tbuckley/cabot-search huggingface dataset:
Assessment of survival from distal esophageal and gastric cardia tumors: A population-based analysis of gastroesophageal carcinomas
Authors: B. A. Whitson, S. S. Groth, Z. Li, R. A. Kratzke, M. A. Maddaus
Journal: Journal of Clinical Oncology (2008)

4556 Background: Despite having different staging systems, is unclear whether or not distal esophageal (DE) and gastric cardia (GC) tumors should be treated similarly (due to comparable biology) or differently (due to dissimilar biology). We hypothesized that tumor location (gastric body or fundus [GBF], GC, DE, and mid-thoracic esophagus [MTE]) has a significant influence on overall survival. Methods: Using the Surveillance Epidemiology and End Results database, we identified 41,143 patients who were diagnosed with invasive MTE (n=8,607), DE (n=12,694), GC (n=13,296) or GBF (n=6,546) carcinomas from 1973 through 2003 and evaluated them for differences in overall survival, by their tumor location. In order to adjust our survival analysis for potential confounding variables (histology, stage, race, cancer directed surgery, and radiation therapy), we utilized a Cox proportional hazards regression model (α=.05). Results: After adjusting for tumor location, histology, stage, race, cancer directed surgery, and radiation therapy, we found no significant difference in overall survival between DE and GC tumors (HR=0.98; 95% CI: 0.94 to 1.02). As compared with DE tumors, survival from GBF tumors is significantly better (HR=0.92; 95% CI: 0.87 to 0.97) while survival from MTE tumors is significantly worse (HR=1.10; 95% CI: 1.05 to 1.15). In bivariate analyses, increasing stage correlated with worse survival (p<.0001); adenocarcinomas were associated with better survival than squamous cell carcinomas (p<.0001). Conclusion: Through a large, population-based analysis, we found that GC and DE tumors have equivalent survival. Distal esophageal tumors and gastric cardia tumors should be treated in a similar fashion (regardless of stage or histology). No significant financial relationships to disclose.
SWOG0345: Prospective phase II trial of imatinib in dermatofibrosarcoma protuberans (DFSP)
Authors: S. M. Schuetze, C. A. Rankin, B. P. Rubin, J. E. Butrynski, E. C. Borden
Journal: Journal of Clinical Oncology (2008)

10580 Background: DFSP is a low-grade, dermal neoplasm characterized by t (17;22) resulting in aberrant production of functional platelet-derived growth factor. Imatinib mesylate, a small molecular inhibitor of platelet-derived growth factor receptor, has induced tumor response in DFSP in case reports. We undertook a prospective phase II study of imatinib in DFSP through the North American Sarcoma Intergroup to assess the RECIST confirmed response rate. Methods: Patients (pts) with unresectable, locally recurrent or metastatic DFSP, ECOG performance score (PS) 0–2, and adequate organ function were enrolled in a single-arm, 2-step trial of imatinib 400 mg per day for 28 days per cycle. Central pathology review and analysis of t (17;22) occurred after enrollment. Response assessment occurred after every even cycle. Pts received a maximum of 12 cycles in the absence of progression or toxicity. Pts with progression were eligible for treatment with imatinib at 400 mg twice daily. Primary endpoint was confirmed objective response in ≥ 5 of 40 pts. Results: Eight pts were registered between 2/2005 and 10/2006 from 4 institutions. DFSP arose in the trunk (4), head/neck (3) or extremity (1), and was unresectable (3), locally recurrent (4) or metastatic (1). Median pt age was 48 years (range 28–66), 5 were female. PS was 0 and 1 in 7 and 1 pts, respectively. A pt with baseline tumor size of 1.9 cm did not meet RECIST definition of measurable disease. After central review of tumor, 5 were classified as DFSP, 2 fibrosarcomatous DFSP and 1 sarcoma, not otherwise specified (nos). Confirmed partial responses were observed in 4, stable disease in 2 and progression as best response in the 1 pt with sarcoma, nos. Three pts completed 12 cycles, 1 pt with stable disease withdrew for personal reasons after 8 cycles and 4 developed progression at 2, 6, 8 and 9 months. Dose escalation to 400 mg twice daily in 2 pts re-induced response in 1 pt but did not induce response in the pt with primary resistance to imatinib. Conclusions: Imatinib 400 mg daily is active in DFSP with an estimated response rate of 57% (95% CI 18–90%). The trial was terminated early because of poor accrual and FDA approval in 2007 of imatinib 400 mg twice daily for advanced DFSP. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Novartis Novartis
Comparison of the 2002 and 2010 version of the TNM classification system regarding the prediction of metastasis-free survival in patients with renal cell carcinoma.
Authors: Georg C. Hutterer, Martin Pichler, Thomas F. Chromecki, Johanna Jesche, Karin Kampel-Kettner, Karl Pummer, Richard Zigeuner
Journal: Journal of Clinical Oncology (2012)

448 Background: A new version of the TNM classification system for renal cell carcinoma (RCC) has been introduced in 2010 by the American Joint Committee on Cancer (AJCC). However, data for it’s ability to predict metastasis-free survival in RCC patients from validation studies of independent cohorts are sparse. Therefore, we decided to compare the predictive ability of the 2010 vs. the 2002 version of the TNM classification system. Methods: Pathological reports of 2595 patients with uni- or bilateral synchronous non-metastatic (pT1-4N0M0) RCCs, treated with radical nephrectomy or nephron sparing surgery between 1984 and 2010 at a single tertiary academic center, were re-evaluated. Metastasis-free survival (MFS) was assessed using the Kaplan-Meier method and pairwise log-rank tests. Results: Mean follow up was 95 (0-322) months and 430 (16.6%) patients were found to develop metastatic disease from RCC. Pairwise comparisons revealed statistically significant differences in MFS between adjacent 2002 primary tumor classifications, including pT1a vs. pT1b (p&lt;0.001), pT1b vs. pT2 (p=0.029), pT3a vs. pT3b (p&lt;0.001), and pT3c vs. pT4 (p=0.007) but excluding, pT2 vs. pT3a (p=0.963) and pT3b vs. pT3c (p=0.968). With the changes to the 2010 primary tumor classification different trends in statistical significance were observed in pairwise comparisons, including pT1a vs. pT1b (p&lt;0.001), pT3a vs. pT3b (p=0.001) but excluding pT1b vs. pT2a (p=0.062), pT2a vs. pT2b (p=0.856), pT2b vs. pT3a (p=0.395), pT3b vs. pT3c (p=0.891) and pT3c vs. pT4 (p=0.933). Conclusions: The 2010 version of the TNM classification system remains a robust predictor of MFS compared to the 2002 version. However, the 2010 version showed less discriminative power in higher pT-stages compared to the 2002 version of the TNM classification system.
Recovery challenges faced by bladder cancer survivors after recent cystectomy and urinary diversion.
Authors: Carmit K. McMullen, Kim N. Danforth, Marilyn L Kwan, Joanna E Bulkley, Maureen Cecelia O'Keeffe-Rosetti, Sheila Weinmann, Robert S. Krouse, Mark C. Hornbrook, Marcia Grant, Michael C Leo, Scott Michael Gilbert
Journal: Journal of Clinical Oncology (2016)

90 Background: Bladder cancer patients who are treated with cystectomy (bladder removal) and urinary diversion (bladder replacement) experience high rates of complications and hospital readmissions, and have substantial supportive care needs. Patient-reported priorities for improving early-phase survivorship care are lacking. Methods: On the basis of focus groups and in-depth interviews with 32 bladder cancer survivors about post-operative challenges, we developed a structured question listing 16 early survivorship challenges. We asked respondents to indicate which challenges had been difficult to manage at home. The item was part of a survey mailed to members of three Kaiser Permanente regions who had undergone cystectomy and urinary diversion for bladder cancer approximately 6 months previously (N = 197). Eligible patients were identified through health plan databases and chart review. Results: The response rate to the survey was 65%. Respondents reported an average of 3 challenges. The most commonly reported challenges pertained to coordination of medical care (69%), such as confusion about follow-up care, problems obtaining medical and ostomy supplies, knowing what complications to look for and who to notify if they occur, receiving home health care, or obtaining prompt medical advice. Other problems were caring for the urinary diversion (53%); dealing with urine leaks and incontinence (49%); problems with balance, vision, and dexterity (32%); difficulty managing emotions (23%); and management of lymphedema (11%) or incisional or parastomal hernias (7%). Conclusions: More than two thirds of bladder cancer survivors who had recently undergone cystectomy and urinary diversion struggled with medical care coordination. Managing self-care, complications, and emotional well-being after this major surgery can be difficult for patients, who must also navigate a variety of supportive services, such as medical follow-up with multiple departments and providers, home health services, and wound or ostomy care. A more formal approach to discharge and better communication among patients and providers will help improve early survivorship care for this group.
Therapy with human monoclonal anti-CTLA-4 antibody, CP-675,206, reduces regulatory T cells and IL-10 production in patients with advanced malignant melanoma (MM)
Authors: J. M. Reuben, B. N. Lee, D. Y. Shen, C. Gutierrez, I. Hernandez, C. A. Parker, V. A. Bozon, J. Gomez-Navarro, G. Lopez-Berestein, L. H. Camacho
Journal: Journal of Clinical Oncology (2005)

7505 Background: T-regulatory (T-reg) cells are CD3+CD4+CD25+ and produce IL-10. Engagement of CTLA-4 on activated T cells with CD80/CD86 on APC diminishes T-cell activation and proliferation via inhibition of IL-2 transcription and production. To block signaling of this repressive pathway, 26 patients (pts) with MM were treated with CP-675,206 in a Multi-dose Phase I/II Trial with the intent of augmenting host T-cell mediated responses against the tumor. Methods: Sixteen pts received monthly infusions of CP-675,206 at 10 mg/kg, and another 10 pts at 15 mg/kg every 3 months; all patients were assessed for objective tumor responses (OR) by WHO criteria. Peripheral blood (PB) was obtained from pts at baseline and day 14 of each course of treatment to determine PB T cells (CD3+) and subsets (CD4, CD8, and CD25) by FACS, IL-2, IL-10, and interferon-gamma production, and proliferation of T cells in response to activation of PB mononuclear cells (PBMC) with anti-CD3. Results: Of the 18 evaluable pts, 5 (3 at the 10 mg/kg and 2 at the 15 mg/kg doses) attained OR, 13 progressed (PD); and 8 were stable (SD) or too early for tumor evaluation. After two months of treatment, OR and SD pts had significant increases in %CD3+CD4+ T cells (48.4% vs 57.6%; p=0.018) and a concomitant decrease in %CD3+CD4+CD25+ T-reg cells (38.9% vs 26.7%; p=0.025) whereas PD pts had a significant increase in %CD3+CD4+ T cells (50.4% vs 55.1%; p<0.05) without a reduction in T-reg cells. PBMC from OR, and not PD, had a significant reduction in the constitutive IL-10 production (11.3 pg/mL vs 2.9 pg/mL; p=0.032). Moreover, the ratio of IL-2/IL-10 production by anti-CD3 activated PBMC of OR, and not PD, pts was significantly higher after 1 cycle of treatment (14.2 vs 29.4; p=0.028), compared to baseline. Conclusions: Multiple doses of CP-675,206 can induce OR in pts with MM. CP-675,206 can also reduce the %CD3+CD4+CD25+ T-reg cells and constitutive IL-10 production, and increase the ratio of IL-2/IL-10 production by anti-CD3 activated PBMC. Collectively, these data suggest that CP-675,206 is biologically active in MM and may improve T-cell mediated immunity in clinical responders. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Pfizer Pfizer Pfizer Pfizer Pfizer
The feasibility of R0 resection of locally advanced pancreatic cancer (LAPC) encasing major visceral arteries (T4 lesions) using arterial resection and reconstruction: Short- and long-term outcomes.
Authors: Yuri Genyk, Afsaneh Barzi, Anthony B. El-Khoueiry, Lea Matsuoka, Vanessa Sutton, James Buxbaum, Syma Iqbal, Jacques van Dam, Rick Selby, Heinz-Josef Lenz
Journal: Journal of Clinical Oncology (2013)

243 Background: LAPC is found in about 40% of patients with pancreatic cancer at initial presentation. Tumors involving major visceral arteries are commonly deemed unresectable. In this study we analyzed the feasibility of R0 resection of LAPC encasing major visceral arteries using arterial resection and reconstruction. Methods: The following data were collected prospectively following pancreatic resection with vascular reconstruction in patients with LAPC: age, gender, operative details, post-operative complications, chemotherapy and/or radiation therapy and overall and disease free survival. Patient survival was calculated utilizing Kaplan-Meier survival probability estimates. Results: From Dec., 2002 to Sep., 2012, 12 patients with LAPC (8 males and 4 females, median age 58.5 yrs (range: 51–78 yrs)) underwent pancreatic resection with concomitant resection and reconstruction of major visceral arteries in our institution. The arterial involvement included celiac artery (n=8), and superior mesenteric artery (n=4). Resections included pancreatico-duodenectomy (n=8), distal pancreatectomy (n=3), and total pancreatectomy (n=1). Management of the arterial involvement included: resection of celiac axis without reconstruction (n=2), resection and reconstruction of one artery (n=6), two arteries (n=3) and three arteries (n=1). R0 resection was accomplished in 9, R1 in 2, and R2 in 1 patient. One patient (8%) died peri-operatively from pulmonary thromboembolism. Chemo- or chemo-radiation therapy was not protocolized. To date, 5 patients are alive and disease free at 7, 9, 11, 23 and 117 months, and 1 patient is alive with recurrence at 107 months. Six-month patient survival was 75% and median overall survival (MOS) was 19 months. Conclusions: The MOS in this patient population with systemic therapy is around 9 months. Although the sample size in our study is limited, observed MOS of 19 months is encouraging and provides the opportunity to reconsider the contraindications to surgical management of such patients with T4 LAPC. Timing of perioperative chemotherapy will be evaluated in a prospective trial.
The Role of Imatinib Plasma Level in the Achievment of Complete Cytogenetic Response (CCyR) in Chronic Myeloid Leukemia (CML) Therapy
Authors: Sergey Kutsev, Oxana Oxenjuk, Sergey Mordanov, Yuri Shatokhin, Tatiana Pospelova, Nina Khoroshko, Anna Turkina
Journal: Blood (2011)
Osteonecrosis of the jaw (ONJ) in patients with prostate (PC) or breast (BC) cancer treated with bisphosphonates: Study of the effect of the application of preventive measures
Authors: A. Bamias, E. Kastritis, I. Melakopoulos, D. Gika, M. Roussou, M. Migkou, E. Eleftherakis-Papaiakovou, M. A. Dimopoulos
Journal: Journal of Clinical Oncology (2008)

16025 Background: Bisphosphonates are used in the treatment of bone metastases but their use is associated with the development of ONJ. Dental problems or interventions are precipitating factors of ONJ. Since 2003, we have implemented assessment (and management) of dental problems of all patients who are candidates for or who are on treatment with bisphosphonates by specialists with experience on ONJ. We also recommend improved oral hygiene and we avoid dental procedures during treatment. We have recently shown that these preventive measures have resulted in reduction of the incidence of ONJ caused by Zoledronic acid in MM. We have investigated whether ONJ also decreased after the implementation of these measures in two solid tumors with high frequency of bone metastases: prostate and breast cancer. Methods: Patients should have had at least six months of treatment with Pamidronate, Zoledronic acid, or successive use of Pamidronate and Zoledronic acid. Patients were classified into two groups depending on the date of initiation of treatment: before (Group A) or after (Group B) the implementation of the preventive measures (January 2003). The proportions of patients with osteonecrosis between the two groups were compared with the Fisher's exact test. Times of exposure were compared using the Mann-Whitney-test. Results: Seventy-seven patients with PC (Group A: 25, Group B: 52) and 109 with BC (Group A: 57, Group B: 52) were included in the analysis. The first bisphosphonate treatment in PC patients was administered on 10/9/1997 and in BC patients on 15/11/1996. Among PC patients, there were 3 cases of ONJ (3.9%) after a median time of exposure of 15 months. All ONJ cases belonged to Group A (12%, p=0.011 for comparison with Group B). The median time of exposure between the two groups was similar (16 months vs. 14 months, p=0.698). There were 2 cases of ONJ among BC patients (1.8%) after a median time of exposure of 18 months. One case was observed in Group A and the other in Group B (p=0.948). Exposure was similar between the two groups (19 vs. 17 months, p=0.335). Conclusions: The implementation of preventive measures seems to reduce the occurrence of ONJ in PC patients. In BC, ONJ is rare and no impact of these measures was found. No significant financial relationships to disclose.
Role for IL2 adjunctive cotherapy for suppression of a solid tumor with designer T cells: Phase I trial data in prostate cancer.
Authors: Richard Paul Junghans
Journal: Journal of Clinical Oncology (2013)

216 Background: We created chimeric antigen receptors (CAR) against prostate specific membrane antigen (PSMA). When expressed in patient T cells, these “designer T cells” (dTc) kill prostate cancer cells in vitro and in vivo in animal models (Ma et al. Prostate2004:61:12-25). A Phase I trial was performed. Methods: Patient T cells are retrovirally transduced and expanded ex vivoto span doses of 10^9 to 10^10 T cells. Patients undergo prior non-myeloablative (NMA) conditioning to create a “hematologic space” into which dTc are infused for stable engraftment and prolonged in vivo efficacy. Continuous infusion low dose IL2 (LDI: 75 kiu/kg/d) is administered. Results: Infused T cells were documented. Safety was shown and partial responses (PR) obtained in 2/5 subjects (40%), with PSA suppressions of 50-70% over 1-2+ mo and PSA progression delay up to 150d. Against expectation, response correlated inversely with engraftment (p=0.06) but directly with plasma IL2 (p=0.03) that was as much as 20-fold lower in non-responders than responders. Low plasma IL2 correlated with high engraftments (p&lt;0.01), prompting an hypothesis that high engrafted numbers of activated T cells absorb out IL2 to a level too low to sustain dTc activation for tumor killing. Conclusions: Encouraging early results were obtained with anti-PSMA dTc in adoptive immune therapy of advanced prostate cancer. It is proposed that adequate higher plasma IL2 will reveal the expected greater potency of higher dTc doses, thereby potentially inducing PSA reductions of 100%, with durable remissions. A study redesign tests moderate dose IL2 (MDI) (300 kiu/kg/8h bolus) versus LDI in a randomized Pilot at the 10^10 cell dose, which is now open to enrolment. To refer patients, please contact the study referral manager by telephone: 401-456-2507 or email: RDavies@rwmc.org. This trial received partial funding from US Army/DOD. Preclinical work was supported by Prostate Cancer Foundation. Clinical trial information: NCT00664196.
PLASMA PROTEIN METABOLISM—ELECTROPHORETIC STUDIES
Authors: L. J. Zeldis, E. L. Alling, A. B. McCoord, J. P. Kulka
Journal: The Journal of Experimental Medicine (1945)

The findings on electrophoretic analysis of plasma proteins during many weeks of low protein feeding in dogs accord in general with those of chemical analysis as concerns the alterations in plasma albumin and globulin concentrations. Long continued restriction of dietary protein results in decreased albumin levels while plasma globulin concentrations remain essentially normal. The degree of depletion of electrophoretic albumin is, however, considerably greater than that of chemical albumin. When large amounts of protein are fed to such depleted dogs complete restoration of normal plasma albumin concentrations requires several weeks. During these weeks large quantities of nitrogen are retained, presumably as tissue protein reserves. Prompt production of plasma globulin is apparent during such periods. These relationships are more clearly shown in electrophoretic than in chemical analyses and are more conspicuous when only moderate protein intakes are fed. These data may indicate that plasma globulins and certain tissue proteins, in contrast to plasma albumin, enjoy prior demands on the total available pool of body protein materials under emergency conditions. Total electrophoretic globulin areas are increased during depletion. Such increases result largely from elevated alpha globulin peaks and are not disclosed by chemical analysis. They are found to be associated with elevated plasma lipid levels which occur in these depleted dogs. These experiments suggest that in potency tests for dietary protein materials, factors other than the quality of fed protein may influence the relative production of plasma albumin and globulin.
Socioeconomic support to improve initiation of tuberculosis preventive therapy and increase tuberculosis treatment success in Peru: a household-randomised, controlled evaluation
Authors: Tom Wingfield, Marco A Tovar, Doug Huff, Delia Boccia, Rosario Montoya, Eric Ramos, Sumona Datta, Matthew Saunders, James J Lewis, Robert H Gilman, Carlton A Evans
Journal: The Lancet (2017)
Prognostic factors for recurrence in resected pancreatic adenocarcinoma: A single-center experience.
Authors: M. Di Marco, M. Macchini, C. Ricci, G. Taffurelli, M. D'Ambra, S. Vecchiarelli, M. C. Pallotti, R. Pezzilli, A. A. Martoni, R. Casadei, G. Biasco
Journal: Journal of Clinical Oncology (2011)

e14541 Background: The aim of the study was to determine prognostic factors for recurrence in resected pancreatic cancer. Methods: We analyzed retrospectively 47 patients who underwent pancreatic resection for pancreatic ductal adenocarcinoma, from January 2006 to July 2010. Demographic (age, sex), surgical (type of resection), pathological data (grading, TNM stage, lymph node ratio, presence of metastatic lymph nodes, number of lymph nodes harvested, R status, perineural and vascular invasion) and type of therapy (surgery alone versus surgery plus adjuvant treatment) were evaluated. Results: Adjuvant chemotherapy was performed in 28 patients: 23 received gemcitabine (GEM) alone (1,000 mg/mq die 1-8-15 every 28) and 5 GEM plus cisplatin (CDDP) (75 mg/mq die 1 every 28). Radiotherapy was preformed only in 9 patients: 6 associated with GEM alone and 3 with GEM plus CDDP. Median follow-up was 16 months. Total recurrences were 34 out of 47 patients (72.3%): local relapse were 10 (29.4 %) and distant metastases were 24 (70.6%). Median OS and DFS were 27.1 ± 2.9 and 15.7 ± 2.1 months, respectively. At univariate analysis patients who underwent total pancreatectomy (P=0.024), with adenocarcinoma on intraductal papillary mucinous neoplasm of the pancreas (IPMN) (P=0.017), low grading (P=0.017), low lymph nodes ratio (P=0.002), low number of metastatic lymph nodes (P=0.001), absence of metastatic lymph nodes (P<0.001) had a statistical significant long disease-free survival. At multivariate analysis the only independent factors related to an increased risk of recurrence were high grading (OR 1.7 CI 95% 1-2.9; P=0.050) and the presence of metastatic node (OR 9.6 CI 95% 2.2-41.8 P=0.002). Conclusions: Grading and lymph nodes metastasis are the most important factors influencing local or distant recurrence after pancreatic resection for pancreatic ductal adenocarcinoma.