tbuckley/cabot-search huggingface dataset:
Characteristics of long-term survivors in a randomized phase III trial (NAPOLI-1) of patients with metastatic pancreatic ductal adenocarcinoma (mPDAC) treated with liposomal irinotecan (nal-IRI; MM-398) + 5-FU/LV.
Authors: Andrea Wang-Gillam, Chung-Pin Li, Gyorgy Bodoky, Andrew Dean, Kyung-Hun Lee, David Cunningham, Richard Hubner, Jens T. Siveke, Fadi S. Braiteh, J. Marc Pipas, Bruce Belanger, Floris de Jong, Purvi D. Mody, Li-Tzong Chen, Daniel D. Von Hoff
Journal: Journal of Clinical Oncology (2017)

293 Background: nal-IRI, a liposomal formulation of irinotecan, plus 5-FU/LV is approved in the United States and Taiwan for patients (pts) with mPDAC previously treated with gemcitabine-based therapy. Primary analysis of the NAPOLI-1 trial (NCT01494506) showed that nal-IRI+5-FU/LV significantly improved median overall survival vs 5-FU/LV (6.1 vs 4.2 months; HR, 0.67; 95% CI, 0.49-0.92; P = 0.012; Wang-Gillam et al, Lancet. 2016). Herein we report baseline characteristics of pts surviving ≥1 year (data cutoff, Nov 2015). Methods: This analysis includes 117 pts assigned to treatment with nal-IRI 70 mg/m 2 (free base) + 5-FU/LV 2400/400 mg/m 2 q2w, and 119 pts assigned to treatment with 5-FU/LV 2000/200 mg/m 2 weekly for weeks 1-4 q6w. Results: A total of 29 (25%) pts in the nal-IRI+5-FU/LV arm and 17 (14%) in the 5-FU/LV arm survived ≥1 year. These pts typically had better performance status, lower CA19-9 (U/mL) levels, and were less likely to have liver metastases at baseline, compared with the overall population (Table). For long-term survivors in the nal-IRI+5-FU/LV arm, a higher proportion of pts had neutrophil-to-lymphocyte ratio (NLR) &gt;5, a marker of poor prognosis, suggesting that higher NLR may potentially be predictive of survival outcome with nal-IRI+5-FU/LV. Conclusions: More pts receiving nal-IRI+5-FU/LV versus 5-FU/LV were alive beyond 1 year. The most prominent prognostic markers of survival ≥1 year included lower CA19-9, KPS ≥90 and absence of liver metastases. These analyses may be limited by small sample sizes. Clinical trial information: NCT01494506. [Table: see text]
Can MRI accurately identify which patients with operable breast cancer will have a pathologic complete response after neoadjuvant therapy?
Authors: Carolyn Nessim, Isabelle Trop, Andre Robidoux, Eleftherios P Mamounas, Jean-Francois Boileau
Journal: Journal of Clinical Oncology (2012)

616 Background: With the introduction of targeted therapy based on tumor subtypes, an increasing number of patients that receive neoadjuvant chemotherapy achieve a pathologic complete response (pCR). Previous studies have shown that the accuracy of MRI is poor at predicting the response to neoadjuvant chemotherapy in locally advanced and often non-resectable breast cancers, where the rate of pCR is low. The purpose of this study is to evaluate MRI’s ability to predict a pCR in operable breast cancers after neoadjuvant therapy. Methods: All patients enrolled in the NSABP B-40, B-41, FB-5 and FB-6 protocols in a single tertiary care centre, that had an MRI done before and after neoadjuvant therapy were reviewed. A radiologist, blinded to the pathology results, interpreted the pre- and post- treatment MRI’s and made a prediction as to whether or not patients would have a pCR. In this study, a true negative was defined as a reading of a complete response on MRI that was confirmed as a pCR on final pathology. pCR was defined as having no residual invasive or in situ disease in the breast. Results: 129 women with a median age of 51 years were identified. 90% had invasive ductal carcinoma; 8% had invasive lobular. 58% were ER+, 21% were triple negative and 21% were Her2+. 16% of patients had a pCR. 25% of patients had no residual invasive cancer in the breast. pCR rates for ER+ tumors was 5%, triple negative 37%, and Her2+ 26%. 19% of patients that had a pCR had a total mastectomy. The sensitivity and specificity of MRI for predicting residual disease were 88% and 52% respectively. The positive predictive value was 90% and the negative predictive value was 46% with an accuracy of 82%. Conclusions: MRI has limited value for determining which patients had a pCR after neoadjuvant chemotherapy, even in operable breast cancers. When residual disease is suspected on MRI, it is unlikely that a pCR has been achieved. Surgical excision following neoadjuvant therapy remains the gold standard to identify which patients have achieved a pCR. Other modalities will need to be used in order to accurately determine which patients would be eligible for studies evaluating non operative management following neoadjuvant therapy.
Pemetrexed and carboplatin in the treatment of malignant pleural mesothelioma (MPM)
Authors: M. Papi, G. Genestreti, D. Tassinari, E. Tamburini, S. Nicoletti, M. Nicolini, P. Fabbri, P. Fabbri, A. Santo, E. Pasquini, A. Ravaioli
Journal: Journal of Clinical Oncology (2007)

18114 Background. MPM is a poor prognosis disease, whose clinical negative outcome is due both to it’s aggressiveness and to the lack of active drugs for clinical practice. To assess activity and safety of pemetrexed-carboplatin combination in the treatment of MPM, an open trial has been recently concluded in our departments. Methods. All the consecutive patients with proven diagnosis of MPM admitted to our departments between 2003 and 2005 were considered eligible and enrolled into the trial. All the patients were treated with pemetrexed 500mg/m 2 and carboplatin AUC 5mg/ml/minute every 21 days until progression of disease or unacceptable toxicity. All the patients were treated with steroid prophylaxis, folinic acid and vitamin B12 supplementation. Results. 26 patients (18 chemotherapy-naive) were considered eligible and enrolled into the trial. 21 patients were male and 5 female; median age of the patients was 67 years (range 49–77). 22 patients were affected by locally advanced or extensive disease and the other 4 ones by localized disease. All the patients were valuable for response, toxicity and survival. Overall response rate was 19,3%, with 5 partial responses and no complete regression of the disease. A stable disease was observed in 7 patients (26.9%), with an overall disease control rate of 46.2%. 201 complete courses of chemotherapy was performed with a median number of 6 courses/patients. Toxicity was mild with grade 3/4 WHO neutropenia in 4 patients (15.3%), grade 3 anemia and thrombocytopenia in 2 patients (7.6%). No grade 3/4 non-hematological toxicity was observed along all the conduction of the trial. Median survival was 9,3 months, assessed with the Kaplan Meyer non-parametric test. Conclusions. Pemetrexed and carboplatin seem to represent an active and well tolerated schedule against MPM, confirming their priority role in the treatment of the disease; nevertheless, further trials are probably needed to improve the outcome of chemotherapy in this rare poor-prognosis disease. Supported by IOR No significant financial relationships to disclose.
The prognostic impact of surgical complications after combined modality treatment of rectal cancer: Long-term results of the CAO/ARO/AIO-94 trial.
Authors: Thilo Sprenger, Tim Beissbarth, Rainer Fietkau, Hans-Rudolf Raab, Werner Hohenberger, Torsten Liersch, Claus Rödel, Michael Ghadimi
Journal: Journal of Clinical Oncology (2017)

670 Background: The influence of major surgical complications on survival in patients with locally advanced rectal cancer undergoing combined modality treatment is still debatable. The aim of this study was to evaluate the impact of surgical complications on oncological outcome in 823 patients with locally advanced rectal cancer treated within the phase III CAO/ARO/AIO-94 trial. Methods: Anastomotic leakages as well as wound healing disorders were prospectively evaluated and correlated with overall survival (OS) and the cumulative incidence of distant metastasis and local recurrence after a long-term follow-up of more than 10 years. Results: Anastomotic leakage after restorative rectal resection is significantly correlated with an impaired 10-year OS (51.0% vs. 65.2%, p = 0.02). Patients with abdominal or sacral wound healing disorders had a significantly reduced OS compared to those with sufficient wound healing (45.2% vs. 62.7%, p = 0.009). Patients developing any surgical complication (anastomotic leakage or/and wound healing disorder) had an impaired OS (50.6% vs 65.3%, p = 0.0002) as well as higher rates of distant metastases (65.3% vs. 72.7%, p = 0.03) and local recurrences (6.0% vs. 12.9%, p = 0.0007). In a multivariate cox regression model the only independent factors for restricted OS were lymph node metastases (p &lt; 0.0001) and the occurrence of surgical complications (p = 0.008). Conclusions: Surgical complications are significantly associated with an adverse oncological outcome and reduced long-term OS in patients undergoing combined modality treatment for locally advanced rectal cancer.
A phase 2 study of vincristine and irinotecan in metastatic diffuse anaplastic Wilms tumor: Results from the Children’s Oncology Group AREN0321 study.
Authors: Najat C. Daw, James Robert Anderson, Fredric A. Hoffer, James I. Geller, John A. Kalapurakal, Elizabeth Jones Perlman, Peter F. Ehrlich, Elizabeth Anne Mullen, Eric J. Gratias, Paul Edward Grundy, Jeffrey S. Dome
Journal: Journal of Clinical Oncology (2014)

10032 Background: Patients with metastatic diffuse anaplastic histology Wilms tumor (DAWT) had an unacceptably low 4-year event-free survival (EFS) and overall survival of 33% on the National Wilms Tumor Study-5. Preclinical and clinical data showed promising antitumor activity of the camptothecins in Wilms tumor. Methods: AREN0321 evaluated the activity of vincristine (Vinc) and irinotecan (Irino) in a phase 2 window in newly-diagnosed patients with Stage IV DAWT. Patients received Vinc (1.5 mg/m2/day) intravenously (IV) on days 1 and 8, and Irino (20 mg/m2/day) IV on days 1-5 and 8-12 of a 21-day cycle. In the absence of progressive disease (PD), a second cycle was administered. Tumor responses after 2 cycles of therapy were centrally reviewed and assessed using the RECIST criteria. Patients with partial response (PR) had Vinc/Irino incorporated into a chemotherapy regimen consisting of Vinc, doxorubicin, cyclophosphamide, carboplatin, and etoposide, plus local and whole lung radiation therapy. Patients with stable disease or PD did not receive additional cycles of Vinc/Irino. A 2-stage design was used with the aim to accrue 10 patients in the first stage and continue accrual if an adequate number of responses was observed. The window study closed after other strata of AREN0321 reached their accrual targets. Results: Twenty-four patients with stage IV DAWT were enrolled from June 2006 to December 2012. Five patients did not have measurable disease and were ineligible for window therapy. Nineteen had measurable disease, 14 of whom elected to participate in the window. Of these 14 patients, 11 (79%) had PR and 3 had PD. Two of the 3 non-responders also did not achieve complete response to the other agents in the chemotherapy regimen. The most common grade 3-4 toxicities during the window were diarrhea (n=3), hypoxia (n=2), elevation of aspartate aminotransferase (n=2), hypoalbuminemia (n=2), and hyperglycemia (n=2). Conclusions: The Vinc/Irino combination was well tolerated and produced a high response rate in patients with metastatic DAWT. Its incorporation into Wilms tumor treatment regimens deserves further evaluation. Clinical trial information: NCT00335556.
A feasibility and phase II study of the hu14.18-IL2 immunocytokine in combination with GM-CSF and isotretinoin in patients with recurrent or refractory neuroblastoma: A Children’s Oncology Group study.
Authors: Suzanne Shusterman, Wendy B. London, Jacquelyn A Hank, Marguerite T Parisi, Barry L. Shulkin, Sabah-E-Noor Servaes, Arlene Naranjo, Hiroyuki Shimada, Jacek Gan, Stephen Gillies, John M. Maris, Julie R. Park, Paul M. Sondel
Journal: Journal of Clinical Oncology (2015)

10017 Background: Combining anti-GD2 (disialoganglioside) monoclonal antibody with GM-CSF, IL2 and isotretinoin is now standard of care for high-risk neuroblastoma (NB) minimal residual disease (MRD) therapy. The humanized anti-GD2 antibody conjugated to IL2 (hu14.18-IL2) has clinical activity in NB and is more effective in NB-bearing mice than antibody and cytokine given separately. We therefore evaluated the safety, tolerability and anti-tumor activity of hu14.18-IL2 given with GM-CSF and isotretinoin in a schedule similar to current MRD therapy. Methods: Hu14.18-IL2 was given at the phase II dose (12 mg/m2) on days 4-6 of a 28 day cycle with GM-CSF (250 μg/m2/dose, days 1-2, 8-14) and isotretinoin (160 mg/m2/day, days 11-25). Tolerability was determined based on the number of patients who developed an unacceptable toxicity (required pressor support or intubation). Response was evaluated every 2 cycles for patients with disease measurable by standard radiologic criteria (stratum 1), and for patients with disease evaluable only by MIBG and/or bone marrow histology (stratum 2). Disease burden was described in stratum 2 patients based on Curie scoring. Results: Fifty-two patients were enrolled on study; 51 were evaluable for toxicity and 44 were evaluable for response. Four patients had unacceptable toxicities, well below the protocol-defined rule for safety. Other grade 3 and 4 non-hematologic toxicities were reversible and expected based on prior trials. No responses were seen in stratum 1 (n = 14). In stratum 2 (n = 30), 7 responses were confirmed by central review (5 CRs and 2 PRs). The median baseline Curie score of the responders was 2 compared to 10 for non-responders (Wilcoxon rank-sum two-sided p-value = 0.0345). Conclusions: Hu14.18-IL2 given with GM-CSF and isotretinoin is safe and tolerable. Patients with only MIBG and/or bone marrow disease had a 23% response rate, confirming activity of the combination. Responders had a significantly lower disease burden than non-responders at study entry. These data support further study of hu14.18-IL2 in high-risk NB patients with MRD or a relatively low disease burden. Clinical trial information: NCT01334515.
Rhenium-188 HEDP for the palliation of painful bone metastases
Authors: M. Tian, H. Zhang, S. Li, K. Endo, S. Tanada
Journal: Journal of Clinical Oncology (2004)

8151 Background: Rhenium-188 hydroxyethylidine diphosphonate (HEDP) is a new and attractive radiopharmaceutical that localizes in skeletal metastases and emits beta particles that may be therapeutically beneficial. In this study, the therapeutic efficacy of Re-188 HEDP was investigated in an initial trial of 61 patients with different types of advanced cancer for the palliation of painful bone metastases. Methods: Sixty-one patients with painful bone metastases of lung, prostate, breast, renal, rhinopharyngeal, and bladder cancers were treated with 1.1 GBq (31 mCi) to 6.9 GBq (188 mCi) Re-188 HEDP. After treatment, the patients were followed at weekly intervals for the first 2 months and monthly thereafter for as long as 1 year. Hematologic function tests were also performed before and after treatment for 6 weeks. Pain responses were scored according to a three-point pain-rating scale as complete, significant, and minimal. Results: Prompt and significant relief of bone pain occurred in 80% of patients overall. Of the specific tumor types, pain relief was achieved in 77% of patients with lung cancer, in 80% with prostate cancer, in 83% with breast cancer, in 100% with bladder cancer, in 50% with renal cancer, in 50% with rhinopharyngeal cancer, and in 87% of patients with other tumor types, with no severe side effects or hematopoietic toxicity. Conclusions: This clinical study indicated that 188Re-HEDP can offer significant pain palliation and is a useful radiopharmaceutical agent to treat painful bone metastases from various tumor types. No significant financial relationships to disclose.
Final results of a phase 1 study of single-agent veliparib (V) in patients (pts) with either BRCA1/2-mutated cancer (BRCA+), platinum-refractory ovarian, or basal-like breast cancer (BRCA-wt).
Authors: Shannon Puhalla, Jan Hendrik Beumer, Shalu Pahuja, Leonard Joseph Appleman, Hussein Abdul-Hassan Tawbi, Ronald G. Stoller, James J. Lee, Yan Lin, Brian Kiesel, Jing Yu, Antoinette R. Tan, Chandra Prakash Belani, Helen K. Chew, Agustin A. Garcia, Robert Morgan, Vincent L. Giranda, Stacie Peacock Shepherd, Alice P. Chen, Edward Chu
Journal: Journal of Clinical Oncology (2014)

2570 Background: Veliparib (V) (ABT-888) is a potent, oral PARP 1/2 inhibitor with preclinical and clinical efficacy in BRCA+ malignancies. As there are known similarities between BRCA+ cancers, serous ovarian cancer, and basal-like breast cancer, we postulated potential for V activity in these groups also. We sought to establish the maximum tolerated dose (MTD), dose-limiting toxicities (DLT), pharmacokinetic (PK) and pharmocodynamic properties, and preliminary efficacy of chronically-dosed V. Methods: A 3+3 dose-escalation phase I trial was performed. Nine dose levels ranging from 50 mg BID to 500 mg BID dosed continuously were enrolled to determine a maximum tolerated dose (MTD) and recommended phase II dose (RP2D). A biopsy cohort in BRCA+ patients was enrolled at the RP2D. Correlative studies included assessment of BRCA reversion mutation analysis, DNA repair pathway analysis, and BRCA promoter methylation status. Results: A total of 88 pts (60 BRCA+ and 28 BRCA-wt) were enrolled to date. DLTs occurred at the following dose levels: BRCA+: gr 3 nausea/vomiting at 400 mg BID, gr 2 seizure at 500 mg BID; BRCA-wt: gr 2 seizure at 400 mg BID. The RP2D was established at 400 mg BID. The most common all-grade toxicities were nausea, fatigue, and lymphopenia. PK was linear and non-saturable with t ½ of 5.2 h. Fifty-two BRCA+ patients (28 ovary, 13 breast, 11 other) were evaluable for response. In BRCA+ patients at all dose levels, the ORR (CR+PR) was 23% with a clinical benefit rate (CBR; CR + PR + stable disease) of 58%. At the MTD and RP2D, 28 BRCA+ patients were evaluable, with an ORR of 40%, and a CBR of 68%. Twenty-four BRCA-wt pts (21 breast and 3 ovary) were evaluable for response, and the ORR was 4% with a CBR of 38%. Conclusions: Single-agent V is well-tolerated with evidence of anti-tumor activity seen in both BRCA+ and BRCA-wt tumors comparable to other single agent PARP inhibitors. Evidence of potential dose responsiveness was observed. Correlative studies from archival tissues and mandatory biopsy cohort, with final data to be presented, will provide early insights on potential mechanisms of response and resistance. Clinical trial information: NCT00892736.
LIGADURA ENDOSCOPICA CON BANDAS COMO TRATAMIENTO DE ECTASIA VASCULAR ANTRAL: EXPERIENCIA EN NUESTRO CENTRO
Authors: LA Castillo Herrera, ML Arias Rivera, EM Fernandez-Marcote Menor, M Perez Ferrer, JL Martinez Albares, LR Rabago Torre
Journal: Endoscopy (2015)

Introducción: La ectasia vascular antral gástrica (GAVE) se asocia a enfermedades autoinmunes, hematológicas, IRC y cirrosis. Se presenta como anemia ferropénica y menos veces por hemorragia digestiva. Su tratamiento fundamental es endoscópico mediante técnicas ablativas de los capilares ectásicos. La ligadura antral con bandas (LEB) ofrece resultados prometedores.
Prognostic impact of peripheral blood counts in patients with non-metastatic clear cell renal cell carcinoma.
Authors: William Adam Hammond, Daniel Lewis, Lauren Hassan, Daniel Serie, Thai Huu Ho, Jeanette Eckel-Passow, Bradley C. Leibovich, Robert Houston Thompson, John C. Cheville, Alexander S. Parker, Richard Wayne Joseph
Journal: Journal of Clinical Oncology (2015)

e15590 Background: Peripheral blood counts (PBC) such as anemia and elevated platelets are associated with a worse prognosis in patients (pts) with metastatic clear cell renal cell carcinoma (ccRCC). The association of PBC in patients with non-metastatic ccRCC remains unclear. We performed a retrospective analysis to assess the impact of PBC on RCC-specific survival (RCC-SS) and relapse free survival (RFS). Methods: We abstracted available PBC values within 30 days of nephrectomy for all pts enrolled in the Mayo Clinic Renal Registry from 1990-2009 treated for localized (M0) ccRCC. PBC values included hemoglobin (HGB), white blood cell (WBC), absolute neutrophil count (ANC), absolute lymphocyte count (ALC), absolute eosinophil count (AEC), absolute monocyte count (AMC), and platelets (PLT). To correct for skewed data, we transformed PBC values via the square root transform. We analyzed the correlation of PBC values with both RFS and RCC-SS using age-adjusted Cox regression models. We then assessed the independent prognostic value of PBC after further adjusting for the validated Mayo SSIGN score that incorporates tumor size, stage, grade, and tumor necrosis. Results: Of 1,657 pts in the renal registry, 1,265 (76.3%) had available PBC from the time of diagnosis. PBC strongly associated with the Mayo SSIGN score. Prior to adjusting for the Mayo SSIGN score, all PBC associated with both RCC-SS and RFS. After adjusting for the Mayo SSIGN score, no PBC values remained significant in terms of RCC-SS and low ANC remained minimally associated with decreased RFS (see Table). Conclusions: PBC values strongly associate with the Mayo SSIGN score but predictably do not add independent prognostic information. Given this association, improved understanding of how ccRCC influences PBC could lead to novel therapeutic options. Marker Prior to adjusting for SSIGN After adjusting for SSIGN RCC-SS RFS RCC-SS RFS HR P HR P HR P HR P HGB 0.18 <0.001 0.25 <0.001 0.97 0.89 1.29 0.17 WBC 1.17 0.004 1.17 0.003 1.04 0.61 0.97 0.73 PLT 1.16 <0.001 1.13 <0.001 1.00 0.68 0.99 0.32 ANC 1.72 <0.001 1.44 <0.001 0.96 0.79 0.71 0.02 ALC 0.40 0.001 0.45 <0.001 0.84 0.54 0.81 0.37 AMC 5.89 <0.001 4.12 <0.001 1.33 0.57 0.89 0.76 AEC 0.39 0.030 0.45 0.033 0.74 0.49 0.71 0.36
Patient expectations from systemic treatment of metastatic prostate cancer (mPC).
Authors: Kelvin A. Moses, David F. Penson, Liping Du, Ivy Ahmed, Alicia Katherine Morgans
Journal: Journal of Clinical Oncology (2017)

218 Background: Multiple systemic therapies prolong the survival of men with mPC, but the disease remains incurable. High-quality treatment decisions require an informed understanding of the purpose of treatment and expected risks and benefits, particularly because cancer patients may accept otherwise unacceptable treatment if they believe there is a ≥ 1% chance of cure. Reconciling patient expectations with expected outcomes of providers is necessary to prevent treatment with toxic therapies that patients would refuse if cure were not possible. We assessed patient expectations from treatment among men receiving systemic therapy for mPC. Methods: Between 6/1/15 and 9/29/16, men with mPC completed surveys defining expectations of cure from their current mPC treatment. We used frequencies and relative frequencies to describe expectations, and proportional odds models with robust standard errors to assess the association between expectations, optimism, clinical characteristics, and sociodemographic factors. Results: Among 96 men completing surveys, 32 (33%) reported that cure was at least a little likely (8% very likely, 14% somewhat likely, and 11% a little likely). Higher optimism scores were associated with higher expectations of cure (adjusted OR 2.5, 95% CI 1.3-4.8 for most versus least optimistic), and non-white race was associated with lower expectations of cure as compared with white patients (adjusted OR 0.08, 95% CI 0.02 – 0.3). Report of excellent or good overall health was associated with greater odds of expecting cure than report of fair or poor health (adjusted OR 13, 95% CI 1.3 – 125). Marital status and age were not associated with expectations. Conclusions: Up to 1/3 of men with mPC receive treatment with an expectation that it may cure their cancer. Men with greater optimism and better reported health status have greater odds of expecting cure. Actions to align patient and physician expectations are necessary to adequately counsel patients and avoid overtreatment with toxic therapies.