tbuckley/cabot-search huggingface dataset:
Complementary role of Ki67 index and 70-gene signature (MammaPrint) high-risk patients in the St Gallen risk group with uncertain chemotherapy suggestion.
Authors: Paolo Pronzato, Giorgio Mustacchi, Daniele Giulio Generali, Alberto Bottini
Journal: Journal of Clinical Oncology (2012)

579 Background: St Gallen (SG) Consensus Panel on adjuvant treatment recommends the use of proliferation markers and multigene assays when choosing the appropriate treatment in addition to traditional parameters. Ki67 predictive/prognostic value is widely accepted; we tested its role in increasing the accuracy of risk prediction among Mammaprint (MP) /High(HR) or /Low Risk (LR) breast cancer patients with a SG risk uncertain for chemotherapy selection. Methods: MP was determined (courtesy of Agendia, Amsterdam) in 3 Italian Hospitals on 305 consecutive samples of breast cancer patients. We focused on SG “Intermediate Risk” Group (HER2 neg, no VI and: ER&gt;10&lt;50%, or G2 or Ki67 &gt;15&lt;30% or N1a or T&gt;2&lt;5cm), where the indication for adjuvant CHT still remains uncertain. In MP/HR cases, a “low” Ki67 value (&lt;15%) was used to eliminate CHT suggestion and viceversa an “intermediate” Ki67 value (&gt;15&lt;30%) in MP/LR cases. Results: Overall, 72/305 pts (26.6%) were in SG intermediate risk group with a median age of 64 years (26-98). Ki67 was non available in 4.1% of cases, MP rejected in 16.6%, HR was detected in 39 (54.2%), whereas LR in 21 (29.2%). Ki67 resulted low in 23 MP/HR cases (59%), intermediate in 6 MP/LR cases (28.5%) and in 3 out 12 MP/Rejected cases (25%). The overall concordance between MP and Ki67 was 28/57 (49.1%), MP rejected excluded. Overall MP suggested 39/60 CHT (65%), Ki67 29/69 (42%). Conclusions: The risk of relapse is a continous variable and MP evaluates it in a dichotomy (low vs high) wich could decrease the accuracy of the test. In the selected SG Group, the average risk of 5 yr relapse is around 20% (EBCTCG, Lancet 2011) and MP HR cases in our experience account for 55%. A low Ki67 value could help avoid more than 20% of cytotoxic treatments suggested by MP. In the same way, according to an ER value &lt;50% (2 cases), an intermediate Ki67 value could suggest a more aggressive treatment in a further 13% of cases MP LR (6/21) or Rejected (3/12). MP probably overestimates the risk in 20% of cases and underestimates it in further 20%. Ki67 could be usefull for a more personalized treatment in patients where the indication for adjuvant chemotherapy added to endocrine treatment is uncertain.
Development of cavitation while on bevacizumab (BV) therapy in patients (pts) with non-small cell lung cancer (NSCLC): Results from ARIES—A bevacizumab (BV) treatment observational cohort study (OCS)
Authors: M. P. Kosty, P. Kumar, A. Wozniak, M. Jahanzeb, C. Chung, L. Wang, A. Sing, T. Lynch
Journal: Journal of Clinical Oncology (2009)

e19045 Background: BV (Avastin), an anti-VEGF monoclonal antibody, prolongs progression-free and overall survival in advanced NSCLC pts. Severe (≥grade 3) pulmonary hemorrhage (sPH) is a rare but serious event that has been associated with BV-based therapy in phase 3 trials (rate of 2–4%). Potential risk factors include squamous histology, prior history of hemoptysis, and presence of tumor cavitation. Rates of baseline (BL) cavitation in NSCLC pts and development of cavitation on BV therapy are unknown. Pts in ARIES, an OCS of approximately 2,000 pts with NSCLC, had BL scans assessed for tumor cavitation. A substudy of approximately 250 pts also had follow-up scans to analyze the likelihood of developing cavitation on BV therapy. For the entire ARIES population, any pt developing sPH is assessed for tumor cavitation. Methods: Pts at specified ARIES sites submitted on-treatment CT scans to an independent review facility (IRF), in addition to BL scans. Evaluable pts had measurable disease at BL and at least one-post-BL scan. Correlations between cavitation (pre-existing or developing on-study) and clinical, tumor and treatment characteristics are evaluated using a chi-squared test or t-test. Incidence of sPH based on cavitation status will be assessed using Fisher's exact test. Results: As of 9/15/08, 210 pts had a post-BL CT scan reviewed by the IRF. Of these pts, 171 had measurable tumors at BL. For the 171 pt cohort: median F/U is 9.2 m; 99% have ≥1 quarterly update. Key BL characteristics for the substudy and overall cohorts, respectively, include: 44% vs 51% ≥65 yrs; 67% vs 67% adenocarcinoma; 6% vs 5% therapeutic AC. BL radiographic features: 41% vs 39% presence of central tumor; 13% vs 15% presence of cavitation. In substudy pts, there is 1 sPH to date in a pt without baseline cavitation. Conclusions: sPH is a rare, potentially serious event in pts with NSCLC receiving BV. Whether cavitation (BL or developing on-treatment) is associated with an increased risk of sPH has not been defined. The final analysis of an ARIES Lung substudy assessing on-study development of cavitation and association with sPH will be presented at the meeting. [Table: see text]
Exploratory study of intraperitoneal paclitaxel plus mFOLFOX6 for gastric cancer patients with peritoneal metastasis and inadequate oral intake.
Authors: Shuntaro Yoshida, Hironori Ishigami, Kei Muro, Shigenori Kadowaki, Yasushi Tsuji, Yumiko Ohta, Hiroharu Yamashita, Hironori Yamaguchi, Joji Kitayama
Journal: Journal of Clinical Oncology (2017)

TPS222 Background: Systemic chemotherapy with oral fluoropyrimidine and platinum is recommended for the first-line treatment for unresectable or recurrent gastric cancer in Japan. However, some patients with severe peritoneal metastasis cannot take oral medications because of obstruction or dysfunction of the gastrointestinal tract. FOLFOX is regarded as one of the candidates for the standard of care for gastric cancer, and is now being evaluated in clinical trials. Intraperitoneal (IP) paclitaxel (PTX) provides sustained high local concentrations, and its efficacy has been shown in ovarian and gastric cancer. We developed a regimen combining IP PTX with S-1/PTX, and the phase III trial comparing with S-1/cisplatin suggested efficacy of this regimen. Therefore, we designed a regimen combining IP PTX with mFOLFOX6, and started an exploratory study in gastric cancer patients with peritoneal metastasis and inadequate oral intake. Methods: This is a prospective, multicenter, single-arm phase I/II study. Eligibility criteria include: pathologically proven unresectable or recurrent gastric adenocarcinoma; peritoneal metastasis; inadequate oral intake; adequate bone marrow function; acceptable liver and renal function; ECOG performance status of 0-2 and age between 20-80 years. Patients undergo diagnostic laparoscopy and are implanted with an IP port in the subcutaneous space of the lower abdomen, with a catheter placed in the pelvic cavity. mFOLFOX6 is administered bi-weekly, and IP PTX 20 mg/m 2 is administered through an IP port on days 1, 8 and 15. The treatment course is repeated every 4 weeks until disease progression or unacceptable toxicity. The primary endpoint is the 1-year overall survival rate. Secondary endpoints are progression free survival, time to treatment failure, response rate, negative conversion rate on peritoneal cytology and safety. Twenty medical institutions from all over Japan participate in this study, and 34 patients are to be enrolled in two years. Toxicity will be evaluated in the early stage, and the protocol will be reconsidered and revised if all of the first 3 or more than 2 of the first 6 patients develop dose-limiting toxicities. Clinical trial information: UMIN000019206.
HOVON 104; Results of First 25 Patients from a Multicenter, Multinational, Prospective Phase II Study of Bortezomib Based Induction Treatment Followed By Autologous Stem Cell Transplantation in Patients with Newly Diagnosed Al Amyloidosis
Authors: Monique Minnema, Kazem Nasserinejad, Bouke Hazenberg, Ute Hegenbart, Lucien Noens, Paula F. Ypma, Sonja Zweegman, Lidwine Winnifred Tick, Annemiek Broijl, Harry R. Koene, Gerard M.J. Bos, Pieter Sonneveld, Stefan O. Schoenland
Journal: Blood (2016)
Masitinib plus FOLFIRI for second line treatment of metastatic colorectal cancer: An open label phase Ib/II trial.
Authors: Julien Taieb, Christophe Borg, Thierry Lecomte, Céline Lepère, Thierry Chatellier, Denis Michel Smith, Patrice Dubreuil, Colin Mansfield, Alain Moussy, Olivier Hermine
Journal: Journal of Clinical Oncology (2015)

3526 Background: Masitinib (MAS) is a selective inhibitor of c-Kit and mast cell function. Increased mast cell activity in the tumor microenvironment is linked to poor prognosis and a protumoral immune response in colorectal cancer (CRC). In vitro, MAS acts as a chemosensitizer of 5-fluorouracil and irinotecan in CRC cell lines. This trial evaluated MAS in combination with chemotherapies. We report here findings from the cohort receiving MAS + FOLFIRI. Methods: Patients (pts) with nonresectable, metastatic CRC after progression to first line treatment received MAS + FOLFIRI until progression, refusal or unacceptable toxicity. Patients previously treated with irinotecan were excluded. Phase 1 evaluated safety of the combination with Dose Limiting Toxicity (DLT) determining subsequent dose and recruitment. DLT was defined as grade 3 non hematological adverse event (AE) or any grade 4 AE related to MAS. Phase 2 evaluated efficacy. Results: Eighteen pts (50% with mutated KRAS) from 6 centers in France were treated. MAS dose was reduced from 9 to 6 mg/kg/day for the final 3 pts based on new mechanistic understanding and to minimize risk of toxicity. No DLT was reported for the phase 1 stage (3 pts) at 9 mg/kg/day. After a median follow-up of 22.8 months, median OS was 17.6 months (95%CI [8.9; 20]) and median PFS was 6.2 months (95%CI [3.1; 9.2]). Overall response rate was 28%, including 1 pt with a confirmed complete response. Efficacy was still evident in the 3 pts treated at 6 mg/kg/day with PFS of 9.2, 6.2 and 5.6 months without any grade 3-4 AE in this cohort. Overall, 6/18 pts (33%) reported grade 3-4 AE and 4/18 pts (22%) experienced serious AE. No treatment related deaths were reported. Conclusions: The safety profile of MAS + FOLFIRI was acceptable. Efficacy findings seem to compare favorably against historic benchmarks (see table). MAS may therefore offer patients a new active compound for mCRC. A confirmatory phase 3 trial evaluating FOLFIRI+/- MAS at 6 mg/kg/day as second line for mCRC is ongoing. MAS + FOLFIRI *FOLFIRI wildtype KRAS *FOLFIRI mutant KRAS OS (months) 17.6 12.5 11.1 PFS (months) 6.2 3.9 4.9 Objective Response Rate 28% 10% 14% Complete 6% 0% 0% Partial 22% 10% 14% * Peeters (2010) J Clin Oncol 28: 4706.
Expression of the CXCL12/CXCR4 chemokine axis as predictor of regional control in head and neck squamous cell carcinoma (HNSCC).
Authors: Antonio Lopez-Pousa, Xavier Leon, Mercedes Camacho, Luis Vila, Miquel Quer, Montserrat Lopez, Jacinto Garcia, Josep M. De Vega, Nuria Farre, Oscar Gallego, M. J. Quintana, Cristina Arqueros, Georgia Anguera, Dhiossett Condori, I. Sullivan
Journal: Journal of Clinical Oncology (2015)

e17093 Background: Locoregional recurrence in HNSCC is related to the stage, nodal invasion (number, size, location, rupture), and treatment. Risk of nodal recurrence after radical treatment is 10-25% of patients. CXCL12 is a ligand of CXCR4 chemokine receptor. The activity of CXCL12/CXCR4 axis is related with progresion in HNSCC: High CXCR4 expression with increased risk of nodal invasion, low CXCL12 expression with low risk of local and distant recurrence. Aim of the study: to evaluate the expression of the CXCR4/CXCL12 axis, and to assess correlations between these biomarkers and the regional control. Methods: Biopsies from 111 consecutive HNSCC (stage II-IV) p. treated with radical intention between 2004-2009, acording clinical practice guidelines. A tissue sample of non-tumoral mucosa was obtained in 77 cases. Surgery was performed in 28 (25%) patients, Radiotherapy (70-72 Gy to the primary tumor and involved nodal areas, 50 Gy in uninvolved nodal areas) or chemoradiotherapy (three cycles of 100 mg/m2 cisplatin on days 1,21and 43 of radiotherapy, or carboplatin 1.5 AUC weekly) in 83 (75%) p. mRNA expression of the genes evaluated and b-actin as endogenous control was studied by PCR. Relative expression expressed as b-actin ratio. The continuous values of the mRNA expression levels were categorized with the classification and regression tree (CRT) method Results: During follow-up, 28 patients (25.2%) presented local recurrence, 19 (17.1%) regional and 14 (12.6%) metastatic disease. There were no differences in the CXCL12 and CXCR4 expression according the location, T or N (N0 vs N+). Recursive partitioning analysis (RPA) did not find significant relation between local control and expression values of CXCL12 and CXCR4. There was significant difference in RFS for patients with highCXCR4/low CXCL12 vs highCXCR4/highCXCL12 (63.3% vs 94.7, p 0.001). In the multivariate analysis the only significant variable for RFS was the expression of the axis CXCL12/CXCR4 (low/high expression) with an increased regional risk of recurrence of 10.7 times (p 0.002) Conclusions: The expression of CXCL12/CXCR4 axis could define a group of patients with high risk of nodal progression, as independent variable.
First-in-human phase I study of a selective c-Met inhibitor volitinib (HMP504/AZD6094) in patients with advanced solid tumors.
Authors: Hui Kong Gan, Jason Lickliter, Michael Millward, Yi Gu, Weiguo SU, Melanie Frigault, Chuan Qi, Hua MU
Journal: Journal of Clinical Oncology (2014)

11111 Background: Volitinib is a selective oral small molecule inhibitor of cMet kinase with potent in vivo inhibitory effects on a variety of human tumor xenografts. Methods: This phase I, first-in-human dose-escalation study was conducted to determine the maximum tolerated dose (MTD), dose-limiting toxicities (DLTs), pharmacokinetics (PK) profile, and preliminary antitumor activity of volitinib. Results: By Dec 31, 2013, 32 patients (pts) had been enrolled and treated with volitinib at doses of 100-1000mg QD or 300-400mg BID. Pts had a median age of 61 (27-78) yrs, 66% were male. The most common tumor types were papillary renal cell carcinoma (PRCC, 6) and CRC (5). The most common adverse events were constipation, diarrhea, fatigue, nausea, vomiting, dizziness and peripheral edema, mostly grade (G) 1/2. Four pts reported 5 DLTs: 1 G3 elevated ALT (600mg QD), 1 G3 fatigue (800mg QD), and 2 G3 fatigues and 1 G3 headache (1000mg QD). 800mg was identified as MTD of the QD regimen. Dose-escalation in the BID cohort is currently ongoing at 400mg BID. PK analysis showed volitinib was rapidly absorbed with Tmax around 2 hours and half-life around 5 hours. Both Cmax and AUC displayed dose-proportional increase and no obvious accumulation occurred. Two PRCC pts in the 600mg QD cohort (one with ongoing treatment at 1 year) and 1 PRCC pt in the 300mg BID cohort achieved partial response. A CRC pt in the 600mg QD cohort achieved 29% tumor reduction. A PRCC pt in the 1000mg QD cohort achieved 27% tumor reduction and remains on study. Analysis of pre-treatment tumor sample showed that the responders had either gene copy number increase (Chromosome7 gains or MET gene amplification) or high MET protein expression. Conclusions: Volitinib was well tolerated at doses up to 800 mg QD and demonstrated promising anti-tumor activity in pts with evidence of dysregulated MET signaling. It demonstrated linear PK without marked drug accumulation. Further clinical studies are warranted. Clinical trial information: NCT01773018.
A clinical prognostic model to predict survival and efficacy in advanced or metastatic non-small cell lung cancer patients who received first-line chemotherapy: A retrospective analysis of 236 patients in northeast China.
Authors: Xiujuan Qu, Jing Gong, Xuejun Hu, Bo Jin, Mingfang Zhao, Ping Yu, Yunpeng Liu
Journal: Journal of Clinical Oncology (2013)

e19004 Background: This study was aimed to build a prognostic model for survival and predict efficacy in patients undergoing first-line chemotherapy in advanced or metastatic non-small cell lung cancer. Methods: Sixteen pretreatment clinical and biological variables were analyzed in 236 NSCLC patients who received first-line chemotherapy in our hospital. The prognostic model was calculated according to the results of multivariate Cox model, and the survival in different score groups were estimated by the Kaplan-Meier method and Long-rank tests. Results: Sixteen factors (smoking history, performance status, gender, disease stage, histological type, LDH, fibrinogen, WBC count, granulocyte count, lymphocyte count, hemoglobin, albumin, FBG, PLT, TP, β2-MG) were analyzed in univariate model for overall survival. The result showed PS=1 (HR=1.85, p&lt;0.001), elevated fibrinogen (HR=1.63, p=0.008), elevated LDH (HR=1.78, p=0.002), granulocyte count &gt;4.85×10 9 /L (median) (HR=1.65, p=0.004) and increased PLT (HR=1.78, p=0.004) were poor prognostic factors. Then these five factors were enrolled in multivariate analysis. The result showed that PS=1 (HR=1.93, p&lt;0.001), elevated LDH (HR=2.22, p&lt;0.001) and increased PLT (HR=1.71, p=0.04) were independent prognostic factors. The patients were separated to low risk group (no adverse factor), intermediate risk group (1 adverse factor) and high risk group (2-3 adverse factors) according to the number of adverse factors. Median overall survival for these groups were 22.7, 14.5, and 7.5 months at a p value of &lt;0.001. Kruskal-Wallis analysis revealed that the differences of efficacy in these three groups were statistically significant different (p=0.016). Conclusions: Prognostic model using PS=1, elevated LDH and increased PLT might be applied to predict survival and efficacy in advanced or metastatic NSCLC patients undergoing first-line chemotherapy. The model constituted by these three economic and easily acquired parameters may provide a tool in clinical decision making and therapy selection.
Role of aggressive surgical debulking in older adults with gastrointestinal neuroendocrine tumors.
Authors: Zeljka Jutric, Aaron G Lewis, Mustafa Raoof, Philip HG Ituarte, Gagandeep Singh, Daneng Li
Journal: Journal of Clinical Oncology (2017)

377 Background: Carcinoid and neuroendocrine tumors are often diagnosed in older adults. However, limited evidence currently exist regarding the role of aggressive surgical debulking of primary gastrointestinal-neuroendocrine tumors (low to medium grade-pancreas, small bowel, colorectal) (GI-NETs) in older adultsage &gt; 70 years. Methods: Patients age 70 years or older with a diagnosis of GI-NETs were identified using the California Cancer Registry between the years 2000 to2012. Linkage to patient discharge records provided information including resection of primary site (RPS), resection of liver metastases (LR), and liver directed therapy (LDT). Treatment group effects on overall survival (OS) were compared by Cox proportional hazard models. Results: A total of 2,039 patients were identified. Among the 1,661 patients without metastases, 74% (n = 1,234) received RPS and demonstrated improved survival (HR 0.50, p &lt; 0.001) compared to those without RPS. Of the 378 number of patients with liver metastases, LDT alone (n = 23) was not significantly associated with survival (HR 0.65, p = 0.082). Reduced risk was similar for RPS alone (n = 149; HR 0.44, p &lt; 0.001) when paired with LDT (n = 17, HR 0.45, p = 0.007). RPS with LR, either with or without LDT, indicated the greatest impact in survival risk (n = 25; HR 0.14, p &lt; 0.001). Conclusions: Surgical management of the primary tumor and liver metastases in older adults age &gt; 70 years with GI-NETs demonstrated a significant survival benefit.Aggressive surgical debulking should be considered among older adultsage &gt; 70 years. Future studies among older adults with GI-NETs are warranted to better identify patients most likely to benefit from aggressive surgical management.
Retrospective review of subsequent treatments (tx) for esophagogastric adenocarcinomas (EGA) refractory to FOLFOX.
Authors: Ciara Marie Kelly, Yelena Yuriy Janjigian, David Paul Kelsen, Marinela Capanu, Joanne F. Chou, David H. Ilson, Geoffrey Yuyat Ku
Journal: Journal of Clinical Oncology (2017)

123 Background: FOLFOX is a preferred 1 st -line tx for advanced EGA. We sought to characterize outcomes on subsequent tx and to see if MSK-IMPACT, a 410-gene next generation sequencing (NGS) platform, increases tx options. Methods: We retrospectively identified patients (pts) with advanced, Her2-negative EGA treated with 1 st -line FOLFOX between Jan 2012 to Dec 2014. Clinicopathologic, tx and outcome data were analyzed. Overall survival (OS) was calculated from start of FOLFOX using Kaplan-Meier methods. Landmark analysis was used to compare OS and response status. Results: 185 pts were identified. The majority were Caucasian (82%), male (76%), ECOG PS 1 (67%), with poorly differentiated histology (72%) and de novo metastatic disease (84%). Median age was 64 years. The disease-control rate (DCR, partial response + stable disease) of FOLFOX was 80% [95%CI: 74%-85%]; 19% were FOLFOX primary refractory (FR). Median time-to-progression (TTP) on FOLFOX was 7 and 2 months (mo) for FOLFOX sensitive (FS) and FR pts, respectively. There was a higher proportion of females (26% vs. 14%, P = 0.18), gastric (43% vs. 23%, P = 0.051) and moderately differentiated tumors (26% vs. 12%, p = 0.113) in the FS vs. FR group. Six mo survival from the landmark time of 2 mo after initiation of FOLFOX was 83% [95%CI: 76%-89%], and 38% [95%CI: 20%-56%] for FS and FR pts, respectively (p &lt; 0.01). A similar proportion of FS and FR pts received 2 nd -line tx (65% vs. 69%). The DCR was similar in both groups (31% vs 29%). 2 nd -line tx included: irinotecan- (51%) and taxane-based regimens (32%) or a clinical trial (CT) (13%). The median TTP on 2 nd -line tx was similar in FS and FR groups (2.5 vs 2 mo). Ramucirumab was given in 14% of 2 nd line regimens. 3 rd -line chemo use was similar in both groups (37% vs 31%) but the DCR was lower in FR patients (18% vs. 9%). 51 pts had IMPACT; 1 pt (2%) enrolled onto a genotyped-matched CT. 14 pts received immunotherapy; 1 FS Pt has ongoing complete response 1+ year. Conclusions: Surprisingly, FS and FR pts derive similar, marginal benefit from 2 nd -line tx, emphasizing the appropriateness of CT options in this setting. NGS rarely expanded tx options. Updated and in-depth NGS data will be presented.