tbuckley/cabot-search huggingface dataset:
A phase I study of TRC105 (anti-CD105 antibody) in patients with advanced solid tumors.
Authors: J. W. Goldman, M. S. Gordon, H. Hurwitz, R. Pili, D. S. Mendelson, B. J. Adams, D. Alvarez, B. K. Seon, C. P. Theuer, B. R. Leigh, L. S. Rosen
Journal: Journal of Clinical Oncology (2011)

3073 Background: CD105, also known as endoglin, is an endothelial cell membrane receptor that is highly expressed on angiogenic tumor vessels but not normal mature vessels. CD105 is essential for angiogenesis and its expression is upregulated by hypoxia and VEGF inhibition. TRC105 is a chimeric IgG1 anti-CD105 monoclonal antibody that inhibits angiogenesis and tumor growth by endothelial cell growth inhibition, ADCC and apoptosis. Methods: Pts with advanced solid tumors, ECOG PS 0-1, and normal organ function were treated with escalating doses of intravenously administered TRC105 in cohorts of 3-6 pts and assessed for safety, PK, angiogenic biomarkers and response. Results: 50 pts were treated including 21 with NS0-produced TRC105 (0.01-1 mg/kg q2wk) and 29 with CHO-produced TRC105 (0.3-15 mg/kg q2wk or 10-15 mg/kg/wk) until disease progression. Dose-limiting toxicity included grade 4 GI hemorrhage (n=1) at 0.1 mg/kg and grade 3 infusion reactions at 0.3-1 mg/kg without premedication (n=3). Infusion reactions were controlled by routine premedication allowing escalation to 15 mg/kg/wk. Serum concentrations expected to saturate CD105 binding sites (>200 ng/mL) were achieved continuously at 15 mg/kg q2wk. TRC105 accumulated with weekly dosing and was associated with grade 3-4 hypoproductive anemia at 15 mg/kg/wk. HAMA/HACA formation was rare in pts treated with NS0-produced TRC105 and absent in those treated with CHO-produced TRC105. One pt with castrate-resistant prostate cancer remains on TRC105 for 3+ years with complete PSA response, bone scan normalization and bone pain resolution, and a pt with metastatic endometrial cancer remains on TRC105 for 6+ months with ongoing minor response. Additional evidence of activity includes SD ≥ 2 months in 21 of 44 pts (47%), SD ≥ 4 months in 6 of 41 pts (15%), CEA, PSA or CA125 decreases in 7 of 29 pts (24%), and a global decrease in key angiogenic biomarkers with treatment. Conclusions: TRC105 is well tolerated at doses with clinical and biological evidence of antiangiogenic and anticancer activity. Future studies will evaluate single-agent TRC105 and combination therapy in a variety of indications.
Pathologic characteristics of breast cancer with special emphasis on prevalence of triple-negative breast cancer from Kenya: A 4-year experience.
Authors: S. Sayed, Z. Moloo, S. Mukono, R. Wasike, R. R. Chauhan, A. Ndonga, M. E. Trinkaus, Y. Rahim, H. Wedad, M. N. Saleh
Journal: Journal of Clinical Oncology (2011)

35 Background: Previous sub classification of breast cancer in Kenya has been fraught by small sample size, non uniform staining methodology and lack of independent review. Triple Negative Breast Cancer (TNBC) is a “special interest” cancer since it represents a significant proportion of breast cancer patients and is associated with a poorer prognosis. We aimed to determine the estrogen receptor (ER), progesterone receptor (PR) and Her2/neu receptor characteristics of breast cancers and the prevalence of TNBC diagnosed at Aga Khan University Hospital, Nairobi (AKUHN) between 2007 to date. Methods: Slides and blocks of archived invasive breast cancers diagnosed at AKUHN were identified, retrieved and reviewed by two independent pathologists. Histological type, grade and pathological stage were documented. Representative sections from available blocks were stained for ER, PR, Her2 with appropriate internal controls. Scores for ER/PR were interpreted based on the ALLRED system, Her2 /neu scoring followed CAP guidelines. The initial 111 cases were validated and confirmed at Sunnybrook Health Sciences Centre, Toronto. Results: 456 cases of invasive breast cancers were diagnosed at AKUHN during the study period. 91% of cases were invasive ductal carcinomas (NOS).The rest were special types. 37% of the tumors were grade 3 and 63% were grade 2. Blocks for 318 of 456 cases were available for receptor analysis. 54% were ER and/or PR positive, with 52% of these in women &lt; 50 yrs. 86% of the ER and/or PR positive tumors were grade 2. Only 12% were Her2/neu positive. Of the 318 cases studied, 111 (32%) were identified as TNBC. Median age was 53 yrs. 88% were grade 3. Conclusions: Invasive ductal carcinoma (NOS) was the most common breast cancer in our study. Nearly half of our cases were ER and/or PR positive and a third were TNBC. Both occurred predominantly in women less than 50 yrs. This represents the largest validated pathologic sub classification of breast cancer from a tertiary academic hospital in Kenya. Expansion of this study to encompass all breast cancers diagnosed in Kenya is underway.
Neoadjuvant chemotherapy with docetaxel, carboplatin, and weekly trastuzumab (TCH) activity in HER2-positive early breast cancer: Results after a median follow-up of 4.5 years.
Authors: Hans-Christian Kolberg, Leyla Akpolat-Basci, Miltiades Stephanou, Carla Hannig, Cornelia Liedtke
Journal: Journal of Clinical Oncology (2015)

140 Background: Most patients with HER2-positive receive chemotherapy and trastuzumab. Data from adjuvant trials have shown that the combination of docetaxel, carboplatin and weekly trastuzumab (TCH) is well tolerated and as effective as anthracycline containing regimes. Previous investigations on neoadjuvant treatment with TCH showed pCR-rates in the range of 40%, however, survival data have not yet been presented. Here we present 4.5-year follow-up data for a cohort of 51 patients treated with neoadjuvant TCH. Methods: We treated 51 patients with operable HER2-positive breast cancer with a neoadjuvant schedule of docetaxel (75 mg/m2) and carboplatin (AUC 6) q3w and trastuzumab (2(4)mg/kg) q1w. Lymph node involvement was verified by SLNB or core-cut-biopsy. Mean age at diagnosis was 55 years, 68.6% had ER positive tumors, 39.2% presented with grade 3 disease and 49% of patients were node-positive. Patients were monitored by ultrasound. After 6 cycles of chemotherapy all patients had surgery. Axillary dissection was performed in case of positive lymph node status prior to TCH. After surgery trastuzumab was continued q3w up to one year. Results: Side effects were mild, no grade III/IV toxicities occurred and no case of cardiomyopathia was observed. 21 (41.18%) patients achieved a pCR, 18 (72.0%) patients converted from cN+ to ypN0. Outcome data at a median follow-up of 53.6 months are as follows (see table). Conclusions: Outcome following neoadjuvant TCH as observed in our analysis compares well to outcome data observed in adjuvant trastuzumab trials such as HERA or BCIRG006. Particularly among patients with ER positive disease and those experiencing axillary conversion we observed an excellent outcome. Importantly, TCH was well tolerated in our cohort. Therefore our data support the use of TCH as neoadjuvant therapy regimen for patients with HER-positive breast cancer. [Table: see text]
Correlation of pathologic findings after brief neoadjuvant sorafenib (neoS) with results of dynamic-contrast enhanced (DCE) and diffusion-weighted (DW) magnetic resonance imaging (MRI) in patients (pts) with locally advanced or metastatic clear cell renal cell carcinoma (RCC).
Authors: Gary R. MacVicar, Frank Miller, Rahul Rustogi, Zong-Ming Chen, Brenda K. Martone, Timothy Kuzel
Journal: Journal of Clinical Oncology (2013)

e15554 Background: Many pts receiving tyrosine kinase inhibitors for RCC manifest stable disease as their best response by RECIST criteria. We hypothesized that tumor necrosis by DCE and DW-MRI after brief treatment with neoS may correlate with pathologic findings. We investigated in a pilot study whether these MRI changes may serve as an imaging biomarker predictive of clinical outcome. Methods: Pts with locally advanced or metastatic clear cell RCC undergoing nephrectomy or metastastectomy were treated with neoS 400mg PO bid for 28 days prior to surgery. The feasibility and safety of neoS was determined. Tumor necrosis detected by DCE and DW MRI’s pre- and post-neoS were compared and correlated with survival and pathologic findings at surgery. RECIST/WHO criteria were also compared. Results: 9 pts were enrolled, and all underwent surgery after neoS, 4 weeks (n=7) or less for toxicity (n=2). Clear cell/sarcomatoid histology was noted in 8 pts, and papillary in 1. All pts had T3 or T4 disease. 7 had M1 disease. No surgical complications occurred. 7 pts (78%) experienced Grade 3 toxicities, including hypertension (n=1), pancreatitis (n=1), hand-foot syndrome (n=1), hyponatremia (n=2), and rash (n=2). No grade 4 or 5 toxicities were observed. 4 of 8 clear cell/sarcomatoid pts (50%) have died, 3 due to progressive disease and 1 of unrelated causes. DCE and DW MRI’s with direct surgical pathological correlation were available in 7 of these pts. The mean ADC DW MRI changes in the renal lesion of 4 longer term survivors (median survival = 43 months) was +.22 vs. –0.07 in the 3 short term survivors (median survival = 13 months). RECIST/WHO criteria did not correlate with response. Evaluation of lack of enhancement on DCE MRI and increase in ADC on DW MRI were seen and correlated with necrosis on pathologic specimens. Conclusions: Four weeks of neoS is associated with significant necrosis that correlates with DCE-MRI and DW-MRI. There may be a trend in survival with greater necrosis, suggesting a role for these imaging biomarkers to assess early benefits of therapy. Clinical trial information: NCT00727532.
Prognostic factors in gemcitabine refractory advanced pancreatic cancer patients
Authors: K. Nakachi, J. Furuse, H. Ishii, M. Yoshino
Journal: Journal of Clinical Oncology (2005)

4244 Background: There is no standard chemotherapy for pancreatic cancer patients (pts) with progressive disease following Gemcitabine (Gem) treatment. This study investigated prognostic factors in pts with progressive disease after Gem. Methods: We retrospectively reviewed 75 consecutive patients who had failed after standard administration of Gem in our institute between April 2001 and March 2004. Of the 75, 16 continued Gem, 2 participated in a phaseIstudy, and the remaining 57 received best supportive care after progression. We divided patients into subgroups according to their backgrounds, and compared survival times to determine prognostic factors. Prognostic factors for survival were analyzed by univariate analysis using the Kaplan-Meier method and by multivariate analysis using the Cox proportional hazards model. Results: The median survival time (MST) was 2.0 months (95% CI 1.57–2.60). On univariate analysis, 7 variables were identified as significant factors associated with prolonged survival: hemoglobin level ≥ 8.0mg/dl (p = 0.007), platlet level ≥ 100000 (p=0.011), serum total bilirubin level < 2.0mg/dl (p = 0.040), serum albumin level ≥ 3.0 (p<0.001), serum CRP level of < 5.0 mg/dl (p<0.001), performance status (PS) of 0–1 (p<0.001), and peritoneal dissemination (p = 0.003). Among these, lower serum CRP level and good PS were associated with favorable prognosis on multivariate analysis. MST was 2.9 months (95% CI 2.37–4.27) in pts with CRP<5.0 and PS 0–1. Conclusions: The prognosis in Gem-refractory pancreatic cancer patients is extremely poor. Good PS and a lower serum CRP level should be included in the eligibility criteria in the second line clinical trials. No significant financial relationships to disclose.
Patients’ and caregivers’ views on the timing and benefits of early palliative care: A qualitative study.
Authors: Breffni Hannon, Nadia Swami, Ashley Pope, Natasha B. Leighl, Monika K. Krzyzanowska, Malcolm J. Moore, Amit M. Oza, Gary Rodin, Camilla Zimmermann
Journal: Journal of Clinical Oncology (2013)

157 Background: Early palliative care referral can improve quality of life and satisfaction with care, and is increasingly encouraged. However, little is known about patients’ and caregivers’ attitudes towards early referral. We conducted qualitative interviews seeking the opinions of advanced cancer patients (who had been randomized to an early palliative care intervention) and their caregivers, to determine whether they perceived a benefit, and if so in which domains. Methods: We recruited participants from medical oncology clinics at a comprehensive cancer centre, following completion of a randomized controlled trial comparing early palliative care referral with standard oncology care. Selective sampling was employed to ensure equivalent numbers of participants based on study arm, age, gender, high vs. low quality of life scores, and high vs. low satisfaction with care. A grounded theory approach was used to explore emerging themes. Results: Twenty-six patients and 14 caregivers completed interviews. Several benefits of early referral were noted. These included: prompt attention to symptom needs; timely, sensitive information about prognosis and end-of-life care options; and destigmatization of palliative care through routine referral. Although some participants did not feel they currently needed palliative care, they did feel comforted that early referral had provided them with a “safety net” that could quickly be put into place if they required future support. Conclusions: Early referral was perceived as useful in several domains, including immediate symptom control, and preparation for the future.
Improved clinical trial accrual using a communication tool: Best case/worst case—Clinical trials.
Authors: Toby Christopher Campbell
Journal: Journal of Clinical Oncology (2015)

26 Background: Clinical trials are crucial to the development of new treatments that may improve survival and quality of life for patients. Cancer clinical trials are hampered by chronically low participation rates. A decision support intervention designed to facilitate a shared decision making discussion with cancer patients regarding chemotherapy options could help oncologists align patient preferences with treatment options, including clinical trials. We performed a retrospective chart review comparing lung cancer patients seen in our integrated onco-palliative care clinic (PC) with standard oncology care (SOC) patients for clinical trial participation as a means of assessing potential effectiveness of the tool. The PC clinic is staffed exclusively by the author who also developed the tool. The tool is a combination of a structured discussion paired with a paper diagram the patient takes home which details all the treatment options including best supportive care alone, standard chemotherapy, and a clinical trial. Methods: Charts of every patient seen in our institution with advanced lung cancer from July 2007-June 2011 were reviewed. Eligible patients were those who received any care at our center thus excluding patient seen only for a second opinion. Demographic, treatment details, survival, and hospice utilization data were obtained. There were five oncologists included the SOC group though the vast majority of patients were seen by two providers. All providers (PC and SOC) are academic physicians who work closely together, meet weekly, have clinic on the same day, share the same research staff and have the same promotion requirements. Results: 207 patients with advanced lung cancer were identified, 82 in the PC group. A significantly higher proportion of patients participated in therapeutic clinical trials in the PC group when compared to the SOC group (29% versus 19%, adjusted OR = 2.54, p = 0.014). No difference in overall chemotherapy utilization was seen between the groups. Conclusions: Our chart review provides initial evidence that the best case/worst case: clinical trials tool may help facilitate clinical trial participation in patients with advanced lung cancer who are exploring their options.
The effect of a varied exercise program (VEP) on shoulder function and lymphedema (LE) in breast cancer survivors (BCs): A pilot study.
Authors: Sophie Hanssens, Christel Fontaine, Lore Decoster, Denis C. C. Schallier, Rik Luyten, Christiaan Watthy, Roxane Van Hemelrijck, Jacques De Greve
Journal: Journal of Clinical Oncology (2012)

82 Background: A common physical sequel after adjuvant therapy is a decrease in shoulder movement of the upper-limb of the affected side and the development of LE. Resistance exercise is known to be safe and does not increase the risk of LE. The objective of this study is to evaluate the effect of a VEP on shoulder range of motion and upper-limb LE after adjuvant therapy in BCs. Methods: 22 BCs treated with surgery and adjuvant therapy were randomly assigned to the VEP (n=12) or the control (n=10). The VEP aimed at improving aerobic endurance, joint mobility and muscle strength. The frequency of the VEP was 2 times a week, during 3 months, with a total of 30 sessions. Primary endpoints included the range shoulder motion and arm volumes of both arms. The secondary outcome was quality of life (QoL) as measured by the EORTC QLQ-C30. All outcome measures were assessed at baseline and after 3 months. Results: After ending the VEP, in the exercise group, the movements such as abduction (p=0.04), external rotation (p=0.02), extension (p=0.03) and flexion (p=0.01) of the affected arm increased significantly but there was no change for internal rotation (0.27). No significant changes in arm volume (p=0.06) were found after 3 months compared to baseline, whereas the quality of life did improve significantly (p=0.01). After 3 months the range of motion of the shoulder of the affected arm (sum of abduction, external rotation, extension and flexion) in the exercise group tended to be better although this was not significant (p=0.50). The arm volume difference between the two groups was not significant (p=0.10) but it was for the QoL (p=0.02). Conclusions: A VEP lead to significant specific improvements in arm mobility compared to baseline. These BCs also compared favourably to the control cohort, but this was not significant. The study confirms that exercising the ipsilateral arm and shoulder has no detrimental effect on LE and has a positive impact on the QoL. Standard guidelines concerning physical therapy to ameliorate shoulder function and LE are not available. Additional patients will be enrolled to develop standard recommendations for physical therapy to improve shoulder and limb function in BCs.
Feasibility of the combination chemotherapy with 5-fluorouracil and oxaliplatin in metastatic gastric or colorectal cancer patients more than age of 80.
Authors: Kyu-Hyoung Lim, Hui-Young Lee, Sung Bae Park, Seo-Young Song
Journal: Journal of Clinical Oncology (2016)

136 Background: The combination chemotherapy of 5-fluorouracil (5-FU) and Oxaliplatin is usually used in gastric cancer (GC) and colorectal cancer (CRC). The safety and efficacy of the combination chemotherapy in patients over 80-years old has not been established yet. The purpose of this study was to assess the clinical outcomes and tolerability in the combination with 5-FU, leucovorin and oxaliplatin as first-line treatment in extremely elderly patients with GC or CRC. Methods: Eligibility included: 1) more than 80-years old, 2) metastatic gastric or colorectal cancer 3) chemotherapy-naive, 4) ECOG PS 0-1, 5) adequate organ function. Patients received the combination chemotherapy of 5-FU, leucovorin and oxaliplatin. Response evaluation was done every 8 weeks with RECIST criteria and toxicity was evaluated with NCI-CTCAE. Results: Between Sep 2008 and Nov 2014, 28 patients were reviewed and composed of equal numbers of GC and CRC. The median age was 82.2 years (80.0-85.6yrs) in GC and 81.1 years (80.0-89.3) in CRC, respectively. Total administrated cycles were 89 with median cycles of 5 in GC and 112 with median cycles of 11 in CRC. The median progression-free survival (PFS) and overall survival (OS) in GC were 5.4 months and 6.6 months, as compared with 7.3 months and 8.1 months, respectively. There were no significant difference in PFS (p = 0.94) and OS (p = 0.28) between GC and CRC. Overall survival rates at 1 year were 35.7% and 42.9%, respectively. After disease progression, salvage chemotherapy in GC and CRC was administrated in 1 and 7 patients, respectively. Common grade 3/4 hematology toxicities in both group were neutropenia, anemia. Frequent non-hematological toxicities were anorexia (60%), neuropathy (40%) and mucositis (25%), which were grade 1/2. Conclusions: The combination chemotherapy of 5-fluorouracil (5-FU) and Oxaliplatin has limited effect on improvement of OS in metastatic gastric or colorectal cancer patients more than age of 80. Further studies on the role of chemotherapy in these extremely elderly patients are needed.
A combined consultation service in geriatrics and palliative care for geriatric oncology patients
Authors: I. Abdel-Karim, S. Sanchez-Reilly
Journal: Journal of Clinical Oncology (2005)

8279 Background: As many as 60% of cancer patients are 65 or older. However, geriatric patients may receive care from physicians lacking formal training in geriatrics. Geriatric oncology is a growing field and seeks to provide expert care to the elderly with cancer, improving outcome measures such as quality of life. Palliative care programs address quality of life issues, but few are specifically related to elderly populations with complementary geriatric expertise. Our combined consultation service provides expertise and interdisciplinary teaching in both: Geriatrics and Palliative Care. Clinical Case: A 67-year-old man with history of lung adenocarcinoma(stage IV: Brain and adrenal metastasis) was admitted to orthopedics with left hip pain after a fall. Further evaluation revealed no fractures but was found to have Hb=3. He was also thrombocytopenic. Our service was consulted for further geriatric medical management. On examination, vital signs were noted for regular tachycardia. He had severe left groin tenderness. He was transfused with good response. Prednisone was started for idiopathic thrombocytopenic purpura. Bone scan showed possible left iliac bone metastasis. Family conference was held and it was decided to pursue further chemotherapy and radiotherapy. Despite treatment, his platelets worsened. Our combined service was also able to address his uncontrolled pain. Morphine dose was adjusted which relieved his pain significantly. Patient was no longer symptomatic. After multiple conversations with family and primary team and given his poor prognosis, comfort care approach was decided upon. Conclusions: Our service provided this patient with appropriate special care at a given time. The literature lacks evidence on the effect of combined programs in geriatrics and palliative care, with physicians that have dual expertise. This setting is ideal to contribute to the management of patients with severe chronic illnesses such as cancer. Geriatric oncology trainees are part of our service. We believe it is essential for oncologists to acquire expertise in the field of geriatrics and palliative care. Future research is needed to evaluate the impact of this type of programs on patient care and quality of life. No significant financial relationships to disclose.