Distribution Of Histological Subtypes Research Articles

Changes in EBV Association Pattern in Pediatric Classic Hodgkin Lymphoma From a Single Institution in Argentina

In classic Hodgkin lymphoma (cHL), Epstein Barr virus (EBV) association varies worldwide.Aims: Our aim was to analyze EBV association with pediatric cHL for the last 28 years.Methods: EBV presence was evaluated by EBERs in situ hybridization and LMP1 immunohistochemistry.Results: Until 2008, we found in pediatric cHL a similar percentage of EBV presence to those observed in adult cHL from developed populations. Nevertheless, in the last 8 years, an unexpected difference in cHL EBV association was proven, along with a slight bias of EBV association with the nodular sclerosis (NS) subtype. Concerning histological subtype distribution, even though MC still prevailed in the whole series, those cases diagnosed as NS showed a sustained rise from 1989 until today.Conclusion: Variations of EBV association of cHL related to geography, age, ethnicity, and histological type have been largely described when compared with different world regions, but interestingly, this single-center revised series brought to light the dynamic process behind the evolution of this relationship over time.

Incidence, distribution of histological subtypes and primary sites of soft tissue sarcoma in China.

ObjectiveSoft tissue sarcomas (STSs) are rare malignancies deriving from mesenchyme. In this study, we reported the epidemiology of STS in China using population-based cancer registry data.MethodsIn 2017, qualified data from 339 cancer registries were included in the national database. All STS cases were retrieved based on the morphological and topographical codes of International Classification of Diseases for Oncology, and were categorized into different histological subtypes and primary sites accordingly. Nationwide new STS cases were estimated using incidence rate of STS and the national population, and were reported for gastrointestinal stromal tumor (GIST) and STSs other than GIST separately by sex and region. Distribution of histological subtypes and primary sites of STS were calculated, as well as primary sites of GIST.ResultsApproximately 39,900 new STS cases occurred nationwide in China in 2014, accounting for 1.05% of overall cancer incidence. The crude incidence rate was 2.91/100,000 and generally increased with age. An overall female predilection was found. GIST was the most common histological subtype, followed by nerve sheath tumor and malignant peripheral nerve sheath tumor, leiomyosarcoma, liposarcoma, and fibrosarcoma. About 67.5% of GIST occurred in stomach while 1.4% were recorded outside the gastrointestinal tract. Connective, subcutaneous and other soft tissues were the most common primary site, of which extremities were the major subsite.ConclusionsThe burden of STS is not serious in China relatively. However, due to their histological and topographical complexity, STSs should not be unnoticed, and more basic and clinical studies should focus on STSs.

Analysis of the clinical characteristics of 8 081 primary lung cancer

Objective: To characterize the clinical epidemiological features of primary lung cancer patients based on massive clinical data. Methods: The demographic and histological information of 8 081 primary lung cancer patients who were initially identified from 1 January 2012 to 31 December 2013 in 16 hospitals from 6 provinces were retrospectively analyzed to determine the characteristics of different histological subtypes among different gender, age-group and birth cohort. Results: Among the 8 081 lung cancer patients, 5 422 (67.10%) were male and 2 659 (32.90%) were female, the average age was (60.96±10.14) years. The most common histological subtypes of lung cancer successively were adenocarcinoma (ADC), squamous cell carcinoma (SCC), small cell carcinoma and large cell carcinoma, and the proportions of these subtypes were 53.13%, 24.51%, 14.59% and 0.66%, respectively, which collectively accounted for 92.89%. The current highest smoking rate was observed in SCC patients, which was 62.45%, while lowest in ADC, which was 29.68%. The incidence of lung cancer in male was significantly higher that that of female, with a sex ratio of 2.04∶1. The highest sex ratio was observed in SCC, which was 9.14∶1, while lowest in ADC, which was 1.14∶1. The distribution of histological subtypes in male lung cancer patients was consistent with the general situation.While among the female lung cancer patients, the proportion of ADC was the highest (75.42%), followed by SCC (10.08%), squamous cell carcinoma (7.34%) and large cell carcinoma (0.39%). Analyzed by the birth cohort, the proportion of ADC gradually increased with the age, while the reduced tendency was observed in SCC (P<0.000 1). Conclusion: Adenocarcinoma is the most important histological subtype of lung cancer, and the distribution characteristics of histological subtypes of lung cancer differs among genders, age and birth cohort.

Minimally invasive radical hysterectomy: an analysis of oncologic outcomes from Hospital Italiano (Argentina).

The Laparoscopic Approach to Cervical Cancer (LACC) trial demonstrated a higher rate of disease recurrence and worse disease-free survival in patients who underwent minimally invasive radical hysterectomy. To evaluate surgical and oncological outcome of laparoscopic radical hysterectomy performed at Hospital Italiano in Buenos Aires, Argentina. This retrospective study included all patients with cervical cancer, 2009 FIGO stage IA1, with lymphovascular invasion to IB1 (<4 cm) who underwent a laparoscopic radical hysterectomy between June 2010 and June 2015. Patients were eligible if they had squamous cell carcinoma, adenocarcinoma, or adenosquamous carcinoma, and no lymph node involvement by imaging. Patients must have undergone a type C1 radical hysterectomy. Only patients who were treated by a laparoscopic approach were included. Patients were excluded if histopathology showed a component of neuroendocrine carcinoma before or after surgery; if they had synchronous primary tumors, history of abdominal or pelvic radiotherapy, or were operated on at an outside institution; and if they had only surgery and no follow-up in our institution. Relapse rate and disease-free survival were evaluated using the Kaplan-Meier method. A total of 108 patients were evaluated. The median age was 41 years (range 27-70). Distribution of histologic sub-types was squamous carcinoma in 77 patients (71%), adenocarcinoma in 27 patients (25%), and adenosquamous carcinoma in four patients (4%). Ninety-nine patients (92%) had stage IB1 tumors and 58 (54%) patients had tumors ≤2 cm. The median surgical time was 240 min (range 190-290), the median estimated blood loss was 140 mL (range 50-500) and the transfusion rate was 3.7%. The median length of hospital stay was 2 days (range 1-11). The median follow-up time was 39 months (range 11-83). The global recurrence rate after laparoscopic radical hysterectomy was 15% (16/108). According to tumor size, the recurrence rate was 12% in patients with tumors ≤2 cm (7/58) and 18% in patients with tumors >2 cm (9/50) (OR=0.76; 95% CI 0.26 to 2.22; p=0.62) The 3- and 5-year relapse rate was 17% (95% CI 11% to 27%). The 3- and 5-year disease-free survival was 81% (95% CI 71% to 88%) and 70% (95% CI 43% to 86%), respectively. Overall survival at 3 years was 87% (95% CI 76% to 93%). The recurrence rate after laparoscopic radical hysterectomy was 15%, and in tumors ≤2 cm it was 12%. The 3-year disease-free survival was 81%. Given these results our hospital has changed the approach to open radical hysterectomy.

Neoadjuvant chemotherapy in patients with advanced endometrial cancer.

Neoadjuvant chemotherapy (NACT) followed by interval debulking surgery (IDS) is a treatment strategy for ovarian cancer patients with unresectable disease or poor performance status (PS). This strategy has been used in the treatment of advanced endometrial cancer and a survival benefit has been shown in patients who are subsequently able to undergo interval cytoreduction. This study sought to review our single institution experience with NACT for advanced endometrial cancer. We conducted a retrospective review of all patients who received NACT for advanced endometrial cancer at two institutions in New York City between 2002 and 2016. We identified 39 patients (median age 61, range 35-89). The histologic subtype distribution was: serous (44%), endometrioid (28%), carcinosarcoma (10%), clear cell (8%), mixed (8%), neuroendocrine (3%). Contraindications to primary surgery included: unresectable disease (72%), poor PS (15%), unresectable disease and poor PS (13%). Twenty-three patients (59%) did not undergo IDS due to: progression of disease (70%), medical ineligibility (4%), unresectable disease (17%), lost to follow-up (4%), death (4%). Sixteen patients (41%) underwent IDS, 81% had an optimal cytoreduction. Disease status at NACT completion was: partial response (56%), stable disease (3%) and progression of disease (41%). There were no complete responses. Patients who responded to NACT had a significantly longer overall survival than those who did not (15 vs. 5months. P = 0.015). IDS was also associated with an improvement in overall survival versus no surgery (16 vs. 6months, P = 0.04). Unlike ovarian cancer, less than half of the patients undergoing NACT for endometrial cancer underwent IDS, none had a complete response, and 41% had disease progression during NACT. However, endometrial cancer patients who underwent IDS had a high rate of optimal cytoreduction. Both response to NACT and IDS were associated with improved survival.

Survival among solid organ transplant recipients diagnosed with cancer compared to nontransplanted cancer patients-A nationwide study.

Solid organ transplant recipients (OTRs) have an increased cancer risk but their survival once diagnosed with cancer has seldom been assessed. We therefore investigated cancer-specific survival among OTRs with a wide range of cancer forms nationally in Sweden. The study included 2,143 OTRs with cancer, and 946,089 nontransplanted cancer patients diagnosed 1992-2013. Hazard ratios (HR) and 95% confidence intervals (CI) were estimated using Cox regression models adjusted for age, sex and calendar year. Median follow-up was 3.1 (range 0-22) years. Overall, OTRs diagnosed with any cancer had a 35% higher rate of cancer death compared to nontransplanted cancer patients (HR: 1.35, 95% CI: 1.24-1.47). Specifically, higher rates of cancer-specific death were observed among OTRs diagnosed with Hodgkin lymphoma (HR: 15.0, 95% CI: 5.56-40.6), high-grade non-Hodgkin lymphoma (HR: 2.68, 95% CI: 1.90-3.77), malignant melanoma (HR: 2.80, 95% CI: 1.74-4.52) and urothelial (HR: 2.56, 95% CI: 1.65-3.97), breast (HR: 2.12, 95% CI: 1.38-3.25), head/neck (HR: 1.55, 95% CI: 1.02-2.36) and colorectal (HR: 1.42, 95% CI: 1.07-1.88) cancer. The worse outcomes were not explained by differences in distribution of cancer stage or histologic subtypes. For other common cancer forms such as prostate, lung and kidney cancer, the prognosis was similar to that in nontransplanted cancer patients. In conclusion, several but not all types of posttransplantation cancer diagnoses are associated with worse outcomes than in the general population. Reasons for this should be further explored to optimize posttransplantation cancer management.

Hepatitis B Virus Associated B-Cell Non-Hodgkin Lymphoma in Non-Endemic Areas

IntroductionHepatitis B virus (HBV) is a hepatotropic virus accounting for chronic hepatitis and cirrhosis. HBV is also known as oncogenic, leading to increased risks of not only hepatocellular carcinoma but also other cancers including B-cell non-Hodgkin lymphoma (NHL) (Odd-ratio: 1.9-2.0). According to the World Health Organization, 257 million people in the world have an active HBV infection, areas of high prevalence being in Africa, Western Pacific, and Southeast Asia. While some studies were performed in endemic area, little is known concerning the characteristics of HBV-related NHL in Occident. Moreover, although the need for antivirals to prevent HBV reactivation is well known in patients with HBV receiving chemo or immunotherapy, their impact on their prognosis is unknown. Our aim is to describe the characteristics and outcomes of patients with NHL and active HBV in non-endemic areas.MethodsThirty-nine consecutive patients diagnosed with active HBV infection and B-cell NHL between 2002 and 2017 were enrolled retrospectively in France and Italy. Active HBV infection was defined by positive antigen HbS (AgHbs) and/or positive HBV-DNA in serum. HCV or HIV positive patients were excluded. Their characteristics and outcomes were analyzed and, for Diffuse Large B-cell Lymphoma (DLBCL), compared with those of HBV-negative patients enrolled in R-CHOP arms of LYSA trials.ResultsMost patients were men (29/39), and median age at NHL diagnosis was 59 years ranging from 29 to 88 years. Twenty-two patients (57%) were born in Europe, 13 in Africa (33%), 4 in Asia (10%). Thirty-three patients had positive AgHbs and 28, positive viral load. The histological subtype distribution was: 23 (59%) DLBCL; 13 low-grade NHL (LG-NHL) including 4 follicular lymphoma (FL), 3 spleen marginal zone lymphoma (SMZL), 3 mucosa associated lymphoid tissue lymphoma and 3 not otherwise specified LG-NHL; 2 mantle cell and one Burkitt lymphoma. Of note, none of the primary DLBCL had a low-grade component but 2 FL and one LG-NHL transformed to DLBCL during follow-up. Five patients had a monoclonal immunoglobulin component. Overall, 26 patients (67%) had an extra-nodal involvement (bone marrow (10), liver (8), digestive (6), and bone (5)).All but one DLBCL patients were treated with R-CHOP/R-CHOP-like regimen leading to complete remission in 19 out of 22 (84%). Treatment of LG-NHL patients was diverse: Rituximab monotherapy, immuno-chemotherapy (R-CHOP, R-Chlorambucil, R-Bendamustine), corticosteroids alone or with radiotherapy, Helicobacter pylori treatment or wait and watch. After front-line therapy, 20 DLBCL patients (87%) and 9 LG-NHL (69%) patients achieved complete remission (CR). Thirty-six patients received antiviral treatment following NHL diagnosis while 3 did not (one DLBCL, 2 LG-NHL). Seven patients (18%) died during follow-up: 4 due to progression of lymphoma (3 DLBCL and one LG-NHL), 2 to hepatocellular carcinoma, one to infection. Median overall survival was 81 months without difference between DLBCL and LG-NHL patients. Lastly, the comparison of the outcomes of the 23 DLBCL patients with those of HBV-negative patients did not show significant difference.ConclusionsTo our knowledge, this is the first study exploring HBV-related NHL in non-endemic areas. Interestingly, more than 40% of patients were born in high-endemic areas. The strong predominance of DLBCL (59%) is concordant with studies performed in high-incidence areas. Strikingly, it contrasts with the peculiar distribution of HCV-related NHL supporting that some different pathophysiological mechanisms contribute to NHL in HBV. However, as in HCV-related NHL, frequent hepatic or digestive involvement raises the hypothesis of home privileged lymphomagenesis favored by viral induced inflammation or by infection of B-cells. No difference was detected when comparing HBV DLBCL outcomes with non HBV patients. Remarkably, all patients, except one, received antiviral therapy combined with chemotherapy. In endemic areas, while some studies reported that patients with HBV NHL had a poorer prognostic, others suggested that antivirals could overcome this pejorative impact.This study, performed in Western Europe, area of low HBV prevalence, underlines the predominance of DLBCL among patients with active HBV infection and the similar outcomes of DLBCL patients to non-HBV patients when treated with a combination of R-CHOP and antivirals. DisclosuresNo relevant conflicts of interest to declare.

P3.04-10 Monocytes and Neutrophils as Predictive Markers of Response to Immune Checkpoint Inhibitors in Metastatic Non-Small Cell Lung Cancer

PD-L1 expression and mutational load in tumor cells have been found to predict response to immune checkpoint inhibitors (ICI) in patients with metastatic non-small cell lung cancer (mNSCLC). These parameters, however, are not readily available clinically. Identification of parameters easily measured in the clinics will help select NSCLC patients most likely to benefit from ICI. A retrospective cohort study was carried out on patients with mNSCLC to identify clinical and laboratory factors associated with response to ICI. Of the 37 consecutive patients identified, only 32 patients were analyzed as 5 patients were not evaluable for response. There were 17 males and 15 females. Their median age was 64.5 years (range 20-84). History of smoking was present in 25/32 (78%) patients. Non-squamous cell tumors were by far the commonest histologic subtype (27/32, 84%). 12 patients received pembrolizumab, 19 patients nivolumab, and one patient received nivolumab followed by pembrolizumab. Responses were observed in 19 (59%) of these 32 patients. All 19 patients had partial response. There was no difference in the distribution of sex, age, smoking status, and histologic subtypes between responders and non-responders. The median time to response (TTR) in this cohort of patients was 12 weeks (range 6-24) and the median duration of response (DoR) was 24 weeks (range 7-112). Higher pre-therapy absolute monocyte counts (AMC) were correlated to shorter TTR (R = -0.50; 95% CI -0.79 – -0.05) (p = 0.03) but not DoR. Patients with AMC > 700/mm3 had a significantly shorter median TTR than those with AMC < 700/mm3 (8 weeks vs 12 weeks; p = 0.048). Lower absolute neutrophil counts (ANC) after dose #1 predicted response to ICI (p = 0.02). Patients with ANC < 4200/mm3 after dose #1 were more likely to respond than those with ANC >4200/mm3 (OR = 6.8; 95% CI 1.1 – 41.8) (p = 0.05). Pre- and post-therapy lymphocyte counts, platelet counts, or hemoglobin did not predict responses or DoR. Higher pre-therapy AMC and lower post-dose #1 ANC in mNSCLC treated with ICI were correlated to improved probability of response. Analysis of AMC and ANC before and during therapy may provide an easy method to identify those mNSCLC patients most likely to respond to ICI.

Abstract B21: Improved efficacy of mitochondrial disrupting agents upon inhibition of autophagy in a mouse model of BRCA1-deficient breast cancer

Abstract Breast cancer is a heterogeneous disease, and stratification of patients is fundamental to the success of treatment modalities. Breast tumors deficient in BRCA1 are mostly associated with basal-like breast cancers, and targeted therapeutics for this disease subtype are still lacking. In order to address whether autophagy inhibition will be effective in BRCA1-deficient mammary tumors, we generated mice with conditional deletion of an essential autophagy gene FIP200 along with Brca1 and Trp53, through utilization of the K14-Cre transgene. We found that FIP200 deletion suppressed tumorigenesis in the BRCA1-deficient model when compared to wild-type and heterozygous FIP200 controls. However, in contrast to previous studies in the MMTV-PyMT model, tumor growth and the distribution of histologic subtypes were not affected by loss of FIP200. Interestingly, loss of FIP200 decreased mitochondrial mass and oxidative respiratory capacity of these tumor cells, along with a decrease in the phosphorylation of mTOR substrates and transcript levels of genes involved in mitochondrial biogenesis. Importantly, we observed an increased sensitivity to mitochondrial disrupting agents upon loss of FIP200. Consequently, our data showed that combination of an autophagy inhibitor, Spautin-1, along with a mitochondrial complex I inhibitor, metformin, was more effective in limiting oxidative respiratory capacity, colony-forming ability, and tumor growth. Altogether, our results indicate that inhibition of autophagy can increase the benefits of metformin treatment in BRCA1-deficient breast cancers. Citation Format: Syn Kok Yeo, Ritama Paul, Michael Haas, Chenran Wang, Jun-Lin Guan. Improved efficacy of mitochondrial disrupting agents upon inhibition of autophagy in a mouse model of BRCA1-deficient breast cancer [abstract]. In: Proceedings of the AACR Special Conference: Advances in Breast Cancer Research; 2017 Oct 7-10; Hollywood, CA. Philadelphia (PA): AACR; Mol Cancer Res 2018;16(8_Suppl):Abstract nr B21.

Radiation‐associated sarcoma after breast cancer in a nationwide population: Increasing risk of angiosarcoma

Radiation‐associated sarcoma (RAS) is a rare complication of radiation therapy (RT) to breast cancer (BC). This study explored RAS after RT to BC in a nationwide population‐based material. The Finnish Cancer Registry was queried for patients with BC treated during 1953‐2014 who were later diagnosed with a secondary sarcoma in 1953‐2014. Registry data, patient files, and sarcoma specimens were analyzed to confirm diagnosis and location of RAS at or close to the RT target volume. A total of 132 512 patients were diagnosed with invasive BC during the study period. A subsequent sarcoma was diagnosed in 355 patients. After exclusion, 96 RAS were identified. Angiosarcoma (AS) was the most prevalent histology in 50 (52%) of 96 patients. However, the first radiation‐associated AS was diagnosed in a patient treated for BC with breast‐conserving surgery in 1984, and thereafter, the proportion of AS continuously increased. The 5‐year sarcoma‐specific survival was 75.1% for RAS treated with a curative intent. The distribution of histologic subtypes of RAS has changed during the 60 years of this registry study. The first radiation‐associated AS was diagnosed in 1989, and presently, AS is the most common histologic subtype of RAS. It is possible that changes in BC treatment strategies are influencing the characteristics of RAS.

Improved efficacy of mitochondrial disrupting agents upon inhibition of autophagy in a mouse model of BRCA1-deficient breast cancer

ABSTRACTBreast cancer is a heterogeneous disease, and stratification of patients is fundamental to the success of treatment modalities. Breast tumors deficient in BRCA1 are mostly associated with basal-like breast cancers and targeted therapeutics for this disease subtype are still lacking. In order to address whether macroautophagy/autophagy inhibition will be effective in BRCA1-deficient mammary tumors, we generated mice with conditional deletion of an essential autophagy gene, Rb1cc1, along with Brca1 and Trp53, through utilization of the K14-Cre transgene. We found that Rb1cc1 deletion suppressed tumorigenesis in the BRCA1-deficient model when compared to wild type and heterozygous Rb1cc1 controls. However, in contrast to previous studies in the mouse mammary tumor virus (MMTV)-polyoma middle T antigen (PyMT) model, tumor growth and the distribution of histological subtypes were not affected by loss of RB1CC1. Interestingly, loss of RB1CC1 decreased mitochondrial mass and oxidative respiratory capacity of these tumor cells, along with a decrease in the phosphorylation of MTOR substrates and transcript levels of genes involved in mitochondrial biogenesis. Importantly, we observed an increased sensitivity to mitochondrial disrupting agents upon loss of RB1CC1. Consequently, our data showed that combination of an autophagy inhibitor, spautin-1, along with a mitochondrial complex I inhibitor, metformin, was more effective in limiting oxidative respiratory capacity, colony-forming ability and tumor growth. Altogether, our results indicate that inhibition of autophagy can increase the benefits of metformin treatment in BRCA1-deficient breast cancers.

Characterization and Management of Borderline Ovarian Tumors – Results of a Retrospective, Single-center Study of Patients Treated at the Department of Gynecology and Obstetrics of the University Medicine Greifswald

Borderline ovarian tumors (BOT) are malignant epithelial ovarian tumors with a very low incidence, therefore lacking sufficient clinical experience in diagnostics and treatment. This study characterized the histology, clinical features, diagnostics and therapy of BOT including patients treated at the Department of Gynecology and Obstetrics of the University Medicine Greifswald. In this retrospective, single-center study, patients with BOT treated between 1990 and 2010 were analyzed according to their histological and clinical reports. A total of 54 patients were enrolled. The median age was 54.6 (range=23-83) years. Distribution of histological subtypes was: serous in 31 patients (57.4 %) and mucinous in 23 patients (42.6%). All patients underwent surgery. Eight patients (14.8%) were treated according to actual therapy recommendations during the initial surgery. Eight patients (14.8%) received adjuvant chemotherapy contrary to treatment recommendations. In the case of 36 patients (66.7%), a frozen section was taken intraoperatively, which matched the definitive histological result in 88.9%. During average follow-up of 70.3 months (range=0-231 months), two patients (3.7%) developed tumor recurrence after 9 and 29 months, respectively, two patients (3.7%) died of causes other than BOT. Our study critically demonstrated that until a few years ago, BOTs were not usually treated according to international therapy recommendations. Nevertheless, the rate of tumor recurrence was very low.

Influence of Ground Glass Opacity and the Corresponding Pathological Findings on Survival in Patients with Clinical Stage I Non-Small Cell LungCancer.

The aim was to clarify the influence on patient prognosis of ground glass opacity (GGO) component in each new TNM stage and propose grouping reflecting the prognosis more accurately. We examined the data on 1290 patients who underwent lung cancer resection from 2003 to 2011. The demographics and overall survival of patients with adenocarcinoma with and without GGO, squamous cell carcinoma, and the others were compared according to clinical stage from 0 to IB. In adenocarcinoma, we examined the distribution of histological subtypes of adenocarcinoma with and without GGO in each clinical stage. Each clinical stage differentiated overall survival well. However, the prognosis of the patients with adenocarcinoma with GGO was considerably more favorable than that of the others in clinical stage IA2 and IA3 but not of those in clinical stage IB. In clinical stage 0 to IA3, patients showing adenocarcinoma in situ, minimally invasive adenocarcinoma, and invasive lepidic predominant adenocarcinoma accounted for about 50% of the total number of patients with adenocarcinoma with GGO (stage 0, 16 of 21; stage IA1, 113 of 143; stage IA2, 80 of 157; and stage IA3, 45 of 94). In clinical stage IB, 20% of adenocarcinomas with GGO showed invasive solid predominant adenocarcinoma (IB, seven of 38). Most of the adenocarcinomas without GGO were in clinical stage IA2 to IB, and the distribution of histological subtypes was similar at each clinical stage. Invasive acinar and solid predominant adenocarcinomas were more common in adenocarcinoma without GGO. Clinical T classification considering GGO component may offer more accurate prognosis for patients with lung cancer less than 3 cm in invasive diameter.

Recent Trends in Ovarian Cancer Incidence and Relative Survival in the United States by Race/Ethnicity and Histologic Subtypes.

Background: Incidence and survival rates of nonserous epithelial ovarian cancer in racial/ethnic minorities remain relatively unknown in the United States. We examined the trends in incidence and survival rates for epithelial ovarian cancer by histologic subtypes and race/ethnicity.Methods: Ovarian cancer incidence and mortality data from 2000 to 2013 were obtained from the Surveillance, Epidemiology, and End Results database. Age-adjusted incidence rate, incidence rate ratio, and annual percentage changes (APC) were calculated by histology and race/ethnicity subgroups and stratified by age at diagnosis. Five-year relative survival rates were calculated by stage and race/ethnicity.Results: A small but significant decrease in incidence rates was seen in non-Hispanic white (NHW), non-Hispanic black (NHB), and Hispanic women (APC -1.58, -0.84, and -1.31, respectively), while incidence rates remained relatively stable in Asian women (APC -0.37). With exception of significant increase in the incidence rate of clear cell carcinoma among Asian woman (APC 1.85), an overall trend toward decreasing incidence rates was seen across histologic subtypes and age-strata, although not all results were statistically significant. Compared with NHW women, NHB women experienced poorer 5-year survival at every stage across histologic subtypes, while Hispanic and Asian women had equivalent or better survival.Conclusions: Over the last decade, incidence rates of epithelial ovarian cancer in the United States have decreased or remained stable across race/ethnic and histologic subgroups, except for clear cell carcinoma. Survival remains poorest among NHB women.Impact: Comparative histologic subtype distribution and incidence trends do not explain the ovarian cancer survival disparity disproportionately affecting NHB women. Cancer Epidemiol Biomarkers Prev; 26(10); 1511-8. ©2017 AACR.

Analysis of racial differences in histologic subtype and survival in renal cell carcinoma at an urban academic cancer center.

e16571 Background: Black patientswithrenal cell carcinoma (RCC) have a unique distribution of histological subtypes and historic worse survival compared to white patients. Little is known about RCC in Hispanics. We investigated histologic and survival differences between racial groups treated for RCC at the Montefiore-Einstein Cancer Center (MECC) in Bronx, NY. Methods: We included via the Cancer Registry 1010 patients who underwent RCC resection at MECC between 2000 and 2015. Demographics, clinical characteristics and pathology reports were collected. Logistic regression and Cox proportional hazards models were built to evaluate the association of histology and survival with clinically and statistically significant risk factors in Non-Hispanic White (NHW), Non-Hispanic Black (NHB), and Hispanic (H) patients. Results: 233 patients were NHW (23.1%), 383 NHB (37.9%), 174 H (17.2%), and 220 other race (21.8%). Median age was 61 (range 22, 91). 58% were male. Histology was 529 (52%) clear cell (CC), 255 (25%) papillary (P), 100 (10%) chromophobe, and 126 (12.5%) other. P was more common in NHB (60.5%) compared to NHW (17%) and less common in H (6.3%) patients (P &lt; 0.0001). On multivariate logistic analysis, patients with P vs. CC were more likely to be NHB (OR 5.06; 95% CI 2.92, 8.76; P &lt; 0.0001) and less likely to have a body mass index &gt; 30 (BMI, OR 0.49; 95% CI 0.32, 0.76, P = 0.001) adjusting for age, race, gender, hypertension (HTN), and end stage renal disease (ESRD). Adjusting for above covariates there were no significant differences for C vs. CC. There was no difference in disease free survival (DFS) for NHB vs. NHW (HR 0.93; 95% CI 0.44, 1.94; P = 0.841) or H vs. NHW (HR 1.29; 95% CI 0.62, 2.71; P = 0.495) patients adjusting for age, gender, histology, ESRD, and BMI. There was no difference in overall survival (OS) for NHB vs. NHW (HR 0.97; 95% CI 0.57, 1.65; P = 0.908) or H vs. NHW (HR 1.37; 95% CI 0.79, 2.38; P = 0.256) patients adjusting for the same covariates. Conclusions: In this cohort of patients with RCC, P histology and lower BMI were significantly associated with NHB race. Unlike historic cohorts there was no significant difference in DFS or OS in NHB compared to NHW patients.

Renal cell carcinoma histological subtype distribution differs by age, gender, and tumor size in coastal Chinese patients.

The distribution pattern of renal cell carcinoma (RCC) histological subtypes according to age, gender and tumor size has not been well illustrated in RCC patients living in fast-developing regions of China. We recruited 2941 patients with clear cell renal cell carcinoma (ccRCC), papillary renal cell carcinoma (PCC) or chromophobe from two hospitals in coastal China (2004−2012) consecutively and draw 538 American Chinese RCC patients’ data with time matched from the Surveillance, Epidemiology, and End Results database. We found that compared with ccRCC patients, chromophobe patients were more likely to be female (OR: 2.538, 95% CI: 1.923−3.350), younger (OR for 51−60 years old: 0.686; OR for over 60 years old: 0.478; reference: age < 50) and to have a larger maximal diameter (Dmax) (OR for Dmax > 7 cm: 1.883; reference: Dmax ≤ 4 cm). Besides, in comparison with coastal Chinese patients, American Chinese individuals had lower Fuhrman grades (P < 0.001) and had an onset age 10 years delay. In conclusion, we were the first to observe marked gender, age and tumor size differences in the proportional subtype distribution of RCCs in coastal Chinese patients, and also the first to compare coastal Chinese with American Chinese data.

Abstract P2-07-11: The association between angiotensin receptor blockers usage and breast cancer characteristics

Abstract Background: Data regarding the impact of angiotensin receptor blockers (ARB) on breast cancer are inconsistent. We evaluate the association between ARB usage and breast cancer characteristics and outcomes. Methods: All patients who were treated in our institute for estrogen receptor positive, human epidermal growth factor receptor 2 negative early breast cancer between 4/2005 and 3/2012 and whose tumors were sent for Oncotype-DX analysis were included. Medical records were retrospectively reviewed for clinical-pathological parameters, related comorbidities, treatment and outcomes. Data regarding ARB usage was retrieved. Usage of several pre-specified medications for hypertension including angiotensin converting enzyme inhibitors (ACEI), mineralocorticoid receptor antagonists (MRA), and β-blockers (BB) was also evaluated. Each medication group was compared to the rest of the study population. Results:671 patients were included in the study cohort. Forty six (7%) were treated with ARB, 93 (14.2%) with ACEI, 14 (2.1%) with MRA, and 115 (17.5%) with BB. ARB usage was associated with different histological subtype distribution (P=0.009), higher incidence of macroscopic nodal involvement (P&amp;lt;0.001) and more advanced stage at diagnosis (p&amp;lt;0.001). These findings remained significant on multivariate analysis. Patients treated with ARB had worse 5-year breast cancer specific survival (94.7% vs. 98.8%, P=0.024) and worse 5-year overall survival (94.6% vs. 98.8%, p=0.015), but these differences were not demonstrated on multivariate analysis (p=0.251 and p=0.441. respectively). Conclusions: Patients treated with ARB presented with more advanced breast cancer disease and some distinct histological features. Further research is required to elucidate the effect of ARB treatment on breast cancer. Tumor burdenPopulation (no.)Tumor size, cm (SD)Macroscopic node posotive1Stage Mean, cm (SD)P, univariate analysis%P, univariate analysisI, %II, %P, univariate analysisAll (671)1.68 (0.8)-9-71.228.3-ARB (46)1.89 (0.81)0.05423.9&amp;lt;0.0013763&amp;lt;0.001ACEI (93)1.93 (0.93)0.0048.50.86363.835.10.355MRA (14)1.88 (0.67)0.32914.30.36357.142.90.907BB (115)1.77 (0.95)0.21613.20.08766.731.60.0911Macroscopic nodes: lymph node metastases&amp;gt; 2 millimeter Histological characteristicsPopulation (no.)Ki67 (%)Estrogen recepator stain intensityHistology subtype Mean, (SD)P, univariate analysisMean, (SD)P, univariate analysisIDC (%)ILC (%)P, univariate analysisAll (671)15.91 (13.58)-2.47 (0.57)-80.912.2-ARB (46)12.27 (7.19)0.0052.57 (0.59)0.24665.226.10.009ACEI (93)17.1 (14.24)0.4032.44 (0.55)0.51575.5160.358MRA (14)21.4 (11.2)0.1972.63 (0.42)0.30385.87.10.841BB (115)15.93 (12.93)0.992.51 (0.58)0.49675.713.90.186IDC- invasive ductal carcinoma, ILC- invasive lobular carcinoma Citation Format: Goldvaser H, Rizel S, Hendler D, Neiman V, Shepshelovich D, Shochat T, Sulkes A, Brenner B, Yerushalmi R. The association between angiotensin receptor blockers usage and breast cancer characteristics [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P2-07-11.

Gastrointestinal lymphoma in Western Algeria: pattern of distribution and histological subtypes (retrospective study).

Primary gastrointestinal (GI) lymphomas (GIL) are uncommon diseases that can involve the whole GI tract. Considerable variation exists in the literature with respect to incidence of the various histological subtypes and sites of involvement. This study was undertaken to establish the anatomic distribution, histological subtypes and sites of GI lymphomas of patients from Western Algeria. The case records of 58 consecutive patients with GIL diagnosed at the Pathologies Departments of Algerian west region (the Military Hospital of Oran city and the Central University Hospital of Sidi Bel Abbes city) from January 2006 to December 2013 were retrospectively evaluated for epidemiology and histopathology report. All lymphomas were reclassified according to the WHO 2008 classification. A total of 58 patients (39 male, 19 female) with mean age of 61 years and a range of 20-89 years were included in this study. Stomach was the most common site involved (70.7%). The commonest histological subtype was mucosa-associated lymphoid tissue (MALT) B cell lymphoma (46.6%), followed by diffuse large B-cell lymphomas (DLBCL) (43.1%).The frequency of Helicobacter pylori (HP) positivity differ between gastric and intestinal location P=0.003 and correlates with the histological type P=0.01. This retrospective study of patients with GI lymphoma from Western Algeria illustrates the pattern of distribution of various common and rare histological subtypes. More studies are necessary to find a potential cause, risk factor or genetic mutation that can explain these specific characteristics of GIL.

Uterine Cancer After Risk-Reducing Salpingo-oophorectomy Without Hysterectomy in Women With BRCA Mutations

The link between BRCA mutations and uterine cancer is unclear. Therefore, although risk-reducing salpingo-oophorectomy (RRSO) is standard treatment among women with BRCA mutations (BRCA+ women), the role of concomitant hysterectomy is controversial. To determine the risk for uterine cancer and distribution of specific histologic subtypes in BRCA+ women after RRSO without hysterectomy. This multicenter prospective cohort study included 1083 women with a deleterious BRCA1 or BRCA2 mutation identified from January 1, 1995, to December 31, 2011, at 9 academic medical centers in the United States and the United Kingdom who underwent RRSO without a prior or concomitant hysterectomy. Of these, 627 participants were BRCA1+; 453, BRCA2+; and 3, both. Participants were prospectively followed up for a median 5.1 (interquartile range [IQR], 3.0-8.4) years after ascertainment, BRCA testing, or RRSO (whichever occurred last). Follow up data available through October 14, 2014, were included in the analyses. Censoring occurred at uterine cancer diagnosis, hysterectomy, last follow-up, or death. New cancers were categorized by histologic subtype, and available tumors were analyzed for loss of the wild-type BRCA gene and/or protein expression. Incidence of uterine corpus cancer in BRCA+ women who underwent RRSO without hysterectomy compared with rates expected from the Surveillance, Epidemiology, and End Results database. Among the 1083 women women who underwent RRSO without hysterectomy at a median age 45.6 (IQR: 40.9 - 52.5), 8 incident uterine cancers were observed (4.3 expected; observed to expected [O:E] ratio, 1.9; 95% CI, 0.8-3.7; P = .09). No increased risk for endometrioid endometrial carcinoma or sarcoma was found after stratifying by subtype. Five serous and/or serous-like (serous/serous-like) endometrial carcinomas were observed (4 BRCA1+ and 1 BRCA2+) 7.2 to 12.9 years after RRSO (BRCA1: 0.18 expected [O:E ratio, 22.2; 95% CI, 6.1-56.9; P < .001]; BRCA2: 0.16 expected [O:E ratio, 6.4; 95% CI, 0.2-35.5; P = .15]). Tumor analyses confirmed loss of the wild-type BRCA1 gene and/or protein expression in all 3 available serous/serous-like BRCA1+ tumors. Although the overall risk for uterine cancer after RRSO was not increased, the risk for serous/serous-like endometrial carcinoma was increased in BRCA1+ women. This risk should be considered when discussing the advantages and risks of hysterectomy at the time of RRSO in BRCA1+ women.

Characteristics and Treatment of Cutaneous Melanoma of the Foot.

BackgroundIn East Asia, the foot is the most common site of cutaneous melanoma. The purpose of this study was to investigate the differences between cutaneous melanoma of the foot and melanomas of other sites.MethodsWe studied 52 patients who underwent surgical treatment for cutaneous melanoma of the foot from September 2000 to January 2015. Through a retrospective review of their medical records, we collected data relating to their sex, age, histopathological subtype, Clark level, tumor thickness, lymph node involvement, stage, and survival rate, and we compared these parameters to those of 61 patients treated for melanoma of other sites. Moreover, we analyzed the surgical procedures, complications, and mortality rates associated with cutaneous melanoma on various parts of the foot.ResultsMelanoma of the foot differed from other melanomas only in the histopathological subtype. Other clinical features, including survival rate, did not differ significantly between the two groups heel was the most common site of melanoma of the foot (22 cases, 42.3%). The method of reconstruction varied depending on the region involved.ConclusionsA comparison of melanoma of the foot to other melanomas showed that melanoma of the foot was associated with a significantly different distribution of histological subtypes. Consistent with previous findings, we found that the acral lentiginous subtype was the most common among melanomas of the foot. Furthermore, in contrast with previous studies, we did not find a worse prognosis or lower survival rate for melanoma of the foot in comparison with other melanomas.