tbuckley/cabot-search huggingface dataset:
Time-dependent patterns of recurrence and death in resected colon cancer (CC): Pooled analysis of 12,223 patients from modern trials in the ACCENT database containing oxaliplatin.
Authors: Lindsay A. Renfro, Manish A. Shah, Carmen Joseph Allegra, Thierry Andre, Aimery De Gramont, Frank A. Sinicrope, Hans-Joachim Schmoll, Daniel G. Haller, Steven R. Alberts, Greg Yothers, Daniel J. Sargent
Journal: Journal of Clinical Oncology (2015)

3593 Background: A 2009 analysis of 20,898 CC patients from 18 randomized studies of adjuvant therapy (AT) in the ACCENT database showed that treatment with AT (versus surgery alone) lowers the risk of recurrence and death at all time points, especially in stage III (versus stage II) disease. However, this analysis evaluated only FU/LV therapies and excluded modern oxaliplatin-based (OX) therapies. Methods: With mature follow-up now available (median 6 years), 12,233 patients from ACCENT enrolled to C-07, C-08, N0147, MOSAIC, and XELOXA (18% stage II, 82% stage III) were pooled to examine the impact of OX and tumor specific factors (tumor stage, nodal stage, tumor location, and tumor grade) on the time course of recurrence and death from all causes. For each endpoint, continuous-time risk was modeled over 8 years post-treatment in (1) OX-treated patients from all trials and (2) patients concurrently randomized to OX versus 5FU/LV, where the latter set of analyses supported time-dependent treatment comparisons. Results: Addition of OX reduced the risk of recurrence and death at all time points and in all disease subgroups, with no differences in the timing of outcomes between treatment groups (i.e., OX did not simply postpone recurrence or death compared to 5FU/LV alone; see Table). OX significantly reduced recurrence risk during the first 4 years, and significantly reduced risk of death from 2 to 6 years post-treatment. Recurrence risk peaked near 14 months for both treatment groups, with 83% of patients treated with OX (80% of patients treated with 5FU/LV) who recurred within 8 years doing so by 3 years post-treatment. Risk of recurrence and death increased with increased tumor and nodal burden. Conclusions: These analyses support the addition of oxaliplatin to fluoropyrimidines as a curative therapy in the adjuvant setting and strongly underscore the need for adequate surveillance of CC patients, especially during the first 3 years after adjuvant therapy. Year 1 Year 2 Year 3 Year 4 Year 5 Recur 5FU 11.0% 10.5% 5.2% 3.4% 2.0% OX 8.6% 8.8% 4.7% 2.2% 1.9% Death 5FU 2.9% 5.4% 5.4% 4.9% 3.8% OX 2.8% 5.3% 4.3% 4.5% 3.2%
High-dose intense doxorubicin-based regimens in aggressive non-Hodgkin's lymphoma: A systematic overview
Authors: H. A. Azim, R. A. Malek, L. Santoro, S. Gandini, R. G. Bociek, H. A. Azim
Journal: Journal of Clinical Oncology (2009)

e19528 Background: Aggressive non-Hodgkin's lymphoma represents around 60% of lymphomas in the Western world and even more in Egypt. CHOP has been long been recognized as the standard chemotherapy regimen in this disease. The addition of rituximab (R) to CHOP in the treatment of B-cell subtypes has resulted in a significant improvement in all treatment endpoints. Nevertheless, still a significant fraction of patients in the developing world are not offered R due to economical reasons. Thus CHOP is still offered to these patients as well as those with T-cell subtypes. Data from the early 1990s have suggested that the dose intensity (DI) of doxorubicin may have a prognostic value. Hence we conducted a metaanalysis on chemotherapy regimens incorporating higher DI doxorubicin and compare them to CHOP in terms of complete response (CR) rate, event free survival (EFS) and overall survival (OAS). Methods: A MEDLINE and COCHRANE library search was performed using the search terms ‘CHOP‘, ‘lymphoma‘ and ‘randomized trials‘. Eligible trials were randomized trials, having CHOP as a control arm and any chemotherapy regimen administering doxorubicin at a higher DI than that of CHOP (16mg/m2/week) as the investigational arm. Pooling of data was performed using the mixed effect model. The outcome measure for pooling the CR rate was the odds ratio (OR) while the hazard ratio (HR) was the outcome measure for EFS and OAS. Confidence intervals were estimated according to the method developed by Parmar. Results: Eight trials published until February 2008 met the inclusion criteria. They included 3,668 patients randomly assigned to either CHOP (1,660 patients) or DI doxorubicin-based regimen (2008 patients). Patients receiving DI doxorubicin-based regimen had a significantly better overall survival (HR; 0.79; 95% CI: 0.66–0.94). As for the EFS and CR analyses, there was a trend in favor of patients who received the DI regimens; however the difference was not statistically significant (HR: 0.86; 95% CI: 0.71–1.03 &amp; OR: 0.8; 95% CI: 0.63–1.02 respectively). Conclusions: High DI doxorubicin-based regimens are associated with a better OAS compared to CHOP. Such approach should be considered in patients with aggressive B-cell lymphomas not offered R as well as those with T-cell lymphomas. No significant financial relationships to disclose.
A pilot study to assess the feasibility of administering a short geriatric assessment (SGA) in older cancer patients.
Authors: Hongbin Chen, Elongia Farrell, Adrienne Groman, Grace K. Dy, Jerome W. Yates
Journal: Journal of Clinical Oncology (2014)

e20520 Background: Given the heterogeneity in older cancer patients, it is important to identify those who can tolerate and benefit from chemotherapy. The SGA was developed as an assessment tool to be administered in a busy outpatient clinic with minimal operational disruption. It incorporates measures of 5 domains in psychosocial support, comorbidity, physical activity and performance, and selected clinical laboratory findings. The purpose of this pilot project was to determine the feasibility of introducing the SGA into oncology clinics. Methods: Cancer patients ≥ 65 years old were identified and consented in the thoracic oncology clinic of a comprehensive cancer center. The clinic nurse administered the 25-item SGA, including the clock drawing and a 4-minute walk, and recorded the time to conduct the entire questionnaire. The assessment was done in the clinic either before or after that clinic visit to minimize disruption of the clinic flow. The primary endpoint was the feasibility of collecting the information by clinic nurses using the SGA, as determined by: the average length of time to complete, the percentage of patients able to complete the instrument in 20 minutes, and missing items because of comprehension or performance difficulties. The patients and nurses were also surveyed on the ease of completing the assessment on a 5-point Likert scale (5 being the easiest). The study will be considered feasible if 40 out of 50 patients complete the SGA in less than 20 minutes. Results: A total of 50 patients were enrolled, with an average age of 73.8 (range 65-88) years. 52% were male and 98% were Caucasian. 43 were non-small cell lung cancer, 6 small cell lung cancer, and 1 mesothelioma. 44% had stage IIIB/IV disease. It took an average of 13.7 (range 10-18) minutes to complete the SGA. No item was missing due to difficulty of comprehension or performance. 78% of patients and all the nurses rated 5 of ease in completing the SGA. Conclusions: This pilot feasibility study met its primary endpoint with 100% completion of the SGA within 20 minutes and low burden to the participating patients and administering nurses. Its validity, reliability and predictive value will be explored subsequently.
Large volume peripheral blood progenitor cell (PBPC) harvest in 27 pediatric solid tumor patients weighing less than 20 Kg
Authors: D. Fernández Sasso, O. López, M. García Lombardi, G. Chantada, M. Figueroa, B. Diez, C. Dengra, B. Koziner
Journal: Journal of Clinical Oncology (2006)

9061 While PBPC collection has become a safe and common procedure in adults, fewer reports exist about its efficacy and safety in low weight pediatric patients. PBPC harvest might be difficult in this patient population and extracorporeal separator line priming with red blood cells is usually required to improve hemodynamic stability and effectiveness of the collection. We present our experience in 27 children (11 females, 16 males) weighing less than 20 kg and autografted between May 2001 and December 2005. Median age and weight at the time of apheresis were 2.7 years (0.7 to 8) and 14.3 kg (9.7 to 20), respectively. Diagnosis were neuroblastoma in 15, brain tumor in 10, and others in 2. Harvest of PBPC started after mobilization with G-CSF 10 ug/kg/day SC for 4 days. A double lumen (Arrow 7Fr) central venous catheter was surgically placed under sedation in the OR. Collections were performed using a COBE Spectra separator primed with irradiated, white cell-depleted and CMV-negative packed red cells. A median of 2 (1 to 7) procedures were performed, resulting in the harvest of 12.9 (3.6–33.1) × 10 8 /kg mononuclear cells and 4.98 (2.33–12.69) × 10 6 /kg CD34 (+) cells. The apheresis were performed in the presence of the parents and did not require sedation. Only 1 patient had as side-effect perioral paresthesias with normal serum calcium. No patient had vasovagal reactions. A median platelet count reduction of 66% was observed, comparing pre and post apheresis values. All patients completed the procedure with a median of 71.800 platelets (25.000 to 152.000) and a median hemoglobin of 10.8 g/dl (8.2 to13.6). All children were successfully transplanted with myeloid engraftment (ANC &gt;500 × 10 9 /L) at a median of 11 days (9 to 14) and independence from platelet transfusions (&gt; 20,000x × 10 9 /L) at a median of 17 days (8 to 39) after PBPC infusion. Median of hospitalization days was 23 (18 to 42). We conclude that PBPC harvesting using large volume continuous flow cell separation was safe, even in this low-weight pediatric population. This procedure shortens the total number of apheresis, providing an adequate number of CD34 + cells, resulting in satisfactory hematological recovery and duration of hospitalization. No significant financial relationships to disclose.
Early toxicity in a prospective phase I/II trial of MRI-assisted focal boost integrated with HDR monotherapy for low- and intermediate-risk prostate cancer.
Authors: Laura D'alimonte, Joelle Antoine Helou, Gerard Morton, Hans T. Chung, Merrylee McGuffin, Ananth Ravi, Andrew Loblaw
Journal: Journal of Clinical Oncology (2017)

120 Background: There is growing evidence for the use of High Dose Rate (HDR) brachytherapy as monotherapy for the treatment of low and intermediate risk prostate cancer patients. With the increasing availability of magnetic resonance imaging (MRI) there is an opportunity to further escalate dose to the dominant intraprostatic lesion (DIL). We report acute toxicity of this prospective phase I/II trial. Methods: Eligible patients had low- and intermediate risk prostate cancer, IPSS &lt; 16, were medically eligible for HDR brachytherapy treatment and had an identified DIL on multiparametric MRI (mpMRI) prior to brachytherapy treatment. Patients were treated with 19 Gy delivered in one fraction to the whole prostate. A 0-5mm expansion was applied to the DIL to define the PTV DIL, with a DIL PTV D90 to receive &gt; 23Gy based on previous experience. Toxicity was assessed using CTCAE v.4.0 at baseline, 6 weeks 3, 6, 9 and 12 months post brachytherapy. Results: A total of 34 patients have undergone HDR monotherapy treatment with an integrated DIL boost with a median follow up of 6 months. The median age was 67 years (range 46-80). At presentation, median PSA was 6.1 ng/mL (range 2.5-16.4). Three, 26, and 6 patients had low, low intermediate and high intermediate risk disease. Baseline characteristics were PIRAD 5 (n = 21) and PIRAD 4 (n = 13), median prostate volume was 38 cc (range 18-54). The median DIL volume was 2.8 cc (range 1.14-7.8). The median DIL D90 was 27 Gy (range 19-35.8). No patients experienced acute or late grade 2+ GI toxicity. The percentage of acute grade 2 GU toxicity were as follows; retention 62%, frequency 18%, urinary tract pain 6%. One patient had acute clot retention requiring catheterization x1 day and has been catheter-free since. Late grade 2 GU toxicity (alpha blockers) was reported in 6/16 patients at 6 months. Conclusions: The use of mpMRI to define and further escalate dose to the DIL using HDR monotherapy is feasible with minimal acute toxicities. Further long term follow up is required to determine the efficacy of treatment, and impact on quality of life and late toxicities. Clinical trial information: NCT02623933.
Real life treatment sequences and survival of men with metastatic castrate-resistant prostate cancer (mCRPC) receiving cabazitaxel in clinical practice across England.
Authors: Alison J. Birtle, Amit Bahl, Mohammad Butt, Shermaine Pan, Angela M Carter, Alastair H Thomson
Journal: Journal of Clinical Oncology (2017)

e573 Background: New life-prolonging anticancer treatments (LPT), including docetaxel (D), cabazitaxel (C), abiraterone (A) and enzalutamide (E) have transformed outcomes for patients with mCRPC; however, optimal treatment sequencing is unclear. The aim of this study was to describe the anticancer treatment sequencing and outcomes of patients receiving cabazitaxel in England. Methods: A multi-centre, observational, retrospective study of mCRPC patients treated with cabazitaxel after docetaxel treatment failure was conducted. Data on patient characteristics, anticancer treatments, toxicity and outcomes were collected from medical records between March 2015 and March 2016. Results: 115 patients with mCRPC from 5 English hospitals were evaluated. Mean age at cabazitaxel initiation was 69.4 (SD: 6.7) years. Median time from mCRPC diagnosis to cabazitaxel initiation was 18.0 (interquartile range: 11.4–28.7) months. Cabazitaxel was 2 nd line therapy after docetaxel in 58/115 (50%) patients. Patients received a median of 3 (range: 2–4) different LPTs: 5 patients received 2 therapies (DC = 5); 89 patients received 3 therapies (DAC = 44, DCA = 32, DCE = 7, ADC = 4, DEC = 1, EDC = 1); 21 patients received 4 therapies (DACE = 9; DCAE = 5; DCEA = 5; DAEC = 2). Median overall survival (OS) from mCRPC diagnosis and from docetaxel initiation according to number of LPTs is presented in the table. Conclusions: A variety of mCRPC treatment sequences are used in real-world practice. OS was greater in those patients receiving ≥3 LPTs, with a non-significant yet intriguing trend to longer OS with DCA. Further follow up may indicate whether this will become statistically significant. [Table: see text]
Skeletal muscle depletion to predict survival of patients with advanced biliary tract cancer undergoing palliative chemotherapy.
Authors: Kyoung Min Cho, Do-Youn Oh, Tae Yong Kim, Kyung-Hun Lee, Sae-Won Han, Seock-Ah Im, Tae-You Kim, Yung-Jue Bang
Journal: Journal of Clinical Oncology (2017)

460 Background: Reports regarding sarcopenia as a prognostic factor in advanced biliary tract cancer (BTC) are rare. Furthermore, no study has investigated the dynamics of body weight with body muscle mass as a prognostic factor in advanced BTC patients undergoing palliative chemotherapy. Hence, we investigated whether sarcopenia affects survival in patients with BTC, with a co-analysis of body weight loss and body mass index (BMI). Methods: We consecutively enrolled patients with advanced BTC who received palliative chemotherapy between 2003 and 2013. Total muscle cross-sectional area (cm 2 ) at the L3 level assessed by computed tomography was analyzed. We defined sarcopenia as a skeletal muscle index (SMI) &lt; 48.5 cm 2 /m 2 (men) and &lt; 39.5 cm 2 /m 2 (women) using ROC curves. Results: The proportion of patients with sarcopenia upon diagnosis was 52.4% and 42.2% for men and women, respectively. By multivariate analysis, sarcopenia at diagnosis and decreased SMI during chemotherapy ( P = 0.008 and P &lt; 0.001, respectively) were poor prognostic factors for overall survival (OS). Subgroup analysis revealed that sarcopenic patients who were overweight or obese (BMI ≥ 25 kg/m 2 ) showed worse OS ( P &lt; 0.001). Additionally, patients with both decreased BMI and SMI during chemotherapy had worse OS ( P &lt; 0.001). Furthermore, patients with decreased SMI had shorter survival regardless of change in BMI. However, for patients with SMI maintained during chemotherapy, decreased BMI had no effect on survival ( P = 0.576). Conclusions: Sarcopenia, sarcopenic obesity and muscle depletion during palliative chemotherapy are meaningful prognostic factors in advanced BTC. Considering muscle depletion with weight change could help to more accurately predict prognosis of patients with BTC.
Risk assessment model for first-cycle chemotherapy-induced anaemia (CIA) in patients with solid tumours (ST): DELFOS Study
Authors: A. López-Pousa, J. Rifà, A. Casas Fernández de Tejerina, J. L. González Larriba, C. Iglesias, J. A. Gasquet, A. Carrato
Journal: Journal of Clinical Oncology (2007)

9122 Background: CIA, a major side effect of systemic cancer chemotherapy, is directly associated with concomitant morbidity, mortality and costs, and therefore has a strong impact on both patient health and healthcare systems. The objective of the present research study is to determine a predictive model for first-cycle CIA in patients with ST in Spain. This will help to establish appropriate protocols in routine patient care, hence improving clinical decision making. Methods: Data were obtained from the DELFOS Study, a multicentre non- interventional prospective-cohort study in Spain. This study has completed enrolment and data were available for this planned analysis. To obtain the predictive logistic regression model (LRM), the hierarchical principle was followed as a way to enable results replication. The model was implemented for CIA defined as anaemia grade = 2 (haemoglobin [Hb]&lt;10 mg/dL). Anaemic patients at baseline according to this criterion were excluded from the studied sample to avoid bias. A receiver operating characteristics (ROC) Curve was used to determine the model's sensitivity and specificity. Results: A total of 1,140 pts (57.3 % female; mean age: 58 yrs [SD: 12]; ECOG = 2) with ST (breast, 38.1%; lung 17.5%; colorectal, 14.3%; other 30.1%) and baseline Hb&gt;10mg/dL were included from 88 Spanish medical oncology health centres. The LRM obtained predicting CIA (p Chi-sq &lt; 0.0005) contained the following factors: gender, baseline haemoglobin, platinum-based chemotherapy (PBC) and baseline bilirubin. Risk factors and size effects included: male gender (p=0.003, OR=2.41, 95%CI (1.34, 4.31)), low baseline Hb (p&lt;0.0005, OR=3.32, 95%CI (2.52, 4.39)), PBC as treatment (p=0.017, OR=2.04, 95%CI (1.13, 3.66)) and baseline bilirubin (p=0.029, OR=1.93, 95%CI (1.07, 3.49)). Inherent sensitivity and specificity of the equation were, respectively, 77.6% and 79.2%. Conclusions: A risk predictive model for first-cycle chemotherapy-induced anaemia in patients with ST in Spain was implemented. Four predictive factors were identified. Baseline Hb values were inversely associated with toxicity. Male gender, platinum-based chemotherapy and high bilirubin values showed themselves as risk factors for anaemia. No significant financial relationships to disclose.
Analysis of tissue and circulating tumor DNA by next-generation sequencing of hepatocellular carcinoma.
Authors: Sadakatsu Ikeda, Jordan S Lim, Razelle Kurzrock
Journal: Journal of Clinical Oncology (2017)

298 Background: Hepatocellular carcinoma (HCC) has limited treatment options. Molecular analysis of its mutational landscape may enable the discovery of new treatment option.However, biopsy is not routinely performed in HCC and involves risks. The utility of analyzing cell-free circulating tumor DNA (ctDNA) by next-generation sequencing (NGS) is not established. Methods: We performed 32 ctDNA NGS and 10 tissue NGS analyses in 26 patients with advanced HCC (January 2015 – October 2015). ctDNA analysis (54 to 70 genes) was performed using Guardant 360, which detects single nucleotide variants, amplifications, fusions, and specific insertion/deletion mutations. The mutant allele fraction for detected alterations was calculated relative to wild type in ctDNA. Tissue NGS was performed using Foundation One or Molecular Health. The study ws conducted in accordance with UCSD Moores Cancer Center Institutional Review Board requirements. Results: Among 32 ctDNA NGS, at least one genomic alteration (excluding variants of uncertain significance (VUS)) was discerned in 27 samples (84.3%) (average = 2.1 alterations per patient [range, 0-5]) with a median mutant allele fraction of 0.92% (range, 0.06% - 40.57%). Ten patients had both ctDNA NGS and tissue NGS. The median time difference between the date of tissue and ctDNA NGS testing was 450 days (range, 29 – 876 days), possibly reflecting the challenge with doing a second tissue biopsy at the time of relapse. The most commonly mutated gene was TP53 (16 samples, 50.0%), followed by CTNNB1 (8 samples, 25.0%), ARID1A (6 samples, 18.6%), EGFR (4 samples, 12.5%) and MYC (4 samples, 12.5%). Amplification was observed in 11 genes, including CDK4, CDK6, CCNE1, EGFR, ERBB2, FGFR1, KRAS, and MYC. No fusions or indels were observed. At least one potentially actionable alteration was observed in 20 of the 26 patients (76.9%). In two patients treated on the basis of the ctDNA alterations alone, a response was seen. Conclusions: ctDNA profiling is feasible in advanced HCC, and may provide a tissue biopsy-free alternative in these difficult-to-biopsy patients. Further study of clinical validity and utility is ongoing.