tbuckley/cabot-search huggingface dataset:
Efficacy and safety of the imatinib in the treatment of 73 gastrointestinal stromal tumors
Authors: Y. Shi, C. Du, Y. Zhou
Journal: Journal of Clinical Oncology (2008)

21512 Background: To evaluate the efficacy and safety of imatinib in the adjuvant therapy or in the management of metastatic/unresectable GIST in China. Methods: Among total 73 GISTs proved pathologically, 18 cases of them were managed as adjuvant therapy and 55 cases were palliative. All the GIST received oral imatinib at the dose of 400–800mg/d. Results: 18 of total 73 GISTs were managed as adjuvant therapy with oral imatinib at the dose of 400mg/d, therapeutic time ranged 4–13 months (median time 7 months), time of follow-up ranged 4–27 months (median time 8 months), no relapse occurred and all of 18 cases were disease-free. 55 cases were advanced GISTs and received oral imatinib at the dose of 400–800mg/d palliatively and median therapeutic time is 8.5 months. 2 of 55 cases (3.6%) achieved complete response (CR), 20 cases (36.4%) had partial response (PR), 25 cases had stable disease (SD), 5 cases (9.1%) had progression disease (PD) and 3 cases were unable to evaluate because of no measured tumor. The total clinical effective rate (CR+PR+SD) is 85.5%. 6 cases experienced disease progression after PR/SD and 1 of them re-achieved stable disease with increasing the dose to 800mg/d. 22 cases had been followed up for more than one year and the 1-year survival was 93.8% in the palliative group. According to the NCI-CTC 3. 0 standard, the main toxicity we observed included grade I-II edema 47.9%; nausea and vomiting 31.5%; leukopenia 27.4%; liver dysfunction 11.0%; kidney dysfunction 2.7%; fatigue 16.4%; alimentary tract hemorrhage 1.4%; skin rash 1.4%. Conclusions: Imatinib was effective and safe to metastatic/unresectable GIST and its toxicity was acceptable. For the high-risk GIST, imatinib may be used as adjuvant therapy after radical operation. No significant financial relationships to disclose.
Long-term survival rates after chemotherapy (CTx) in patients (pts) with nonseminomatous (NS) germ cell tumors (GCT) with teratoma (T).
Authors: Sujata Patil, Darren Richard Feldman, Dean F. Bajorin, Robert John Motzer, Joel Sheinfeld, Satish Tickoo, Victor E. Reuter, George J. Bosl
Journal: Journal of Clinical Oncology (2013)

334 Background: Debate surrounds the clinical importance of T in NSCGT pts who receive CTx. The WHO no longer distinguishes between mature (MT) and immature teratoma (IT). Two studies suggested that immunohistologic (IHC) markers of apoptosis, p53 and Ki67 expression were independent markers of outcome in pts with embryonal carcinoma (JCO 21: 2679, 2003) and a differentiation genotype was an independent marker of worse outcome in NSGCT (JCO 27: 5240, 2009). We extend these analyses to NSGCT with and without T. Methods: In an IRB-approved study, archived pre-CTx tumor was obtained from 191 pts who received platinum-based CTx for initial treatment of NSGCT between 4/75 and 5/1996. Histology was confirmed and % cells displaying apoptosis (TUNEL assay) or expressing p53 and Ki67 (IHC) determined at MSKCC. 110 pts’ tumors had ≥ 1 NSGCT cell types without T and 81 had MT (n=39) and/or IT (n=52); 10 pts had both. Tumors with T had ≥ 1 additional NSGCT cell types. Overall survival (OS) differences were tested using Kaplan-Meier, Cox regression and log-rank test. Results: Median age was 27 years; primary site was testis (96%) and mediastinum (3%). 57% were IGCCCG good risk, 29% intermediate risk with no difference with and without T (P=0.53). With median follow-up of 7 yrs, 5-yr OS was 84% (95% CI: 75-90) without T and 72% (61-81) with T, and at 10 yrs 84% (75-90) and 65% (52-76), respectively (P=.06). OS differed by T subgroup: 5-yr OS was 80% if IT alone; 75% if both IT and MT; 61% if MT alone (P=.001). Adjusting for risk strata, this difference remained significant (P=.02). For IT, %Ki67 expression was borderline associated with OS (P=.06), but not %apoptosis (P=.56) or %p53 (P=.93). For MT, %apoptosis was associated with OS (P=.01) but not %Ki67 (P=.70) or %p53 (P=.29). Conclusions: The presence of T, particularly MT, in mixed NSGCT was associated with worse OS than tumors without T. T subtype was important: OS was associated with %Ki67 for IT and %apoptosis for MT. These data suggest that the presence of T should be considered in treatment decision-making. The absence of T subtyping in the WHO classification will likely result in a loss of prognostic information.
Primary melanoma features associated with increased risk of brain metastasis.
Authors: M. W. Ma, M. Qian, D. Lackaye, R. S. Berman, R. L. Shapiro, A. C. Pavlick, J. Golfinos, E. Parker, E. Hernando, Y. Shao, I. Osman
Journal: Journal of Clinical Oncology (2011)

8560 Background: Metastatic melanoma has a known tropism for the brain, which is often regarded as merely a late metastatic site. A subset of melanoma patients present with brain metastasis (B-Met) as the isolated first site of organ metastasis, challenging the current understanding of the natural history of melanoma B-Met. Our objective was to characterize clinical patterns of progression to B-Met in melanoma and to identify primary tumor characteristics associated with an increased risk of B-Met, particularly B-Met as isolated first site of visceral metastasis. Methods: Melanoma patients enrolled in 3 consecutive prospective databases at New York University Medical Center from 1972–2009 were studied. B-Met patients were divided into two groups: 1) B-Met as isolated first site of organ metastasis and 2) visceral metastasis with concomitant or subsequent B-Met. Associations of primary tumor characteristics with the development of B-Met were examined. The two different groups of B-Met patients were also compared with those who progressed to organ metastasis without B-Met. Results: B-Met developed in 227/2581 patients (9%) during follow-up (median: 5.5 years): 88 (39%) with B-Met as isolated first site of organ metastasis, 139 (61%) with B-Met concomitant with or subsequent to other visceral metastases. Thicker (p<0.0001), ulcerated (p<0.0001) primaries with a mitotic rate ≥1/mm2 (p<0.0001) were associated with greater risk of developing B-Met. Primary melanomas of patients who progressed to B-Met as the first site of organ metastasis, however, were thinner (p=0.05 by Wilcoxon test) and more likely to have a mitotic rate of 0/mm2 (OR=2.25, p=0.01) compared to those of patients who first developed other visceral metastases with or without B-Met. Conclusions: Our data suggest that some primary melanoma features can distinguish patients at increased risk of B-Met as well as their B-Met pattern. There is also evidence that metastatic potential to the brain may be acquired at the time of primary diagnosis. A risk assessment model that includes primary tumor characteristics is needed to identify these patients early so that they can be enrolled in clinical trials evaluating the survival impact of increased surveillance and/or targeted therapy.
Characterization of patients with high serum level of IL-6 in advanced pancreatic cancer.
Authors: Tomofumi Miura, Shuichi Mitsunaga, Satoshi Shimizu, Izumi Ohno, Hideaki Takahashi, Hiroyuki Okuyama, Akiko Kuwahara, Masafumi Ikeda
Journal: Journal of Clinical Oncology (2014)

197 Background: IL-6 is a key mediator of cancer cachexia. The degree of cachexia affects serum IL-6 level in pancreatic cancer (PC) and is varied according to disease progression. The study population to characterize advanced PC patients with high IL-6 level needs the homogeneity in disease status. This study was aimed to identify IL-6-related factors in patients who were scheduled to undergo first-line chemotherapy for treatment-naïve advanced PC. Methods: Patients with treatment-naïve advanced PC were eligible for inclusion in this study. Patients with obvious infection or biliary drainage were excluded. Serum IL-6 levels and clinical parameters (e.g. symptoms, body composition) were prospectively collected. A high IL-6 level was defined as a value greater than the median value in all of the analyzed patients, and analyses were performed to identify risk factors for high IL-6 levels. Results: Eighty patients were analyzed. A multivariate analysis determined that the following parameters were associated with high IL-6: the presence of liver metastasis [Odds ratio (OR): 4.8, p &lt; 0.01], fatigue (OR 3.4, p = 0.02), high carcinoembryonic antigen (CEA) levels (OR: 6.9, p = 0.03), anemia (OR: 9.5, p = 0.01), and high C-reactive protein (CRP) levels (OR: 12.4, p = 0.02). A decreased skeletal muscle mass tended to be frequently observed in patients with high IL-6 levels. Conclusions: High serum IL-6 related the presence of liver metastasis, severe fatigue, high CEA, high CRP and anaemia. Additionally, skeletal muscle loss might be the IL-6 related factor.
Organ preserving surgery in testicular cancer - long-term results of the German Testicular Cancer Study Group
Authors: A. Heidenreich, P. Albers, L. Weiβbach
Journal: Journal of Clinical Oncology (2005)

4523 Background: Evaluation of indication, techniques and outcome of organ preserving tumor enucleation in patients with meatchronous/synchronous bilateral testicular germ cell tumors (TGCT) or TGCT in a solitary testicle. The longterm data of 101 patients are presented. Methods: Tumor enucleation resection was performed in 101 patients with 72 (71.3%) bilateral TGCT and 23 (22.8%) bilateral TGCT developing metachronously and synchronously, resp.; 6 (5.9%) TGCT developed in a solitary testicle. Histology of the enucleated TGCT revealed seminoma in 57 cases (56.4%), embryonal carcinoma in 20 cases (19.8%), mature teratoma in 15 cases (14.8%), mixed/combined TGCT in 9 cases (8.9%). Mean tumor diameter was 15mm (5–30mm). Associated testicular intraepithelial neoplasia (TIN) was diagnosed in 84% of the cases, 80 (79%) patients underwent local radiation with 18 Gy, 21 patients underwent close follow-up. Results: After a median follow-up of 80 (4–191) months 100 patients (99%) are NED, 1 patient died due to systemic tumor progression. In 80 patients with associated TIN treated by local radiation 2 local relapses developed, whereas 4 patients developed local recurrences after 3, 6, 12, and 165 months without radiation, all patients have been salvaged by inguinal orchiectomy. Testosterone levels are normal in 84 (83.1%) patients, 10 patients (9.7%) developed hypogonadism, 6 patients (6.3%) remained on their preoperatively low testosterone levels. 4/6 patients who postponed local radiation for paternity reasons, successfully fathered a child after organ sparing surgery. Conclusions: After longterm follow-up of more than 6 years organ sparing surgery represents a viable therapeutic approach in patients with bilateral TGCT with an excellent postoperative outcome. Tumor enucleation might be considered as standard approach if the guidelines/recommendations are respected: organ confined tumor < 20mm, multiple biopsies of the tumor bed, normal LH and testosterone serum levels preoperatively, adjuvant local irradiation postoperatively in selected cases, close follow-up and high compliance. No significant financial relationships to disclose.
Neoadjuvant chemotherapy with gemcitabine and S-1 for resectable and borderline pancreatic ductal adenocarcinoma: A prospective, multi-institutional, phase II trial.
Authors: Masamichi Mizuma, Fuyuhiko Motoi, Kazuyuki Ishida, Fumiyoshi Fujishima, Shigeru Ottomo, Masaya Oikawa, Takaho Okada, Hiromune Shimamura, Shinichi Takemura, Fuminori Ono, Masanori Akada, Kei Nakagawa, Yu Katayose, Shinichi Egawa, Michiaki Unno
Journal: Journal of Clinical Oncology (2014)

283 Background: Although surgical resection is the only curative treatment for pancreatic ductal adenocarcinoma (PDAC), recurrence rates are very high even if complete resection is performed. Accordingly, a new therapeutic strategy against PDAC is needed. Combination with gemcitabine and S-1 (GS) as first line chemotherapy is promising. The purpose of this study is to evaluate the feasibility and efficacy of GS for resectable and borderline PDAC in the neoadjuvant chemotherapy (NAC). Methods: This study is a prospective, multi-institutional, single-arm, phase II trial. Neoadjuvant chemotherapy with gemcitabine and S-1(NAC-GS) for resectable and borderline PDAC was performed as follows. Gemcitabine was given at a dose of 1,000 mg/m 2 on days 1 and 8 of each cycle. S-1 was administered orally at a dose of 40 mg/m 2 twice daily for the first 14 consecutive days followed by a 7-day rest. Each cycle was repeated every 21 days. The primary endpoint was the 2-year survival rate. Secondary endpoints were feasibility, resection rate, pathological effect, recurrence-free survival and tumor marker status. Results: 36 patients were enrolled between 2008 and 2010. 35 were eligible for participation in this trial. The most common toxicity was neutropenia in response to 90% of the relative dose intensity. Radiological tumor shrinkage and decreases of CA19-9 levels were seen in 69% and 89%, respectively. R0 resection rate was 87%, and the morbidity rate (40%) was acceptable. The 2-year survival rate of the total cohort was 45.7%. Patients undergoing surgical resection without distant metastases after NAC-GS (n=27) showed an increased median overall survival (34.7 months), compared with 10.0 months for resection with distant metastases or non-resection (p=0.0017). Conclusions: NAC-GS is safe and well tolerated in a multi-institutional setting. NAC-GS is encouraging patients with resectable and borderline PDAC because of better outcomes. Clinical trial information: UMIN-000001504.
Do pathological parameters of primary tumor correlate with overall survival (OS) of metastatic clear-cell renal cell carcinoma (ccRCC)?
Authors: Umberto Basso, Marco Maruzzo, Anna Paola Fraccon, Teodoro Sava, Francesco Massari, Cosimo Sacco, Francesca Valcamonico, Francesca Maines, Giovanni Lo Re, Donatella Donati, Susanne Baier, Emilia Durante, Mariella Soraru', Maurizio Nicodemo, Alessandra Bearz, Donata Sartori, Pasquale Fiduccia, Fable Zustovich, Felice Pasini, Vittorina Zagonel
Journal: Journal of Clinical Oncology (2016)

549 Background: T and N stage, Fuhrman grade, necrosis and sarcomatoid features in the primary tumor are key prognostic factors for relapse of ccRCC, but they are not part of Heng's algorithm applied to predict OS in the metastatic setting, which instead is based on 6 clinical/laboratory items. Methods: Retrospective analysis on correlation between pathological parameters and OS (from start of first-line targeted therapy) and Heng's prognostic factors in a multicenter cohort of pts with advanced ccRCC, all of whom had undergone surgery on the kidney. Results: From 2006 to 2012, data of 903 eligible metastatic pts were collected from 33 Italian Oncology Institutions, median age 66 years, 72.6% males, 36.4 metastatic at diagnosis. After a median observation of 42 mo, 70,5% of pts died, estimated OS is 28.5 mo. Heng good prognosis pts were 14.45%, intermediate 69.1% and poor 16.45%. Univariate analysis showed that all pathological parameters significantly correlated with OS: T stage 3-4 vs 1-2 (HR 1.3), N1 vs N0 (1.3), Fuhrman grade 3-4 vs 1-2 (1.7) presence of necrosis (1.5) and sarcomatoid features (1,6). All pathological parameters had a strong correlation with a time to metastases &lt; 1 year, while only weak correlations were found with the other clinical prognostic items of Heng's model. At multivariate analysis only N stage showed an independent impact on OS (table). Conclusions: T3-4 stage, N1, Fuhrman grade 3-4, presence of necrosis and sarcomatoid features negatively affect OS of metastatic ccRCC, but clinical items of Heng's model confirm to have a more robust prognostic significance at multivariate analysis. [Table: see text]
Impact of proteolytic factors on surgical success and survival in ovarian cancer
Authors: B. Schmalfeldt, R. Kates, J. Dorn, A. Scorilas, L. Grass, A. Soosaipillai, E. Diamandis, M. Kiechle, M. Schmitt, N. Harbeck
Journal: Journal of Clinical Oncology (2005)

5068 Background: Proteolytic factors of the plasminogen activation system and the human tissue kallikreins (hK4–15) have been implicated in tumor progression in ovarian cancer. Methods: In 142 ovarian cancer patients FIGO 1–4 operated on between 1985 and 1999 in the Dept. of OB&GYN of Munich Technical University (median follow-up 33 months), uPA, PAI-1, hK5–8,10,11,13 were measured by ELISA in primary tumor tissue extracts; 72 patients were optimally debulked. All patients received postoperative platinum-containing chemotherapy. Results: In univariate Cox models of progression free survival (PFS) including these measurements (fractionally ranked) plus age, pN, grading, ascites volume, and residual tumor, the strongest single predictor was presence of residual tumor (HR=4.37; 2.55–7.47). pN (HR=1.94; 1.12–3.38) and ascites volume (HR=2.37; 1.45–3.88) were also separately significant, but none of the others. In multivariate analysis of PFS, residual tumor (HR=4.76; 2.75–8.23) and hK11 (HR=0.30; 0.12–0.77) both entered the model, higher values of hK11 being associated with improved survival. Due to the strong impact of residual tumor on PFS, any factor influencing residual tumor, thus predicting surgical outcome could also be of considerable clinical interest. hK5 and 13 had significant impact on residual tumor. In univariate logistic regression, higher hK5 significantly predicted poor surgical outcome (OR=1.52; 1.25–16.6). In multivariate analysis, both hK5 and hK13 entered the model: Higher hK5 was strongly associated with residual tumor (OR=6.4; 1.63–25.0), whereas higher hK13 was associated with better surgical outcome (OR=0.16; 0.03–0.74). A ROC curve from this model classifies surgical success with AUC=0.65 (0.56–0.75). For OS, residual tumor (HR=8.7; 4.1–18.3) and hK10 (HR=0.21; 0.07–0.64) were significant in multivariate analysis. hK13 (HR=0.27; 0.08–0.85) was significant in univariate analysis only. Higher hK10 and hK13 are associated with better OS. Conclusions: Our results demonstrate that proteolytic factors are linked to tumor aggressiveness in ovarian cancer and have the potential to support clinical therapy decisions. Validation in independent data sets is currently being performed. No significant financial relationships to disclose.
Utilization and outcome of radiotherapy among patients with limited stage indolent follicular lymphoma in the United States
Authors: W. T. Swenson, J. E. Wooldridge, B. K. Link
Journal: Journal of Clinical Oncology (2005)

6642 Background: Radiotherapy is frequently advocated as a standard therapy for patients with limited stage follicular small cleaved lymphoma (FSC) and follicular mixed small and large cell lymphoma (FM). Long-term analysis of institutional series have demonstrated one-third to one-half of patients have prolonged relapse free survival. Methods: This retrospective review of the SEER-9 database was conducted to determine the frequency and outcome of radiotherapy administration as part of the first course of treatment among a population-based cohort. ICD-O-2 diagnostic morphology codes were used to identify a cohort of patients with limited stage FSC and FM, diagnosed between 1983 and 2001. Results: A cohort of 3,165 patients was identified from nine SEER registries. The cohort was comprised of 1,687 (53.3%) females, 1,822 (57.9%) FSC, and 1,326 (42.1%) FM. The most frequent anatomic sites of presentation included head and cervical lymph nodes (37.2%), inguinal lymph nodes (22.0%), axillary lymph nodes (9.8%), intra-abdominal lymph nodes (8.3%). Among the cohort, 1,204 (38.0%) received radiotherapy. Among patients age ≥60, 692 (34.7%) received radiation, compared to 512 (45.0%) patients age <60 (P < 0.001). Radiotherapy administration was associated with improved survival (P < 0.001) by log rank test. Median survivals were 102 months (95% confidence interval: 97, 110) and 161 months (143, 173) for no radiotherapy and radiotherapy recipients, respectively. The 15-year survival rates were 42.4% and 29.1% for patients radiotherapy and no radiotherapy recipients, respectively. Higher survival rates in the cohort receiving radiotherapy were seen in patients age <60 as well as those age ≥60. There was no difference in patterns of survival among the four most common sites of disease. A multivariate analysis controlling for age, gender, ethnicity, region, year of diagnosis, and registry site revealed a decreased relative risk of death for patients who underwent radiotherapy (HR = 0.654, P < 0.001). Conclusions: Radiotherapy is utilized in less than 50% of patients with limited stage follicular lymphoma and is associated with a long-term survival benefit. No significant financial relationships to disclose.
“Real world” effectiveness of different postoperative adjuvant chemotherapy regimens in stage III colon cancer patients.
Authors: Jy Ming Chiang, Hsin Yuan Hung
Journal: Journal of Clinical Oncology (2016)

754 Background: In clinical practice, choosing oral chemotherapy or FOLFOX may depend to drug toxicity and patients’ age and comorbidities, in addition to heterogeneous stage III colon cancer. The benefit of oxaliplatin in the real world practice remained further clarified. Methods: 688 stage III colon cancer patients were collected. Treatment outcomes were retrospectively compared based on the type of chemotherapy in terms of OS and DFS. Multivariate Cox-regression modeling was used to adjust for the potential confounders. Results: This study included capecitabine (259 patients), fluorouracil-leucovorin plus oxaliplatin (FOLFOX) (283 patients) and Tegafur-uracil(146 patients). Comparing patients with capecitabine and tegafur regimens, patients receiving FOLFOX were significantly younger (mean age 56.5 yrs v.s. 65,1 yrs and 66,9 yrs ), more poor differentiation (15.9% v.s. 8.1% and 8.2%), deeper tumor invasion (T4 lesion 25.1% v.s. 15.8% and 17.1%), more advanced nodal involvement (N2/3 51.9% v.s. 18.1% and 20.5%) and had less comorbidity (50.2% v.s. 61.4% and 65.1%). Rate of completeness of chemotherapies (88.0% v.s. 87.6% and 81.5%) was no significant difference. Comparing treatment outcome, by univariate analysis, demonstrated significant (p = 0.0258) difference in OS for N2/3 patients but no difference in N1 patiens. However, by balancing confounding factors including co-morbidities, multivariate analysis showed that impact on overall survival in patients receiving capecitabine was statistically significant better than Tegafur (HR = 0.59, p = 0. 03) while no difference comparing with FOLFOX regimen (HR = 0.76, p = 0.3219). However, disease free survival (DFS) was no significantly different for FOLFOX comparing with capecitabine HR 0.97 and Tegafur HR 0.89 by multivariate Cox regression analyses. Conclusions: As post-operative adjuvant setting, oral chemotherapy either Capecitabine or Tegafur-uracil showed similar effectiveness as folfox in terms of DFS while in terms of OS, Capecitabine demonstrated similar effectiveness to folfox but better than Tegafur-urecil.