Type Of Adjuvant Treatment Research Articles

Effects of Adjuvant Oxaliplatin on Anal Function in Locally Advanced Rectal Cancer Treated with Preoperative Chemo-Radiotherapy and Low Anterior Resection

Background: The main objective of this study was to find out if the application of adjuvant oxaliplatin (OXA) influences sphincter function in patients with locally advanced rectal cancer (LARC) treated with preoperative capecitabine/ radiotherapy followed by lower anterior resection (LAR). Methods: Patients with LARC treated at our medical center with LAR and with absence of loco-regional relapse for at least two years were retrospectively analyzed independently of the type of adjuvant treatment that they received. Anal sphincter function was assessed by Wexner´s incontinence score (0 to 20 points, with score points inversely proportional to sphincter function). All questionnaires were completed between January 2010 and December 2012. Sphincter function as assessed by the Wexner test was compared between patients with and without OX treatment, using the non-parametrical Mann-Whitney test. Statistical analyses were conducted with IBM SPSS Statistics package, version 20. Results: 92 patients were included in our study since 2006. The mean time from LAR to fecal function assessment was 58 months (25 to 96 months). Wexner test median values did not differ significantly (p=0.450) between patients with and without adjuvant OXA. The median (IQR) for the group of patients without adjuvant OXA treatment was 6.0 (1.0-11.25), and of 5.0 (1.0-10.0) for the group that received adjuvant OXA. Conclusions: Based on our findings, OXA could be used as adjuvant treatment in LARC according to the absence of deleterious effects over sphincter anal function. Due to the retrospective nature of our study, prospective studies should be warranted in similar scenarios.

Conjunctival malignant melanoma in Denmark. Epidemiology, treatment and prognosis with special emphasis on tumorigenesis and genetic profile.

Conjunctival malignant melanoma is a rare disease associated with considerable mortality. Most published data have been based on case reports or series of referred patients. In addition, very little is known about the genetic and epigenetic profile of conjunctival melanoma. The purpose of this thesis was: To relate clinicopathological features and choice of treatment of conjunctival melanoma patients to prognosis (paper I) and to determine the incidence rate of conjunctival melanoma in Denmark (paper II). A further aim was to determine the prevalence of BRAF mutations in conjunctival melanoma, using droplet digital polymerase chain reaction (ddPCR) and immunohistochemistry (IHC), and to determine whether BRAF mutations are early events in pathogenesis and relate clinicopathological features and prognosis to BRAF mutation status (paper I and II). Finally, we wanted to identify tumour specific and prognostic microRNAs in conjunctival melanomas using a microarray-based analysis and to compare these with the microRNA expression of other melanoma subtypes (paper III). The study was based on: 139 conjunctival melanomas that had been surgically removed in Denmark over a period of 52 years (1960–2012). Conclusions: The overall incidence of conjunctival melanoma was 0.5/1 000 000/year and it increased in Denmark over 52 years. The increase was mainly caused by an increase in older patients (>65 years), bulbar lesions and lesions associated with a primary acquired melanosis with atypia (Larsen et al. 2016). Clinicopathological features significantly associated with a poor prognosis were extrabulbar location, involvement of adjacent tissue structures, tumour thickness exceeding 2 mm and local tumour recurrence. Patients undergoing incisional biopsy and/or treatment involving excision without adjuvant therapy fared worse than patients treated with excision and any type of adjuvant treatment (Larsen et al. 2015; Larsen 2016). We found that 35% (39/110) of conjunctival melanomas were BRAF mutated and the incidence of BRAF mutations was constant over time. BRAF mutation status corresponded in conjunctival melanoma and paired premalignant lesions. BRAF mutations were more frequent in males, in young patients and in tumours with a sun-exposed tumour location (bulbar conjunctiva or caruncle), with a mixed or non-pigmented colour, with absence of primary acquired melanosis and with origin in a nevus. Immunohistochemistry was able to accurately detect BRAF V600E mutations (Larsen et al. 2016). In univariate analysis, distant metastatic disease was associated with BRAF mutations; however, no prognostic associations with BRAF mutations were identified in multivariate analyses (Larsen et al. 2015, 2016). MicroRNA expression analysis revealed 24 upregulated and one downregulated microRNAs in conjunctival melanoma, several of these microRNAs have key functions in the pathogenesis and progression of cutaneous melanoma. Additionally, we identified seven upregulated microRNAs (miR-30d-5p, miR-138-5p, miR-146a-5p, miR-500a-5p, miR-501-3p, miR-501-5p and miR-502-3p) specific for stage T1 and T2 conjunctival melanoma, whose expression was associated with increased tumour thickness. No stage T3-specific microRNAs were identified. Our analysis revealed that the microRNA expression did not differ significantly between conjunctival melanoma and sinonasal or laryngeal mucosal melanoma (Larsen 2016). From our findings of a distinct pattern of BRAF mutations and differentially expressed microRNAs, conjunctival melanoma seems closely related to cutaneous and other mucosal melanomas and bears less resemblance to uveal melanomas. This means that conjunctival melanoma patients may benefit from therapies that are effective for cutaneous and mucosal melanoma. Additionally, the identification of several upregulated microRNAs may prove to be useful as future prognostic or therapeutic targets in conjunctival melanoma.

Colorectal cancer in southern Israel: Comparison between Bedouin Arab and Jewish patients

PurposeColorectal cancer (CRC) is the second most common malignancy and the third leading cause of cancer deaths in Israel; it is less common among the Arab than the Jewish population. This study compares the clinico-pathologic features, treatment, and prognosis between Bedouin-Arab (BA) and Jewish CRC patients treated at our medical centre. MethodsThe medical records of 56 BA patients with CRC were compared retrospectively to 115 Jewish patients. Collected data included age, gender, history of smoking, family history of cancer, presenting symptoms, laboratory tests, previous malignancy, tumor characteristics, surgery type, stoma formation and closure, types of adjuvant treatment, and outcome. ResultsBA patients were younger (mean age 68 versus 57 years, p < 0.001), showed a higher incidence in females (p = 0.045), and had a lower frequency of a family history of cancer (p = 0.005) compared to Jewish patients. BA patients had a higher presentation of rectal bleeding and a lower rate of anemia at tumor diagnosis (p = 0.05 and p = 0.004, respectively) with a more distal location of the tumor (p = 0.003). BA patients more often received chemotherapy and radiotherapy (p = 0.02 and p = 0.04, respectively). Disease-free survival was shorter among BA patients (p = 0.023); overall survival was similar in both groups. ConclusionsCRC in BAs is characterized by a higher proportion of female, younger age, and higher proportion of distal location compared to Jewish patients. These differences in biology may be related to differences in past lifestyles and diet of BA compared to Jewish patients, and are expected to decrease in the following years as the BA population continues to undergo “westernization” changes.

Endocrine Therapy for Hormone Receptor-Positive Metastatic Breast Cancer: American Society of Clinical Oncology Guideline.

To develop recommendations about endocrine therapy for women with hormone receptor (HR) -positive metastatic breast cancer (MBC). The American Society of Clinical Oncology convened an Expert Panel to conduct a systematic review of evidence from 2008 through 2015 to create recommendations informed by that evidence. Outcomes of interest included sequencing of hormonal agents, hormonal agents compared with chemotherapy, targeted biologic therapy, and treatment of premenopausal women. This guideline puts forth recommendations for endocrine therapy as treatment for women with HR-positive MBC. Sequential hormone therapy is the preferential treatment for most women with HR-positive MBC. Except in cases of immediately life-threatening disease, hormone therapy, alone or in combination, should be used as initial treatment. Patients whose tumors express any level of hormone receptors should be offered hormone therapy. Treatment recommendations should be based on type of adjuvant treatment, disease-free interval, and organ function. Tumor markers should not be the sole criteria for determining tumor progression; use of additional biomarkers remains experimental. Assessment of menopausal status is critical; ovarian suppression or ablation should be included in premenopausal women. For postmenopausal women, aromatase inhibitors (AIs) are the preferred first-line endocrine therapy, with or without the cyclin-dependent kinase inhibitor palbociclib. As second-line therapy, fulvestrant should be administered at 500 mg with a loading schedule and may be administered with palbociclib. The mammalian target of rapamycin inhibitor everolimus may be administered with exemestane to postmenopausal women with MBC whose disease progresses while receiving nonsteroidal AIs. Among patients with HR-positive, human epidermal growth factor receptor 2-positive MBC, human epidermal growth factor receptor 2-targeted therapy plus an AI can be effective for those who are not chemotherapy candidates.

Conjunctival malignant melanoma in Denmark: epidemiology, treatment and prognosis with special emphasis on tumorigenesis and genetic profile.

Conjunctival malignant melanoma is a rare disease associated with considerable mortality. Most published data have been based on case reports or series of referred patients. In addition, very little is known about the genetic and epigenetic profile of conjunctival melanoma and the resemblance to uveal, cutaneous and mucosal melanoma. The aim was to determine the incidence rate of conjunctival melanoma, and to relate clinicopathological features and treatment to prognosis. A further aim was to determine the prevalence of BRAF mutations in conjunctival melanoma, to determine whether BRAF mutations are early events in pathogenesis, and relate clinicopathological features and prognosis to BRAF-mutation status. Finally, we wanted to identify tumour-specific and prognostic microRNAs in conjunctival melanoma, and to compare these with the microRNA expression of other melanoma subtypes. In order to investigate these rare tumours, we studied all the conjunctival melanomas that had been surgically removed in Denmark over a period of 52years (1960-2012). Tissue samples, clinical files, pathology reports and follow-up data were collected and re-evaluated. Using droplet digital polymerase chain reaction and immunohistochemistry, we investigated BRAF mutations; and using microRNA expression profiling, we investigated differentially expressed microRNAs. The overall incidence of conjunctival melanoma was 0.5/1000000/year, and it increased in Denmark over 52years. The increase was mainly caused by an increase in older patients (>65years) and bulbar lesions. Clinicopathological features significantly associated with a poor prognosis were extrabulbar location, involvement of adjacent tissue structures, tumour thickness exceeding 2mm and local tumour recurrence. Patients undergoing incisional biopsy and/or treatment involving excision without adjuvant therapy fared worse than patients treated with excision and any type of adjuvant treatment. We found that 35% (39/110) of conjunctival melanomas were BRAF-mutated, and the incidence of BRAF mutations was constant over time. BRAF-mutation status corresponded in conjunctival melanoma and paired premalignant lesions. BRAF mutations were more frequent in males, in young patients, and in tumours with a sun-exposed tumour location (bulbar conjunctiva or caruncle), with a mixed or non-pigmented colour, with absence of primary acquired melanosis, and with origin in a nevus. Immunohistochemistry was able to accurately detect BRAF V600E mutations. In univariate analysis, distant metastatic disease was associated with BRAF mutations. No prognostic associations with BRAF mutations were identified in multivariate analyses. MicroRNA expression analysis revealed 25 tumour-specific microRNAs in conjunctival melanoma. Five possibly oncogenic miRNAs (miR-20b-5p, miR-146b-5p, miR-146a-5p, miR-506-3p and miR-509-3p) were up-regulated. Seven microRNAs (miR-30d-5p, miR-138-5p, miR-146a-5p, miR-500a-5p, miR-501-3p, miR-501-5p and miR-502-3p) were significantly and simultaneously up-regulated in both stage T1 and stage T2 tumours, and were associated with increased tumour thickness. The expression of the 25 tumour-specific microRNAs did not differ significantly between conjunctival melanoma and oral or nasal mucosal melanoma. In conclusion, the incidence of conjunctival melanoma increased in the Danish population from 1960 to 2012. From our findings of a distinct pattern of BRAF mutations and differentially expressed microRNAs, it is evident that conjunctival melanoma is closely related to cutaneous and other mucosal melanomas and bears less resemblance to uveal melanomas. This means that conjunctival melanoma patients may benefit from therapies that are effective for cutaneous and mucosal melanoma. Additionally, the identification of several up-regulated microRNAs may prove to be useful as prognostic or therapeutic targets in conjunctival melanoma.

Clinical Significance of Positive Pelvic Washings in Uterine Papillary Serous Carcinoma Confined to an Endometrial Polyp.

Uterine papillary serous carcinoma (UPSC) represents 10% of endometrial carcinomas. Significant number of patients initially present with extrauterine disease. The role of adjuvant treatment in low stage, especially polyp-confined UPSC is controversial. This multi-institutional study evaluated the significance of positive pelvic washing (PW) and adjuvant treatment on disease recurrence in a setting of endometrial polyp-confined UPSC. Surgical pathology files from 3 institutions were searched for cases of endometrial polyp-confined UPSC. Following histologic review, cases were clinically staged as Stage I, without myoinvasion or lymphovascular invasion. Clinicopathologic characteristics, results of PW, and type of adjuvant therapy were recorded. Statistical analysis using the Kaplan-Meier method for survival and Fisher exact test were performed. Thirty-three patients were included in the study. All patients were diagnosed with polyp-confined UPSC. The size of the polyp ranged from 0.3 to 4.3 cm. PW was positive for tumor cells in 8/33 (24%) patients. Twenty-two patients (66.6%) received some type of adjuvant treatment. Six patients (18%) developed recurrent disease. There was no significant difference in disease-free survival in the patients receiving adjuvant treatment versus not (P=0.375). However, there was significant association (P=0.0013) between positive PW and disease recurrence. Data are conflicting whether positive PW affects prognosis in low-stage endometrial carcinomas. Our study showed that in UPSC, malignant cells can be present in PW without lymphovascular invasion or myoinvasion and may have negative prognostic implication. Our data also reflect the controversies in the role of adjuvant treatment in endometrium-confined UPSC.

Effects of adjuvant oxaliplatin on anal function in locally advanced rectal cancer treated with preoperative chemoradiotherapy and low anterior resection.

718 Background: The main purpose of the present study was to determine if the addition of adjuvant oxaliplatin (OXA) could have some influence on sphincter function in patients with locally advanced rectal cancer (LARC) treated with preoperative capecitabine/radiotherapy followed by lower anterior resection (LAR). Methods: Those patients with LARC treated at our center with LAR and without two-years loco-regional relapse were retrospectively analyzed independent of the type of adjuvant treatment received. Anal sphincter function was assessed by Wexner´s incontinence score (0 to 20 points, being punctuation inversely proportional to sphincter function). All questionnaires were completed between January 2010 and December 2012. Comparisons of sphincter function measured with the Wexner test between patients with and without OX were conducted with the Mann-Whitney test. Statistical analyses were conducted using IBM SPSS Statistics, version 20. Results: From 2006, 92 consecutive patients were included in our study. Mean time from LAR to fecal function assessment was 58 months (25 to 96 months). Wexner test median values did not differ significantly (p=0.450) between patients with and without adjuvant OXA. The median (IQR) for the group without adjuvant OXA was 6.0 (1.0-11.25), being for group that received adjuvant OXA of 5.0 (1.0-10.0). Conclusions: Based on our findings, OXA could be used as adjuvant treatment in LARC, due to its absent of deleterious influence over the sphincter anal function. Because of the retrospective nature of our study, prospective studies should be warranted in similar scenarios. This study has been supported by a grant of “Mutua Madrileña Fundation.”

Adjuvant therapeutic decisions in elderly breast cancer patients: the role of chemotherapy in a retrospective analysis.

Decisions on the type of adjuvant treatment in older breast cancer patients are challenging. Side effects of chemotherapy have to be weighed against life expectancy, comorbidities, functional status, and frailty on the basis of studies usually excluding patients over 69 years. To aid this decision, we analyzed a database of 6000 unselected patients and of those evaluated elderly primary breast cancer patients with hormone receptor-negative tumors from 1963 until 2003 in respect of survival data depending on adjuvant treatment. A total of 131 elderly (i.e., >65 years) patients were observed retrospectively for a median of 72 months. Patients received breast-conserving therapy or mastectomy and adjuvant radiotherapy, chemotherapy, and endocrine therapy. Data were collected from a hospital-intern database. Median age at diagnosis was 72 years. Mostly, tumors were small (81 % T1, 17 % T2) but of unfavorable grading (40 % G2, 35 % G3). Lymph nodes were positive in 42 %. Mastectomy was performed in 65 %. While 42 % of patients received radiotherapy, only 10 % were treated with chemotherapy. Patients with G2 and G3 tumors (p = 0.027), younger women (p = 0.012), and patients with positive lymph node status (p < 0.0001) more likely received chemotherapy. Recurrence-free survival was longer in patients without chemotherapy (37 vs. 29 months, p = 0.234). Overall survival was non-significantly shorter in patients who received chemotherapy (59 vs. 81 months, p = 0.131). In this analysis, adjuvant chemotherapy was not associated with improved survival, presumably caused by an a priori poor prognosis of these patients. For an aging society more data are urgently needed to help selecting and personalizing adjuvant treatment within subgroups of breast cancer in older women.

Abstract P4-11-27: Prospective comparison of conventional clinicopathological factors, uPA/PAI-1 and EndoPredict®-clin score (EPclin) for adjuvant clinical decision making in ER-positive, HER2-negative breast cancer: Progesterone receptor expression is strongly associat

Abstract Background: Recently, EPclin, a second generation multigene test has been introduced into clinical practice. Aim of this prospective study is to compare conventional clinicopathological factors, uPA/PAI-1 and EPclin and to determine, how these parameters influence adjuvant treatment decisions. Methods: 217 consecutive cases of ER-pos, HER2neg, breast cancer cases were enrolled in this study. Conventional clinicopathological factors, uPA/PAI-1 and EPclin were obtained by central pathology assessment of the patients' surgical specimen. Decision for type of adjuvant treatment was made twice – once with and once without EPclin result- after case discussion in an interdisciplinary tumor conference. Results: 217 Patients (pt) have been evaluated. Tumor grading within the presented cohort was as follows: G1: 44 pt (20%), G2: 146 pt (68%), G3: 27 pt (12%). 59 pt (27%) had positive axillary lymph node involvement. 57 pt (26%) were pT1a/b. EPclin could be assessed in all patients. 85 pt (39%) were classified as "high risk" whereas 132 pt (61%) were classified as "low risk". uPA/PAI was obtained from 123 pt (57%). 64 pt (52%) out of these had high uPA/PAI-1 levels whereas 59 pt (48%) showed low uPA/PAI-1 levels. Level of progesterone receptor (PR) expression was obtained from 216 pt. 39 pt (18%) had low or absent PR expression (PR ≤ 20%). 26 pt (67%) of this low PR expression group were classified as EPclin high risk. Furthermore 118 pt (67%) of the high PR expression group (177 pt) were classified as "low risk" via EPclin (p&amp;lt;0,0001). In 89 cases (41%) treatment decision was influenced by EPclin: In 73pt (34%) adjuvant chemotherapy (ctx) was omitted whereas in 16 pt (7%) ctx was added following the EPclin result. Conclusions: This prospective study shows for the first time, that PR expression is strongly associated with risk score evaluated by EPclin testing. In comparison with uPA/PAI-1 and conventional clinicopathological factors EPclin is the more powerful tool to help reduce unnecessary adjuvant chemotherapy. Citation Format: Johannes Ettl, Kirsten Große Lackmann, Alexander Hapfelmeier, Evelyn Klein, Stefan Paepke, Christoph Petry, Katja Specht, Laura Wolff, Heinz Höfler, Marion Kiechle. Prospective comparison of conventional clinicopathological factors, uPA/PAI-1 and EndoPredict®-clin score (EPclin) for adjuvant clinical decision making in ER-positive, HER2-negative breast cancer: Progesterone receptor expression is strongly associat [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P4-11-27.

Comparing survival of vulvar melanoma and squamous cell carcinoma: An analysis of 13,112 patients in the Surveillance, Epidemiology and End Results database

leiomyosarcoma treated at two institutions from 1988 through 2009 was performed. Datawere collected on patient age, stage of disease, types of surgical procedure, types of adjuvant treatment (if any), recurrence, and survival. Results: Fifty-nine patients were identified with early-stage, high-grade uterine leiomyosarcoma. Of these, 27 (46%) received chemotherapy, 4 (7%) received chemotherapy with radiation, 8 (14%) received radiation alone, and 20 (34%) received no further treatment. Mean patient age was 51.2 years. Median follow-up for survivors was 71 months. Forty (67.8%) patients recurred and 37 (62.7%) died. In the no treatment or radiation alone group, 19 (68%) patients recurred and died of disease. In the chemotherapy or chemotherapy with radiation group, 21 (67.7%) patients recurred and 18 (58.1%) died of disease. There was no difference in median time to recurrence or site of recurrence, pelvic or extrapelvic, among the groups. There was a trend toward decreased recurrence rate with the doxorubicin/ifosfamide combination (P=0.06) compared to other chemotherapy regimens. In the group of patients who received doxorubicin and ifosfamide, 25% of patients recurred and 50% of patients were alive at last follow-up. In the gemcitabine and docetaxel group, although 67% of patients recurred, many of these recurrences were salvageable, and 67% of patients were alive at last follow-up. Conclusions: Uterine leiomyosarcoma is associated with a high recurrence rate and poor prognosis. Adjuvant therapy has not been shown to improve survival. Although there was a trend toward a decreased risk of recurrence with doxorubicin/ifosfamide, large prospective randomized studies are needed to assess the benefit of adjuvant therapy in this disease.

Association between Parenchymal Enhancement of the Contralateral Breast in Dynamic Contrast-enhanced MR Imaging and Outcome of Patients with Unilateral Invasive Breast Cancer.

To retrospectively investigate whether parenchymal enhancement in dynamic contrast material-enhanced magnetic resonance (MR) imaging of the contralateral breast in patients with unilateral invasive breast cancer is associated with therapy outcome. After obtaining approval of the institutional review board and patients' written informed consent, 531 women with unilateral invasive breast cancer underwent dynamic contrast-enhanced MR imaging between 2000 and 2008. The contralateral parenchyma was segmented automatically, in which the mean of the top 10% late enhancement was calculated. Cox regression was used to test associations between parenchymal enhancement, patient and tumor characteristics, and overall survival and invasive disease-free survival. Subset analyses were performed and stratified according to immunohistochemical subtypes and type of adjuvant treatment received. Median follow-up was 86 months. Age (P < .001) and immunohistochemical subtype (P = .042) retained significance in multivariate analysis for overall survival. In patients with estrogen receptor-positive and human epidermal growth factor receptor 2 (HER2)-negative breast cancer (n = 398), age (P < .001), largest diameter on MR images (P = .049), and parenchymal enhancement (P = .011) were significant. In patients who underwent endocrine therapy (n = 174), parenchymal enhancement was the only significant covariate for overall survival and invasive disease-free survival (P < .001). Results suggest that parenchymal enhancement in the contralateral breast of patients with invasive unilateral breast cancer is significantly associated with long-term outcome, particularly in patients with estrogen receptor-positive, human epidermal growth factor receptor 2-negative breast cancer. Lower value of the mean top 10% enhancement of the parenchyma shows potential as a predictive biomarker for relatively poor outcome in patients who undergo endocrine therapy. These results should, however, be validated in a larger study.

Acid ceramidase is associated with an improved prognosis in both DCIS and invasive breast cancer

Acid ceramidase (ASAH1) a key enzyme of sphingolipid metabolism converting pro-apoptotic ceramide to sphingosine has been shown to be overexpressed in various cancers. We previously demonstrated higher expression of ASAH1 in ER positive compared to ER negative breast cancer. In the current study we performed subtype specific analyses of ASAH1 gene expression in invasive and non invasive breast cancer. We show that expression of ASAH1 is mainly associated with luminal A – like cancers which are known to have the best prognosis of all breast cancer subtypes. Moreover tumors with high ASAH1 expression among the other subtypes are also characterized by an improved prognosis. The good prognosis of tumors with high ASAH1 is independent of the type of adjuvant treatment in breast cancer and is also detected in non small cell lung cancer patients. Moreover, even in pre-invasive DCIS of the breast ASAH1 is associated with a luminal phenotype and a reduced frequency of recurrences. Thus, high ASAH1 expression is generally associated with an improved prognosis in invasive breast cancer independent of adjuvant treatment and could also be valuable as prognostic factor for pre-invasive DCIS.

Functional and quality-of-life outcomes of transoral robotic surgery for carcinoma of unknown primary

To determine speech, eating, aesthetics, social disruption, and overall quality-of-life outcomes over a year period in patients who underwent transoral robotic surgery as part of carcinoma of unknown primary diagnosis and treatment. Observational prospective study. Twenty-two patients who underwent transoral robotic surgery for the management of carcinoma of unknown primary were included. Patients prospectively completed the Head and Neck Cancer Inventory during a preoperative visit, and at 3-week, 3-month, 6-month, and 12-month postoperative visits. Patients' demographic, pathological, and follow-up information were also collected. The mean follow-up time was 19.8 months. There were overall declines in all quality of life scores during treatment period, which was followed by a continuous recovery. The scores immediately after transoral robotic surgery (3 weeks) were significantly higher than the scores after conclusion of adjuvant therapy (3 months) in multiple domains (P < .05) and the 6-month scores in speech (P = .02) and eating (P = .008) domains. All scores, except for eating (P = .01) returned to pretreatment levels at 1 year. Patients with detected primaries displayed similar quality-of-life scores compared to patients with occult primaries. Human papillomavirus status and type of adjuvant treatment had no significant impact on quality of life. Transoral robotic surgery is a promising, minimally invasive procedure for the surgical management of carcinoma of unknown primary. Patients maintain high functional and quality-of-life status at 1 year after surgery.

Surgically treated oropharyngeal cancer: risk factors and tumor characteristics

To assess risk factors of patients with oropharyngeal squamous cell carcinoma in the Munich area of Southern Germany in relation to human papillomavirus (HPV) association of the tumors. To demonstrate differences in tumor characteristics and their impact on adjuvant treatment. Between November 2010 and July 2013, patients were prospectively interviewed for risk factors before they underwent surgical resection of their tumors. HPV association was evaluated by p16 immunohistochemistry; tumor characteristics and type of adjuvant treatment were recorded. Follow-up data were collected after a median follow-up of 12.1 month. In contrast to many recent studies, we could not detect any difference in overall age and age at sexual debut between p16-positive and p16-negative patients. P16-negative patients are characterized by a more intensive tobacco and alcohol use, a more abusive way of consumption, less nonoral and less oral sex partners. P16-positive patients had a significantly higher risk of lymph node metastases, but nevertheless a significant lower risk to recur or to die. No difference in the incidence of synchronous second primary tumors was seen. P16-positive patients generally received a more aggressive adjuvant treatment because of more frequently involved lymph nodes. Lifestyle risk factors such as smoking, drinking, and sexual habits were independent from age, but showed marked differences between the p16-positive and p16-negative group. Since p16-positive patients were treated more aggressively, it is not possible to distinguish whether the better outcome of HPV-positive patients is a result of less aggressive cancers or more aggressive treatment. With regard to the ongoing debate about treatment deintensification, we should keep in mind that the survival of HPV-positive cancer patients is not 100 %.

Prognostic Factors in Patients with Squamous Cell Carcinoma of the Oral Tongue Treated With Adjuvant Therapy Following Surgery

Background. There is limited data on adjuvant treatment following surgery in patients with squamous cell carcinoma of the oral tongue. Aims. This retrospective study investigates prognostic value of different factors for local relapse-free survival (LRFS), regional relapse-free survival (RRFS), disease-free survival (DFS), and overall survival (OS) in patients with oral tongue cancer treated with adjuvant therapy following surgery. Materials and methods. Forty six patients with surgically treated oral tongue cancer were enrolled in the analysis. Adjuvant therapy consisted of postoperative radiotherapy (PO-RT) or postoperative concurrent chemoradiotherapy (PO-CCRT). All patients received three dimensional conformal radiotherapy. Weekly cisplatin was given as concurrent chemotherapy. Identification of prognostic factors for survival was done with univariate analysis. Multivariate analysis was used for factors confirmed as significant on univariate analysis. Results. Independent prognostic factors negatively influencing LRFS, DFS, and OS were ECOG performance status (p = 0.002, p = 0.013 and p = 0.022, respectively), overall stage (p = 0.011, p = 0.010 and p = 0.009, respectively), and pathologic nodal classification (p = 0.016, p = 0.011 and p = 0.015, respectively). Surgical margin status was an independent prognostic factor for RRFS, DFS, and OS (p = 0.032, p = 0.027 and p = 0.028, respectively). The type of adjuvant treatment used was independently prognostic for lower rates of LRFS and DFS (p = 0.029 and p = 0.010, respectively). Conclusions. Positive postoperative nodal status and close or positive resection margins had the most prominent negative prognostic influence on patients’ survival.

Feasibility and safety of laparoscopic surgery for obese Korean women with endometrial cancer: long-term results at a single institution.

The purpose of this study was to evaluate the surgical feasibility of and survival outcome after laparoscopy in obese Korean women with endometrial cancer which has recently been increasing. We reviewed the medical records of the patients treated at our medical institution between 1999 and 2012. The patients were divided into three groups, non-obese (Body Mass Index [BMI]<25.0), overweight (BMI 25-27.99), and obese (BMI≥28.0). These patient groups were compared in terms of their clinical characteristics, treatment methods, as well as surgical and survival outcomes. In total, 55 of the 278 eligible patients were obese women. There were no differences in the three groups in terms of the proportion of patients who underwent lymphadenectomy, their cancer stage, histologic type, type of adjuvant treatment administered, intra-, post-operative, and long-term complications, operative time, number of removed lymph nodes, blood loss, and duration of hospitalization (P=0.067, 0.435, 0.757, 0.739, 0.458, 0.173, 0.076, 0.124, 0.770, 0.739, and 0.831, respectively). The Disease-Free Survival (DFS) times were 139.1 vs. 121.6 vs. 135.5 months (P=0.313), and the Overall Survival (OS) times were 145.2 vs. 124.8 vs. 139.5 months (P=0.436) for each group, respectively. Obese women with endometrial cancer can, therefore, be as safely managed using laparoscopy as women with normal BMIs.

Primary medulla oblongata germinomas: two case reports and review of the literature

An intracranial germinoma is a tumor that is sensitive to radiotherapy. As medulla oblongata germinomas are extremely rare, determining an accurate preoperative diagnosis is challenging. Two cases of medulla oblongata lesions were surgically treated, and a postoperative diagnosis of germinoma was determined in both of the cases. The tumor in one patient completely resolved after a treatment course consisting of surgical intervention, radiotherapy and chemotherapy; the other patient, who did not receive any type of adjuvant treatment after surgery, suffered from tumor relapse and died from pneumonia 8 months following surgery. A preoperative diagnosis of medulla oblongata germinoma is difficult because of the lack of specific clinical signs and symptoms. If the correct diagnosis is reached, patients can have a favorable prognosis with proper evaluation and treatment. An invasive operation can potentially lesion and impair the function of the medulla oblongata, which is fatal to the patient.

Significance of HER2/neu overexpression in pure ductal carcinoma in situ: A clinicopathologic study with long-term follow-up.

85 Background: The prognostic value of HER2 (c-ERB2) overexpression in invasive breast cancer is well known, and correlates with aggressivene behavior. HER2 overexpression was reported in 13-56% of ductal carcinoma in-situ (DCIS). The significance of HER2 overexpression in DCIS has yet to be elucidated. The aim of this study was to correlate HER2 status with known prognostic indicators of DCIS and to evaluate whether the HER2 overexpression correlates with disease recurrence. Methods: All cases of DCIS diagnosed at our institution between 2000 and 2005 were retrieved. Cases without follow-up, those treated with mastectomy or those with concurrent invasive component were excluded. Clinicopathologic data were collected, including age at time of diagnosis, size of the lesion, nuclear grade, presence of comedo necrosis, margin status, estrogen (ER) and progesterone receptor (PR) status, type of adjuvant treatment received and length of follow-up. A representative block from each case was immunostained using the Hercept test. Slides were reviewed by 2 pathologists and interpreted in accordance with ASCO/CAP guidelines. Equivocal cases were reflexed for FISH testing. Results: A total of 152 cases were examined. Mean follow-up period was 77 months (range 12 to 138 months). HER2 was overexpressed in 49 cases (33%), and was significantly associated with high nuclear grade and presence of comedo necrosis. HER2-positive patients were more likely to be ER and PR negative. HER2 positive and negative patients did not differ significantly with respect to age at presentation or size of DCIS. On univariate analysis, HER2-type DCIS showed a higher risk of recurrence (P=0.037), however, this trend did not reach statistical signifance on multivariate analysis. Conclusions: HER2 overexpression was found to be associated with high nuclear grade, comedo necrosis as well as negativity for ER and PR but not with age or the size of DCIS. Patients with HER2-type DCIS (ER/PR-, HER2+) had a higher risk of disease recurrence than other types. However, after adjusting for all the other clinical variables, the molecular phenotype did not withhold its statistical significance as an independent predictor for recurrence.

Adjuvant Therapy in Stage III Endometrial Cancer

As adjuvant treatment of advanced-stage endometrial cancer remains undefined, we sought to review and describe the outcomes of patients with International Federation of Obstetrics and Gynecology stage III endometrial cancer treated with chemotherapy and/or radiotherapy after primary surgery. We conducted a retrospective cohort study of patients with stage III disease treated at University College London Hospitals from 2002 to 2009. Patients were eligible if they received adjuvant treatment at our center. We excluded those with any synchronous gynecologic tumor and patients who underwent surgery but not adjuvant treatment at the center. Stages IIIA, IIIB, and IIIC tumors accounted for 60%, 10%, and 30%, respectively. The median age was 67 years (range, 37-94 years). Sixty-five percent were pure endometrioid tumors, and 65% were high-grade (grade 3) tumors. Eighty-one patients received adjuvant treatment, 9% received chemotherapy alone, 28% received radiotherapy alone, and 63% received sequential combined chemotherapy followed by external beam radiotherapy with vaginal vault brachytherapy. In multivariate analysis, there was a significant difference between the adjuvant treatment groups for disease-free survival (DFS) and overall survival (OS) with those who received chemotherapy (DFS: P = 0.0001; hazard ratio [HR], 6.2; 95% confidence interval [CI], 2.47-15.8; OS: P = 0.003; HR, 6.0; CI, 2.2-16.6) or radiotherapy alone (DFS: P = 0.06; HR, 1.88; CI, 0.97-3.7; OS: P = 0.025; HR, 2.1; CI, 1.1-4.1) having a poorer survival compared to combined treatment. Overall survival at 3 years and 5 years were 57% and 47%, respectively, for all 81 patients who received any adjuvant treatment. Sequential combined adjuvant chemotherapy and radiotherapy may be associated with a significant improvement in survival compared with chemotherapy or radiotherapy alone. Univariate and multivariate analysis showed that advanced age, high grade, and presence of lymphovascular space invasion were associated with poor DFS and OS. For patients with documented recurrence (n = 41), there was no clear relationship between site of recurrence and type of adjuvant treatment given.

Postoperative detection of circulating EGFR transcripts as a surrogate marker for circulating tumor cells to predict tumor recurrence after adjuvant radio(chemo)therapy in locally advanced squamous cell carcinoma of the head and neck (LASCCHN).

6014 Background: The prognostic role of circulating tumor cells (CTCs), occurring in up to 35% of LASCCHN patients, is still largely undetermined. In this prospective study we tested whether the detection of CTCs was associated with treatment outcome of adjuvant radio(chemo)therapy. Methods: Patients with LASCCHN (N=64) of the oropharynx (N=40), oral cavity (N=15), hypopharynx (N=3) or CUP (N=6) presenting after tumor surgery for adjuvant treatment were enrolled in this study. Peripheral blood samples were collected before start and at the end of adjuvant radio- (N=22) or radiochemotherapy (N=42). Transcripts of epidermal growth factor receptor (EGFR) were detected using RT-PCR. Samples positive in at least 2 of 3 PCR replicates were considered CTC-positive, according to previous studies. CTC detection was correlated with failure-free (FFS) and overall survival (OS). Results: CTCs were detected in blood samples from 21 of 64 patients (33%) whereas all 30 samples from healthy donors used as control were negative. The CTC+ and CTC- patient cohorts were comparable with relation to sex, age, smoking history, T and N stage, tumor localization, type of adjuvant treatment and the median follow-up for OS and FFS. Detection of CTCs before or after adjuvant treatment was not predictive for OS. However, the presence of CTCs at the start of adjuvant radio(chemo)therapy identified patients with reduced FFS (CTC- vs CTC+ [% of patients without relapse at 2 years]: 89% vs. 60%, HR: 0.30, 95% CI: .08-.92, p=.037). Multivariate Cox regression analysis revealed that the prognostic value of the CTC status was not influenced by the T and N stage and independent of whether the adjuvant treatment consisted of radio- or radiochemotherapy. Conclusions: Persistence of CTCs after tumor resection as detected by EGFR transcripts was established as an independent marker for tumor recurrence in LASCCHN. Postoperative detection of CTCs might prove useful for risk stratification in future clinical trials for optimization of adjuvant treatment, especially for the poor-prognosis group of CTC+ patients.