tbuckley/cabot-search huggingface dataset:
Activity of MVA 5T4 alone or in combination with either interleukin-2 (IL-2) or interferon-α (IFN) in patients (Pts) with metastatic renal cell cancer (MRCC)
Authors: A. Cao, J. Hernandez-McClain, J. Willis, R. Harrop, W. Shingler, P. Chikoti, N. Drury, R. Amato
Journal: Journal of Clinical Oncology (2007)

3069 Background: MVA 5T4 consists of the highly attenuated modified Vaccinia Ankara virus containing the gene encoding the human TAA 5T4. Ninety percent or more of RCCs overexpress the 5T4 antigen. A series of clinical trials were conducted to evaluate the effectiveness of MVA 5T4 as a single agent or in combination with Interleukin-2 or Interferon Alpha 2B. Methods: Eligibility: pathologic diagnosis of clear cell or papillary RCC, progressive measurable metastases, any prior therapy, adequate physiologic parameters, Karnofsky performance status (KPS) = 80%, and no active CNS involvement. A regimen of MVA 5T4 alone or in combination with IFN or IL-2 was given. Results: A total of 41 patients received MVA 5T4 alone or in combination. 33 patients received MVA 5T4 with low dose IL-2 or IFN. 23 pts had clear cell; 12 papillary; 5 mixed clear cell; and 1 mixed papillary. 19 pts continue to receive therapy. 2 pts (both clear cell RCC) developed complete responses, 3 pts/partial responses (2 clear cell, 1 papillary) 8 pts/stable for 3+months and 6 pts are too early to be staged at this time. Median duration of therapy is 3.0+ (1+-13+) months. Conclusion: Although comparable antibody response were observed in papillary and clear cell histotypes, clear cell patients appeared to be more likely to respond in terms of clinical benefit parameters, to be presented. Of note is that preliminary analysis of clear cell patients suggests a relationship between the anti-5T4 immune response and tumor response. With the immunological potency and encouraging clinical activity, the future research will focus on the phase 3 randomized, double-blind, placebo controlled parallel group study to investigate whether MVA 5T4, added to first line standard of care therapy, prolongs the survival of patients with locally advanced or metastatic clear cell as well as studies to further optimize MVA 5T4 potency. [Table: see text]
Prognostic relevance of lymphocytopenia, monocytopenia and lymphocyte-to-monocyte ratio in primary myelodysplastic syndromes: a single center experience in 889 patients
Authors: L Saeed, M M Patnaik, K H Begna, A Al-Kali, M R Litzow, C A Hanson, R P Ketterling, L F Porrata, A Pardanani, N Gangat, A Tefferi
Journal: Blood Cancer Journal (2017)

Abstract Current prognostic models for myelodysplastic syndromes (MDS), including the Revised International Prognostic Scoring System (IPSS-R), do not account for host immunity. We retrospectively examined the prognostic relevance of monocytopenia, lymphocytopenia and lymphocyte-to-monocyte ratio (LMR) in a cohort of 889 patients with primary MDS. After a median follow-up of 27 months, 712 (80%) deaths and 116 (13%) leukemic transformation were documented. In univariate analysis, subnormal absolute lymphocyte count (ALC) &lt;0.9 × 10 9 /l; P =0.001), ALC&lt;1.2 × 10 9 /l ( P =0.0002), subnormal absolute monocyte count (AMC) &lt;0.3 × 10 9 /l ( P =0.0003), LMR ( P ⩽0.0001) and LMR⩾5 ( P =0.03) were all associated with inferior overall survival. In multivariable analysis that included other risk factors, significance was retained for LMR ( P =0.02) and became borderline for ALC &lt;1.2 × 10 9 /l ( P =0.06). Analysis in the context of IPSS-R resulted in P -values of 0.06 for ALC&lt;1.2 × 10 9 /l, 0.7 for monocytopenia and 0.2 for LMR. Leukemia-free survival was not affected by ALC, AMC or LMR. The observations from the current study suggest a possible detrimental role for altered host immunity in primary MDS, which might partly explain the therapeutic benefit of immune-directed therapy, including the use of immune modulators; however, IPSS-R-independent prognostic value for either ALC or AMC was limited.
Significant upstaging of patients with stage I pancreatic cancer from clinical to pathologic staging.
Authors: Heather Stuart, Caroline Ripat, Basem Azab, Danny Yakoub, Dido Franceschi, Alan S Livingstone, Vikas Dudeja, Nipun B. Merchant
Journal: Journal of Clinical Oncology (2017)

349 Background: Clinical staging of patients with pancreatic cancer is essential to determine if neo-adjuvant treatment, surgery or palliative treatment is required. Patients with early stage disease often receive upfront surgery, where as patients with more advanced disease often receive neo-adjuvant therapy. Therefore the accuracy of clinical staging significantly influences management decisions. This study investigates the correlation between clinical and pathologic staging for patients with stage I pancreatic cancer. Methods: A retrospective review of patients with pancreatic cancer in National Cancer Data Base from 1998-2006 was preformed. The clinical stage of patients with presumed stage I disease was compared to the postoperative pathologic stage. Cox proportional hazard ratio model and regression analysis were used to determine factors associated with mortality and upstaging, respectively. Results: 1697 patients with clinical stage I pancreatic cancer were divided into two groups. Group 1 was comprised of patients who were stage I postoperatively and Group 2 was comprised of patients that were upstaged to either stage II, III or IV postoperatively. There were 704 (41%) in group 1 and 993 (59%) in group 2. Within group 2, 595 (60%) were stage II, 321 (32%) were stage III and 77 (8%) were stage IV. Patients that were upstaged after surgery had an increased risk of mortality (HR 1.414, p &lt; 0.001), whereas patients that received adjuvant chemotherapy had a decreased risk of mortality (HR 0.799, p &lt; 0.001). Compared to Grade 1 tumors, Grade 2 and 3 tumors on biopsy were most likely to be upstaged on final pathology (p &lt; 0.001). Conclusions: Patients with stage I pancreatic cancer are often candidates for upfront surgery, however this study demonstrates that a large number are upstaged on postoperative staging. Recognizing this may lead clinicians to administer neo-adjuvant treatment in a greater number of patients with early stage disease in order to optimize survival.
A two-stage, open-label, phase II study of bortezomib plus oxaliplatin in previously treated patients with malignant pleural or peritoneal mesothelioma.
Authors: Gleneara Elizabeth Bates, Robert N. Taub, Alain C. Borczuk
Journal: Journal of Clinical Oncology (2014)

e22191 Background: Malignant mesothelioma is a rare, aggressive, and seldom curable malignancy, arising from the mesothelial cells that line the serosal surfaces of the pleural and peritoneal cavities. At the time of diagnosis, almost 75% of these patients will present with pleural disease, while the remaining 25% will have peritoneal mesothelioma. In pleural mesothelioma, the tumor usually grows in the space between the visceral and parietal pleura forming a hardened rind encasing the lung. This is different than peritoneal mesothelioma, which arises from the peritoneal membranes and is characterized by rapid local invasion. Although commonly recognized as being linked to occupational asbestos exposure, MM can also develop in individuals without prior exposure to asbestos. Survival of untreated patients is dismal, with a median survival of less than 12 months. Malignant mesothelioma is refractory to most chemotherapy treatments. We studied the combination of bortezomib plus eloxatin in patients who have had one or more prior chemotherapy regimen to determine if this regimen could increase overall survival and slow tumor progression. Methods: Between 2007 and 2013, 21 patients with malignant mesothelioma were enrolled. The median age was 58 years (range: 31-80). Of the 21 patients, 7 were female (33.0%) and 14 were male (67.0%); 10 with primary pleural disease (47.6%) and 11 with primary peritoneal disease (52.4%); 19 with epithelioid subtype (90.0%), 1 with biphasic subtype (5.0%) and 1 with sarcomatoid (5.0%); 3 had no prior chemotherapy (14%) and 18 had one or more prior regimens (86%). A total of 206 doses of 1.3 mg of bortezomib were administered and total of 98 doses of 8.5mg of eloxatin were administered. Results: We report 18 of the 21 patients died from disease by the end of the study. Three patients (14%) were still alive, and therefore considered to be alive with stable disease. The median survival time was 10 months (with a 1-year survival rate of 29.0%). The median time to progression (TTP) was 4.5 months. Conclusions: This data shows that bortezomib combined with eloxatin may be effective in mitigating disease progression in patients with malignant pleural or peritoneal mesothelioma. Clinical trial information: NCT00996385.
Do patients learn from survivorship care plans?
Authors: Joanna Bodmann, Bridgett Ann Harr, Lisa A. Rybicki, Shlomo A. Koyfman, Jessica Lyn Geiger, Pauline Funchain, Nikhil Purushottam Joshi, Neil McIver Woody, Denise I. Ives, Jean F Hamker, David J. Adelstein
Journal: Journal of Clinical Oncology (2017)

73 Background: At the Cleveland Clinic, a formal, patient (pt) specific survivorship care plan (SCP) is given to all pts who have completed definitive treatment (DT) for loco-regionally advanced head and neck cancer (HNC). We sought to assess the impact of this SCP on pt understanding of disease and treatment, potential symptoms of recurrence, and follow up (FU) expectations. Methods: In an unselected series of HNC survivorship eligible pts, the same IRB approved survey was administered both before SCP delivery and again at the next routine FU. The survey evaluated pts’ pre-existing knowledge of the information included in the SCP, and whether it had improved and was retained over time. Results: Pre and post-survey responses were collected from 29 pts who had completed DT between 7-23 months (mo) prior. Eighteen (62%) had a diagnosis of oropharyngeal cancer, all were treated with intensity modulated radiation therapy and most (93%) received concurrent cisplatin. Only 24 of the 29 pts (83%) recalled receiving a SCP when queried at their next FU. However, even before SCP administration, most were well educated about their disease, its treatment, symptoms of recurrence, and FU expectations; all of which were reviewed in the SCP. The post-survey, administered at next FU, suggested that the only group to benefit from SCP administration were those who received it within 6 mo of DT. Conclusions: Pt understanding of disease, treatment and future expectations appears to improve after SCP administration only in those receiving their SCP within 6 mo of DT, likely reflecting ongoing pt education during subsequent FU visits. This small study supports current recommendations to administer SCPs within 6-12 mo of DT.[Table: see text]
Medical oncologists’ skill and understanding of epidemiology and statistical principles need to be strengthened to maximize their use of clinical trial results
Authors: K. R. Hoffman
Journal: Journal of Clinical Oncology (2006)

6139 Background: Clinical oncologic practice is based on evaluating data from studies whose results are statistically defined, increasingly from interim analyses. How well the practicing oncologist understands the correct use of these statistical and epidemiologic methods is unknown. Methods: Twenty (20) board-certified community based medical oncologists agreed to take a ninety minute, twenty-five question exam on epidemiology and statistics to test their competence in evaluating current treatment data. This test was based on abstracts and articles presented within the last three years and basic statistical and epidemiology concepts taught to second-year medical students Results: Only 11/20 oncologists had a passing grade of 70% (range 92–24%, mean 72%). The recognition of different phased clinical trials was correctly identified by 17/20 doctors. While the identification between a retrospective vs. prospective study was perfect, only 7/20 respondents correctly identified what information can be obtained from a retrospective study. 11/20 respondents correctly explained a ‘p‘ value. Correct calculations and explanations of the sensitivity, specificity, positive and negative predictive value of screening test ranged between 8/20 and 13/20. The importance of a study’s sample size in defining statistical ‘significance‘ was recognized by 9/20 respondents. Only 5/20 oncologists could explain a ‘hazard ratio‘ while14/20 correctly found survival information off of a Kaplan-Meier survival plot. Only10/20 correctly explained a ‘forest plot.‘ Most doctors knew ‘incidence‘ and ‘prevalence‘ but not ‘lead time bias.‘ The identification of ‘absolute risk‘ vs. ‘relative risk‘ (6/20) and understanding the concept of a ‘Type I‘and ‘Type 2‘ error was poor (8/20). After completion of the exam all respondents agreed that CME opportunities in this field would be very helpful. Conclusions: A confirmatory study should be done. In the meantime, there seems to be a need to improve the competence of the practicing oncologist in evaluating data and clinical trials. ASCO should include this topic in future free (not ticketed) educational symposiums at our national meetings and as part of their regional programs. No significant financial relationships to disclose.
Underuse of microsatellite instability testing and predictors of high microsatellite instability disease among young colorectal cancer patients.
Authors: Talha Shaikh, Elizabeth Handorf, Joshua E. Meyer, Michael J. Hall, Nestor F. Esnaola
Journal: Journal of Clinical Oncology (2017)

534 Background: The purpose was to identify predictors of non-adherence to MSI testing in young CRC patients and identify factors associated with an increased risk of high microsatellite instability (MSI-H) disease. Methods: Patients 18-49 years old diagnosed with invasive colorectal adenocarcinoma between 2010-2012 and known MSI testing status were identified using the National Cancer Data Base. Multivariable logistic regression was used to identify independent predictors of receipt of MSI testing, as well as MSI-H status among those tested. Results: Among 17,218 patients identified, only 7,422 (43%) underwent MSI testing; the proportion of patients tested increased between 2010 (36%) and 2012 (48%; p &lt; 0.001). Higher educational level, early stage disease, and number of regional lymph nodes examined &gt; 12 were independently associated with MSI testing, whereas older age (40-49), Hispanic ethnicity, non-private insurance status, non-academic/research facility, facility location, rectosigmoid/rectal tumor location, non-mucinous histology, unknown grade, non-receipt of definitive surgery were associated with underuse. Among 6,358 tested patients with known MSI status, 531 (8%) patients had MSI-H disease. Lower income, previous cancer history, and stage II disease were independently associated with MSI-H status, whereas older age (40-49), female sex, advanced comorbidity, non-metropolitan facility status, facility location, distal tumor location, non-mucinous histology, unknown/lower tumor grade, and non-receipt of chemotherapy were inversely associated with MSI-H status. Conclusions: Despite national guidelines, significant underuse of routine MSI testing in young patients diagnosed with colorectal cancer persists. Interventions are warranted to improve adherence to guideline-based care in these patients, particularly among those at increased risk of MSI-H disease. [Table: see text]
Caregiver needs during transition from acute cancer: Findings from focus group discussions with cancer survivors and caregivers.
Authors: Elliott Tolbert, Janice Bowie, Claire Frances Snyder, Barraw Makia, Katherine Clegg Smith
Journal: Journal of Clinical Oncology (2017)

84 Background: The Institute of Medicine recommends that all cancer patients receive a survivorship care plan to help alleviate challenges faced when transitioning from acute treatment to long-term survivorship. As nearly three million Americans act as caregivers for a loved one with cancer, it is important that the survivorship care planning process consider the needs of not only the survivor, but also caregivers. Methods: In preparation for a randomized controlled trial of survivorship care planning, we conducted four focus groups with adult survivors of breast, prostate, and colorectal cancer (n = 28) and two with self-identified caregivers of people who had been treated for these three cancers (n = 20). Focus group participants were recruited from a large, urban academic medical center and a rural community cancer center. Discussions focused on needs and expectations during the transition from cancer treatment to survivorship. Each discussion was recorded, transcribed, and analyzed qualitatively. Data analysis also included review of findings by an advisory board of patients and caregivers. Results: Six themes emerged, some raised by both survivors and caregivers, and some only by caregivers. The need for information on side effects and follow-up care recommendations, confusion regarding the role each provider plays once treatment is complete, and the need for resources and support to help deal with issues such as physical and emotional distress and living a healthy lifestyle were brought up by both caregivers and survivors. In addition, caregivers discussed uncertainty about their role as a caregiver, their own mental and emotional health needs, and the idea that adjusting to ‘a new normal’ is not just for the patient, but also caregivers. Conclusions: Caregivers have distinct needs in addition to those of the patient. These caregiver concerns may need to be addressed during the survivorship care planning process. Based on these findings, we are including a caregiver-specific resource in our survivorship care planning randomized controlled trial.
Safety and efficacy of MET inhibitor tivantinib (ARQ 197) combined with sorafenib in patients (pts) with hepatocellular carcinoma (HCC) from a phase I study.
Authors: Robert E. Martell, Igor Puzanov, Wen Wee Ma, Armando Santoro, Grace K. Dy, Laura Williams Goff, Gerald J. Fetterly, Shaunita A. Michael, Julie Ann Means-Powell, Feng Chai, Maria Lamar, Matteo Simonelli, Wendy M. Chiang, Jamie Jarboe, Brian E. Schwartz, Alex A. Adjei
Journal: Journal of Clinical Oncology (2012)

4117 Background: The multikinase inhibitor sorafenib is standard of care for pts with advanced HCC. Tivantinib, an oral, selective MET inhibitor, demonstrated synergistic antitumor activity when combined with sorafenib in several tumor models. The phase 1 dose-escalation study assessed the safety profile of tivantinib plus sorafenib in pts with advanced solid tumors. Methods: Endpoints were safety, the recommended phase 2 dose (RP2D) of tivantinib plus sorafenib, and antitumor activity. Dose escalation previously established the RP2D as tivantinib 360 mg twice daily (BID) plus sorafenib 400 mg BID. Extension cohorts enrolled ≤ 20 pts each with HCC or other tumors. Patients were treated until disease progression or unacceptable toxicity. After a safety review in HCC pts in other studies and a report of febrile neutropenia in this study, the tivantinib dose for newly enrolled pts was reduced to 240 mg BID. Results: 20 pts with HCC (mean age, 62 yr; Child-Pugh [CP] A [n = 14], or CP B [n = 6]) were treated at the RP2D (n = 10) or at the reduced tivantinib dose plus sorafenib (n = 10). 10 pts received ≥ 1 previous systemic anticancer treatment (median, 0.5; range, 0-3). The most common adverse events (≥ 25%) were rash (40%), palmar-plantar erythrodysesthesia syndrome (35%), fatigue and diarrhea (30% each), and nausea and anorexia (25% each). Neutropenia was reported in 2 pts. Best response was 1 complete response (CR), 1 partial response (PR), and 12 stable disease (SD). Overall response rate and disease control rate were 10% and 70%, respectively. Median progression-free survival (mPFS) was 3.5 mo (95% CI, 2.8-11.1 mo). Among 8 pts previously treated with vascular endothelial growth factor (VEGF) inhibitors (6 sorafenib; 1 sunitinib; 1 sorafenib plus sunitinib), best response was 1 CR, 1 PR, and 3 SD, and mPFS was 15.9 mo (95% CI, 1.6-15.9 mo). 2 pts are still on study. Conclusions: The combination of tivantinib (360 mg BID) plus sorafenib (240 mg BID) was well tolerated. Preliminary evidence of antitumor activity indicates that combined inhibition of MET and angiogenic signals may have therapeutic potential in this setting, including pts pretreated with VEGF inhibitors.
A phase II study of combined fulvestrant and everolimus in metastatic estrogen receptor (ER)+ breast cancer after aromatase inhibitor (AI) failure.
Authors: Suleiman Alfred Massarweh, Edward H. Romond, Jessica Jones Croley, Esther P. Black, Mara D. Chambers, Mark Stevens, Brent Shelton, Vera Kadamyan, Richard M. Elledge
Journal: Journal of Clinical Oncology (2013)

541 Background: Fulvestrant, an ER downregulator, can be effective in metastatic ER+ breast cancer but resistance is a problem. Everolimus inhibits mTOR; a key pathway in endocrine resistance. We hypothesized that everolimus may delay resistance to fulvestrant and thus improve its efficacy. Methods: We enrolled postmenopausal women with ER+ breast cancer who experienced disease relapse or progression within 6 months of AI use and had measurable/evaluable disease. Fulvestrant was given at 500 mg IM on day1, 250 mg d14, d28, and monthly thereafter. Everolimus was given at 10 mg po daily. Primary endpoint was time to progression (TTP) and secondary endpoints included safety, response, and biomarker analysis. A sample size of 40 patients was calculated to meet a median TTP of 7 vs. 3.7 months for fulvestrant alone as reported in the EFECT trial. Tumor blocks were collected and biopsies done for accessible disease. Results: 33 patients were enrolled. 2 were ineligible and are excluded from analysis. Median age was 54 years (range 40-85). Most common disease sites were bone 84%, liver 62%, and lung 55%. 81% of patients received prior tamoxifen, 71% had prior chemotherapy and 23% had multiple AIs. Median TTP is currently 7.4 months with 4 patients remaining on therapy. Responses include complete response 3%, partial response 10%, and stable disease 42%. 32% of patients had primary refractory disease and 13% discontinued therapy before disease assessment. Most common adverse events were elevated AST 81% or ALT 68%, hyperglycemia 61%, anemia 61%, elevated cholesterol 60%, hypokalemia 52%, mucositis 48%, and weight loss 48%. The majority of adverse events were grade I/II. Fasting lipid profile data is summarized. Conclusions: These results suggest that adding everolimus to fulvestrant improves its efficacy in heavily pretreated ER+ metastatic breast cancer. Toxicity was manageable but needs close monitoring. Biomarker analysis is ongoing in order to identify patients not likely to benefit from this treatment strategy. Clinical trial information: NCT00570921. [Table: see text]