IB Disease Research Articles

Evaluation of the stage IB designation of the 7th edition of the AJCC Staging System.

1130 Background: Recent data from large cooperative group trials have questioned the relevance of small volume metastases identified in the sentinel lymph nodes (SLN) of early stage breast cancer patients. The 7th ed. of the AJCC staging system differentiates node negative patients (stage IA) from those with micrometastases (stage IB) or macrometastases (stage II or III). This study was undertaken to determine the utility of the stage IB designation. Methods: Review of a prospectively maintained database identified 3474 patients who underwent SLN biopsy between 1993 and 2007. Clinicopathologic and outcomes data were recorded and patients staged according to the 7th ed. AJCC system. Recurrence-free (RFS), disease-specific (DSS) and overall survival (OS) were determined using the Kaplan-Meier method and compared using the log-rank test. Results: AJCC stage distribution included: 2246 (65%) stage IA, 207 (6%) stage IB, 685 (20%) stage IIA, 209 (6%) stage IIB, and 127 (3%) stage III. For patients with stage IB disease, SLN micrometastasis was identified by H&E in 173 (84%) and immunohistochemistry (IHC) in 34 (16%); suggesting that 16% would have been staged IA if enhanced evaluation had not been performed. Median follow-up was 6.1 yrs (range 0-17.2). The 5-yr RFS,DSS and OS rates for patients with stage IB disease were 98.0%, 99.5%, and 95.9% respectively, which did not differ significantly from patients with stage IA disease who had 5-year RFS,DSS and OS rates of (97.5%, p=.9), (98.8%, p=.7) and (96.2%, p=.8). When all stage I patients (IA and IB) were evaluated by ER status or grade (grade 1 vs 2 vs 3), these biologic factors were able to significantly discriminate patients with respect to RFS, DSS and OS. Conclusions: Differentiating patients with micrometastases from node negative patients does not stratify patients with respect to survival. Biologic factors (ER status and grade) are better discriminants of survival than the presence of small volume nodal metastases in patients with early stage disease. These data do not support routine use of IHC or alterations in adjuvant therapy decisions based on identification of SLN micrometastases.

Prognostic value of pathologic complete response to preoperative chemotherapy in early-stage non small cell lung cancer: Combined analysis of two IFCT randomized trials.

7057 Background: Our study aimed to evaluate whether pathologic complete response (pCR) in early-stage non-small cell lung cancer (NSCLC) following neoadjuvant chemotherapy resulted in improved outcome and to determine predictive factors for pCR. Methods: Eligible patients with stage IB or II NSCLC were included in two consecutive Intergroupe Francophone de Cancérologie Thoracique (IFCT) phase III trials evaluating platinum-based neoadjuvant chemotherapy, with pCR defined by the absence of viable cancer cells in the resected surgical specimen. Results: Among the 492 patients analyzed, 41 (8.3%) achieved pCR. In the pCR group, 5-year overall survival (OS) was 80.0% compared to 55.8% in the non-pCR group (p=0.0007). In multivariate analyses, pCR was a favorable prognostic factor of OS (RR=0.34; 95% CI=0.18-0.64) in addition to squamous cell carcinoma (SCC), weight loss ≤5%, and stage IB disease. Five-year disease-free survival (DFS) was 80.1% in the pCR group compared to 44.8% in the non-pCR group (p<0.0001). Two patients (4.9%) in the pCR group experienced disease recurrence compared to 193 patients (42.8%) in the non-pCR group. SCC subtype was the only independent predictor of pCR (OR=4.30; 95% CI=1.90-9.72). Conclusions: Our results showed that pCR after preoperative chemotherapy was a favorable prognostic factor in Stage IB-II NSCLC. Our study is the largest published series evaluating pCRs following preoperative chemotherapy. The only factor predictive of pCR was SCC. Identifying molecular predictive markers for pCR may help in distinguishing patients likely to benefit from neoadjuvant chemotherapy and in choosing the most adequate preoperative chemotherapy regimen.

Rhabdomyosarcoma of the cervix in adult women and younger patients

ObjectivesCervical rhabdomyosarcoma is extremely rare, and there is a paucity of literature on the subject. The purpose of this study was to describe the clinical and pathologic features of cervical rhabdomyosarcoma. MethodsWe retrospectively reviewed all patients with cervical rhabdomyosarcoma who presented to our institution from 1980 to 2010. We reviewed pathologic, demographic, and clinical information. ResultsDuring the study period, 11 females presented with cervical rhabdomyosarcoma. The median age at presentation was 18.4years, and 6 patients were <19years old at diagnosis. Vaginal bleeding was the most common presenting symptom, and a vaginal mass was often a co-presenting symptom. Eight patients (73%) presented with stage IB disease, and 8 (73%) presented with the embryonal (botryoid) histologic subtype. Nine patients (82%) received multimodal therapy consisting of surgery with chemotherapy, radiation therapy, or both. All patients were without evidence of disease after completion of primary therapy, but 3 patients experienced local recurrence. At a median follow-up of 23months, 6 patients (55%) were without evidence of disease, 1 (9%) was alive with disease, 1 (9%) had died of disease, and 3 (27%) had died of other causes. Three patients (27%) had other primary malignancies in addition to rhabdomyosarcoma—1 had a Sertoli–Leydig tumor, 1 had a Sertoli–Leydig tumor and a pinealoblastoma, and 1 had thyroid cancer and a parotid adenocarcinoma. ConclusionsWith multimodal therapy, cervical rhabdomyosarcoma appears to be associated with a good prognosis. Favorable prognostic factors such as early stage at diagnosis and a favorable histologic subtype may contribute to the excellent observed survival.

Combination of squamous cell carcinoma‐antigen, carcinoembryonic antigen, and carbohydrate antigen 19‐9 predicts positive pelvic lymph nodes and parametrial involvement in early stage squamous cell carcinoma of the uterine cervix

We examined the correlations between the pretreatment values of four tumor markers (squamous cell carcinoma [SCC]-antigen, carcinoembryonic antigen [CEA], carbohydrate antigen [CA]19-9, and CA125) and postsurgical high-risk factors (parametrial involvement and positive pelvic lymph nodes) in women with SCC of the uterine cervix who had International Federation of Gynecology and Obstetrics clinical stage IB and IIA disease and underwent radical hysterectomy. In this retrospective study, we reviewed 291 patients between April 1989 and December 2008. The first 200 subjects, studied between 1989 and 2001, served as the training set, and another 91 subjects, studied between 2002 and 2008, comprised the test set. To evaluate the correlations between pretreatment tumor markers and postsurgical high-risk factors, the χ²-test and logistic regression analysis were used for univariate and multivariate analysis, respectively. Multivariate analysis with receiver-operator curves showed that the combination of SCC-antigen, CEA, and CA19-9 strongly predicted postsurgical high-risk factors. Analysis of the training set showed that 66.7% (95% confidence interval, 52.6-84.8%) of patients who tested positive for at least two of these three tumor markers had postsurgical high-risk factors. Similar results were obtained with the test set. Preoperative levels of SCC-antigen, CEA, and CA19-9 are useful for predicting the status of postsurgical high-risk factors in women with SCC of the uterine cervix who undergo radical hysterectomy.

Adjuvant chemotherapy for surgically resected non–small cell lung cancer

Despite surgical resection, patients with early-stage (I to IIIA) non-small cell lung cancer (NSCLC) are at considerable risk of recurrence and death from their lung cancer. In recent years, multiple, large, randomized trials assessing the efficacy of adjuvant chemotherapy for resected NSCLC have been reported. Three of 6 trials with 300 or more patients with early-stage NSCLC have demonstrated that adjuvant cisplatin-based chemotherapy can significantly improve 5-year survival in carefully selected patients with resected NSCLC. These benefits have been confirmed in a meta-analysis of modern cisplatin-based adjuvant trials. The most consistent benefit has been reported in patients with resected stage II and IIIA NSCLC. The benefit of adjuvant chemotherapy in patients with resected stage IB NSCLC is less concrete. Herein, we review the results of the major adjuvant chemotherapy trials and their implications for the treatment of patients with completely resected NSCLC. A future challenge will be to identify the subsets of patients who will derive the greatest benefit from adjuvant chemotherapy. Current trials are also underway to define the role of novel targeted therapies, such as inhibitors of the epidermal growth factor receptor and monoclonal antibodies, in adjuvant treatment strategies.

Reproductive outcomes of patients undergoing radical trachelectomy for early-stage cervical cancer

ObjectiveTo report the reproductive outcomes of patients undergoing fertility-preserving radical trachelectomy (RT) for the treatment of early-stage cervical cancer. MethodsWe analyzed data from our institution's first 105 patients who underwent attempted fertility-sparing surgery with radical trachelectomy, pelvic lymphadenectomy, and cerclage from November 2001 to October 2010. ResultsOf the 105 patients who underwent attempted RT, 77 (73%) did not require a conversion to radical hysterectomy or postoperative treatment. The median age was 32 (range, 25–38years). Most patients (75%) had stage IB1 disease. Sixty-six patients (63%) were nulliparous. Thirty-five women were actively attempting conception 6months after surgery, and 23 (66%) women were successful in conceiving: there were 20 live births, 3 elective terminations, and 4 spontaneous miscarriages. Four patients had 2 pregnancies each; all delivered their second pregnancy between 32 and 36weeks. Cerclage erosion through the vaginal wall occurred in 6 cases and was treated by transvaginal removal of protruding suture material. One of these patients experienced a second trimester miscarriage. ConclusionsThe majority of women who attempted to conceive after radical trachelectomy were successful, and most of their pregnancies resulted in full-term births. Assisted reproduction played an important role in select women. Cerclage likely contributed to a post-trachelectomy uterine ability to carry a pregnancy to the third trimester. The second post-trachelectomy pregnancy appears to be at higher risk for preterm delivery than the first pregnancy.

Coeliac disease in irritable bowel syndrome (Rome III) in Southeast Iran

Background and study aimsIrritable bowel syndrome (IBS) is a common functional gastrointestinal (GI) disorder and coeliac disease (CD) is an auto-immune enteropathy that can mimic almost any functional GI disorder. Both IBS and coeliac disease share common symptoms. The aim of the present study was to estimate the prevalence of CD in patients with IBS and its sub-types. Patients and methodsIn this cross-sectional study (2008–2010), all consecutive patients with IBS who fulfilled the Rome III criteria attending the GI units in Zahedan (Southeast Iran) were included. Patients based on the sub-type of IBS were classified as diarrhoea-predominant irritable bowel syndrome (D-IBS), constipation-predominant irritable bowel syndrome (C-IBS) and alternating symptoms (mixed type). Immunoglobulin A (IgA) tissue transglutaminase (anti-tTG) was used to screen patients for CD. In the case of positive serologic test, duodenal biopsies were taken to confirm the diagnosis. ResultsA total of 364 (221 females and 143 males) patients with IBS were included. The mean±standard deviation (SD) age of patients was 37.4±12.4years. Twenty (5.5%) patients were found to have positive IgA anti-tTG. Main symptoms of patients were diarrhoea (11/20), bloating (10/20) and abdominal distension (6/20). Thirteen (10.5%) patients were found to have positive IgA anti-tTG among the D-IBS, two (1.6%) in the C-IBS and five (4.2%) in M-IBS groups. ConclusionThe prevalence of CD in IBS is high. IBS subjects whose main complaint is diarrhoea, bloating or even abdominal distension should be evaluated for CD.

Influence of Age and IB Status After Resection of Node-Negative Non-Small Cell Lung Cancer

Anatomic segmentectomy has been proposed as a reasonable alternative to lobectomy in the management of small early-stage non-small cell lung cancers. We reviewed our outcomes with anatomic segmentectomy versus lobectomy for stages IA and IB non-small cell lung cancer stratified by age and stage. We conducted a retrospective review of prospectively-collected data analyzing outcomes after anatomic segmentectomy (n=305) for stage IA (n=187) or IB (n=118) NSCLC from 1999 to 2010. Lobectomy was performed in 594 patients for stage IA (n=290) and IB (n=304) disease during the same period. Surgical approach was stratified by stage and by the following age groups: less than 70, 70 to 79, and 80 or greater. Primary outcome variables included complications, mortality, recurrence patterns, and survival. Mean follow-up was 37 months. Segmentectomy was associated with reduced complications (43.6% vs 58.7%) and mortality (0% vs 7.8%) in patients greater than 80 years old, without a difference in recurrence rates. There was no difference in complications or mortality in the younger age groups. Freedom from recurrence was similar between segmentectomy and lobectomy for stage IA tumors across all age groups. A reduced recurrence-free survival was seen with segmentectomy for stage IB tumors, especially with visceral pleural invasion (median 22.7 vs 29.6 months), p=0.048). Segmentectomy appears to be a reasonable approach for early-stage NSCLC in patients 80 years of age or greater due to reduced morbidity and mortality with equivalent freedom from recurrence. Although equivalent survival was seen in all age groups for stage IA, these data further support the use of lobectomy for resection of stage IB tumors.

077 Ectopic endometriosis in neurological practice

Ectopic endometriosis by definition describes presence of functioning ectopic endometrium outside the uterus. Author presents two cases of ectopic endometriosis causing focal neurological symptoms. 42 years old woman, with past...

Re‐consideration of lymphadenectomy for stage Ib1 cervical cancer

Because of less frequent lymph node metastasis and parametrial involvement, patients with stage Ib1 cervical cancer may benefit from a curtailment of surgery. We retrospectively investigated the distribution of lymph node metastasis in stage Ib1 patients. After comparing the data with that of higher stages and sentinel lymph node navigation (SLNN), the appropriate extent of lymphadenectomy (LA) in stage Ib1 disease was newly suggested. A total of 303 patients underwent a radical hysterectomy with LA and the region-specific rate of node metastasis was obtained. SLNN was performed for 50 patients using (99m) Tc phytate injection into the cervix and intra-operative detection by a gamma-probe. The rate of node metastasis and the average number of nodes removed, respectively, were: 23/189 (12.2%), 65.2 in stage Ib1; 14/47 (29.8%), 70.1 in stage Ib2; 7/20 (35.0%), 78.2 in stage IIa; and 26/47 (55.3%), 69.1 in stage IIb. Lymph node metastasis in stage Ib1 was prevalent in the obturator (Ob) (9.5%), inter-iliac (Ii) (4.9%), superficial common iliac (Sc) (2.3%), cardinal (Cd) (2.2%) and external iliac (Ei) (1.7%) nodes. In patients with upper stage disease, lymph node metastasis could occur in all lymph nodes. In stage Ib1 patients, the sentinel nodes were assigned only to the Ob, Ii, Sc and Ei nodes, being identical with frequent metastatic sites in stage Ib1 (excluding Cd). The extent of LA can be routinely completed with the removal of Ob, Ii, Ei, Sc and Cd nodes, which may provide a higher quality of life, including the reduction of lymphedema by preventing the removal of the inguinal nodes.

Genetics and Gastrointestinal Symptoms

Gastrointestinal (GI) symptoms including nausea, vomiting, diarrhea, constipation, abdominal discomfort/pain, and heartburn are ubiquitous and as such are often the focus of nursing interventions. The etiologies of these symptoms include GI pathology (e.g., cancer, inflammation), dietary factors (e.g., lactose intolerance), infection, stress, autonomic nervous system dysregulation, medications, as well as a host of diseases outside the GI tract. This review focuses on a common condition (irritable bowel syndrome [IBS]) that is linked with both bowel pattern and abdominal discomfort/pain symptoms. Family and twin studies give evidence for a role of genetic factors in IBS. Whether genes are directly associated with IBS or influence disease risk indirectly by modulating the response to environmental factors remains unknown at this time. Given the multifactorial nature of IBS, it is unlikely that a single genetic factor is responsible for IBS. In addition, gene-gene (epistatic) interactions are also likely to play a role. Four genes coding for proteins involved in neurotransmission (i.e., the serotonin reuptake transporter [SERT], tryptophan hydroxylase [TPH], alpha2-adrenergic receptor [alpha2-ADR], catechol-o-methyl transferase [COMT]) and their potential relevance to GI symptoms and IBS will be reviewed. Further research using genome-wide association approaches with samples well characterized by ethnicity and standardized symptom subgrouping is needed.

Adjuvant chemotherapy for resected non-small-cell lung cancer: future perspectives for clinical research

Adjuvant chemotherapy for non-small-cell lung carcinoma (NSCLC) is a debated issue in clinical oncology. Although it is considered a standard for resected stage II-IIIA patients according to the available guidelines, many questions are still open. Among them, it should be acknowledged that the treatment for stage IB disease has shown so far a limited (if sizable) efficacy, the role of modern radiotherapies requires to be evaluated in large prospective randomized trials and the relative impact of age and comorbidities should be weighted to assess the reliability of the trials' evidences in the context of the everyday-practice. In addition, a conclusive evidence of the best partner for cisplatin is currently awaited as well as a deeper investigation of the fading effect of chemotherapy over time. The limited survival benefit since first studies were published and the lack of reliable prognostic and predictive factors beyond pathological stage, strongly call for the identification of bio-molecular markers and classifiers to identify which patients should be treated and which drugs should be used. Given the disappointing results of targeted therapy in this setting have obscured the initial promising perspectives, a biomarker-selection approach may represent the basis of future trials exploring adjuvant treatment for resected NSCLC.

Prognostic factors and treatment comparison in early-stage small cell carcinoma of the uterine cervix

Small cell carcinoma of the uterine cervix (SCCUC) is rare and its biologic behavior is aggressive. To analyze prognostic factors and determine optimal therapy in patients with International Federation of Gynecology and Obstetrics (FIGO) stage IB1-IIA SCCUC, we retrospectively reviewed 96 patients (14 patients treated in our center and 82 patients identified by a search on PubMed) treated with radical surgery (SU), surgery plus adjuvant chemotherapy (SU+Chemo), or surgery plus adjuvant chemotherapy and radiotherapy (SU+Chemo+RT) between 1990 and 2010. Of the 96 patients, 11 patients were treated with SU, 33 with SU+Chemo, and 52 with SU+Chemo+RT. The 5-year survival rate for the 96 patients was 45%. A total of 6% (2/32) of patients had local recurrence, 75% (24/32) had distant metastases, and 19% (6/32) had both. The 5-year survival rate in stage IB1 and IB2-IIA disease was 58 and 34%, respectively (P=0.049). For patients with and without lymph node metastases (LNM), survival was 33 and 60%, respectively (P=0.045). Patients with inner 1/3 stromal invasion had a better survival than those with deep stromal invasion (DSI) (100 vs. 34%, P=0.003). Survival was not significantly different in patients treated with the above three modalities, albeit treatment selection was related to LNM (P=0.000) and DSI (P=0.027). Thus, FIGO stage, LNM and DSI are significant predictors of survival. Adjuvant therapy after SU has not improved survival compared with surgery alone. Thus, newer multimodality therapy should be evaluated.

Evaluation and Management of Acute Gastroenteritis in a Community Hospital

Purpose: The incidence of acute diarrhea in the U.S. is 375 million and nearly 1 million hospitalizations are attributed to acute diarrhea per year. The aims of this study were to (1) identify the number of ED visits at Lenox Hill Hospital during August 2010 for acute diarrhea; (2) identify the number of patients admitted with the following WGO/ACG criteria (signs of dehydration, changing mental status, fevers >101F, visible blood in stool, frequency > 6/day, intractable vomiting, and/or symptom duration >48 hrs); (3) identify the number of patients treated with antimicrobial therapy according the following WGO/ACG criteria (dysentery, age >50, mod-severe travelers diarrhea (>6 episodes/day), fevers >101, positive stool cultures, fecal leukocyte positive); (4) identify the percentage of patients who received (CT) scans; and (5) identify the number of patients who were ordered stool cultures according to WGO/ACG recommendations and the incidence of a positive result. Methods: We performed a retrospective clinical review of patients who visited the Lenox Hill Hospital ED and were given ICD diagnoses of diarrhea, gastroenteritis, colitis, and enteritis during August 2010. Patients were excluded from the study if they had a history of IBD, IBS, and/or malabsorptive disease. Also excluded were patients with diarrhea > 3 wks (subacute/chronic), less than 18 years old, and patients with ICD codes that did not correlate with their presenting illness. For each patient, the electronic medical record from ED was reviewed to extract the following data: age, number of stools, dysentery, fevers>101, symptoms >48hrs, dehydration (clinically/vital signs), mental status changes, antimicrobial therapy, CT findings, travel history, fecal leukocytes/fecal occult positive, admitted or discharged, past medical history of IBD, IBS, or malabsorptive diseases. Results: Ninety nine charts were reviewed and 74 patients were included in our study. The admission rate was 25.7% (19/74) and all patients were admitted according to WGO/ACG recommendations. 41.9% (31/74) of patients were given antibiotics, yet 25.6% of patients were given antibiotics not in adherence with WGO/ACG recommendations. 27% received CT scans, with a 75% incidence of a positive colitis finding. All these patients were treated with antibiotics. Stool cultures were ordered on 24.3%, 66.6% had documented results, zero cultures yielded a positive result, and 83.3% of stool cultures were ordered appropriately according to recommendations. Conclusion: The majority of our patients were appropriately evaluated and managed, yet one-quarter of our patients inappropriately received antibiotics and all stool cultures were negative, which may contribute to higher cost and possible antibiotic resistance.

Simple conization and lymphadenectomy for the conservative treatment of stage IB1 cervical cancer. An Italian experience

Objectives Simple conization represents a plausible treatment scheme for managing stage IA1-2 tumors conservatively. However its curative potential has not been widely exploited as regards stage IB1 lesions. Recent studies suggest that, in selected circumstances, patients with stage IB1 disease undergoing radical hysterectomy could have been safely cured by simple hysterectomy and even by cervical conization. Methods Patients with stage IB1 cervical cancer desiring conservative management underwent simple conization and pelvic lymphadenectomy in three Italian institutes. Results Thirty-six women received the conservative treatment since 1995 to 2010. Median age was 31 (range 24–40) years and median tumor size was 11.7 mm (range 8–25 mm). Adenocarcinoma was present in 12 cases (33%) and grade 3 neoplasia in 5 (14%). Lymph-vascular space involvement was detected in five patients (14%). Eleven had already a child while two had experienced an early abortion and a fetal loss at second trimester. After a median follow-up of 66 months (range 6–168) only one pelvic lymphnodal relapse was observed. Twenty-one pregnancies occurred in 17 patients and 14 live babies have been born (two preterm at 27 and 32 weeks) while one is ongoing. Three first-trimester miscarriages, one second-trimester fetal loss, an ectopic pregnancy and a termination of pregnancy have been recorded. Five patients decided to undergo hysterectomy after 3–12 years after conservative therapy: in one residual microinvasive adenocarcinoma was found. Conclusions Cervical conization represents a feasible conservative management of stage IB1 cervical cancer and shows a low risk of relapse, provided that patients are selected carefully. Conization would be suitable to treat stage IB lesions smaller than 15–20 mm. with pathologic negative lymphnodes.

Sentinel lymph node detection in patients with vulvar carcinoma; Feasibility of intra-operative mapping with technetium-99m-labeled nanocolloid

Aims Sentinel lymph node (SLN) mapping appears to be feasible in patients with primary vulvar cancer. Previous protocols describe the injection of the technetium-99m-nanocolloid at least 3 h before surgery which involves two invasive procedures for the patient. In this study, we assessed the feasibility, safety, and accuracy of an intra-operative rather than preoperative SLN mapping in patients with primary vulvar cancer. Methods Patients with histologically confirmed squamous cell vulvar cancer and clinically FIGO stage Ib disease underwent intra-operative SLN mapping by intradermal injection of the nanocolloid around the tumor. SLN were identified and removed before a complete inguinofemoral lymphnode dissection was performed. Surgical and pathologic data on all patients were prospectively entered into a database. Results An SLN procedure was performed in 16 patients; 3 patients received unilateral lymphadenectomy, and 13 women underwent surgery on both groins. In all groins but 4 at least one SLN was clearly identified (detection rate 25/29, 86%). A median number of 2 SLN and 4 non-SLN per groin were removed. 3 of 16 patients (19%) had metastatic disease in the lymph nodes. There was no false negative SLN result. Conclusion Intra-operative SLN detection seems feasible in patients with early stage vulvar cancer. More patients need to be enrolled in this ongoing study before this more convenient technique can be considered safe.

Utility of Tumor Marker HE4 to Predict Depth of Myometrial Invasion in Endometrioid Adenocarcinoma of the Uterus

The purpose of this pilot study was to determine whether the biomarker human epididymis protein 4 (HE4) correlates with depth of myometrial invasion, histologic grade, lymph vascular space invasion, positive cytologic washings, and nodal metastases in patients with endometrioid adenocarcinoma of the uterus. This was a prospective, observational study in women with biopsy-proven endometrioid adenocarcinoma. Concentrations of HE4 were assessed before surgery, and all surgical specimens were reviewed by dedicated gynecologic pathologists. Included were a total of 96 women with endometrioid adenocarcinomas of the uterus, most (77%) with stage I disease. Levels of serum HE4 greater than 70 pM displayed a sensitivity of 94% and a negative predictive value of 97% in identifying stage IA (<50% myometrial invasion) versus stage IB (≥ 50% myometrial invasion) tumors and a sensitivity of 82% and negative predictive value of 82% versus all more advanced tumors. Human epididymis protein 4 may be a useful marker preoperatively in the clinical decision process for determining the need for lymph node dissection in women with endometrioid endometrial cancer.

Impact of Adjuvant External-Beam Radiation Therapy in Early-Stage Uterine Papillary Serous and Clear Cell Carcinoma

Adjuvant radiation therapy (RT) in early-stage high- to intermediate-risk endometrioid adenocarcinoma is well established and has been shown to improve locoregional control. Its role in the management of early-stage clear cell carcinoma and uterine papillary serous carcinoma (UPSC) remains controversial. Using the Surveillance Epidemiology and End Results database, we identified women with American Joint Committee on Cancer Stage Sixth Edition. Stage IA-IIB clear cell carcinoma or UPSC who underwent hysterectomy with or without adjuvant RT between 1988 and 2003. We used Kaplan-Meier and Cox regression analysis to compare overall survival (OS) for all patients. We identified 1,333 women of whom 451 had clear cell carcinoma and 882 had UPSC. Of those patients, 775 underwent surgery alone and 558 received adjuvant RT as well. For Stages I-IIB disease, the median OS with surgery alone was 106 months, vs. 151 months with adjuvant RT (p = 0.006). On subgroup analysis, we saw the benefit from adjuvant RT only in Stage IB-C patients. For Stage IB disease, patients undergoing surgery alone had a median OS of 117 months, vs. median survival not reached with the addition of RT (p = 0.006). For Stage IC disease, surgery alone had a median OS of 35 months vs. 120 months with RT (p = 0.001). Although the apparent benefit of RT diminished when measured via multivariate analysis, the impact of RT on survival did show a trend toward significance (hazard ration 0.808, confidence interval 95% 0.651-1.002, p = 0.052) In FIGO Stage IB-C papillary serous and clear cell uterine carcinoma, adjuvant RT seems to play an important role in improving survival.

How Well Does the New Lung Cancer Staging System Predict for Local/Regional Recurrence After Surgery?: A Comparison of the TNM 6 and 7 Systems

To evaluate how well the tumor, node, metastasis (TNM) 6 and TNM 7 staging systems predict rates of local/regional recurrence (LRR) after surgery alone for non-small cell lung cancer. All patients who underwent surgery for non-small cell lung cancer at Duke between 1995 and 2005 were reviewed. Those undergoing sublobar resections, with positive margins or involvement of the chest wall, or those who received any chemotherapy or radiation therapy (RT) were excluded. Disease recurrence at the surgical margin, or within ipsilateral hilar and/or mediastinal lymph nodes, was considered as a LRR. Stage was assigned based on both TNM 6 and TNM 7. Rates of LRR were estimated using the Kaplan-Meier method. A Cox regression analysis evaluated the hazard ratio of LRR by stage within TNM 6 and TNM 7. A total of 709 patients were eligible for the analysis. Median follow-up was 32 months. For all patients, the 5-year actuarial risk of LRR was 23%. Conversion from TNM 6 to TNM 7 resulted in 21% stage migration (upstaging in 13%; downstaging in 8%). Five-year rates of LRR for stages IA, IB, IIA, IIB, and IIIA disease using TNM 6 were 16%, 26%, 43%, 35%, and 40%, respectively. Using TNM 7, corresponding rates were 16%, 23%, 37%, 39%, and 30%, respectively. The hazard ratios for LRR were statistically different for IA and IB in both TNM 6 and 7 but were also different for IB and IIA in TNM 7. LRR risk increases monotonically for stages IA to IIB in the new TNM 7 system. This information might be valuable when designing future studies of postoperative RT.

Does the revised International Federation of Gynecology and Obstetrics staging system for endometrial cancer lead to increased discrimination in patient outcomes?

Recent changes were made to the International Federation of Gynecology and Obstetrics (FIGO) staging system for endometrial cancer. The objective of this study was to compare survival outcomes for patients who were staged according to the 1988 FIGO staging system versus the 2009 FIGO staging system. Data were obtained from the Surveillance, Epidemiology, and End Results Program for the years 1998 to 2006. Patients who had a diagnosis of adenocarcinoma of the uterus with complete staging information were included. Patients were staged according to the 1988 and 2009 FIGO staging systems, and Kaplan-Meier estimates were derived for cause-specific survival (CSS). Univariate and multivariate analyses using Cox proportional hazards models were used to identify the factors associated with survival. In total, 47,284 patients were included. The median follow-up was 37 months. The 5-year CSS rates for patients who had 2009 FIGO stage IA and IB disease were 96.6% and 89.9%, respectively (P < .0001). After accounting for age, grade, and race, this survival difference remained significant (hazard ratio [HR], 1.97; 95% confidence interval [CI], 1.74-2.24; P < .0001). Patients who had 1988 FIGO stage IIA disease had a 5-year CSS rate similar to that of patients who had 1988 FIGO stage IC disease (88.6% vs 89.9%, respectively; P = .09). Patients who had positive pelvic washings had a 5-year CSS rate similar to that of patients who had stage IIIA disease according to the 2009 FIGO system (74.2% vs 72.1%, respectively; P = .37). The 5-year CSS rate for patients who had stage IIIC1 disease was significantly improved compared with that for patients who had stage IIIC2 disease (68.2% vs 57.3%, respectively; P < .0001). In the multivariate model, the survival difference remained (HR, 1.49; 95% CI, 1.26-1.76; P < .0001). The 2009 staging system for endometrial cancer produced better discrimination in CSS outcomes compared with the 1988 system.