tbuckley/cabot-search huggingface dataset:
Do margin details matter? The prognostic significance of capsule invasion at the site of involved margin in prostatectomy specimens.
Authors: John Morgan Watkins, James Kyle Russo, Michael Laszewski, Mark Rodacker, Patricia L. Watkins, Tarek A. Dufan, Nadim Koleilat
Journal: Journal of Clinical Oncology (2015)

131 Background: An involved surgical margin at prostatectomy has long been associated with elevated risk of prostate cancer recurrence; however, not all patients with an involved margin will relapse, and thus details of the involved margin may provide an opportunity for risk subset stratification. The present investigation seeks to determine whether a difference exists in recurrence rates when the margin involvement is at a site of prostate capsule invasion versus within the prostate parenchyma proper. Methods: Patients were retrospectively identified for inclusion by clinically localized disease and PSA &lt;30 at diagnosis, managed with prostatectomy alone and identified to have involvement of surgical margin(s). Exclusion criteria were: pT3b or pN1 disease, immediate/non-salvage post-operative radiation or hormone therapy, or insufficient follow-up (&lt;12 months). Pathology slides were reviewed by a pathologist blinded to outcome, for determination of capsule invasion at a site of margin involvement. Disease recurrence was defined as PSA &gt;0.2 and rising, per contemporary guidelines. Kaplan-Meier method was employed for disease control estimates. Results: Between 2003 and 2010, 155 patients were identified for inclusion in the present study. The median age was 61 years, and all had cT1-2 disease (75% T1c). At diagnosis, the Gleason score was 6, 7, and 8-9 for 103 (66%), 42 (27%), and 10 (6%) patients, respectively, with median PSA 5.6 (85% &lt;10). For 149 patients with reviewable margin site data, 51 (34%) demonstrated involvement within or beyond the capsule. At a median follow-up of 68 months (range 13-137), 62 patients had experienced PSA relapse. The estimated 5-year PSA relapse rates for patients with an involved margin at the site of capsule invasion versus prostate parenchyma were 49% versus 34%, respectively (p=0.015). Conclusions: Early PSA relapse rates for all patients with involved surgical margin(s) but negative seminal vesicles and nodes at prostatectomy are high; however, for patients who are followed without immediate adjuvant therapy, presence of tumor cells at the margin in a site of capsule invasion or penetration confers a higher risk of recurrence.
The influence of surgical oncology fellowship programs in training hepatopancreatobiliary surgeons.
Authors: Rebecca Lynn Wiatrek, Wendy Lee, Curtis Jackson Wray, Gagandeep Singh, John H Yim, Steven L. Chen, Julio Garcia-Aguilar, Joseph Kim
Journal: Journal of Clinical Oncology (2012)

358 Background: It is unclear how the physician shortage in the US will affect cancer care for our aging population and specifically how it will affect the care of hepatopancreatobiliary (HPB) malignancies. Our objective was to assess the clinical practices of recent surgical oncology fellowship graduates to determine their contribution in caring for this patient population. Methods: Practice data was gathered for surgeons who completed Society of Surgical Oncology (SSO)-approved surgical oncology fellowship programs between 2003-2008. Types of practice were defined as: (1) University Hospital or NCI-designated Cancer Center (NCICC); (2) University-affiliated hospital with resident training; (3) Private/community hospital with residency training program; (4) Private practice; (5) Military; and (6) International. Results: Of 253 surgeons who matched into SSO approved programs during our study period, 10 did not complete training, 11 entered military positions, and 17 are practicing internationally. Of the remaining 215 surgeons, 75% (n=161) obtained teaching positions and 25% (n=54) entered private practice. Of those in teaching positions, the majority were at University Hospitals/NCICC (n=133); followed by University-affiliated hospitals (n=16) and private/community hospitals with resident training (n=12). Overall, the practice focus was most commonly general surgical oncology (60%, n=130) followed by primary HPB (20%, n=43), breast/endocrine or melanoma/sarcoma (17%, n=36), and breast alone (3%, n=6). Conclusions: Our investigation shows that the majority of trainees from surgical oncology fellowship training programs obtain teaching positions with at least a portion of their practice covering HPB malignancies. Thus, recent surgical oncology fellowship graduates are positively contributing to the workforce treating HPB malignancies.
Evaluation of basal and luminal subtypes of urothelial carcinoma in African American and non-African American patients.
Authors: Jordan Kardos, Jonathan J Melquist, David D. Chism, Woonyoung Choi, Katherine Cockerill, Ravi Kumar Paluri, Kelvin A Moses, Guru Sonpavde, David James McConkey, William Y. Kim, Colin P. N. Dinney, Matthew I. Milowsky
Journal: Journal of Clinical Oncology (2015)

305 Background: African American (AA) patients with urothelial carcinoma (UC) have been known to have a worse prognosis even when corrected for variables such as tumor stage and grade. Analysis of gene expression of several malignancies has resulted in the discovery of molecular subtypes with well-defined intrinsic biology. Recent studies in high grade (HG), muscle-invasive UC have led to the identification of two intrinsic, molecular subsets termed “luminal” and “basal” with characteristics of stages of urothelial differentiation, and that remarkably reflect the luminal and basal-like molecular subtypes of breast cancer. Patients with basal-like UC have a significantly worse overall survival. Methods: A total of 215 HG muscle-invasive UC tumors from the MDACC (n=75) and TCGA (n=140) were used to make intrinsic subtype calls using gene expression profiling (MDACC: DASL [cDNA-mediated Annealing, Selection, extension, and Ligation] and TCGA: RNA seq). Basal and luminal subtype calls were derived using previously published subtype classifiers (Damrauer et. al. PNAS, 2014 and Choi et. al. Cancer Cell, 2014). Patients were classified into AA and non-AA (white, Hispanic, or Asian) based upon self-reported race. Results: In total there were 16 and 199 tumors from AA and non-AA patients respectively. In non-AA patients, the proportion of tumors that were classified as basal and luminal were approximately equal (93 and 106 respectively), while in AA patients, there was enrichment of basal tumors (12 basal and 4 luminal) (p=0.03735, Fisher’s exact test). Conclusions: AA patients are enriched in the basal molecular subtype of UC. Similar findings have been previously documented in AA women with breast cancer. The enrichment of basal UC in AAs suggests that a biological explanation may in part underlie the poor outcomes seen in AA patients. Future studies will explore the prognostic and predictive implications of basal subtype in AA patients with UC.
Management of brain metastases from germ cell tumours
Authors: H. J. Boyle, J. Droz, E. Jouanneau, A. Flechon
Journal: Journal of Clinical Oncology (2008)

16076 Background: Brain metastases (BM) from germ cell tumours (GCT) are rare events for which treatment is not yet standardized. Methods: The clinical data of patients with BM from GCT treated in a single cancer hospital from January 1993 to September 2007 was reviewed. Patients with primary central nervous system GCT were excluded. Results: 35 men with GCT with BM were treated at our center. Thirteen patients had BM at initial diagnosis. All had metastases at diagnosis. Six patients had non- histology proven choriocarcinoma syndromes, 5 of the 7 other patients had histology proven choriocarcinoma. HCG levels were higher than 50.000 UI/L in 9 patients. Five patients had single BM, 5 had 2 and 3 had more. All patients received cisplatin-based chemotherapy. Three also received radiotherapy and 1 was operated on. Seven patients have died. Median time between diagnosis and death was 7.5 months (1 day-19 months). With a median follow-up of 83.5 months for the 6 other men, 5 are in complete remission. Twenty-two patients developed BM at recurrence and 10 of them had only brain metastasis. All but one had non-seminomatous GCT at the diagnosis. Median time from initial diagnosis to BM was 8.25 months (3 to 175 months). In 11 cases there was only one metastasis, in 5 cases there were two, in 6 more than 2. Brain histology was available in 9 cases: 8 showed embryonal carcinoma and 1 choriocarcioma. Treatment was radiotherapy alone for 5 patients, chemotherapy alone for 3 and supportive care only for 3. Nine patients were operated on: 6 received post-operative chemotherapy and 1 post- operative radiotherapy. Only 2 patients are still alive. Median time from BM to death was 3 months (1 week - 20.5 months) Conclusions: Patients with GCT who present with BM at diagnosis tend to do better than patients who develop them at relapse. Chemotherapy can be adequate treatment for initial BM. Embryonal carcinoma is often present at relapse. Treatment for these patients is still not optimal. No significant financial relationships to disclose.
Utility of PCA3 and TMPRSS2:ERG urinary biomarkers in African American men undergoing prostate biopsy.
Authors: Allison H. Feibus, A. Oliver Sartor, Krishnarao Moparty, Michael W. Kattan, Kevin M. Chagin, Elisa M. Ledet, Justin Levy, Benjamin Lee, Raju Thomas, Jonathan L. Silberstein
Journal: Journal of Clinical Oncology (2016)

126 Background: To determine the performance characteristics of urinary PCA3 andTMPRSS2:ERG (T2:ERG) in a racially diverse group of men. Methods: Following IRB approval, from 2013-2015, post digital rectal exam (DRE) urine was prospectively collected in patients without known prostate cancer (PCa), prior to biopsy. PCA3 and T2:ERG RNA copies were quantified and normalized to PSA mRNA copies using Progensa assay (Hologic, San Diego, CA). Prediction models for PCa and high-grade PCa were created using standard of care (SOC) variables (age, race, family history of PCa, prior prostate biopsy and abnormal DRE) plus PSA. Decision Curve Analysis was performed to compare the net benefit of using SOC, plus PSA, with the addition of PCA3 and T2:ERG. Results: Of 304 patients, 182 (60%) were AA; 139(46%) were diagnosed with PCa (69% AA). PCA3 and T2:ERG scores were greater in men with PCa, ≥ 3 cores, ≥ 33.3% cores, &gt; 50% involvement of greatest biopsy core and Epstein significant PCa (p-values &lt; 0.04). PCA3 added to the SOC plus PSA model for the detection of any PCa in the overall cohort (0.747 vs 0.677; p &lt; 0.0001), in AA only (0.711 vs 0.638; p = 0.0002) and non-AA (0.781 vs 0.732; p = 0.0016). PCA3 added to the model for the prediction of high-grade PCa for the overall cohort (0.804 vs 0.78; p = 0.0002) and AA only (0.759 vs 0.717; p = 0.0003) but not non-AA. Decision curve analysis demonstrated significant net benefit with the addition of PCA3 compared with SOC plus PSA. For AA, T2:ERG did not improve concordance statistics for the detection any or high-grade PCa. Conclusions: For AA, urinary PCA3 improves the ability to predict the presence of any and high-grade PCa. However for this population, T2:ERG urinary assay does not add significantly to standard detection and risk stratification tools.
Validation of the prognostic impact of lymphocyte infiltration (LI) in patients (pts) with stage III colon cancer (CC) treated with adjuvant FOLFOX+/- cetuximab: A PETACC8 translational study.
Authors: Jean-François Emile, Karine Le Malicot, Josep Tabernero, Enrico Mini, Gunnar Folprecht, Jean-Luc Van Laethem, Catherine Julie, Marc Antoine Allard, Jaafar Bennouna, Come Lepage, Pierre Laurent-Puig, Julien Taïeb
Journal: Journal of Clinical Oncology (2016)

553 Background: The prognostic value of LI of CC has been demonstrated by several groups. However no validated test is available for clinical practice. We previously described an automated and reproducible method for testing LI (Allard MA et al 2012) and aimed to validate it for clinical use. Methods: According to NIH criteria, we designed a prospective analysis of this biomarker in pts included in the PETACC8 phase III study. Primary objective was to compare % of pts without recurrence at 2 years in pts with high versus low LI (#NCT02364024). Secondary objectives were comparison of disease free (DFS) and overall (OS) survivals, and prognostic value of LI on these endpoints. Automated testing of LI was performed on virtual slides without access to clinical data. Results: Among the 1,220 CC pts enrolled, LI was high, low and not evaluable in 241 (20%), 790 (65%) and 189 (15%), respectively. High and low LI groups did not differ except for treatment arm (p=0.04) and microsatellite status (MSI/MSS) status (p=0.04). Primary objective was met with a 2-year recurrence rate of 14.4% versus 21.1% in pts with high and low LI respectively (p=0.02). Pts with high LI also had better DFS and OS (table). Stage, grade, KRAS status and LI were the only prognostic markers in multivariate analysis. Sub-group analyses revealed that high LI had better DFS and OS in MSS pts, and in pts without KRAS codon 12-13 mutation, but not in MSI neither in KRAS mutated pts. Conclusions: This is the first prospective validation of a LI testing in pts with stage III CC treated with FOLFOX adjuvant. Automated testing of LI also had a prognostic value for DFS and OS. Funding: Merck-Serono, Sanofi, Région Ile de France. Clinical trial information: NCT02364024. [Table: see text]
Randomised trial comparing gemcitabine plus vinorelbine (Gem/Vin), gemcitabine plus cisplatin (Gem/Cis), and gemcitabine plus capecitabine (Gem/Cap) in pretreated metastatic breast cancer (MBC)
Authors: W. Freier, H. J. Stemmler, H. Tessen, G. Gitsch, W. Jonat, W. Brugger, E. Kettner, H. Tesch, W. Abenhardt, V. Heinemann
Journal: Journal of Clinical Oncology (2008)

1054 Background: Breast cancer patients are increasingly exposed to anthracyclines and/or taxanes during perioperative therapy. Reinduction with these agents for treatment of metastatic disease is frequently limited by drug resistance or cumulative toxicity. Consequently, there is a need to develop new regimens free of anthracyclines or taxanes. Methods: This randomised phase II trial investigated pretreated MBC patients who were attributed to one of three gemcitabine-based regimens applied at 3-week intervals. Patients received either Gem/Vin (gemcitabine 1,000 mg/m2 days 1+8 plus vinorelbine 25 mg/m2 days 1+8) or Gem/Cis (gemcitabine 1,000mg/m2 days 1+8 plus cisplatin 30 mg/m2 days 1+8) or Gem/Cap (gemcitabine 1,000 mg/m2 days 1+8 plus capecitabine 650 mg/m2 bid orally days 1+14). ORR was evaluated as a primary end-point, while TTP, OS, and safety were analysed as secondary endpoints. Results: 134 eligible MBC patients were randomized and received either Gem/Vin (n=41), Gem/Cis (n=44), or Gem/Cap (n=49). Baseline characteristics regarding median age (58 vs 59 vs 61 years), and estrogen receptor positivity of the primary tumor (46% vs 49% vs 38%) were well balanced between Gem/Vin, Gem/Cis, and Gem/Cap treatment arms. All patients had previously received anthracyclines for adjuvant or palliative therapy. A median of 3 cycles was performed. According to an ITT analysis, overall response rates were in the Gem/Vin arm 32.5% (95% CI, 18.6–49.1%), in the Gem/Cis arm 47.7% (95% CI, 32.5–63.3%), and in the Gem/Cap arm 30.6% (95% CI, 18.3–45.4%). Progression-free survival for Gem/Vin, Gem/Cis, and Gem/Cap was 5.8 months, (95% CI, 3.9–8.2), 7.3 months (95% CI, 5.8–10.4), and 8.2 months (4.3–9.1), respectively, while overall survival was 17.8 months (12.5–37.2), 13.2 months (11.1–24.8), and 20.2 months (17.0–34.3), respectively. When overall grade 3–4 toxicities were compared, no significant difference between arms was detected (chi-square test). Conclusions: Three gemcitabine-based chemotherapy regimens, independent of anthracyclines and taxanes, were shown to be effective treatment options for pretreated MBC patients. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Lilly Germany Lilly Germany Lilly Germany
Risk factors for significant prostate cancer in radical cystoprostatectomy specimen: A retrospective analysis.
Authors: Andrea Katharina Thissen, Daniel Porres, David J. K. P. Pfister, Axel Heidenreich
Journal: Journal of Clinical Oncology (2016)

136 Background: Prostate cancer (Pca) has been found incidentally in radical cystoprostatectomy (RCP) specimens in 27-70%. We evaluated histopathological features and clinical outcome of patients with incidental Pca undergoing RCP for urothelial bladder cancer and identified potential risk factors for the presence of significant Pca, being defined as Gleason Score ≥7b, primary tumor ≥T2c or Pca volume ≥0.5cm 3 . Methods: A retrospective analysis of patients who underwent RCP between 01/2005-03/2015 was performed with regard to clinical data and pathohistological features. Whole mount serial sections of specimens were examined in the same urological and pathological institution. Pca grade, p-stage, cancer volume and surgical margins were recorded. Preoperative PSA values and follow-up were analysed. Results: We identified 71 patients with incidental Pca with a mean age of 71.7 years (47-84 years). 33/71 patients (46.5%) had significant Pca (28.2% ≥T2c, 4.2% GS ≥7b [+≥T2c], 14.1% cancer volume ≥0.5cm 3 [+≥T2c]). Other features were as follows: pT2a, n=36 (50.7%); pT2b, n=2 (2.8%); GS 6, n=50 (70.4%); GS 7a, n=18 (25,3%). All patients were R0 and N0 for Pca. Mean preoperative PSA level was 2.7ng/ml. None of the patients developed biochemical recurrence (median follow-up: 29.5 [1-124 months]). Patients with significant Pca were older than those with insignificant Pca (median age 71.2 years vs 70.1 years) and had higher preoperative PSA levels: 90% of patients with a PSA level of 4-10ng/ml had a ≥T2c Pca, while 81.5% of patients with PSA levels of 0-1ng/ml had a pT2a Pca. P-stages in patients with PSA values between 1-4ng/ml were found to be equally distributed between pT2a-pT2c. Conclusions: The occurence of incidental Pca is a common finding in patients undergoing RCP, with a considerable proportion having the characteristics of significant Pca. Potential risk factors for significant Pca are older age and PSA levels &gt;4ng/ml. However, none of the patients experienced biochemical relapse or Pca-related death during the follow-up. In line with published data, incidental Pca does not impact on the oncological outcome of patients undergoing RCP. The prognosis is primarily determined by bladder cancer.
Pegylated recombinant human arginase (rhArg-peg 5000mw) has <i>in vitro</i> and <i>in vivo</i> anti-proliferative potential and apoptotic activities in human hepatocellular varcinoma (HCC)
Authors: P. N. Cheng, T. W. H. Lo, T. W. H. Leung, A. T. L. Lam, W.-M. Lam
Journal: Journal of Clinical Oncology (2005)

3179 Background: Our group has previously reported that in vivo arginine depletion with rhArg-peg is safe and that it has marked anti-HCC activities. We report here the combined in vivo anti-tumor effect of rhArg-peg and 5-Fluorouracil (5-FU). With flow cytometry and RT-PCR analyses on tumor argininosuccinate synthetase (ASS), we propose a different treatment mechanism to account for anti-tumor activities of rhArg-peg. Methods: BALB/c nude mice bearing human HCC xenografts Hep3B, HepG2 & PLC were tested with rhArg-peg with or without 5-FU. Group 1 with weekly 200 μl PBS i.p. as control, group 2 weekly 250 i.u. rhArg-peg, group 3 weekly 250 i.u. rhArg-peg plus 5-FU at 10 mg/kg, group 4 with weekly 5-FU alone (10 mg/kg). Hep3B cells were seeded in 6-well plates. After treatment rhArg-peg and doxorubicin (12 μM), both floating and trypsinized adherent cells were washed, fixed and stained with propidium iodide and analysed using FACSort flow cytometer. Tumor mRNAs from Hep3B, HepG2, PLC and Huh7 were prepared and RT-PCR performed using standard technique. Results: moderate tumor retarding activities of rhArg-peg in Hep3B, HepG2 & PLC was augmented with concurrent use of 5-FU, in particular in the Hep3B. The flow cytometric data on Hep3B is tabulated below. All four HCC cell lines expressed ASS. PLC expressed ASS markedly while Huh7 had the least expression of ASS. Conclusion: At higher concentrations of rhArg-peg, more HCC cells enter into G0/G1 (67.06% at 10 i.u./ml) and die from apoptosis (9.57% at 10 i.u/ml). rhArg-peg exerts its anti-tumor activity mainly through anti-proliferative potential and apoptosis. Since some cells are still in “S” phase after AD, they responded to a phase specific drug such as 5-FU. ASS is uniformly expressed on RT-PRC in all our cell lines and we believe that tumor deficiency of ASS may not be the only mechanism at play with AD. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Bio-Cancer International Ltd.
Adjuvant therapy in the treatment of biliary tract cancer (BTC): A systematic review and meta-analysis.
Authors: A. M. Horgan, E. Amir, T. Walter, J. J. Knox
Journal: Journal of Clinical Oncology (2011)

4050 Background: The benefit of adjuvant therapy (AT) for BTC is unclear with conflicting results from non-randomized studies. We report a systematic review and meta-analysis to determine the impact of AT on survival, and hence identify treatment strategies and disease subgroups that merit further study in prospective trials. Methods: A systematic review of studies and abstracts published from 1960 to November 2010 was conducted. Eligible studies evaluated outcomes with chemotherapy (CT), radiotherapy (RT) or both (CRT) in resected BTC. Only studies where the comparator group was curative intent surgery alone were included. BTC included tumors of the gallbladder and intrahepatic, perihilar and distal bile ducts. Ampullary tumors were excluded. The endpoint of interest was the odds of death at 5 years (OR). Data on lymph node (N+) or resection margin positivity (R1) were collected. Data were pooled using random effect modeling. Results: 20 studies involving 6,712 patients were analyzed (surgery alone: 4,915; AT: 1,797). These included 1 randomized trial of CT, 2 registry analyses and 17 institutional series, largely RT or CRT. In the overall population, pooled data showed a trend to improved survival with any AT compared to surgery alone, OR 0.74 (95% CI 0.55 - 1.01; p=0.06). There was no difference between individual disease sites (gallbladder OR 0.81, bile ducts OR 0.71). The association was significant when 2 studies of largest weight, both registry analyses, were excluded. On sensitivity analysis, the effect was dependent on treatment modality, those receiving CT or CRT deriving greater benefit than RT alone (OR 0.39, p <0.001, OR 0.61, p=0.049 and OR 0.63, p=0.14 respectively). Eight studies reporting nodal (n=230) or margin status (n=216) were analyzed. Pooled data confirmed a significant benefit for AT in N+ disease, OR 0.49 (95% CI 0.30-0.80). Similarly, a benefit for AT was seen in R1 disease, OR 0.36 (95% CI 0.19-0.68). Conclusions: With the caveats of limited data, this review supports AT for BTC. International randomized trials are needed to provide better rationale for this commonly used strategy in BTC subgroups. Based on our data, such trials could involve CRT vs. CT alone in patients with N+ or R1 disease.