IA Disease Research Articles

Impact of hospital care volume on clinical outcomes of laparoscopic radical hysterectomy for cervical cancer: A systematic review and meta-analysis.

In cervical cancer, the impact of hospital volume of laparoscopic radical hysterectomy (LRH) has not been investigated systematically as in ovarian cancer.The aim of this study was to investigate the impact of hospital care volume of LRH on treatment outcomes of patients with cervical cancer. The PubMed, Embase, and Cochrane Library databases were searched with the terms "cervical cancer," "radical hysterectomy," and "laparoscopy." The selection criteria included studies presenting operative outcomes and/or perioperative complications of LRH from high-volume hospitals (HVHs) (≥15 cases/year) and low-volume hospitals (LVHs) (<15 cases/year). Fifty-nine studies including 4367 cases were selected. Linear regression analysis weighted by the average annual case number in each study was performed to evaluate differences between the groups. In HVH, a higher number of lymph nodes (24.5 vs 21.1; P = .037) were retrieved by LRH in older women (48.4 vs 44.5 years; P = .010) with tendencies of shorter operation time (224.4 vs 256.4 minutes; P = .096) and less blood loss (253.1 vs 322.2 mL; P = .080). Compared with LVH, HVH had fewer patients with stage IA disease (13.8 vs 24.4%; P = .003) and more patients with stage IIA disease (15.3 vs 7.1%; P = .052) with comparable 5-year overall survival (93.1 vs 88.6%; P = .112). HVH is a prognostic factor for operative outcome and perioperative complications in patients with cervical cancer undergoing LRH. The exact effect of hospital volume on survival outcome needs to be evaluated.

Adjuvant Chemotherapy Improves Survival in Surgically Resected Stage IB Squamous Lung Cancer

At present there is a significant lack of clinical data for patients with surgically resected stage I squamous lung cancer. The purpose of this study was to investigate the impact of postoperative chemotherapy in this specific population. We retrospectively identified patients who had undergone complete squamous lung cancer resection at the Shanghai Chest Hospital between January 2008 and January2014. A total of 596 patients (236 stage IA, 360 stage IB) were included in this study. Results demonstrated that adjuvant chemotherapy (ACT) could provide longer overall survival for patients with p-stage IB disease (hazard ratio [HR], 0.56; 95% confidence interval [CI], 0.34-0.90; p= 0.017). Among p-stage IB patients the ACT-treated cohort trended toward a benefit (HR, 0.69; 95% CI, 0.45-1.04) in recurrence-free survival but failed to reach statistical significance (p= 0.076). After propensity score matching the HRs of recurrence-free survival and overall survival were 0.58 (95% CI, 0.35-0.96; p= 0.033) and 0.49 (95% CI, 0.27-0.88; p= 0.017), respectively. With regards to patients with p-stage IA disease, neither overall survival (HR, 0.87; 95% CI, 0.34-2.27; p= 0.783) nor recurrence-free survival (HR, 0.79; 95% CI, 0.38-1.65; p= 0.534) was significantly different when compared between patients receiving ACT and those who did not. Similar results were also achieved after propensity score matching. The data presented herein demonstrated that ACT might provide survival benefits for squamous lung cancer patients with p-stage IB disease.

247P - Clinicopathological and survival analysis of endometrial carcinoma: A single center experience in Pakistan

Background: Endometrial carcinoma is the most common malignancy of the female genital tract. Adjuvant chemotherapy sequentially with radiation has shown to improve progression free survival in previous studies. Methods: From 12 March 2005 till 15 June 2016, 239 patients with Endometrial Cancer treated at Aga Khan University Hospital, Karachi were identified and retrospectively reviewed for survival analysis. We aimed to determine the progression free survival and overall survival of patients with Endometrial Cancer and factors affecting them. Results: The mean age at tumor diagnosis was 60.2 ±10.53 years. One hundred and thirty four (56.30%) patients had T1a tumor size and 120 (50.21%) patients had histological Stage IA disease. The most common histopathology was endometroid (81.56%). One hundred and nineteen (49.79%) patients had Grade II, and 62 (25.94%) had grade III disease. Fourteen patients (5.86%) presented with metastatic disease, with lung (50%) being the most common site involved. Surgery was done in 184 patients (94.36%), with complete debulking in 166 patients (90.22%). Adjuvant chemotherapy was received by 40 patients (20.51%) whereas adjuvant radiation therapy was received by 88 patients (45.13%). Median progression free survival was 30.56 months and median overall survival was 27.34 months. Grade II tumors were associated with improved survival (101 months P = 0.035). Among patients 86.15% of the patients showed no evidence of progression, where as 13.85% of the patients had documented progression. Conclusions: The patient population primarily had early stage disease with endometrioid histology. The five year progression free survival and overall survival was 75% and 94% respectively. Legal entity responsible for the study: The authors. Funding: Has not received any funding. Disclosure: All authors have declared no conflicts of interest.

Primary cutaneous lymphomas: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up

Primary cutaneous lymphomas: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up

Disparities in the use of fertility-sparing surgery for early stage cervical cancer

Women with early stage cervical cancer who are of reproductive age and wish to preserve fertility may be candidates for fertility-sparing surgery (FSS). The goal of this study was to examine the presence of disparities in the use of fertility-preserving surgery (FSS) and to investigate outcomes in this group. Retrospective cohort study. The National Cancer Database was used to identify patients aged <=35 years diagnosed with cervical cancer between 2004-2015. Those with stage IA2 or IB1 squamous cell carcinoma (SCC) or adenocarcinoma (AC) who underwent definitive treatment by hysterectomy (HYST) versus cone resection or trachelectomy (FSS) were identified. Univariate analysis was performed with chi-square and Mann-Whitney tests. Overall survival (OS) was evaluated for cases diagnosed between 2004-2014 after generation of Kaplan-Meier curves and compared with the log-rank test. A Cox model was constructed to control for confounders. A total of 2623 patients met the inclusion criteria. Median patient age at the time of diagnosis was 31 years (IQR:5). The majority had squamous cell carcinoma (62.4%) and stage IB1 disease (84.1%). The rate of FSS was 13.6%. Compared to patients who underwent HYST, those who received FSS were younger (median 30 vs 32 yrs, p<0.001), had fewer co-morbidities (3.6% vs 7.6%, p=0.007), were more likely to reside in large metropolitan areas (61.1% vs 49.5%, p<0.001), have private insurance (75.8% vs 62.9%, p<0.001), higher median income (p<0.001), present with stage IA2 disease (25.2% vs 14.4%, p<0.001) and adenocarcinoma (45.4% vs 36.3%, p=0.001). No differences were noted based on patient race (p=0.14). After controlling for clinical stage, histology, age, presence of co-morbidities, and area of residence, private insurance and higher income were associated with the receipt of FSS. There was no difference in OS between patients who received HYST (n=2036) and FSS (n=305), p=0.37; 5-yr OS rates were 93.5% and 94.5%, respectively. After controlling for age, clinical stage, histology, presence of medical comorbidities and performance of lymph node dissection, receipt of FSS was not associated with a worse survival (HR: 0.75, 95% CI: 0.42, 1.37). Socio-economic disparities exist in the utilization of FSS for early stage cervical cancer. For this selected population no difference in OS was found. This is critical information for patients referred for oncofertility consultation.

Improved survival with adjuvant brachytherapy in stage IA endometrial cancer of unfavorable histology

PurposeWe evaluated the utilization of vaginal brachytherapy (BT) and the resulting impact on survival in stage IA endometrial cancer of clear cell (CC), papillary serous (PS), and carcinosarcoma (CS) histology. MethodsPatients with uterine cancer diagnosed from 2004 to 2015 were identified from the National Cancer Database. Patients underwent hysterectomy, showing FIGO stage IA disease with CC, PS, or CS histology. Logistic regression was used to evaluate predictors of BT utilization and to generate propensity scores. Survival was compared using log-rank test and Cox proportional hazards modeling, with propensity score adjustment. ResultsWe identified 5711 patients who underwent hysterectomy showing FIGO pT1a, N0 or NX endometrial cancer with CC, PS, or CS histology, of which 29.5% received BT. Multivariate predictors of increased receipt of BT were identified. With a median follow-up of 3.3 years, 3-year overall survival (OS) was 87% for those receiving BT versus 78% for those without (p < 0.001). A survival benefit to BT was maintained across histologies. Similar results were seen whether tumor was confined to endometrium or had <50% myometrial invasion. On multivariate analysis, receipt of BT was associated with increased survival (hazard ratio [HR] 0.75, 95% confidence interval 0.65–0.87, p < 0.001). The benefit of BT persisted after propensity score adjustment (HR 0.76, p < 0.001). ConclusionsIn this cohort of women with stage IA endometrial cancer of unfavorable histology, the use of BT was associated with improved survival. In this study, 29.5% of patients in our cohort received BT.

The First Year of the AEVD Primary Cutaneous Lymphoma Registry

Background and objectivePrimary cutaneous lymphomas are uncommon. This article describes the Primary Cutaneous Lymphoma Registry of the Spanish Academy of Dermatology and Venereology (AEDV) and reports on the results from the first year. Patients and methodsDisease registry for patients with primary cutaneous lymphoma. The participating hospitals prospectively recorded data on diagnosis, treatment, tests, and disease stage for all patients with primary cutaneous lymphoma. A descriptive analysis was performed. ResultsIn December 2017, the registry contained data on 639 patients (60% male) from 16 university hospitals. The most common diagnoses, in order of frequency, were mycosis fungoides/Sézary syndrome (MF/SS) (348 cases, 55%), primary cutaneous B-cell lymphoma (CBCL) (184 cases, 29%), primary cutaneous CD30+ T-cell lymphoproliferative disorder (CD30+ CLPD) (70 cases, 11%), and other types of T-cell lymphoma (37 cases, 5%). In total, 105 (16.5%) of the cases recorded were incident cases. The most common diagnosis in the MF/SS group was classic MF (77.3%). Half of the patients with MF had stage IA disease when diagnosed, and the majority were either in partial remission (32.5%) or had stable disease (33.1%). The most widely used treatments were topical corticosteroids (90.8%) and phototherapy. The most common form of primary CBCL was marginal zone lymphoma (50%). Almost all of the patients had cutaneous involvement only and nearly half had stage T1a disease. Most (76.1%) were in complete remission. The main treatments were surgery (55.4%) and radiotherapy (41.9%). The most common diagnosis in patients with CD30+ CLPD was lymphomatoid papulosis (68.8%). Most of the patients (31.4%) had stage T3b disease and half were in complete remission. The most common treatments were topical corticosteroids (68.8%) and systemic chemotherapy (32.9%). ConclusionThe characteristics of patients with primary cutaneous lymphoma in Spain do not differ from those described in other series in the literature. The registry will facilitate clinical research by the AEDV's lymphoma group.

Classical Hodgkin lymphoma arising from heterotopic Warthin's tumor in the cervical lymph node: A case report.

Heterotopic Warthin's tumor (WT) arising from the cervical lymph nodes is uncommon and WT presenting concomitantly with classical Hodgkin's lymphoma has only been previously reported three times in English literature. The current study presents an unusual case of classical Hodgkin lymphoma (CHL) involving the heterotopic WT in a 59-year-old male. Histopathologic examination revealied a WT with extensive expansion of mixed-cellularity CHL in a lymph node in the right of the neck. Clinical staging was determined as stage IA disease. The patient received four courses of chemotherapy and local consolidative radiotherapy, no evidence of disseminated lymphoma was observed over the 6-month follow-up. To the best of our knowledge, this is the first well documented collision tumor between CHL and heterotopic WT of the cervical lymph nodes. The present case also expands the anatomical site of malignant lymphomas associated with WT.

(OA21) Outcomes After Salvage Therapy for Recurrent Early Stage Endometrial Cancer

We sought to analyze our institutional experience and oncologic outcomes for salvage treatment for recurrence of early stage endometrial cancer patients. We analyzed women of all ages diagnosed with FIGO stage I-II endometrial cancer of any grade between 2000-2016 at our institution. All women received hysterectomy. Leiomyosarcoma histology was excluded. Recurrences in the pelvis or vagina were considered locoregional (LRR). Overall survival (OS), disease free survival (DFS) and recurrence were assessed using Kaplan-Meier survival analysis. Univariate (UV) and multivariate (MV) Cox proportional hazards modeling was used to identify factors associated with survival and recurrence. 988 women were included. 73% had stage IA disease; 88% had endometrioid histology. 5% of women had adjuvant chemotherapy and 29% had adjuvant radiation (66% vaginal brachytherapy [VB] alone, 23% external beam radiation [EBRT] alone, and 11% EBRT + VB). At a median follow up of 4.8 years there were 101 (10.2%) failures (29 vaginal failures, 29 pelvic failures, and 43 distant failures). 17% of vaginal failures and 59% of pelvic failures had prior radiation. The median OS for patients without recurrence was 16.0 years vs. 5.2 years for those with recurrence, p<0.001. Of the 58 women with LRR, 28% had salvage surgery, 74% had salvage radiation (66% EBRT alone, 27% EBRT + VB, and 7% VB alone), and 35% had salvage chemotherapy. With a median follow up of 1.5 years after initial recurrence, 5/58 women had second LRR and 7/58 failed distantly. The median and 3 year DFS after initial recurrence for those without a second recurrence was 3.6 years and 51.2%, respectively, compared to 1.3 years and 8.3%, respectively, for those with a second recurrence (p=0.0064). On MV analysis, increasing age (Hazard Ratio [HR] 1.05, p=0.046) and pelvic site of initial recurrence (HR 2.6, p=0.034) were associated with worse DFS. When analyzing vaginal only recurrences, on MV analysis, salvage radiation was the sole treatment modality associated with improved DFS (HR 0.19, p=0.013). For women with early stage endometrial cancer rates of failure are low, but not insignificant. However, the majority of women with LRR were successfully salvaged with additional treatment. Salvage radiation appears to be the most important element of salvage therapy for vaginal recurrences.

Final validation of the ProMisE molecular classifier for endometrial carcinoma in a large population-based case series

BackgroundWe have previously developed and confirmed a pragmatic molecular classifier for endometrial cancers; ProMisE (Proactive Molecular Risk Classifier for Endometrial Cancer). Inspired by the Cancer Genome Atlas, ProMisE identifies four prognostically distinct molecular subtypes and can be applied to diagnostic specimens (biopsy/curettings) enabling earlier informed decision-making. We have strictly adhered to the Institute of Medicine (IOM) guidelines for the development of genomic biomarkers, and herein present the final validation step of a locked-down classifier before clinical application. Patients and methodsWe assessed a retrospective cohort of women from the Tübingen University Women’s Hospital treated for endometrial carcinoma between 2003 and 2013. Primary outcomes of overall, disease-specific, and progression-free survival were evaluated for clinical, pathological, and molecular features. ResultsComplete clinical and molecular data were evaluable from 452 women. Patient age ranged from 29 to 93 (median 65) years, and 87.8% cases were endometrioid histotype. Grade distribution included 282 (62.4%) G1, 75 (16.6%) G2, and 95 (21.0%) G3 tumors. 276 (61.1%) patients had stage IA disease, with the remaining stage IB [89 (19.7%)], stage II [26 (5.8%)], and stage III/IV [61 (13.5%)]. ProMisE molecular classification yielded 127 (28.1%) MMR-D, 42 (9.3%) POLE, 55 (12.2%) p53abn, and 228 (50.4%) p53wt. ProMisE was a prognostic marker for progression-free (P=0.001) and disease-specific (P=0.03) survival even after adjusting for known risk factors. Concordance between diagnostic and surgical specimens was highly favorable; accuracy 0.91, κ 0.88. DiscussionWe have developed, confirmed, and now validated a pragmatic molecular classification tool (ProMisE) that provides consistent categorization of tumors and identifies four distinct prognostic molecular subtypes. ProMisE can be applied to diagnostic samples and thus could be used to inform surgical procedure(s) and/or need for adjuvant therapy. Based on the IOM guidelines this classifier is now ready for clinical evaluation through prospective clinical trials.

Registro de linfomas cutáneos primarios de la AEDV: primer año de funcionamiento

Background and objectivePrimary cutaneous lymphomas are uncommon. This article describes the Primary Cutaneous Lymphoma Registry of the Spanish Academy of Dermatology and Venereology (AEDV) and reports on the results from the first year. Patients and methodsDisease registry for patients with primary cutaneous lymphoma. The participating hospitals prospectively recorded data on diagnosis, treatment, tests, and disease stage for all patients with primary cutaneous lymphoma. A descriptive analysis was performed. ResultsIn December 2017, the registry contained data on 639 patients (60% male) from 16 university hospitals. The most common diagnoses, in order of frequency, were mycosis fungoides/Sézary syndrome (MF/SS) (348 cases, 55%), primary cutaneous B-cell lymphoma (CBCL) (184 cases, 29%), primary cutaneous CD30+ T-cell lymphoproliferative disorder (CD30+ CLPD) (70 cases, 11%), and other types of T-cell lymphoma (37 cases, 5%). In total, 105 (16.5%) of the cases recorded were incident cases. The most common diagnosis in the MF/SS group was classic MF (77.3%). Half of the patients with MF had stage IA disease when diagnosed, and the majority were either in partial remission (32.5%) or had stable disease (33.1%). The most widely used treatments were topical corticosteroids (90.8%) and phototherapy. The most common form of primary CBCL was marginal zone lymphoma (50%). Almost all of the patients had cutaneous involvement only and nearly half had stage T1a disease. Most (76.1%) were in complete remission. The main treatments were surgery (55.4%) and radiotherapy (41.9%). The most common diagnosis in patients with CD30+ CLPD was lymphomatoid papulosis (68.8%). Most of the patients (31.4%) had stage T3b disease and half were in complete remission. The most common treatments were topical corticosteroids (68.8%) and systemic chemotherapy (32.9%). ConclusionThe characteristics of patients with primary cutaneous lymphoma in Spain do not differ from those described in other series in the literature. The registry will facilitate clinical research by the AEDV's lymphoma group.

Uterine adenosarcoma in Japan: Clinicopathologic features, diagnosis and management.

Uterine adenosarcoma is a rare malignancy with limited cohort data in Asian countries. This study evaluated the clinicopathologic features of Japanese patients with uterine adenosarcoma and their potential treatment challenges. A retrospective chart review was performed at the National Cancer Center Hospital, Japan from 2000 to 2016. A literature search for Japanese cases of uterine adenosarcoma was conducted using PubMed, Japanese Central Review of Medicine, and the Annual of Pathological Autopsy Cases in Japan. Only histologically confirmed cases of uterine adenosarcoma were included. All collected data were analyzed. A total of 110 cases was identified (6 from our hospital and 104 from the literature review). Most baseline characteristics were similar to those reported in western countries. Death due to the disease was observed in 34% (29/86) of patients, whereas patients with stage IA disease showed a 13% (4/30) recurrence rate and a 3.3% (1/30) mortality rate. Preoperative radiological and pathological examinations occasionally failed to help reach the correct diagnosis. In cases of sarcomatous overgrowth, the recurrence and mortality rates were 45% (9/20) and 35% (7/20), respectively. Distant recurrence occurred in 44% (12/27) of cases, 75% of which included lung metastasis. This study showed the clinicopathologic features of Japanese patients with uterine adenosarcoma and suggested potential solutions for improving prognosis including early treatment based on a timely diagnosis, the development of effective adjuvant therapy for patients at high risk of recurrence, and optimal follow-up focusing on late recurrence and lung metastasis.

Abstract P1-06-03: Breast cancer-specific survival (BCSS) in SEER patients with 21-gene Recurrence Score® (RS) results &amp;lt;11 classified as prognostic stage IA by new 8th edition AJCC staging manual

Abstract Introduction: The 8th edition of the AJCC Staging Manual added molecular features for the first time and now includes ER, PR, HER2, and the 21-gene assay for prognostic staging. We obtained real-world evidence of BCSS by age, tumor size, and grade in a population-based SEER analysis of N0, HR+, HER2-negative breast cancer and RS &amp;lt;11 (tumor size up to 5 cm) to obtain more detailed information on clinically “unfavorable” subgroups. Methods: RS results were provided to SEER registries as mandated by their methods for linkage (Petkov npj Breast Cancer 2016). Patients (pts) with RS &amp;lt;11 and size up to 5 cm were eligible if N0, HR+, HER2-negative, had no prior malignancy, and were diagnosed between Jan 2004 and Dec 2012 (SEER survival updated through 2013). 5-year BCSS was estimated using actuarial methods. Results: 9,304 pts had RS &amp;lt;11 (19% of those meeting all other eligibility), with median follow-up of 40 months. Median age was 59 y, with 22% &amp;lt;50 y and 16% ≥70 y. Tumor size was &amp;gt;2 cm in 21% of pts. Tumor grade was moderate in 54% and poor in 8% of pts. Overall, 5-year BCSS for pts with RS &amp;lt;11 was 99.6% (95% CI 99.4%, 99.7%), with reported chemotherapy (CT) use in 3.3% of pts. In contrast, BCSS for pts with RS &amp;gt;25 and RS ≥31 was 3.5% and 4.7%, respectively, with frequent CT use. 5-year BCSS for important clinicopathologic subgroups show high 5-year BCSS despite “unfavorable” age, tumor size, and grade (Table). 5-y BCSS for RS &amp;lt;11, by Clinicopathologic FactorsRS &amp;lt;11 and Age &amp;lt;50 yRS &amp;lt;11 and Tumor Size 2.1-5.0 cmRS &amp;lt;11 and Poor Tumor GradeN (% of N with CT ‘Yes’)5-y BCSS (95% CI)N (% of N with CT ‘Yes’)5-y BCSS (95% CI)N (% of N with CT ‘Yes’)5-y BCSS (95% CI)2009 (6.2%)100% (100%, 100%)1976 (5.5%)99.3% (98.5%, 99.7%)686 (5.8%)99.5% (97.9%, 99.9%) Conclusions: In this SEER population-based study, pts with RS &amp;lt;11 had a wide range of clinicopathologic features. 5-year BCSS was high (&amp;gt;99%), regardless of age, tumor size, or grade. These results support the new AJCC staging criteria that classify N0, HR+, HER2-negative pts with RS &amp;lt;11 and tumor size up to 5 cm as having Prognostic Stage IA disease. Citation Format: Baehner FL, Petkov VI, McCullough D, Shak S. Breast cancer-specific survival (BCSS) in SEER patients with 21-gene Recurrence Score® (RS) results &amp;lt;11 classified as prognostic stage IA by new 8th edition AJCC staging manual [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P1-06-03.

Variability in invasive mediastinal staging for lung cancer: A multicenter regional study

ObjectivePrior studies have reported underuse of—but not variability in—invasive mediastinal staging in the pretreatment evaluation of patients with lung cancer. We sought to compare rates of invasive mediastinal staging for lung cancer across hospitals participating in a regional quality improvement and research collaborative. MethodsWe conducted a retrospective study (2011-2013) of patients undergoing resected lung cancer from the Surgical Clinical Outcomes and Assessment Program in Washington State. Invasive mediastinal staging included mediastinoscopy and/or endobronchial/esophageal ultrasound-guided nodal aspiration. We used a mixed-effects model to mitigate the influence of small sample sizes at any 1 hospital on rates of invasive staging and to adjust for hospital-level differences in the frequency of clinical stage IA disease. ResultsA total of 406 patients (mean age, 68 years; 69% clinical stage IA; and 67% lobectomy) underwent resection at 5 hospitals (4 community and 1 academic). Invasive staging occurred in 66% of patients (95% confidence interval [CI], 61%-71%). CI inspection revealed that 2 hospitals performed invasive staging significantly more often than the overall average (94%, [95% CI, 89%-96%] and 84% [95% CI, 78%-88%]), whereas 2 hospitals performed invasive staging significantly less often than overall average (31% [95% CI, 21%-44%] and 17% [95% CI, 7%-36%]). ConclusionsRates of invasive mediastinal staging varied significantly across hospitals providing surgical care for patients with lung cancer. Future studies that aim to understand the reasons underlying variability in care may inform quality improvement initiatives or lead to the development of novel staging algorithms.

Non-small cell lung cancer in surgically treated women.

To determine whether female patients operated on for non-small cell lung cancer (NSCLC) have a survival advantage compared to male patients. We analyzed data from 1,426 prospectively collected patients submitted to lung resection for NSCLC between 1999 and 2008. Two groups, including 1,014 male and 412 female patients, were compared. Female patients were significantly younger, were more frequently asymptomatic, were less likely to be smokers, had better preoperative respiratory function, had a lower frequency of COPD, and were less commonly affected by cardiovascular comorbidity than men. Adenocarcinoma was more frequently present and early pathological stage (stage IA) more frequently detected in women at diagnosis. The operative mortality was significantly lower among women (1.6% vs 4.6%) (P = 0.012), and women underwent significantly more segmentectomies and fewer pneumonectomies (P = 0.001). The disease-related 5-year survival rate was significantly higher in women (66% vs 51%) (P = 0.0008). At univariate analysis the absence of symptoms at presentation, lower pathological stage, squamous cell type, and female gender were positive factors influencing long-term survival. At multivariate analysis low pathological stage, squamous cell type and female gender were confirmed as independent positive prognostic predictors. Women had a significant survival advantage irrespective of the histological subtype at pathological stage IA, IB, IIB and IIIA disease (P <0.05). Female gender was confirmed to be a particular subset amongst patients affected by NSCLC and exerted a positive effect on disease-related survival of patients submitted to surgical resection. This important effect of gender should be cautiously kept in mind in analyzing the results of current and future trials for lung cancer therapy.

ES 10.04 Carbon-ion Therapy

ES 10.04 Carbon-ion Therapy

P3.16-051 Implications of Preoperative Serum Tumor Levels on Pathological Characteristics in Patients with Lung Adenocarcinoma

Although preoperative serum tumor marker levels, such as carcinoembryonic antigen (CEA) and squamous cell carcinoma antigen (SCC) are often evaluated in non-small cell lung cancer patients, the implication of these levels are still unknown. This study examined the predictive effect of preoperative tumor marker levels on pathological characteristics of lung adenocarcinoma. We retrospectively reviewed patients with lung adenocarcinoma who underwent macroscopic complete resection. The pathological metastasis and/or involvement was defined that positive pleural effusion or lavage cytology, pleural involvement, pulmonary metastasis, lymph node metastasis, and/or lymphovascular involvement were identified on pathological examination. To identify predictors for the pathological metastasis and/or involvement, tumor markers (CEA, SCC, Sialyl Lewisx-1 [SLX], cytokeratin-19 fragments [CYFRA], neuron-specific enolase [NSE], and pro-gastrin-releasing peptide [ProGRP]), and demographic and clinical factors were analyzed by a univariate analysis and multivariate logistic regression analysis. For the significant tumor markers, optimal cutoff points were determined with a receiver operating characteristic analysis. Of the 263 eligible patients, 138 were male and 125 were female. The median age was 70 years. The median preoperative CEA, SCC, SLX, CYFRA, NSE, and ProGRP levels were 3.7 ng/ml, 0.8 ng/ml, 28 U/ml, 1.8 ng/ml, 8.4 ng/ml, and 46.9 pg/ml, respectively. According to the 7th edition of the TNM classification, 186 patients (71%) had c-stage IA disease, 48 (18%) had c-stage IB disease, 26 (10%) had c-stage II disease, and 3 (1%) had c-stage III disease. Positive pleural effusion, positive pleural lavage cytology, pleural involvement, pulmonary metastasis, lymph node metastasis, lymphatic permeation, and vascular invasion were identified in 3 (1%), 4 (2%), 48 (18%), 9 (3%), 28 (11%), 20 (8%), and 35 patients (13%), respectively, and in total, 83 patients (32%) developed the pathological metastasis and/or involvement. The univariate analysis identified CEA, smoking index, size, solid size, and c-stage as significant predictors. A multivariate analysis revealed CEA (OR: 1.113, p=0.005) and solid size (OR: 1.052, p<0.001) as significant predictors. The optimal cutoff point was determined as 6.0 ng/ml for the preoperative CEA, and 35 of the 63 patients (56%) with ≥6.0 ng/ml of CEA developed the pathological metastasis and/or involvement whereas 48 of the 200 patients (24%) with <6.0 ng/ml of CEA developed pathological metastasis and/or involvement. Our results suggested the predictive effect of the high preoperative CEA level on pathological metastasis and involvement in patients with lung adenocarcinoma, and thus, we may consider preoperative CEA to decide surgical procedure for these patients, such as the extent of pulmonary resection and lymphadenectomy.

Salvage EBRT and HDR Brachytherapy for Isolated Vaginal Recurrence of Endometrial Cancer in Patients with No Prior Adjuvant Therapy

The goal of the study was to evaluate clinical outcomes for women with isolated vaginal recurrence of endometrial cancer after hysterectomy without adjuvant radiation or chemotherapy, who received salvage treatment with both external beam radiation therapy (EBRT) and high dose rate (HDR) brachytherapy. 30 women with recurrences treated between 2000 and 2010 were included in this single institution retrospective study. Median time to recurrence from surgery was 16.7 months, range 3.2 to 170.7 months. Median age at recurrence was 73 years, range 57 to 94 years. Initial histology was endometrioid adenocarcinoma in 25 patients (83%); others were papillary serous, clear cell, or adenosquamous. Initial disease was known to be grade 1 or 2 in 19 patients (63%), and 2009 FIGO stage IA in 19 patients. All patients received pelvic EBRT in 1.8 Gy daily fractions to a total of 45 or 50.4 Gy. Interstitial brachytherapy was used in 27 patients (90%) and 3 received intracavitary brachytherapy only. CT-based inverse planning was used for all patients. The median brachytherapy EQD2 dose was 24 Gy, range 16 to 33.3 Gy. The median total EQD2 dose was 68.3 Gy, range 63 to 77.6 Gy. Three patients received concurrent hormonal or cytotoxic systemic therapy with salvage radiation. Kaplan-Meier estimates of overall survival (OS), cause specific survival (CSS), progression free survival (PFS), locoregional failure free survival (LRFFS), and distant failure free survival (DFFS) were calculated. Univariate Cox proportional hazard ratio models were used to identify features prognostic for outcomes. Median follow-up for vital status was 76.4 months, range 10.8 to 149.2 months. Median follow-up for disease status was 57.7 months, range 0 to 103.3 months. At last follow-up, 12 patients (40%) had died of which 7 (23%) were due to endometrial cancer progression. At last follow-up for disease status, 8 patients (27%) had known disease recurrence after salvage, with 3 patients (10%) recurring locoregionally and 5 patients (17%) recurring with distant metastases. Of the 3 patients with locoregional failure, 2 had died. Of the 5 patients with distant failure, all 5 had died. The 5-year Kaplan-Meier estimated OS, CSS, and PFS were 77%, 83%, and 75% respectively. The 5-year LRFFS and DFFS were 87% and 86%. Initial grade of disease (1-2 vs. 3) was prognostic for OS, CSS, and DFFS (5-year OS 95% vs. 29%, p = 0.005). Initial stage of disease (IA vs. >IA) was prognostic for CSS, PFS, and DFFS (5-year CSS 93% vs. 74%, p = 0.025). Initial stage remained prognostic for DFFS when restricted to 23 patients with stage IA or IB disease only (5-year DFFS 100% vs. 50%, p = 0.043). There was one treatment related death, otherwise no reported grade ≥ 3 toxicity. Salvage EBRT and HDR brachytherapy resulted in a high rate of long-term locoregional control. Initial higher grade and higher stage disease were associated with distant failure and cancer related mortality.

Association of Delayed Adjuvant Therapy and Overall Survival in Early Stage Endometrial Cancer

The primary treatment for early stage endometrial cancer includes definitive surgical staging procedure followed by adjuvant therapy in women with high risk of recurrence. The objective of the study is to assess differences in survival according to time interval between surgery and initiation of adjuvant therapy in early stage endometrial cancer. 349,404 patients with primary uterine carcinoma diagnosed from 2004 and 2012 were extracted from National Cancer Database (NCDB). We limited the study population to patients with FIGO 2009 stage I and II endometrial cancer with endometroid, mucinous, clear cell, or serous histology. Adjuvant therapy included radiation therapy, chemotherapy, or a combination. Interval time (IT) was defined as time between surgery and initiation of any type of adjuvant therapy. Patients who died within 90 days post surgery were excluded. We used maximally selected rank statistics to identify an interval time cutoff that generates the most statistically significant difference in overall survival, and Cox proportional hazards model was used to analyze patient characteristics associated with delayed initiation of adjuvant therapy. We identified 117,106 early stage endometrial cancer patients who underwent definitive surgical treatment. Final analysis included 28,647 of 117,106 patients who received some form of adjuvant therapy. Median age was 63 (interquartile range, IQR, 57-71). 10,975 patients (38%) had stage IA disease, 11,153 (39%) patients had stage IB disease, and 6,519 (23%) patients had stage II disease. 13,715 (48%) patients received intra-vaginal brachytherapy alone, 8,996 (31%) patients received pelvic external beam radiation, and 2,098 (7%) patients received a combination of chemotherapy and brachytherapy. The median time from surgery to initiation of adjuvant therapy was 49 days (IQR 40-67 days) and the median follow-up time from start of adjuvant therapy for surviving patients was 49.2 months. Analysis with maximally selected rank statistics revealed an interval time cutoff of 86 days. Interval time shorter than or equal to 86 days was associated with improved overall survival compared to longer than 86 days (Log-rank test p<0.0001). On multivariable analysis, Interval time longer than 86 days compared to shorter or equal to 86 days is independently associated with higher mortality (hazard ratio 1.26, 95% CI 1.15-1.38). Other factors associated worse overall survival included age > 70, serous or clear cell histology, Hispanic race, Medicare/Medicaid as primary payer, facilities located in South and Central U.S. Income level > $63,000 is associated with improved survival. In this large cohort of early stage endometrial cancer patients, interval time between surgery and adjuvant therapy longer than 86 days is associated with significantly increased mortality. Further analysis will be carried to elucidate factors associated with delayed initiation of adjuvant therapy.

Observation after Surgery for Stage IA Nodular Lymphocyte-Predominant Hodgkin Lymphoma

Nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL) frequently presents with limited stage IA disease and has a relatively indolent course. Although definitive radiation therapy (RT) is the standard treatment in this setting, national guidelines suggest that observation may be appropriate for stage IA patients with a completely excised solitary lymph node. As this is a rare histology (∼5% of Hodgkin lymphoma cases), there are few prospective studies characterizing present-day clinical management. We hypothesized that RT is being omitted frequently, particularly in younger patients to limit long-term toxicity and risk of secondary malignancy. We used the National Cancer Data Base (NCDB) to interrogate patterns of care for stage IA NLPHL. In particular, we sought to evaluate how often RT is omitted and if there are factors that can predict for patients that receive surgery followed by observation. The NCDB was queried for patients with stage IA NLPHL who received surgery followed by observation or RT. Multiple logistic regression was used to identify factors that were significantly associated with receipt of surgery followed by observation. Variables examined included facility type, age, sex, race, insurance status, distance to treatment facility, Charlson-Deyo comorbidity scores, median household income and year of diagnosis. 441 patients treated from 2004 – 2013 were identified with a median follow-up of 50.4 months. Median age was 40 years old (range, 4-86 years). 40% (175/441) did not receive RT after surgery with a median age of 35 (range, 4-86 years). 68% (54/80) of pediatric patients (<21 years) did not receive RT after surgery. Observation after surgery in age groups 21-40, 41-60, and >60 years was 37% (53/144), 27% (40/149) and 41% (28/68), respectively. Median time from diagnosis to receipt of RT was 2.3 months. Under multiple logistic regression, receipt of RT was significantly associated with increasing age (ρ = 0.011, odds ratio 1.030, 95% CI: 1.007 – 1.053) and lower income (median household income < $38,000/year) (ρ = 0.012, odds ratio 2.454, 95% CI 1.222- 4.927). Patients with Medicare (ρ = 0.007, odds ratio: 0.155, 95% CI 0.040 – 0.598) and a higher Charlson-Deyo comorbidity index of 1 (ρ = 0.049, odds ratio: 0.510, 95% CI 0.261 – 0.998) were more likely to be observed following surgery. Facility type, sex, race, distance to treatment facility and year of diagnosis were not significantly associated with receipt of RT or observation. In this analysis, a large percentage of stage IA NLPHL patients (including more than 2/3 of pediatric patients) were observed following surgery. Increasing age was significantly associated with receipt of RT after surgery. Our results suggest that omission of RT (“watch and wait”) is occurring frequently in contemporary clinical practice, especially for younger patients, and may be a reasonable consideration in select patients with stage IA NLPHL.