tbuckley/cabot-search huggingface dataset:
Do drugs that offer PFS or modest OS benefits improve quality of life in patients with advanced cancer?
Authors: Lesley Fallowfield, Susan L. Catt, Shirley F May, Valerie M Shilling, Lucy A Matthews, Valerie A. Jenkins
Journal: Journal of Clinical Oncology (2017)

223 Background: Patients value quality of life (QoL) not just quantity of life but QoL data from measures in advanced disease are sparse for drugs with only progression-free survival (PFS) or modest overall survival (OS) benefits. We examined if stabilisation of metastatic disease and/or disease symptom burden were worth treatment side effects in the AVALPROFS study. Methods: Patients with metastatic cancers starting drugs with PFS or modest OS benefits were interviewed at baseline and following 6 weeks of treatment. Further interviews were conducted at progression or if treatment was stopped for toxicity. Interviews comprised trade-off type assessments exploring worthwhileness of treatment compared with side effects.Patients completed FACT tumor and treatment specific questionnaires monthly for 6 months. Global QoL was measured across time and between patients who died or progressed on study (A), remained on study (B) or withdrew from study due to toxicity (C). Results: 90/120 (75%) eligible patients participated. 31/90 (21%) patients died or progressed within 6 months of study entry (Group A). 12 patients withdrew due to toxicity (Group B) and 47 patients stayed on treatment for 6 months (Group C). At first interview 43/90 (48%) patients had started treatment and by 6 weeks (66/69, 96%) were experiencing side effects. At both interviews patients were significantly less inclined to feel that benefits of cancer control were worthwhile as the possible side effect severity increased (X2=75.6004. p&lt; 0.00001; 50.6896 p&lt; 0.00001 respectively). There was an effect of patient group on general QoL (F=4.978; p = 0.007) but no group by time interaction (F=0.419; p = 0.888). Also, a significant overall group effect (A vs. C) for emotional (F=6.583, p = 0.011) and functional well-being (F=5.138, p = 0.024). More patients in Group C had stable/improved QoL over time. Conclusions: Over 6 months, QoL was stable in those patients receiving drugs with PFS only or minimal OS who could tolerate treatment side effects. As severity of side effects increased, patients were less likely to feel that treatment was worthwhile but a proportion were still willing to accept these for a relatively short increase in the time drugs controlled the cancer.
Effect of beta blocker on breast cancer progression in minority population.
Authors: Rajshekhar Chakraborty, Shiva Kumar Reddy Mukkamalla, Natalia Calderon, Linda Bulone
Journal: Journal of Clinical Oncology (2013)

e12564 Background: Recent pharmaco-epidemiological studies have shown positive effects of beta blockers (BB) on breast cancer progression, recurrence, metastasis, and cancer specific mortality. To the best of our knowledge none of these studies specifically targeted the minority population. The purpose of our study was to determine the effect of beta blockers on the Progression Free Survival (PFS) of breast cancer patients belonging to the minority subgroup of US population. Methods: We retrospectively reviewed 142 consecutive cases of breast cancer in a city hospital in Queens County of New York City (Asians 36%, Blacks 42%, Hispanics 18% and Whites 4%) diagnosed between January 2007 and December 2009. Patients using beta blockers prior to diagnosis were compared to those who were not on any in terms of PFS after adjusting for the confounding effect of stage at presentation. Kaplan-Meier survival curves were used to look for any significant difference in the PFS between these two groups in minority population. Results: Patients on beta blockers (n=25) were compared to those who were not (n=111). The median follow-up time of this study was 54 months. The study population was stratified according to the stage of presentation (Stage I=32%, Stage II=36%, Stage III=22%, Stage IV=10%).Using Kaplan Meier survival analysis we found significant differences in PFS of patients in stages II and IV (Wilcoxon Test p&lt;0.0001, Log-Rank Test p&lt;0.0001). There was no progression of disease in stage I irrespective of beta blocker intake. In stage II, PFS at the end of study in patients on BB vs. not on BB was 91% vs. 87%. In stage IV the PFS was 100% vs. 10% in patients on BB vs. not on BB. However, in stage III the PFS was better in patients not on BB, which could be explained by the small number of patients on BB (50% vs. 77% in BB vs. no BB subgroup). Conclusions: In this study of breast cancer PFS in minority population, we found that beta blocker use was associated with improved PFS in stages II and IV. However, additional studies with larger sample size are required to substantiate this finding.
Characterization of candidate tissue and blood biomarkers in a rare cohort of myxopapillary ependymoma patients.
Authors: Aysegul Ilhan-Mutlu, Anna Sophie Berghoff, Friedrich Wrba, Christine Marosi, Ludwig Wagner, Christoph Zielinski, Matthias Preusser
Journal: Journal of Clinical Oncology (2013)

2040 Background: Myxopapillary ependymoma (MPE) is a very rare tumor of the distal spinal cord. Despite benign histopathology, local recurrences occur in approximately 30% of patients and distant metastases have been described in few cases. We investigated candidate tissue and blood biomarkers in a rare MPE series. Methods: Formalin fixed paraffin embedded (FFPE) tumour tissues from 21 MPE patients were immunohistochemically investigated for expression of isocitrate dehydrogenase 1 R132H (IDH-R132H), Secretagogin, glial fibrillary acidic protein (GFAP), epidermal growth factor receptor (EGFR), human epidermal growth factor receptor 2 (HER2), progesterone receptor (PR), estrogen receptor (ER), Ki-67, arg, plateled derived growth factor a (PDGFRa) and b (PDGFRb), pc-kit and pc-abl. EGFR gene was evaluated using exon-sequencing. In addition, we analyzed circulating plasma-GFAP using ELISA in 3 patients with completely resected MPE, 1 patient with locally advanced MPE, 2 patients with pleuropulmonary metastases of MPE and 12 control subjects. Results: Secretagogin and GFAP were expressed in all tissue samples. arg, PDGFRa, PDGFRb, pc-kit and pc-abl were positive in 15, 1, 2, 3 and 2 patients, respectively. The Ki-67 index ranged from 1% to 12.8% (median=7.1%). We detected no expression of EGFR, IDH-R132H, HER2, PR or ER. One patient showed a silent mutation in exon 21 of the EGFR gene (c.2508C&gt;T). We found very high concentrations of plasma-GFAP in two MPE patients with pleuropulmonary metastases, while all other MPE patients were negative. Conclusions: Our data indicate that (i) targeted tyrosine kinase inhibitors may be rational for the therapy of selected MPE patients and that (ii) circulating GFAP could be useful as circulating marker for the early detection or follow-up of distant metastases in MPE patients.
Current patterns of chemotherapy and supportive care for early-stage breast cancer (ESBC).
Authors: Gary H. Lyman, David C. Dale, Dianne Tomita, Sadie Whittaker, Jeffrey Crawford
Journal: Journal of Clinical Oncology (2012)

1062 Background: ESBC is commonly treated with myelosuppressive chemotherapy, and high relative dose intensity (RDI) correlates with improved overall survival. A retrospective analysis of patients with ESBC treated from 1997–2000 showed that 56% received an RDI &lt; 85% (Lyman et al. JCO. 2003;21:4524-4531). To determine current practice, we evaluated ESBC treatment patterns at 24 US community- and hospital-based oncology practices. Methods: Data were abstracted from medical records of 532 patients with ESBC treated from January 2007–December 2009. Inclusion criteria included surgically resected ESBC (stage I-IIIA); ≥ 18 years old; and completion of at least 1 standard chemotherapy cycle on an every 2 or 3 week schedule. The primary endpoint was RDI over planned cycles. Other endpoints were incidence of dose delays ≥ 7 days, dose reductions ≥ 15% from standard, grade 3/4 neutropenia (SN), febrile neutropenia (FN), FN-related hospitalization, granulocyte-colony stimulating factor (G-CSF) use, and antimicrobial therapy. Descriptive statistics were generated for all endpoints. Results: In this study, mean (range) age was 55 (29–85) years. Relative to previously published results, chemotherapy regimens have shifted from mainly doxorubicin + cyclophosphamide (AC) (previously 35%) to docetaxel + cyclophosphamide (TC; n = 221; 42%) and AC followed by paclitaxel (AC-T; n = 163; 31%). Mean RDI is now higher (93% for both TC and the most common AC-T schedule [dose dense AC-T; n = 84] vs 79% previously); the incidence of dose delays (16% vs 25% previously) and dose reductions (21% vs 37% previously) have decreased; and primary prophylactic use of G-CSF has increased (76% vs 3% previously). In this study, 40% of patients had SN, 3% had FN, 2% had an FN-related hospitalization, and 30% received antimicrobial therapy. These measures were not available in the previously published results. Conclusions: The observed changes between the two studies are noteworthy though inferential comparisons are limited by changes in treatments and other factors. RDI has improved over time, but 16% of patients in this study received an RDI &lt; 85%. Further evaluation is needed to identify factors associated with lower RDI and determine outcomes for these patients.
Recurrence following surgical resection of gastroenteropancreatic neuroendocrine tumors (NETs): An analysis from the NCCN oncology outcomes database.
Authors: Katherine Van Loon, Li Zhang, Jennifer M Creasman, Michael A. Choti, James C. Yao, Matthew H. Kulke, Eric K. Nakakura, Mark Bloomston, Al Bowen Benson, Manisha H. Shah, Jonathan R. Strosberg, Carrie C. Zornosa, Sarah Bobiak, Emily K. Bergsland
Journal: Journal of Clinical Oncology (2015)

4107 Background: Resection of gastroenteropancreatic NETs is known to prolong survival. Current NCCN guidelines recommend that complete surgical resection of the primary tumor and metastases should be performed if possible. However, large multicenter studies of recurrence patterns following resection have not been performed. Methods: Patients ≥18 years who presented to 7 participating NCCN institutions after 2004 with a new diagnosis of a small bowel, pancreas, or colorectal NET were included. All underwent complete (R0) resection of the primary tumor and of synchronous metastases if present. Descriptive statistics were used to determine recurrence rates. Kaplan-Meier estimates were used to calculate time-associated endpoints. Comparisons were assessed by the log-rank test. Results: Of 1,125 patients with small bowel, pancreas, or colorectal NETs in the database, 301 patients underwent R0 resection. 50% of patients included in the analysis were male, 88% were Caucasian, and 99% had an ECOG PS 0-1. The median age was 55 years (range 20-90); however, patients with a colorectal NET were younger (p<0.001). Median follow-up time from R0 resection was 62.1 months. Among patients with small bowel NET (n=110), 18% recurred. Among patients with pancreatic NET (n=141), 26% recurred. Among patients with colorectal NET (n=50), 10% recurred. The proportion of patients without recurrence and the proportion alive at 12, 24, 36, 48, and 60-month follow-up are below. Stratification according to stage will be presented. Conclusions: R0 resection was associated with variable risk of recurrence across subtypes during 5 years of follow-up. Greater than 90% of patients who underwent an R0 resection were alive at 5-year follow-up; similarly, the majority of patients were disease-free. Further inquiry into appropriate surveillance strategies following R0 resection is needed. Small bowel Pancreas Colon/rectum Follow-up (months) Proportion without recurrence following R0 resection (p=0.01) 12 95% 96% 95% 24 93% 86% 90% 36 87% 74% 90% 48 83% 69% 90% 60 78% 62% 90% Proportion alive following R0 resection (p=0.5) 12 98% 98% 100% 24 97% 96% 100% 36 92% 96% 96% 48 92% 95% 96% 60 92% 94% 96%
A phase II, dose-optimization trial of autologous T cells genetically engineered to express anti-CD19 chimeric antigen receptor (CART-19) in patients with relapsed or refractory (r/r) CD19+ chronic lymphocytic leukemia (CLL).
Authors: David L. Porter, Noelle V. Frey, Alison W. Loren, Bruce Levine, Michael Kalos, Holly McConville, Joan Gilmore, Anne Chew, Angela Shen, Charlene So, Michele Sharr, Patricia Ann Wood, Carl H. June
Journal: Journal of Clinical Oncology (2013)

TPS7132 Background: The poor prognosis and lack of effective treatment options for patients with r/r CLL highlight the need for novel therapies in this setting. CD19 is a promising anticancer target because it is broadly expressed on normal and malignant B cells through several stages of maturation but absent on pluripotent stem cells. CART-19 (CTL019) therapy involves adoptive transfer of autologous T cells genetically modified via lentiviral transduction to express chimeric antigen receptors (CAR) designed to target CD19+ cells. CART-19 cells express a CD19 antigen recognition domain combined with intracellular signaling domains, CD137 (4-1BB) and CD3-zeta, which mediate cytolytic T-cell activity. In patients with r/r CLL, CART-19 therapy showed potent antileukemic activity with long-term persistence of transduced cells at doses from 1.4 × 10 7 to 1.1 × 10 9 CART-19 cells. As of August 2012, 3 of 8 evaluable CLL patients achieved CR (two &gt; 24 months and one &gt; 5 months) and remain in CR with detectable CART-19 cells. Two patients had PR lasting 3 and 5 months, and 3 patients did not respond (Porter et al. NEJM. 2011; Kalos et al. Sci Transl Med. 2011; Porter et al. ASH 2012). Here, we describe a study to determine the optimal dose of CART-19 cells (NCT01747486). Methods: Adults with relapsed or persistent CLL or SLL after ≥ 2 previous therapies will undergo leukapheresis to obtain T cells, which will be stimulated, expanded, and lentivirus transduced ex vivo to express the CD19/4-1BB/CD3-zeta CAR. Patients will undergo lymphodepletion chemotherapy prior to infusion of CART-19 cells. In stage I of the II-stage trial, 30 patients will be randomized 1:1 and receive either 1-5 × 10 8 or 1-5 × 10 7 CART-19 T cells. The optimal dose in stage I will be selected based on clinical responses, feasibility, and tolerability. In stage II, 8 additional patients will be enrolled into the selected dose cohort. Study objectives are to determine the efficacy (CR rate within 3 months) and safety (CTCAE v 4.0) of each dose, in vivo CART-19 expansion, and manufacturing feasibility. Three patients have been enrolled as of January 2013. Clinical trial information: NCT01747486.
Assessing the value of an optional radiation oncology clinical rotation during the core clerkships in medical school.
Authors: Nicholas George Zaorsky, Theresa Maria Malatesta, Robert Benjamin Den, Evan John Wuthrick, Maria Werner-Wasik, Wenyin Shi, Peter H. Ahn, Adam Dicker, Pramila R. Anne, Voichita Bar-Ad, Timothy Norman Showalter
Journal: Journal of Clinical Oncology (2012)

e19507 Background: Few medical students are given proper clinical training in oncology, much less radiation oncology. We evaluate the value of adding a radiation oncology clinical rotation to the medical school curriculum. Methods: In July 2010, Jefferson Medical College offered a 3-week radiation oncology elective rotation for third-year medical students during the core surgical clerkship. During 2010-2012, 52 students chose to enroll in this rotation. The rotation included outpatient clinics, inpatient consults, didactic sessions, and case-based presentations by the students. Tests of students’ knowledge of radiation oncology were administered anonymously before and after the rotation to evaluate the educational effectiveness of the rotation. Students and radiation oncology faculty were given surveys to assess feedback about the rotation. Results: The students’ pre-rotation test scores had an average of 64% (95% confidence interval [CI]: 61%, 66%), which improved after the rotation to 82% (95% CI: 80%, 83%; 18% absolute improvement). In exam question analysis, scores improved in clinical oncology from 63% to 79%, in radiobiology from 70% to 77%, and in medical physics from 62% to 88%. Improvements in all sections but radiobiology were statistically significant. Students rated the usefulness of the rotation as 8.1 (scale 1-9, 95% CI: 7.3, 9.0), their understanding of radiation oncology as a result of the rotation as 8.8 (95% CI: 8.5, 9.1), and their recommendation of the rotation to a classmate as 8.2 (95% CI: 7.6, 9.0). Radiation oncology faculty rated their belief that this rotation would be valuable to students as 8.2 (scale 1-9), that students had appropriate responsibilities in the clinic as 7.9, and that the lectures and meetings that students attended were at an appropriate level as 8.1. Conclusions: Integrating a radiation oncology clinical rotation into the medical school curriculum improves student knowledge of radiation oncology, including aspects of clinical oncology, radiobiology, and medical physics. The rotation is appreciated by both students and faculty. We recommend including exposure to radiation oncology as part of the core clinical curriculum for all medical students.
Patterns of care in renal cell carcinoma (RCC): Impact of duration of first-line (1L) treatment on second-line (2L) treatment choice.
Authors: Bruce A. Feinberg, David Garofalo, Jason Drenning, Jim Montgomery
Journal: Journal of Clinical Oncology (2015)

e17618 Background: RCC represents a dynamic therapeutic area with multiple classes of treatments and several new agents on the horizon with novel mechanisms of action. Understanding current patterns of care in real-world populations may inform current sequential therapy decisions and provide context for the adoption of new therapeutics. We conducted a retrospective analysis evaluating the sequential use of tyrosine kinase inhibitors (TKIs) for RCC and the impact of duration of 1L TKI treatment with sunitinib on 2L treatment choice. Methods: Using claims data (MORE2 Registry), patients with RCC who started and completed at least 1 line of treatment with a TKI and/or mammalian target of rapamycin (mTOR) inhibitor during the study period (01/2012 to 02/2014) were identified by ICD9 code 189.0. Each patient’s treatment history was analyzed by line of therapy, defined as the line of therapy at disease progression or last regimen 90 days prior to date of data extraction (02/01/2014). Patients were evaluated by duration of 1L sunitinib and 2L treatment choice. Results: Treatment histories for 917 patients meeting the study criteria were evaluated. Patients received 1240 complete lines of therapy. A total of 361 patients received 1L sunitinib; of those patients, 105 received a complete course of 2L treatment. For patients who received 1L sunitinib for < 3 months (n = 58), 40% received a TKI as 2L treatment. For patients who received 1L sunitinib for > 6 months (n = 17), 65% received a TKI as 2L treatment. The difference in rates of 2L TKI use between these two groups was statistically significant, P< .10. Conclusions: The longer patients remained on 1L sunitinib, the greater the likelihood they received 2L treatment with a TKI. The finding that 40% of patients received a 2L TKI despite primary refractory disease or intolerance is surprising and warrants further investigation. The adoption of emerging therapies may be based on challenging the accepted paradigm and prescriber comfort with TKI/TKI and TKI/mTOR inhibitor treatment sequence. Duration of 1L TKI 1L Sunitinib No. patients (n = 105) 2 L TKI % patients (n = 50) 2L mTOR % patients (n = 51) < 3 mo 58 40 55 3-6 mo 30 53 43 > 6 mo 17 65 35
Phase I study of the mTOR inhibitor sirolimus and the HDAC inhibitor vorinostat in patients with advanced malignancies.
Authors: Haeseong Park, Ignacio Garrido-Laguna, Aung Naing, Siqing Fu, Gerald Steven Falchook, Sarina Anne Piha-Paul, Jennifer J. Wheler, David S. Hong, Vivek Subbiah, Apostolia Maria Tsimberidou, Ahmed Omar Kaseb, Yasuhiro Oki, Ralph Zinner, Shreyaskumar Patel, Vivianne Marie Velez Bravo, Michelle A. Fanale, Funda Meric-Bernstam, Razelle Kurzrock, Filip Janku
Journal: Journal of Clinical Oncology (2015)

2584 Background: Preclinical models suggest synergistic anticancer activity of histone deacetylase (HDAC) and mTOR inhibitors by reducing activity of AKT/mTOR and HDAC. Methods: This is a phase I study (NCT01087554) to determine the safety, maximum tolerated dose (MTD)/recommended phase II dose (RP2D) and dose limiting toxicities (DLT) of the mTOR inhibitor sirolimus (1mg-5mg PO daily q 28 days) and HDAC inhibitor vorinostat (100mg-400mg PO daily q 28 days) in patients with advanced cancers. The expansion cohorts at RP2D, which included optional pre- and post-treatment tumor biopsies and other pharmacodynamic (PD) and pharmacokinetic (PK) endpoints, enrolled patients with classical Hodgkin lymphoma (cHL), hepatocellular carcinoma (HCC), perivascular epithelioid cell tumor (PEComa) and other cancers. Results: From March 2010 to August 2014, 102 patients were treated (dose escalation, n = 69, expansions, n = 33). cHL (n = 22) and HCC (n = 12) were most common diseases. Patients (n = 66), who either had DLT or completed the first cycle without dose modifications were evaluable for DLT asessment, which included grade (G) 4 thrombocytopenia (n = 10) and G3 mucositis (n = 1). Sirolimus 5mg and vorinostat 300mg was declared as MTD. Because of significant non-DLT hematological toxicities, sirolimus 4mg and vorinostat 300mg was established as RP2D. All G 3/4 drug related toxicities (including DLT) were thrombocytopenia (37%), neutropenia (13%), anemia (8%), mucositis (3%), diarrhea (3%), fatigue (2%), febrile neutropenia (1%), peripheral neuropathy (1%). 57 (56%) patients required dose modifications. Of 102 patients, 78 had at least one restaging imaging;7 (7%; cHL, n = 6; peripheral T-cell lymphoma, n = 1) had a complete response, 7 (7%; cHL, n = 6; PEComa, n = 1) had a partial response and 3 (3%, HCC, n = 2, fibromyxoid sarcoma, n = 1) had stable disease for 12 months or longer. Among the responders, two had known aberrations in the PI3K pathway (TSC2 and PIK3CA). PD studies and PK analysis are pending. Conclusions: The combination of sirolimus and vorinostat is well-tolerated at RP2D and demonstrates promising activity in lymphoma, PEComa and HCC. Further investigation is warranted in these disease types. Clinical trial information: NCT01087554.