tbuckley/cabot-search huggingface dataset:
Pancreas cancer: Influence of gender and other demographic and clinical parameters on survival.
Authors: Patricia Renee Blank, Thomas D. Szucs
Journal: Journal of Clinical Oncology (2013)

e12529 Background: Research suggests that lower excess mortality risk for females compared to men do exist for several cancer types. The primary aim of this study was to investigate whether gender affects pancreatic cancer prognosis. In addition, the relationship of sex and survival adjusted for clinical and demographic factors was assessed. Methods: The Surveillance, Epidemiology, and End Results (SEER) database (version 1973-2009) was used to identify patients with primary histological confirmed pancreas cancer (≥18 years, 80,689 males and 82,356 females). The analysis was stratified by five different stages (in situ, locally invasive, regional, distant, unstaged). The crude effect of gender was assessed in the total sample and in age-stratified Kaplan-Meier Curves (&lt;55 years) in all five stages, respectively. Univariate and multivariate Cox proportional hazard models were run within the local stage. The predictors included in the models were demographic and clinical factors. P-values (2-sided) of 0.05 were assumed as statistical significant. Results: Between 1973 and 2009, 128,645 pancreas cancer-related deaths were reported. The median follow-up time of the censored patients was 13 months. The Kaplan-Meier curves showed a significant difference in survival among men and female in the locally invasive group (median survival in male and female: 7 months; 1-year survival: 35.5% and 35.1% among female and men, respectively; Log-Rank: p=0.0072). Of the remaining strata, all others had non-significant differences, except the unstaged group (Log-Rank: p= &lt;.0001). The univariate Cox-regression indicated a 5.6% (95%CI: 1.4%, 9.9%, p=0.0081) higher rate of dying among men compared to female (local recurrence). Among the younger population (&lt;55 years), the gender difference was significant across all disease stages, except the in situ group. Histology grade, age, race, and marital status was associated with survival from pancreatic cancer in the multivariate analysis. Conclusions: The present study indicates a gender difference in survival among pancreas cancer patients. The study findings are, however, preliminary and hypothesis generating and a matter for further investigation to give a distinct conclusion.
Prognostic relevance of resection margin distance for loco-regional control in vulvar cancer.
Authors: L. Woelber, C. Eulenburg, M. Hager, M. Choschzick, J. Schwarz, J. Dowaji, F. Gieseking, M. Ihnen, F. Jaenicke, S. Mahner
Journal: Journal of Clinical Oncology (2010)

5110 Background: A tumor-free resection margin of at least 8 mm is currently considered state of the art in vulvar cancer. However, this standard is based on small and heterogeneous patient cohorts and its implementation often results in mutilation. We therefore reanalyzed the impact of the margin distance for loco-regional control in primary vulvar cancer in a large, homogeneously treated cohort of patients. Methods: One-hundred consecutive patients with primary squamous cell vulvar cancer treated at our center were prospectively analyzed. All patients received primary surgery via triple incision resulting in complete tumor resection. Median follow-up was 18 months. Two patients were lost to follow-up and excluded from further analysis. Minimal margin distances were pathologically determined in all dimensions. Results: Median age of the patients was 62 years; 44.9% had FIGO stage I, 19.4% stage II, 26.6% stage III and 9.1% stage IV disease. The median minimal resection margin was 5 mm (range 0.5-24 mm). Nine patients (9.2%) developed disease recurrence (88.9% at the vulva). The margin distance had no significant impact on disease-free survival when analyzed as a continuous variable (p = 0.354). Cases were then divided into 3 subgroups of ≤ 3 mm (40.8%), >3-7.99mm (31.6%) and ≥ 8 mm (27.6%) resection margin. Neither univariate nor multivariate analysis revealed a difference in disease-free survival between these subgroups. Furthermore patients with a minimal resection margin of ≤ 3 mm were not at higher risk for disease recurrence compared to those with a wider margin. There was no significant difference between any of the subgroups regarding tumor stages and adjuvant radiotherapy of the vulva. Conclusions: Tumor-free resection margins are essential for loco-regional control in vulvar cancer. However, in this largest single-center analysis of homogenously treated patients we could not observe any prognostic impact of the margin distance. No significant financial relationships to disclose.
Adherence to the BCLC guidelines and impact on overall survival.
Authors: Jesna Mathew, Sasha Slipak, Anil Kotru, Joseph Blansfield, Nicole Woll, Mohsen Shabahang
Journal: Journal of Clinical Oncology (2014)

345 Background: Multiple studies exist that validate the prognostic value of the Barcelona Clinic Liver Cancer (BCLC) staging. However, none have established a survival benefit to the treatment recommendations. The aim of this study was to evaluate the adherence to the BCLC guidelines at a rural tertiary care center, and to determine the effect of following the treatment recommendations on overall survival. Methods: A retrospective chart review was conducted for 97 patients newly diagnosed with hepatocellular carcinoma (HCC) from 2000 to 2012. The treatment choice was compared with the BCLC guidelines and percentage adherence calculated. Overall survival was estimated using the Kaplan-Meier method and the log rank test was used to test the difference between the two groups. Cox regression tests were used to determine independent effects of stage, treatment aggressiveness, and guideline adherence on survival. A p-value &lt;0.05 was considered statistically significant. Results: Of 97 patients, 75% (n=73) were male. Median overall survival was 12.9 months. In 59.8% (n=58) of the patients, treatment was adherent to stage specific guidelines proposed by the BCLC classification. There was no significant difference in overall survival between the adherent and non-adherent groups (11.2 vs 14.1 months, p&lt;0.98). However on stage specific survival analysis, we noted a significant survival benefit for adherence to the guidelines for early stage HCC (27.9 vs 14.1 months, p&lt;0.05), but a decrease in survival for adherence in the end stage (20 days vs 9.3 months, p&lt;0.01). On univariate analysis, more aggressive treatment was associated with increased survival (hazard ratio [HR], 0.4; 95% confidence interval [CI], 0.22 to 0.87; p = 0.018). Multivariate analysis revealed that adherence did not independently affect survival when stage and aggressiveness of treatment were included in the model (HR, 1.3; 95% CI, 0.76 to 2.2, p = 0.34). Conclusions: Although the BCLC guidelines serve as a practical guide to the management of patients with HCC, they are not universally practiced. These results indicate that survival of patients with hepatocellular cancer is determined by stage and aggressiveness of treatment, not adherence to BCLC guidelines.
Cytomorphologic and clinical features of AML with translocation (8;16) mimicking APL.
Authors: S. Jhanwar, A. Diab, L. Zickl, G. A. Manji, J. Patel, O. I. Abdel-Wahab, J. G. Jurcic, P. G. Maslak, P. G. Steinherz, E. Paietta, J. Feldstein, R. L. Levine, M. S. Tallman
Journal: Journal of Clinical Oncology (2011)

6626 Background: AML with t(8;16) represents a rare cytogenetic subtype of adult AML with distinctive morphologic and clinical features. It is associated with very poor prognosis and the molecular pathogenesis of AML is not understood. In several published reports, including the patients reported here, it was initially misdiagnosed and treated as acute promyelocytic leukemia (APL). Furthermore t(8;16) AML is reported to be more frequently found among therapy-related AMLs, which may make it more relevant to the patient population treated at tertiary cancer centers. Methods: Using a retrospective, multimodal diagnostic approach, we present a cohort of patients with t(8;16) AML, describing the clinical history, cytomorphology, immunophenotype and cytogenetics associated with this unique subclass of AML. Results: 14 patients Median age 51, 50% of patients have extramedullary manifestations, most commonly leukemia cutis, which seemed to precede systemic involvement. Cytomorphology from 7 patients showed blasts with clefted nuclei, promyelocytes, and promyeloblasts-like cells similar to APL, with histiocytes showing hemophagocytosis and erythrophagocytosis. Interestingly, a high percentage of promyelocytes in the peripheral blood was associated with a higher incidence of DIC (P value<0.05), again mimicking the clinical presentation of APL. DIC was noticed in most patients and was associated with worse prognosis (P value<0.005, Fig1). The median overall survival in this series was 8.6 months and this poor prognosis associated with t(8;16) AML is consistent with prior published reports. The observation that 5 of the 14 t(8;16) AML patients in this series had therapy-related AML is also consistent with prior findings. Conclusions: t(8;16)AML is a unique but complicated subtype of AML that has clinical and cytomorphologic but not immunophenotypic features that mimic APL. To more thoroughly understand the biology of this AML, detailed cytogenetic as well as comprehensive genomic and transcriptomic analysis will be performed to identify the relevant leukemogenic fusion and common collaborating genetic events which may also lead to the identification of specific therapy.
EUS combined with CT in predicting SMV/PV resection in patients with borderline resectable pancreatic carcinoma.
Authors: Evan Scott Glazer, Omar Maen Rashid, Jason Klapman, Cynthia L. Harris, Pamela Joy Hodul, Jose Mario Pimiento, Mokenge Peter Malafa
Journal: Journal of Clinical Oncology (2016)

432 Background: Guidelines recommend pancreatic protocol CT scan (CT) for staging vascular involvement in patients with pancreatic cancer (PC). While endoscopic ultrasound (EUS) has been demonstrated to be effective in venous staging of PC, its role when combined with CT is poorly defined. We evaluated the utility of EUS in addition to CT in staging PC. We hypothesized that EUS complements CT in identifying SMV/PV tumor involvement as measured by the requirement for vein resection. Methods: We reviewed our database of patients with borderline resectable PC who went to surgery with curative intent. Inclusion criteria were pre-operative staging with CT scan, EUS, PET scan, and CA 19-9 levels, as well as completion of neoadjuvant chemotherapy and radiation. Results: We identified 62 patients with 74% of tumors in the pancreatic head. 97% of resections were R0. The average age was 65 ± 9 years; 60% were male. Patients were classified as borderline resectable by EUS alone in 29%, CT alone in 23%, and both modalities in 48% of patients, respectively. 34 patients required vein resection; EUS identified 88% of these patients pre-operatively while CT identified 68%. EUS identified 11 patients who required vein resection that CT did not identify while CT identified 4 patients that EUS did not identify. EUS had higher sensitivity and specificity than CT in identifying patients requiring venous resection (Table). On multivariate logistic regression analysis, EUS was predictive of vein resection (P &lt; 0.02) but CT scan findings, PET scan findings, tumor size, and CA19-9 values were not predictive (each P &gt; 0.1). In margin negative resected patients, median survival was longer when both CT and EUS identified borderline status compared to only 1 modality (43 vs 23 months, P &lt; 0.05). Conclusions: EUS complemented CT in identifying patients with borderline resectable PC requiring vein resection- 29% of patients were identified with EUS alone. This observation supports the use of EUS in addition to CT scan for the vascular staging of patients with PC. [Table: see text]
A retrospective single-study analysis of survival outcomes in metastatic colorectal cancer.
Authors: F. M. McCarthy, L. Tookman, M. Phillips, P. Wilson, D. Propper, J. P. C. Steele, N. Sarwar, T. Hagemann, S. Slater
Journal: Journal of Clinical Oncology (2011)

e14137 Background: Colorectal cancer (CRC) is the third most common cancer in the UK with approximately 20% of patients (pts) presenting with metastatic disease. In 2008 there were over 16,000 deaths from CRC in the UK. The treatment of metastatic colorectal cancer has changed significantly over the last decade. Developments in cytotoxic agents, the use of combination chemotherapy and the introduction of biological treatments have made incremental survival gains. The UK has poorer survival rates from certain cancers when compared to its European counterparts, with a significant poor outcome of patients in the east end of London; This is thought to be due in part to the later diagnosis of cancer.Here a retrospective single centre analysis of survival data is reported in pts treated with palliative chemotherapy for locally advanced and metastatic CRC over a 10 year period. Methods: The survival data in pts with metastatic and locally advanced CRC treated between the years 2000 to 2010 was analysed. Results: 482 pts were deemed suitable for palliative chemotherapy. Pt characteristics of the analysed population was equally distributed over the years analysed. No differences in survival regarding age or gender were uncovered. A significant survival improvement was observed for the pts treated from 2007-2010. Overall survival from 2000-2002 was 11.6months (n=136), 2003-2006 10.9 months (n=174) and 2007-2010 (n=189) 16.0 months. This compares to the overall UK survival (13.7 months) and Europe(20.6 months). Conclusions: This retrospective analysis demonstrates a significant improvement in overall survival over the last 3years of pts with metastatic CRC treated at a UK tertiary referral centre. This is likely to be attributable to a variety of factors including the introduction of biological agents, developments in cytotoxic agents, the use of combination chemotherapy, improvements in supportive care and better patient selection for treatment. Updated data analysis will be made available at the meeting.
Extent of lymphadenectomy in patients with node-positive (FIGO stage IIIC) endometrial carcinoma.
Authors: S. S. Khalil, L. A. Dos Santos, O. Zivanovic, N. Abu-Rustum, R. A. Soslow, K. M. Alektiar, P. Sabbatini, V. Makker, E. L. Jewell, G. J. Gardner, R. R. Barakat, M. M. Leitao
Journal: Journal of Clinical Oncology (2011)

e15566 Background: The therapeutic role of comprehensive lymphadenectomy has been questioned recently; however, nodal metastases are prognostic and impact treatment decisions. Extent of lymphadenectomy with associated improved survival in patients with stage IIIC disease has been reported in single-institution series. We sought to further assess the association of extent of lymphadenectomy and survival in this group of patients. Methods: All patients with newly diagnosed stage IIIC disease treated at our institution from 1/1/93 to 5/31/06 were identified. Patients with intraperitoneal disease or non-epithelial histologies were excluded. Data were abstracted from electronic medical records. Lymph node ratio (LNR) was defined as the number of positive nodes over the total number of nodes excised and dichotomized (≤10%, >10%). Overall survival (OS) was determined from date of diagnosis to date of death from any cause. Appropriate statistical analyses were performed using SPSS 19.0. Results: 144 cases were included in our cohort. The median age was 64 yrs (33-87 yrs). The median follow-up was 26.5 mo (1.0-176 mo). High-risk histologies were seen in 48 cases (33%). Nodal metastases were microscopic in 63 cases (44%). Postoperative therapy was administered in 137 cases (95%). Age (P=0.002), total number of lymph nodes retrieved (P=0.005), and LNR (P=0.002) were associated with OS. The number of total positive nodes (P=0.25) was not associated with OS. In patients with microscopic nodal disease, LNR (P=0.02) was associated with OS, and the total number of positive nodes (P=0.24) was not associated with OS. In patients with gross nodal disease, LNR (P=0.06) approached an association with OS. The total number of nodes retrieved (P=0.02) was associated with OS in this group. Conclusions: LNR appears to be prognostic in patients with stage IIIC disease. The extent of lymphadenectomy is not associated with improved OS in patients with microscopic nodal disease, suggesting that removing microscopic nodal disease beyond staging or prognosis may not be beneficial. These findings suggest that further investigation into sentinel lymph node mapping to avoid the morbidity of lymphadenectomy is warranted.
Comparative effectiveness of transitional care services in patients discharged from the hospital with heart failure: a systematic review and network meta‐analysis
Authors: Harriette G.C. Van Spall, Tahseen Rahman, Oliver Mytton, Chinthanie Ramasundarahettige, Quazi Ibrahim, Conrad Kabali, Michiel Coppens, R. Brian Haynes, Stuart Connolly
Journal: European Journal of Heart Failure (2017)
Randomized phase II study of oxaliplatin and S-1 (OS) versus oxaliplatin and capecitabine (XELOX) in patients with advanced or recurrent colorectal cancer.
Authors: Dae Young Zang, Ik-Joo Chung, HO-Suk OH, Keon Uk Park, Kyung Hee Lee, Boram Han
Journal: Journal of Clinical Oncology (2012)

595 Background: Combination oxaliplatin and S-1 or oxaliplatin and capecitabine chemotherapy have shown significant efficacy in advanced colorectal cancer. To evaluate those efficacy and safety, we performed a randomized phase II study in patients with metastatic or recurrent colorectal cancer. Methods: Eligible patients were those who had measurable lesions and had no previous history of chemotherapy except adjuvant chemotherapy. The patients of age greater than 18 were enrolled to this study. Oxaliplatin 130 mg/m 2 was administered intravenously on day 1 and S-1 80 mg/m 2 (OS, Arm A) or capecitabine 2,000 mg/m 2 (XELOX, Arm B) was administered orally on days 1-14. Cycles were repeated every 21 days. Patients were treated until proved to have disease progression or unacceptable toxicity. The primary endpoint of the study was to assess the overall response rate (ORR). Results: Eight-two patients (male/ female 57/ 31; median age 67, range 29-83; median ECOG PS 1; Arm A/ B 43/45) were enrolled to this study. Twenty-five patients had recurred cancer after surgery and 63 patients were diagnosed as metastatic diseases. A total of 268 cycles (median 5, range 1-34) in Arm A; 278 cycles (median 5, range 1-18) in Arm B were administered. Eighty-two (41 for each arm) patients were evaluated for toxicity and response. The main toxicities were thrombocytopenia [grade 1/ 2/ 3/ 4 = 11/ 7/ 6/ 1 patients (A); 9/ 10/ 7/ 5 (B)], neutropenia [grade 1/ 2/ 3/ 4 = 8/ 6/ 1/ 0 (A); 9/ 9/ 5/ 2 (B)], anemia [grade 1/ 2/ 3/ 4 = 21/ 13/ 3/ 1 (A); 20/ 10/ 3/ 0 (B)], peripheral neuropathy [grade 1/ 2/ 3 = 11/ 8/ 0 (A); 10/ 8/ 2 (B)], and hand-foot syndrome [grade 1/ 2/ /3 = 2/ 0/ 0 (A); 7/ 1/ 2 (B)]. There were 3 CR, 10 PR, 27 SD and 1 PD (A); 3 CR, 15 PR, 17 SD and 6 PD (B). The confirmed ORR in the intention-to-treat population was 30.2 (95% CI: 16.5-43.9) % (A); 40.0 (95% CI, 25.7-54.3) % (B). The median time to progression was 6.6 (95% CI, 4.4-8.8) months (A); 8.1 (95% CI, 6.3-10.0) months (B). The median survival time was 19.0 (95% CI, 7.3-30.8) months (A); 22.0 (95% CI, 12.1-32.0) months in (B). Conclusions: These data suggest that both OS and XELOX regimen are active and are well tolerated regimens in patients with advanced colorectal cancer.
<i>BRAF</i> mutations in patients with large cell neuroendocrine carcinoma of the colon (LCNECC).
Authors: Karuna Ganesh, Nitya Prabhakar Raj, Rona D. Yaeger, Michael F. Berger, Jinru Shia, Diane Lauren Reidy
Journal: Journal of Clinical Oncology (2016)

567 Background: LCNECC is a rare, poorly differentiated neoplasm with a median survival of 13 months. The cell of origin, genetic mediators and optimal clinical management of LCNECC are unknown. Current guidelines recommend treatment with platinum and etoposide, but nearly all patients rapidly fail therapy. Identification of actionable genomic alterations in LCNECC may lead to improved outcomes. Methods: We identified 123 patients (1.1%) with LCNECC or non-small cell high-grade neuroendocrine carcinoma of the colon or rectum, out of 11134 colorectal cancers treated at MSKCC from 1991-2015. Genomic testing had been performed on 8 tumors: 5 using mass spectrometry based genotyping of 8 genes and 3 using hybridization exon capture of 341 cancer-associated genes (MSK IMPACT). Results: BRAF V600E mutations were identified in 5/8 (62.5%) LCNECCs. One patient each had KRAS Q61H and G12V mutations. Only 2/8 patients had TP53 mutations. All 5 patients with BRAF V600E mutations had non-regional lymphadenopathy, consistent with the metastatic pattern seen in BRAF-mutant colorectal adenocarcinoma (CRC). One patient, a 52-year old female with metastatic LCNECC, was first treated with cisplatin/irinotecan but progressed after 2 cycles. She was treated with FOLFOX, with dramatic clinical and radiological response lasting 7 months. BRAFV600E mutation was identified, and she was treated with dabrafenib+trametinib with radiologically stable disease at 2 months. In sum, 4/6 evaluable patients treated with first line FOLFOX, and 3/3 patients receiving second line FOLFOX after disease progression on cisplatin-based therapy achieved radiological responses. Conclusions: BRAF and KRAS hotspot mutations are near universal features of LCNECC, suggesting that LCNECC is an ERK driven tumor. BRAF inhibitor therapy was associated with clinical benefit in one LCNECC patient. Mutations in TP53, RB1 and PTEN, frequent in small cell cancer, are uncommon in LCNECC. Moreover, several patients responded to FOLFOX, a standard of care for CRC. Together, the mutation patterns and therapy responses suggest some similarities between LCNECC and CRC. MSK IMPACT analysis of further LCNECCs is underway and will be reported at the meeting.
Docetaxel in elderly patients: Phase I and pharmacokinetic study
Authors: V. Girre, P. Beuzeboc, A. Livartowski, J.-Y. Pierga, F. Lokiec, M.-N. Guilhaume, V. Laurence, S. Piperno-Neumann, P. Pouillart, V. Diéras
Journal: Journal of Clinical Oncology (2005)

2113 Background: Elderly patients (>70 years) receive chemotherapy less frequently than younger and usually are excluded from clinical trials. The taxanes are among the most active agents available for the therapy of a variety of solid tumors, particularly breast, non-small cell lung cancer (NSCLC) and prostate cancer. Methods: In order to determine the Dose Limiting Toxicity (DLT) and the Maximum Tolerated Dose (MTD) of Docetaxel in elderly patients with advanced disease, to characterize the pertinent pharmacokinetic parameters in this population and to evaluate the response rate, two strata were defined: (A) 70 to 75 years and (B) older than 75 years. Patients received Docetaxel from 50 mg/m2 (50/ 60/ 70/ 75/ 80 mg/m2), administrated as 1 hour infusion every 3 weeks. A geriatric evaluation was performed with the Mini Nutritional Assessment (MNA> or = 12), the Activity Daily Life scale (Katz scale > or = 5) and the mini-Mental Score (MMS) before inclusion. Results: The median number of cycles was 5 in 30 patients. Patients characteristics were: 16 pts >75, 14 pts 70–75, Tumor types : Metastatic Breast Cancer (21), prostate (7), NSCLC (2). EGOG PS 0–1 (27), 2 (3). The main toxicity was neutropenia grade 3–4 (12/150 cycles); fatigue, fluid retention, nausea-vomiting were common but rarely severe (grade 1–2). DLT: 1 febrile neutropenia in stratum A at dose level 70 mg/m2, 2 in stratum B at dose level 60 mg/m2 (1 febrile neutropenia and 1 sepsis). Conclusion: MTD was not reached, Docetaxel is well tolerated in elderly patients. Accrual at dose level 80 mg/m2 is ongoing in both strata. PK and response rate results will be presented. No significant financial relationships to disclose.