high-risk histologies.

The influence of conservative surgical practices for malignant ovarian germ cell tumors.

OBJECTIVE: To evaluate demographics, survival, and surgical trends for patients with malignant ovarian germ cell tumors. METHODS: SEER data abstracted from 1988 to 2001 and analyzed using Kaplan-Meier and Cox regression models. RESULTS: Of 760 patients, the median age was 23 years. Seventy-six percent of patients presented with stage I-II disease, and 24% with stage III-IV. Fifty-five percent were immature teratomas, 32% dysgerminomas, and 13% yolk sac tumors. Fertility-preserving surgery was performed in 41.2% (n = 313) of patients. In those <45 years old, the use of fertility-preserving surgery increased from 40.5% to 44.5% to 48.4% over the time periods 1988-1992, 1993-1997, 1998-2001 (P = 0.25). The survival of patients who underwent fertility-preserving surgery was not statistically different compared to those who underwent standard surgery (P = 0.26). Patients with stage I-II disease had improved survival compared to stage III-IV disease (97.6% vs. 85.5%, P < 0.001). The overall survival of women with dysgerminomas, immature teratomas, and yolk sac tumors was 99.5%, 94.3%, and 85.4%, respectively (P < 0.001). In multivariate analysis, older age, advanced stage, and yolk sac tumor histology predicted for poorer survival. CONCLUSION: Our data suggests that the use of fertility-preserving surgery with concomitant surgical staging for germ cell cancers has increased without compromising survival.

Gynecologic cancer prevention in Lynch syndrome/hereditary nonpolyposis colorectal cancer families.

OBJECTIVE: Women from Lynch syndrome/hereditary nonpolyposis colorectal cancer (Lynch/HNPCC) families have an increased lifetime risk of developing endometrial and ovarian cancer. This study models a comparison of management strategies for women who carry a Lynch/HNPCC mutation. METHODS: A decision analytic model with three arms was designed to compare annual gynecologic examinations with annual screening (ultrasonography, endometrial biopsy, CA 125) and with hysterectomy with bilateral salpingo-oophorectomy at age 30 years The existing literature was searched for studies on the accuracy of endometrial and ovarian cancer screening using endometrial biopsy, transvaginal ultrasonography, and serum CA 125. The Surveillance, Epidemiology and End Results database from 1988 to 2001 was used to estimate cancer mortality outcomes. RESULTS: In the surgical arm, 0.0056% of women were diagnosed with ovarian cancer and 0.0060% of women with endometrial cancer. These numbers increased to 3.7% and 18.4% in women being screened, and 8.3% and 48.7% in women undergoing annual examinations, respectively. Surgical management led to the longest expected survival time at 79.98 years, followed by screening at 79.31 years, and annual examinations at 77.41 years. If starting at age 30 and discounting life years at 3%, surgery still leads to the greatest expected life years. When comparing prophylactic surgery with the screening option, one would need to perform 75 surgeries to save one woman's entire life. For cancer prevention, however, only 28 and 6 prophylactic surgeries would need to be performed to prevent one case of ovarian and endometrial cancer, respectively. CONCLUSION: Risk-reducing hysterectomy and bilateral salpingo-oophorectomy may be considered in women with Lynch/HNPCC to prevent gynecologic cancers and their associated morbidities.

Adjuvant radiotherapy in incompletely staged IC and II endometrioid uterine cancer.

OBJECTIVES: To estimate if adjuvant radiotherapy improves the disease-specific survival of patients with clinical stage IC and II endometrioid corpus cancer who did not undergo lymphadenectomy. METHODS: Information was obtained on patients with endometrioid corpus cancer from the National Cancer Institute database between 1988 and 2001. Data were analyzed using Kaplan-Meier and Cox proportional hazards regression methods. RESULTS: A total of 3,664 patients (median age 70 years) with clinical stage IC to II endometrioid carcinoma did not undergo lymphadenectomy, of which 2,170 had stage IC and 1,494 stage II disease. Of these, 1,175 had grade 1, 1,637 had grade 2, 693 had grade 3, and in 159, grade was unknown. The 5-year disease-specific survival rates of clinical stage IC compared with stage II patients were 91.3% and 86.7% (P<.001). Of the 1,964 who received adjuvant radiotherapy, the 5-year disease-specific survival rate was 89.9% compared with 87.8% in those who did not undergo further treatment (P=.04). Adjuvant radiation improved the disease-specific survival rate of those with stage II disease, (86.5% compared with 81.9%; P=.02), but not in those with stage IC disease (91.7% compared with 92.6%; P=.68). The benefit of radiotherapy was significant in patients with grade 3 disease and patients 70 years or older (88.2% compared with 83.3%; P<.001). On multivariable analysis, age, stage, and grade were significant independent prognostic factors for disease-specific survival. CONCLUSION: Adjuvant radiotherapy marginally improved the survival of clinically staged IC-II endometrioid uterine cancer patients without lymphadenectomy. After excluding those without hysterectomy, radiotherapy did not significantly affect disease-specific survival. LEVEL OF EVIDENCE: II.

Association of lymphadenectomy and survival in stage I ovarian cancer patients.

OBJECTIVE: To estimate the survival impact of lymphadenectomy in women diagnosed with clinical stage I ovarian cancer. METHODS: Demographic and clinicopathologic information were obtained from the Surveillance, Epidemiology and End Results Program between 1988 and 2001. Data were analyzed using Kaplan-Meier methods and Cox proportional hazards regression. RESULTS: A total of 6,686 women had clinical stage I ovarian cancer (median age 54 years, range 1-99). Of this total, 75.9% of patients were Caucasian, 8.3% were Hispanic, 5.8% were African American, and 7.3% were Asian. Epithelial tumors were present in 85.8% of the women, and 2,862 (42.8%) patients underwent lymphadenectomy. Patients aged 50 years or more were less likely to undergo lymphadenectomy compared with their younger cohorts (39.8% compared with 60.2%, P<.001). Only 32.7% of African-American women had lymphadenectomy compared with 42.7% of Caucasian women, 47.2% of Hispanics, and 48.8% of Asians (P<.001). Lymphadenectomy was associated with improved 5-year disease-specific survival of all patients from 87.0% to 92.6% (P<.001). More specifically, lymphadenectomy improved the survival in those with non-clear cell epithelial ovarian cancer (85.9% to 93.3%, P<.001) but not in those with clear cell carcinoma, germ cell tumors, sex cord stromal tumors, and sarcomas. Moreover, the extent of lymphadenectomy (0 nodes, less than 10 nodes, and 10 or more nodes) increased the survival rates from 87.0% to 91.9% to 93.8%, respectively (P<.001). On multivariable analysis, the extent of lymphadenectomy was a significant prognostic factor for improved survival, independently of other factors such as age, stage, histology, and grade of disease. CONCLUSION: Our data suggest that women with stage I non-clear cell ovarian cancers who underwent lymphadenectomy had a significant improvement in survival. LEVEL OF EVIDENCE: II.

Prognostic factors for uterine cancer in reproductive-aged women.

OBJECTIVE: To determine the prognostic factors that influence the survival of younger women diagnosed with uterine cancer. METHODS: Demographic and clinico-pathologic data were collected from the National Cancer Institute database between 1988 and 2001. Data were analyzed with Kaplan-Meier methods and Cox proportional hazards regression. RESULTS: Of the 51,471 women diagnosed with uterine cancer in the study period, 2,076 (4.0%) patients were aged 40 years or younger, and 49,395 (96.0%) were older than 40. The mean age in the younger group was 35.6 years, compared with 65.2 years of the older group. The overall distribution by stage was stage I 75.4%, II 8.1%, III 6.7%, and IV 9.8%. Younger patients were more likely to be nonwhite (42.4% versus 18.3%, P<.001) and have stage I disease (79.2% versus 75.3%, P<.001), grade 1 lesions (47.6% versus 35.6%, P<.001), and sarcomas (15.9% versus 8.2%, P<.001) compared with their older counterparts. The overall 5-year disease-specific survival for younger patients was significantly better than that of older women (93.2% versus 86.4%, P<.001). On multivariable analysis, younger age, earlier stage, lower grade, nonblack race, endometrioid histology, and surgical treatment remained as significant independent prognostic factors for improved survival. CONCLUSION: This large population-based study demonstrates that patients 40 years and younger have an overall survival advantage compared with women older than 40 years, independent of other clinico-pathologic prognosticators. LEVEL OF EVIDENCE: III.

A novel technique for the enrichment of primary ovarian cancer cells.

OBJECTIVE: Primary cancer cells that are extracted from ovarian tumors can serve as an optimal substrate to study the biologic characteristics of ovarian cancer. We describe an efficient and effective method of enriching ovarian tumor cells from ascitic fluid using an immunomagnetic-based method. STUDY DESIGN: Mononuclear cells were isolated from ascites specimens by Ficoll gradient separation. Epithelial ovarian cancer cells were labeled magnetically with monoclonal human epithelial antigen-125 that is conjugated to microbeads. After immunomagnetic separation, the purity of tumor cells before and after purification was quantified by cytologic analysis and confirmed by fluorescence-activated cell sorter analysis. RESULTS: Peritoneal ascites specimens were obtained from 6 patients with ovarian cancer. The median age of our patients was 61.5 years (range, 46-79 years). Three patients had papillary serous carcinoma; 2 patients had clear cell carcinoma, and 1 patient had an undifferentiated adenocarcinoma. The mean tumor purity was only 22.8% +/- 10% (range, 1%-60%) before separation. After enrichment, the purity improved to 82.3% +/- 4.0% (range, 70%-90%). Our enrichment technique increased the tumor purity by 59.5% +/- 8.4%. The mean percent yield after positive enrichment was 30.1% +/- 14.5%. CONCLUSION: The immunomagnetic cell separation technique is an efficient and effective method for isolating and purifying ovarian tumor cells from ascites. Results from experiments with fresh tumor cells rather than cancer cell lines may be more relevant for clinical application.

Enhanced killing of primary ovarian cancer by retargeting autologous cytokine-induced killer cells with bispecific antibodies: a preclinical study.

Cytokine-induced killer (CIK) cells are ex vivo activated and expanded CD8+ natural killer T cells that have been shown to have antitumor activity. This is the first study exploring cell killing of primary ovarian carcinoma cells with and without bispecific antibodies. Primary cancer cells and autologous CIK cells were collected from women with epithelial ovarian cancer. Bispecific antibodies against cancer antigen-125 (BSAbxCA125) and Her2 (BSAbxHer2) were developed using chemical heteroconjugation. On fluorescence-activated cell sorting analysis, the expansion of CIK cells resulted in a significant increase of CD3+CD8+ and CD3+CD56+ T cells. With enhancement by bispecific antibodies, the mean percent lysis in a 51Cr release assay of fresh ovarian cancer cells exposed to autologous CIK cells increased from 21.7 +/- 0.3% to 89.4 +/- 2.1% at an E:T ratio of 100:1 (P < 0.001). Anti-NKG2D antibodies attenuated the CIK activity by 56.8% on primary cells (P < 0.001). In a xenograft severe combined immunodeficient mouse model, real-time tumor regression and progression was visualized using a noninvasive in vivo bioluminescence imaging system. Four hours after CIK cell injection, we were able to visualize CD8+NKG2D+ CIK cells infiltrating Her2-expressing cancer cells on fluorescence microscopy. Mice that underwent adoptive transfer of CIK cells redirected with BSAbxCA125 and BSAbxHer2 had significant reduction in tumor burden (P < 0.001 and P < 0.001) and improvement in survival (P = 0.05 and P = 0.006) versus those treated with CIK cells alone. Bispecific antibodies significantly enhanced the cytotoxicity of CIK cells in primary ovarian cancer cells and in our in vivo mouse model. The mechanism of cytolysis seems to be mediated in part by the NKG2D receptor.

False Positive Positron Emission Tomography / Computed Tomography Scans in Treated Head and Neck Cancers.

OBJECTIVE: Positron emission tomography/computed tomography (PET/CT) imaging for head and neck cancers (HNC) is commonly utilized for post-treatment assessment. Though PET/CT in this setting has been reported to have high negative predictive values (> 90%), positive predictive values have been reported at approximately 50%, leading to high rates of false positivity (FP) and troubling management decisions for both patient and practitioner. The objective of this study was to identify patient, disease, treatment and imaging factors that might be associated with a higher likelihood of FP on initial post-treatment PET/CT imaging for patients treated for HNC. MATERIALS AND METHODS: A retrospective chart review was performed on 84 patients treated for HNC who received radiation therapy (RT) as part of their overall management from October 2005 to August 2013. Of the patients screened, 19 were found to have mucosally based squamous cell carcinoma (SCC) with positive initial post-treatment PET/CT studies (23%). Fisher's exact test was used to analyze the association between categorical variables and FP, including patient's gender, disease laterality, primary tumor site and stage, nodal and overall stage, high dose RT fraction size, number of RT fractions completed, total RT dose, biologically effective dose and timing of PET/CT acquisition. Wilcoxon rank-sum test was used to analyze the association between continuous variables and FP, including patient age, total elapsed days of RT, an amount of infused fluorodeoxyglucose 18F-FDG, pre-PET/CT serum glucose levels, and maximum standardized uptake value SUVmax. Statistically significant findings were those that were deemed p <0.05. RESULTS: Among patients with positive initial post-treatment PET/CT scans for treated HNC, there was a lower proportion of higher primary disease stage associated with FP versus true positivity (T-stage 3-4: 20 vs 78%, respectively, p=0.023). We also discovered that 50% of patients that underwent confirmation for FP findings suffered serious complications as a direct consequence of invasive exploratory procedures. CONCLUSIONS: Although PET/CT is known for its exceptional negative predictive value (> 90%) in the post-treatment setting for HNC, high rates of FP remains a clinical challenge. Our study suggests that tumor stage (T-stage) may impact FP rates in positive initial post-treatment PET/CT scans. We recommend careful multidisciplinary discussion regarding positive PET/CT studies in the post-treatment setting for HNC, particularly if invasive intervention is considered.

Efficacy of Clarithromycin-Naproxen-Oseltamivir Combination in the Treatment of Patients Hospitalized for Influenza A(H3N2) Infection: An Open-label Randomized, Controlled, Phase IIb/III Trial.

BACKGROUND: Influenza causes excessive hospitalizations and deaths. The study assessed the efficacy and safety of a clarithromycin-naproxen-oseltamivir combination for treatment of serious influenza. METHODS: From February to April 2015, we conducted a prospective open-label, randomized, controlled trial. Adult patients hospitalized for A(H3N2) influenza were randomly assigned to a 2-day combination of clarithromycin 500 mg, naproxen 200 mg, and oseltamivir 75 mg twice daily, followed by 3 days of oseltamivir or to oseltamivir 75 mg twice daily without placebo for 5 days as a control method (1:1). The primary end point was 30-day mortality. The secondary end points were 90-day mortality, serial nasopharyngeal aspirate (NPA) virus titer, percentage of neuraminidase-inhibitor-resistant A(H3N2) virus (NIRV) quasispecies, pneumonia severity index (PSI), and duration of hospital stay. RESULTS: Among the 217 patients with influenza A(H3N2) enrolled, 107 were randomly assigned to the combination treatment. The median age was 80 years, and 53.5% were men. Adverse events were uncommon. Ten patients died during the 30-day follow-up. The combination treatment was associated with lower 30-day mortality (P = .01), less frequent high dependency unit admission (P = .009), and shorter hospital stay (P < .0001). The virus titer and PSI (days 1-3; P < .01) and the NPA specimens with NIRV quasispecies ≥ 5% (days 1-2; P < .01) were significantly lower in the combination treatment group. Multivariate analysis showed that combination treatment was the only independent factor associated with lower 30-day mortality (OR, 0.06; 95% CI, 0.004-0.94; P = .04). CONCLUSIONS: Combination treatment reduced both 30- and 90-day mortality and length of hospital stay. Further study of the antiviral and immunomodulatory effects of this combination treatment of severe influenza is warranted. TRIAL REGISTRY: BioMed Central; No.: ISRCTN11273879 DOI 10.1186/ISRCTN11273879; URL: www.isrctn.com/ISRCTN11273879.

Patterns and progress in ovarian cancer over 14 years.

OBJECTIVE: To estimate the change in survival rates of women with ovarian cancer during the past 14 years. METHODS: Women diagnosed with epithelial, germ cell, sarcomas, and sex-cord stromal ovarian tumors were identified from the Surveillance Epidemiology and End Results Database. Demographic and clinicopathologic factors, and survival information were extracted and tested using chi 2 and Kaplan-Meier and Cox regression analyses. RESULTS: A total of 30,246 women were diagnosed with ovarian cancer, including 26,753 non-clear cell epithelial, 1,411 clear cell, 818 sarcoma, 778 germ cell, and 486 sex-cord stromal tumors. The 5-year disease-specific survival rate across 1988-1992 and 1993-1997 improved from 45.4% to 48.6% (P < .001). The corresponding estimates show increases for non-clear cell epithelial carcinoma from 42.5% to 45.8% (P < .001), and for sarcomas from 33.5% to 38.8% (P = .07). However, improvements were not observed in those with clear cell, 64.3% to 63.9% (P = .82), and sex-cord stromal, 89.7% to 85.7% (P = .18), tumors of the ovary. In multivariable analyses, younger age, early stage, favorable histologic cell types, low-grade tumors, standard surgery, and recent time interval from 1993-1997 were independent prognostic factors for improved survival. CONCLUSION: In this large population-based study, there has been some improvement in the overall survival of women with ovarian cancers during a 14-year period. However, new treatment strategies are warranted for those with epithelial cancer and sarcomas of the ovary, given their overall poor prognosis. These results from our updated analyses might help to counsel women diagnosed with ovarian cancers.

Improved survival of Asians with corpus cancer compared with whites: an analysis of underlying factors.

OBJECTIVE: To compare the clinicopathologic prognosticators and survival of Asians and whites with corpus cancer. METHODS: Demographic, clinicopathologic, and survival data were obtained from the 1992-2001 Surveillance, Epidemiology, and End Results Program. Statistical analyses were performed by Kaplan-Meier methods and Cox proportional hazards model. RESULTS: A total of 2,144 Asians and 32,999 whites with corpus cancer were identified. The age-adjusted incidence of uterine cancer in Asians compared with whites was 16.8 compared with 26.1 per 100,000. Asians presented at a younger age (mean 58.4 years compared with 65.1; P < .01) and with more advanced stage disease than whites (21.5% compared with 15.4%; P < .01). The 5-year survival rate for Asians was 79.4% compared with 75.2% for whites (P < .01). Asians with stage I-II and III-IV cancers had 5-year survival rates of 89.3% and 41.2% compared with 82.3% and 34.0% for the whites, respectively (P < .01, early stage; P < .01, advanced stage). The survival advantage of Asians persists in endometrioid (P < .01) and uterine papillary serous carcinomas (P < .01), but not in clear cell carcinoma (P = .62) or sarcomas (P = .78). In multivariate analysis, younger age (P < .01), earlier stage (P < .01), favorable histology (P < .01), and lower grade (P < .01) remained as significant independent prognosticators for improved survival. However, race was not an important prognosticator. CONCLUSION: The overall survival advantage experienced by Asians with uterine cancer is attributable to their younger age at diagnosis. Because Asian women present at a younger age with more advanced disease, physicians should have an increased index of suspicion for malignancy in young Asian women with suspicious symptoms and consider a lower age threshold for biopsy in this group. LEVEL OF EVIDENCE: II-2.

A cost-effectiveness analysis of prophylactic surgery versus gynecologic surveillance for women from hereditary non-polyposis colorectal cancer (HNPCC) Families.

Women at risk for Lynch Syndrome/HNPCC have an increased lifetime risk of endometrial and ovarian cancer. This study investigates the cost-effectiveness of prophylactic surgery versus surveillance in women with Lynch Syndrome. A decision analytic model was designed incorporating key clinical decisions and existing probabilities, costs, and outcomes from the literature. Clinical forum where risk-reducing surgery and surveillance were considered. A theoretical population of women with Lynch Syndrome at age 30 was used for the analysis. A decision analytic model was designed comparing the health outcomes of prophylactic hysterectomy with bilateral salpingo-oophorectomy at age 30 versus annual gynecologic screening versus annual gynecologic exam. The literature was searched for probabilities of different health outcomes, results of screening modalities, and costs of cancer diagnosis and treatment. Cost-effectiveness expressed in dollars per discounted life-years. Risk-reducing surgery is the least expensive option, costing $23,422 per patient for 25.71 quality-adjusted life-years (QALYs). Annual screening costs $68,392 for 25.17 QALYs; and annual examination without screening costs $100,484 for 24.60 QALYs. Further, because risk-reducing surgery leads to both the lowest costs and the highest number of QALYs, it is a dominant strategy. Risk-reducing surgery is the most cost-effective option from a societal healthcare cost perspective.

Treatment options for stage I non-small-cell lung carcinoma patients not suitable for lobectomy.

The standard of care for stage I non-small-cell lung carcinoma is generally accepted to be lobectomy. In patients who are deemed not to be candidates for lobectomy, various treatment strategies are available, including observation, sublobar resection, conventional fractionated radiotherapy, stereotactic body radiotherapy and radiofrequency ablation. However, there is no standardized, clearly established therapy to offer patients in this situation. While ongoing prospective trials will allow refinement of these techniques, the role of these treatment modalities warrants further investigation for this setting.

The outcomes of 27,063 women with unstaged endometrioid uterine cancer.

BACKGROUND: Over two-thirds of patients with endometrioid uterine cancer in the Surveillance, Epidemiology and End Results program from 1988 to 2001 did not undergo a lymphadenectomy. These patients were compared to those who had a lymphadenectomy. METHODS: Kaplan-Meier methods and Cox proportional hazards regression analyses were employed. RESULTS: Of 39,396 women (median age: 65 years) with endometrioid uterine cancers, 12,333 (31.3%) underwent surgical staging procedures including lymphadenectomy. The remainder did not receive a lymphadenectomy. The 5-year disease-specific survival (DSS) of stages I-IV women who underwent lymphadenectomy were 95.5%, 90.4%, 73.8%, and 53.3% compared to 96.6%, 82.2%, 63.1%, and 26.9% in those without lymphadenectomy (p>0.05 for stage I; p<0.001 for stages II-IV). In stage I patients, those who did not receive lymphadenectomy had a higher proportion of tumors with grade 1 histology and/or disease limited to the endometrium compared to those who underwent lymphadenectomy (54.8 % vs. 34.7%; p<0.001, grade 1 disease; 26.6% vs. 15.9%; p<0.001, no myometrial invasion). In patients with stage I grade 3 disease, those who underwent lymphadenectomy had a better 5-year DSS than those without lymphadenectomy (90% vs. 85%; p=0.0001); however, no benefit for lymphadenectomy was seen for patients with stage I grade 1 (p=0.26) and grade 2 (p=0.14) disease. On multivariable analysis, younger age, Caucasian race, early-stage disease, low grade histology, and lymphadenectomy were independent prognostic factors for improved disease-specific survival. CONCLUSIONS: Our data suggest that lymphadenectomy is associated with an improved survival in stage I grade 3 and more advanced endometrioid uterine cancers.