tbuckley/cabot-search huggingface dataset:
Review of efficacy and safety of the new oral anticoagulants (NOACS) in the treatment of venous thromboembolism in gastrointestinal (GI) oncology patients.
Authors: Hitendra Patel, Reem Diri, Ahmed Aljabri, Christopher Jon Campen, Emad Elquza, Steve Malangone, Ivo Abraham, Ali McBride
Journal: Journal of Clinical Oncology (2016)

761 Background: The occurrence of venous thrombosis (VTE) has been reported to increase the likelihood of death for cancer patients by 2- to 6-fold. Additionally, cancer patients have both a higher rate of VTE recurrence during oral anticoagulant therapy with warfarin and a higher anticoagulation-associated hemorrhagic risk as compared with non-cancer patients. New oral anticoagulants (NOACs) have administration and monitoring advantages treatment options for patients, however, there is limited data on the use of NOACs for cancer patients. Methods: We performed a single-institution retrospective review of electronic medical records of patients with GI cancer who received rivaroxaban with an active VTE diagnosis. Data collected included patient demographics, diagnosis, previous and active chemotherapy, previous history of VTE, and clinical outcomes. Results: Thirty-two patients were identified, with 28 patients concurrently treated with chemotherapy. Rivaroxaban was given to treat DVT = 23 patient and PE = 9 patients with average length of therapy 181 days. Forty-one percent of patients started on rivaroxaban, while 25% received enoxaparin, and 22% received warfarin prior to rivaroxaban. Overall, 13/32 (41%) patients experienced a bleeding episode; 7 patients had their dose held and 6 patients were noted to have minor bleeding. Conclusions: In our retrospective study, rivaroxaban did show efficacy in secondary prophylaxis for VTE in patients with active cancer. However our results revealed a rather high rate of bleeds in patients being treated with chemotherapy and rivaroxaban as compared to previous studies. [Table: see text]
Sisir Kumar Roy
Authors: John Scott
Journal: BMJ (2017)

Sisir Kumar Roy was born on 11 July 1926 in Jamshedpur, India. He was the eldest son of a physician who was active in the Indian independence movement. He started his higher education by studying engineering at Benares University but quit at the end of his first year. After a period of reflection, he realised that medicine was his vocation and enrolled in the RG Kar Medical College, Calcutta, from which he graduated in 1955. The following year he married Satyavathi, a fellow medical graduate. Together they came to Britain in 1957. For the following 10 years they undertook postgraduate training in London, Aberdeen, and Manchester. It was in Aberdeen that he had his …
Community survivorship program: Kansas Hope in the Valley program.
Authors: Cynthia Chauhan, Winston Tan
Journal: Journal of Clinical Oncology (2016)

34 Background: Patient run community based survivorship programs are rare; most are affiliated with clinics and hospitals. Aim: To highlight a community based non-hospital affiliated program that had operated successfully for 32 years and review their best practices and challenges. Methods: Data collected from Hope in the Valley support group program. In Wichita, Kansas there is a patient formed community based support group/survivorship program supported and operated privately by survivors. Results: Todate a total of 16 disease specific and 13 general cancer support groups are affiliated with the organization and all the services are housed in a building. The support groups meet in different places and are grouped according to their proximity to their residences. Services provided include lodging assistance, women's boutique, support group meetings, transportation, patient assistance program, and a hospitality center. Every new patient with cancer in the community was given a referral to the center. Cancer support groups include breast, gynecologic, lung, kidney, gastrointestinal, lymphoma, leukemia, adolescent, childhood and general cancer group. In 2014 67, 709 patients attended support groups meetings and 2000 patients attended between January- April 2015. The hospitality center had 20, 160 visits and 19,877 physician's office treatment visits were conducted in 2014. There are 3 full time staff, 7 part time staff and 200 volunteers run the organization. Challenges include recruitment of volunteers, funding for the organization, existing as an independent program from churches, hospital, clinics, or national organizations, public awareness of the program, the governance and structure of the organization. Details of the challenges and how their organization is run will be presented. Many of the patients used their services often give back as volunteers, facilitators and others. Conclusions: This is a survivorship program run by patients, actively addressing patients concerns and issues. This could provide a framework for future groups that want to form a community based patient centered cancer support group.
Second-look axillary ultrasound after breast MRI for enhanced preoperative nodal staging in newly diagnosed breast cancer patients.
Authors: Tina J. Hieken, Katie N. Jones, Judy Caroline Boughey, Sejal Shah, Katrina N. Glazebrook
Journal: Journal of Clinical Oncology (2013)

98 Background: Concomitant with widespread adoption of axillary ultrasound (AUS) with ultrasound-guided needle biopsy (USNB) of suspicious lymph nodes (LN) for preoperative nodal staging of breast cancer patients, utilization of breast MRI, which includes axillary imaging, has increased. Little is known about the added value of MRI imaging of the axilla in this context. We undertook this study to assess the role of breast MRI in preoperative axillary nodal staging. Methods: We studied 988 consecutive invasive breast cancers in patients undergoing primary operation including axillary surgery, without neoadjuvant therapy, from 2010-2011. Results: 505 patients (51%) underwent MRI of which 168 (33%) demonstrated suspicious findings in the axilla. Abnormal axillary MRI findings included cortical thickening, edema, enhancement, hilar effacement, and/or altered shape and size. 114 patients had findings concordant with AUS. 54 patients had suspicious LNs on MRI either without a preceding AUS (33 cases) or after an initially negative AUS (21 cases). Second look AUS was performed in 29 of these cases and was abnormal in 3 (10%) in whom USNB confirmed metastatic adenopathy. Of the 54 cases with MRI-detected suspicious LNs 20 (37%) were node positive at operation with a pN stage of N0 (63%), N0i+ (5%), N1mic (4%), N1 (20%), N2 (6%), N3 (2%); extranodal extension was seen in 7 of 20 node-positive patients (35%). Conclusions: Second look AUS, when performed secondary to suspicious axillary MRI findings, identified LN metastasis preoperatively in 10% of patients. When MRI is done to evaluate the breast in newly diagnosed breast cancer patients, axillary findings can enhance the accuracy of preoperative nodal staging. We recommend second look AUS when MRI demonstrates suspicious axillary LN findings. [Table: see text]
The effect of the immunomodulatory peptide gamma-D-glutamyl-L-tryptophan in leukemia, lymphoma, and head and neck cancer xenograft models.
Authors: C. W. Tuthill, J. Papkoff, B. A. Watkins, S. T. Sonis
Journal: Journal of Clinical Oncology (2011)

5592 Background: Gamma-D-glutamyl-L-tryptophan (SCV-07) is being studied for attenuation of oral mucositis in head and neck cancer patients receiving chemoradiation therapy. A challenge for agents which target regimen-related toxicities is to provide clinical benefit without detracting from the anti-tumor effects of the cancer therapy. Results of animal studies showed that SCV-07 decreased tumor growth in various xenograft models and did not alter the tumoricidal effect of radiation. Here we further describe SCV-07’s anti-tumor efficacy. Methods: Mice were inoculated with cell lines from the ATCC: EL-4 murine T cell lymphoma in C57/B6 mice; MOLT-4 human acute lymphoblastic leukemia, HL-60 human acute promyelocytic leukemia, and FADU human HNC in nude mice. When tumors reached 100 mm3, animals were treated daily with saline or various doses of SCV-07. Tumor size was measured every two days with micro-calipers; animals were weighed every day to assess possible toxicity. Any animal exhibiting a loss of >20% of starting weight or whose tumor grew to 1500 mm3 was euthanized. Statistical differences between treatment groups were determined using Mann-Whitney Rank Sum or ANOVA tests with a critical value of 0.05. Results: No animal deaths occurred as a direct result of SCV-07 treatment and no statistically significant differences in weight gain were seen between the SCV-07 and control groups. Tumors in SCV-07-treated animals grew more slowly than those in control animals; the reduction was dose-dependent and statistically significant. For EL-4 differences were seen in the groups treated with SCV-07 at 20 mg/kg (p=0.001) and 40 mg/kg (p<0.001); for MOLT-4 at10 mg/kg (p=0.003), 20 mg/kg (p=0.002) and 40 mg/kg (p<0.001); for HL-60 at 20 mg/kg (p=0.025) and 40 mg/kg (p=0.005); and for FADU at 20 mg/kg (p=0.004) and 40 mg/kg (p=0.004). Conclusions: The immune modulating peptide SCV-07 is able to inhibit growth of a variety of tumor cell line types, including a human head and neck tumor line in nude mice. These results suggest that the use of SCV-07 as an intervention for mucositis should not interfere with therapy, but may enhance the tumor response to conventional therapy.
Postoperative chemoradiation FOLFOX 4-based for R1 resected gastric cancer: A retrospective mono-institutional study.
Authors: Ferdinando De Vita, Michele Orditura, Maria Maddalena Laterza, Alessio Fabozzi, Beatrice Savastano, Jole Ventriglia, Luigi Marano, Guido Giordano, Angelica Petrillo, Erika Martinelli, Teresa Troiani, Floriana Morgillo, Natale Di Martino, Fortunato Ciardiello
Journal: Journal of Clinical Oncology (2014)

143 Background: Improved DFS and OS were seen in curatively resected patients (pts.) with gastric and gastroesophageal adenocarcinoma treated with the Int0116 protocol of postoperative adjuvant chemoradiotherapy compared to surgery alone. However, there are very limited data about the efficacy of this approach in pts. with R1 resection. To evaluate the efficacy of a combined chemoradiation regimen in this setting, we reviewed our case records from 43 pts. with R1 resection treated between May 2008 and July 2012. Methods: 43 pts. with histologically confirmed gastric adenocarcinoma, received combined adjuvant chemotherapy with FOLFOX-4 for 8 cycles and concomitant radiotherapy (45 Gy in 25 daily fractions over 5 weeks). Radiotherapy was begun after 2 cycles of CT, (reduced by 20% during the period of concomitant radiotherapy). Pts. were followed at 3-month intervals for 2 years, at 6-month intervals for the next 3 years and yearly thereafter. Results: The median age was 62 years (range, 22-74) and the majority of pts. (76.7%) were males. Tumor location was equally distributed in the stomach. Most of the patients had locally advanced disease: 93% had T3-4 tumors and 74.4% had lymph node involvement. There was no treatment related death. Gastrointestinal G3 toxicity was observed in 11.6% of pts., while haematologic G3-4 toxicity was observed in 9.3%. Experienced toxicities led to chemotherapy dose reductions in 9 pts. and dose delay in 11 patients; 7 pts. had a delay in radiotherapy. With a median follow-up of 36 months (range 2-49) for the 43 R1 pts., 74.4% died of gastric cancer, 11.6% are alive with no evidence of recurrence and 13.9% are alive with disease. 66.6% of the relapses in this group occurred at distant sites and 33.3% were locoregional. The estimated 3-year OS was 19%. The median DFS was 14.5 months and the median OS was 16 months. Conclusions: These results seem to imply some benefit for the postoperative treatment, as nearly 19% of the R1 pts. in our study remained free of recurrence at 3 years from surgery. In the absence of phase III data and consequently lack of clear guidelines in this setting, our results support the common practice of adding postoperative chemoradiation after R1 gastrectomy.
Phase Ib trial of combining aldoxorubicin plus doxorubicin.
Authors: Kamalesh Kumar Sankhala, Sant P. Chawla, Victoria S Chua, Doris Quon, Allison Bonk, Vivek Narasimhan, Monish Sodhi, Nina Krishna, Hillary Dinh, Scott Wieland, Daniel Levitt
Journal: Journal of Clinical Oncology (2013)

2550 Background: Aldoxorubicin is a novel drug that covalently binds to albumin in the circulation with release in low pH environments. Preclinical studies in pancreatic and ovarian tumor xenograft models demonstrated that aldoxorubicin plus doxorubicin administered at 50% of their MTD provided complete and prolonged tumor remission in these models with less toxicity than each drug administered at their MTD. We evaluated the toxicity profile of a fixed dose of doxorubicin and escalating doses of aldoxorubicin in subjects with advanced solid tumors. Methods: Phase 1b open label, dose-escalation study of aldoxorubicin administered at either 175, 240 or 320 mg/m 2 (130, 180, or 240 mg/m 2 doxorubicin equivalents) iv + 35 mg/m 2 doxorubicin iv, both on Day 1 of 21 day cycles, for up to 8 cycles. The MTD is the dose level immediately below where 2/6 subjects experience a dose limiting toxicity (DLT) , or the maximum dose of 320 mg/m 2 aldoxorubicin. Additional subjects may be enrolled at the MTD to provide more safety data. Results: 10 subjects have been treated as of January 21, 2013. No DLT was observed and the MTD was defined as 320 mg/m 2 aldoxorubicin and 35 mg/m 2 doxorubicin iv administered on Day 1 of 21 day cycles. A median of 4.5 cycles have been received. 3/10 subjects were terminated due to either progressive disease (2) or death (1). No subject was terminated due to an adverse event. Grade 3 or 4 neutropenia was seen at all dose levels (8/10 subjects). 4/10 subjects exhibited grade 3 or 4 thrombocytopenia and 3/10 subjects had grade 3 or 4 anemia. Neutropenic fever occurred in 3/10 subjects. Other grade 3/4 adverse events seen in 2 or fewer subjects included fatigue, increased liver enzymes and dehydration. No significant mucositis or cardiotoxicity was observed. At this time the best response has been stable disease in 6/10 subjects and a partial response in 1 subject (malignant fibrous histiocytoma). Conclusions: The combination of aldoxorubicin (320 mg/m 2) ) + doxorubicin (35 mg/m 2 ) can be safely administered to subjects with solid tumors. Hematologic toxicity is common and can be controlled with growth factors. The dose of aldoxorubicin is 90% of the MTD of aldoxorubicin administered as a single agent. Thus, doxorubicin does not appear to add to the toxicity of this combination. Clinical trial information: NCT01673438.
Phase I-II trial of TLK286, a novel glutathione analog prodrug, in combination with carboplatin (C) and paclitaxel (P) as first-line treatment for advanced non-small cell lung cancer (NSCLC)
Authors: L. V. Sequist, P. Fidias, J. Temel, B. A. Kennedy, P. A. Ostler, M. S. Rabin, M. Huberman, J. Keck, G. L. Brown, T. J. Lynch
Journal: Journal of Clinical Oncology (2005)

7275 Background: TLK286 is a novel glutathione analog prodrug activated by glutathione S-transferase P1–1 that induces apoptosis via the stress response pathway. Pre-clinical data demonstrate that TLK286 is active against tumors that exhibit resistance to C and P and that the triplet TLK286/C/P is synergistic. Methods: The objectives of this phase I-II study are to determine the maximum tolerated dose (MTD), dose-limiting toxicities (DLTs), and overall response rate (ORR) of TLK286/C/P in chemotherapy-naïve patients (pts) with advanced NSCLC. A cohort-based dose-escalation treatment with planned doses of TLK286 of 400, 500, 750 or 1000 mg/m2 combined with standard doses of C (AUC 6) and P (200 mg/m2) intravenously every 3 weeks until tumor progression or unacceptable toxicity is ongoing. DLTs are assessed on day 21 and are defined as any ≥ grade 3 non-hematologic toxicity or ≥ grade 4 hematologic toxicity persisting to day 21. If ≥ 2 pts have a DLT within a dose level, that level will be the MTD and will be further examined in the phase II portion. Tumor response is assessed for each pt after every 2 treatments. Results: At interim analysis, 9 pts (4 M, 5 F), median age 63 (range 43–74), have been treated at 3 dose levels and have received 32 cycles (median 4 cycles/pt, range 2–6). No DLTs have been observed. The MTD has not been reached. The most common toxicities observed have been grade 1–2 alopecia, anemia, thrombocytopenia and myalgias. 2 pts had grade 3–4 neutropenia that resolved before the next cycle was due. No febrile neutropenia or unexpected toxicities were seen. Significant anti-tumor activity was observed in the first 8 pts with 5 partial responses, 2 stable disease, and 1 progression (ORR=63%). Conclusions: The combination of TLK286/C/P has been well tolerated and has shown clinical activity in advanced NSCLC pts. Accrual continues at the 1000mg/m2 dose level, and expansion of the MTD into a phase II study to further assess the efficacy of the combination will be performed. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Telik Telik Telik
Integrative model for breast cancer survivorship.
Authors: Raquel E. Reinbolt, Charles L. Shapiro, Julia Garrett, Heidi Basinger, Joanne L. Lester, Nicole Muscari, Kathleen Ries, Maryam B. Lustberg
Journal: Journal of Clinical Oncology (2013)

132 Background: Efforts to better address needs of survivors, summative care plans, and point of delivery are ongoing at academic, research, and community institutions. Lacking are empiric data to support one method over another. Methods: A quasi-experimental approach was used to measure a multidisciplinary integrative care model that involved the primary nurse, nurse practitioner, and medical oncologist to determine the best time, method, and application of cancer survivorship care planning. A concomitant cross-sectional study was ongoing in which patients completed the Distress Thermometer (0-10 analog score) plus a problem list (34 items) in early survivorship (e.g. during treatment, at its end, at 3- and 6-months later). Results: As a result of our teamwork, data from the electronic medical record (EMR) was integrated into end-of-treatment summaries and care plans; ‘smart-phrases’ provided links to personalized patient data which resulted in individualized care plans. The average self-reported distress level in early survivorship was 4.8, indicating a moderate to severe level of distress. Patients stated practical problems (e.g. finances, work) were of highest concern, followed by physical symptoms (e.g. fatigue, aches/pains), then emotional and family issues were prime distressors. The integrative model allowed our work teams to provide personalized services with a greater understanding of each individual patient. Data is presently being collected to quantify these services. Through this multidisciplinary approach, team-driven initiatives, and EMR integration, the preparation, delivery and follow up required for survivorship encounters was greatly streamlined. Conclusions: An integrative care model that is linked to the electronic medical record provides personalized care in a timely manner that is neither time nor resource intensive. We ‘listened’ to our patients and have diligently worked to increase and expand resources. Future initiatives include group educational sessions, earlier discussion of survivorship goals, and treatment summary generation at diagnosis. We believe this model will serve as the foundation for survivorship care expansion in our breast program, and can potentially be generalized to other institutions.
Panitumumab treatment of head and neck cancer after cetuximab-induced aseptic meningitis: Case report.
Authors: C. E. Riggs
Journal: Journal of Clinical Oncology (2011)

e16033 Background: Aseptic meningitis is a rare complication of the initial, loading-dose infusion of cetuximab, with 4 reported cases (2 lung cancer, 2 head/neck cancer.) Re-treatment with cetuximab at standard, lower weekly dosage with corticosteroid preparation was possible in 2 cases. Methods: I report a 54 y.o. man with risperidone-controlled Tourette syndrome, who presented for initial loading dose of cetuximab for stage IV-A, HPV-positive squamous cell carcinoma of left base of tongue, as part of definitive IMRT radiation treatment plan. Hydrocortisone was added to ranitidine-diphenhydramine premedication to lessen chances of adverse neurological reaction. He received standard cetuximab loading dosage of 400 mg/m2 by 90-minute intravenous (i.v.) infusion. Results: The initial test and loading infusions of cetuximab were uneventful. Sixteen hours later, he developed headache, nausea, fevers, photophobia, and blurred vision. Imaging by CT and MRI of brain revealed no hemorrhage, edema, leptomeningeal enhancement, or metastases. Lumbar puncture yielded clear, colorless fluid with 661 nucleated cells/µl (97% neutrophils), no red blood cells, glucose 94 mg/dl, and protein 74 mg/dl. He received empiric antibiotics and antiviral therapy for 3 days. Cultures of spinal fluid and blood were negative. He defervesced and symptoms returned to baseline in 2 days. Radiation therapy was initiated 5 days later, and he received i.v. panitumumab, 3 mg/kg/week, with the same premedications, as adjuvant beginning on day 1 of definitive radiation. There were no further neurological, anaphylactic, or allergic events during therapy. He did develop typical eczematoid skin rash during therapy. Response status is pending. Conclusions: Panitumumab was an effective, safe adjuvant systemic therapy in this man with severe neurological reaction to cetuximab. This agent is currently under investigation as adjuvant with definitive radiation therapy for head and neck cancers, and appears to be a safe alternative to cetuximab in this setting. Possible mechanisms for this phenomenon will be presented.
Perioperative management of pancreatoduodenectomy patients: Are North American practices any different? A survey involving IHPBA/AHPBA members.
Authors: Sandeep Anantha, Fransisco Igor Macedo, Alice J Race, Awinderpreet Singh, Janak A Parikh, Vijay K Mittal, Michael J Jacobs
Journal: Journal of Clinical Oncology (2016)

447 Background: Pancreatoduodenectomy is performed worldwide with significant variations in the perioperative management. The aim of this study is to evaluate the practice patterns across regions of the world. Methods: A pilot cross-sectional 25-item survey questionnaire was electronically distributed using Survey Monkey to IHPBA and AHPBA members between May and August 2015 regarding practice patterns and perioperative care of patients undergoing pancreatoduodenectomy. Results: A total of 285 responses were obtained. The majority of participants were from United States (34.7%), Europe (28.1%) and Asia (14.3%). North American (NA) surgeons are less likely to culture intraoperative bile (36.5% vs. 53.1%, p&lt;0.02), routinely check postoperative drain amylase (80.5% vs. 91.3%, p&lt;0.03) or irrigate the wound with Betadine solution (7.7% vs. 29.1%, p&lt;0.001) as compared to European members. Overall, NA surgeons are more likely to use 1 drain (46.3% vs. 88.7% other regions (2 drains), p&lt;0.001), limit the prophylactic antibiotic use within 24 hours of surgery (70.1% vs. 68.5%, p&lt;0.001) and do not culture drain fluid routinely (91.5% vs. 67.1%, p&lt;0.001). Conclusions: Our survey evaluated a wide range of practice patterns globally amongst surgeons performing pancreatoduodenectomy. North American surgeons do not routinely check for amylase rich fluid in the drains, utilize one drain routinely when compared to European surgeons. Further studies are warranted to evaluate if these variations translate into impacts upon surgical outcomes on patients undergoing Whipple operation.