tbuckley/cabot-search huggingface dataset:
Clinical experience with sunitinib (SU) in patients over age 65 with metastatic gastrointestinal stromal tumors (GIST): A retrospective study from the French Sarcoma Group (FSG).
Authors: Florence Duffaud, Isabelle Ray-Coquard, Frederic Marchal, Loic Chaigneau, Olivier Bouche, Thanh Khoa Huynh, Julien Mancini, Nicolas Isambert, Emmanuelle Bompas, Thomas Ryckewaert, François Bertucci, Axel Le Cesne, Bruno Landi, Maria Rios, Antoine Adenis, Jean-Yves Blay
Journal: Journal of Clinical Oncology (2013)

10546 Background: Elderly GIST patients (pts) represent a consistent portion of all GIST pts, but are under-represented in clinical trials. Data on benefits, tolerance of SU in elderly GIST pts and their specific outcome are very limited. Methods: Charts of elderly pts (≥ 65 yrs)treated with SU in routine clinical practice from 11 Centres of the FSG were reviewed to evaluate the efficacy and safety of SU. Results: 71 elderly GIST pts were reviewed, with a median age of 74, [distributed as 65-74, n=36; 75-84, n=30; ≥ 85, n=5], 41 (57%) men, with median ECOG-PS= 1 (0-2), and median active comorbities of 1 (0-4). SU was administered after progression on first-line Imatinib (400 mg/d for 21 pts, 400 then 800 mg/d for 45 pts) or masitinib (5 pts). SU was started at 50 mg/d 4-wks-on/2 wks-off in 37 pts (52%), at 37.5 mg daily in 32 pts (45%), and at 25 mg daily in 2 pts. All but 2 pts experienced at least one adverse event (AE). Drug related AE were mainly of grade 1 or 2 (298/388, 76%), and medically manageable. Most frequent AE were fatigue (20%), diarrhea (11%), mucositis (7%), abdominal pain (7%), hand-foot syndrome (6%), neutropenia (6%), and hypertension (5%). Permanent dose reduction was reported in 33 pts (46%). In 17 pts (24%) SU was permanently stopped due to grade 3 or 4 AE. ; this occurred within 3 months after starting SU in 10 pts. At a median 36 months follow-up, 53 pts progressed, and 28 pts were alive. The median PFS and OS were 10.2 (0.2-54) and 21 (0.5-77) months, respectively. Univariate analysis showed that age (≤ 80), PS (&lt;1), WBC (≤ 4 Giga/l), Hb and Albumin have a positive impact on OS (all p &lt; 0.04) and PFS (all p &lt; 0.05). In multivariate analysis, Albumin and Hb had an impact on OS and PFS, PS had an impact only on OS, and WBC only on PFS. A correlation was found between comorbidities and Grade 3/4 toxicities, but no correlation between any toxicities and outcome. Conclusions: Compared to data from clinical trials, SU yields similar rates of GIST control and OS in elderly pts despite frequent dose reductions or interruptions. Since comorbidities may increase the risks of AEs, careful follow-up to assess tolerance is particularly indicated in elderly GIST pts.
Quantitative analysis of the impact of deepness of response on post-progression survival time following first-line treatment in patients with mCRC.
Authors: Ulrich Robert Mansmann, Ute Sartorius, Ruediger Paul Laubender, Clemens Albrecht Giessen, Regina Esser, Volker Heinemann
Journal: Journal of Clinical Oncology (2013)

3630 Background: The extent of tumor shrinkage in patients (pts) receiving chemotherapy with or without monoclonal antibodies is prognostic for PFS and OS. The ‘Deepness of response (DpR)’ concept aims to relate tumor shrinkage to post-progression survival (PPS). If tumor shrinkage occurs, DpR is the percentage of shrinkage observed at the nadir compared with baseline. DpR is 0 for no change and negative if the tumor load increases. Longest diameter (LD) based on RECIST or a calculated tumor volume (ASCO GI 2012 #635) can be used to quantify the tumor load. A joint model was presented (ASCO GI 2012 #580, ASCO 2012 #3603) which allows the prediction of a pt PPS time based on DpR. Methods: Based on data from the randomized CRYSTAL and OPUS trials, 4 treatment regimens (FOLFIRI +/- cetuximab and FOLFOX4 +/- cetuximab) were studied. A joint model was used to quantify individual changes in tumor size over time and to relate these changes to PFS and OS. Relationships between baseline tumor load and DpR and PPS were studied. A Spearman correlation was used to study the relationship between DpR and PPS for KRAS wild-type (wt) pts with progressive disease. Results: Results are reported using LD-based measures for 841 pts with KRAS wt tumors and imaging data. The 348 pts treated with FOLFIRI alone had a median DpR of 33.3% (interquartile range [IR]: 8.0%, 58.0%) while the 315 pts treated with FOLFIRI + cetuximab had a significantly higher median DpR of 50.9% (IR: 18.4%, 78.6%), p&lt;0.0001. The 96 pts treated with FOLFOX4 alone had a median DpR of 30.7% (IR: 4.0%, 55.9%) and the 82 pts treated with FOLFOX4 + cetuximab had a significantly higher median DpR of 57.9% (IR: 24.0%, 92.9%), p=0.0008. Correlation between DpR and PPS for pts with documented progression is statistically significant in each treatment group for both LD-based and volume-based measurements (p&lt;0.0001 for the CRYSTAL study and p&lt;0.005 for the OPUS study). Conclusions: Our results emphasize the value of DpR as a new efficacy outcome measure for clinical trials. The tumor-shrinking capacity of cetuximab was shown to be associated with its ability to prolong PPS.
Inotuzumab ozogamicin (IO) in combination with low-intensity chemotherapy as front-line therapy for older patients (pts) and as salvage therapy for adult with R/R acute lymphoblastic leukemia (ALL).
Authors: Elias Jabbour, Susan Mary O'Brien, Nitin Jain, Deborah A. Thomas, Guillermo Garcia-Manero, Farhad Ravandi, Gautam Borthakur, Sergernne York, Rebecca Garris, Jorge E. Cortes, Hagop M. Kantarjian
Journal: Journal of Clinical Oncology (2014)

7019 Background: Outcome of older pts with ALL and those with R/R disease is poor. Addition of IO to effective low-intensity chemotherapy might improve outcome. IO is a CD22 monoclonal antibody bound to a toxin, calecheamicin, and has shown single-agent activity in R/R ALL. Methods: Pts ≥60 years (yrs) with newly-diagnosed ALL and pts ≥18 yrs with R/R disease were eligible. Chemotherapy was low intensity and referred to as mini-hyper-CVD (cyclophosphamide and dexamethasone at 50% dose reduction, no anthracycline, methotrexate at 75% dose reduction, cytarabine at 0.5 g/m2 x 4 doses). Rituximab and IT chemotherapy were given for first 4 courses. IO was given on Day 3 of each of the first 4 courses. The first 6 pts received 1.3 mg/m2 for course 1 and 0.8 mg/m2 for subsequent cycles; pt 7 onwards received 1.8 mg/m2 for course 1 and 1.3 mg/m2 for subsequent cycles. Results: 44 pts were treated so far (Table). Grade 3-4 non-hematological toxicity included increased LFTs in 5 (11%): VOD in 1 (2%). 10 pts (23%) were switched early to maintenance due to thrombocytopenia and infectious complications. Of the 20 pts with de novo ALL, 16 (80%) are alive:14 (70%) in CR from 1 to 25 mos, 2 relapsed after 12 and 3 mos; and 4 died, 3 in CR (sepsis in 2, gun shot in 1) and 1 did not achieve CR and died 2 mos later after receiving a salvage regimen. At the last follow-up, 17 of the 24 pts (71%) with R/R ALL are alive:15 (63%) in response from 1 to 10 mos, 2 relapsed after 1 and 2 mos; and 7 died: 4 early death within 3 weeks, and 3 from resistant disease. Conclusions: IO + low-intensity mini-hyper-CVD is safe and shows very encouraging results (95% ORR) in the frontline setting in older pts with ALL and as a salvage approach (75% ORR). These results appear to be better than those achieved with a chemotherapy only approach and may become the new standard of care. Clinical trial information: NCT01371630. Parameter Front line (N=20) Salvage (N=24) N (%); Median [range] Follow-up (mos) 13 [2-26] 6 [1-11] Age (yrs) 69 [60-79] 35 [17-71] Salvage 1 - 13 (54) ≥ Salvage 2 - 11 (46) CR 15 (75) 11 (46) CRp 4 (20) 6 (25) Cri 0 1 (4) Neg MRD at D21 12/16 (75) - overall 19/20 (95) - Early death 0 4 (17) ORR 19 (95) 18 (75) PFS % at 1-yr, 83 at 6-mos, 87 OS % at 1-yr, 84 at 6-mos, 74
Protection from late-occurring anthracycline-related cardiotoxicity among childhood cancer survivors with a RARG coding variant.
Authors: Emily S. Tonorezos, Vijai Joseph, Dana Barnea, Danylo Villano, Jaya Satagopan, Danielle Novetsky Friedman, Charles A. Sklar, Kevin C. Oeffinger, Kenneth Offit
Journal: Journal of Clinical Oncology (2017)

130 Background: Susceptibility to late-occurring anthracycline-related left ventricular (LV) dysfunction is poorly understood. While higher dose of anthracyclines, radiation therapy, and younger age at exposure are relevant, heterogeneity persists. A recent report suggests that survivors with the rs2229774 retinoic acid receptor γ (RARG) variant represent a high-risk group. We sought to replicate this finding in our population of adult survivors of childhood and young adult cancer. Methods: We collected germline DNA among 455 survivors of childhood and young adult cancer seen in the Memorial Sloan Kettering Long-Term Follow-Up Programs. Participants were 48% male and more that 90% were white, non-Hispanic. Median age at diagnosis was 15 years and median time from diagnosis was 17.8 years. The most common diagnosis was Hodgkin Lymphoma (31%) followed by sarcoma (29%) and leukemia (10%). Initial genetic testing was performed using a low density SNP array (Illumina Exomearray), followed by full gene analysis by LD block testing. LV dysfunction was defined as ventricular ejection fraction less than 55%. Bonferroni-adjusted p values were used to determine significance in a multivariate model. Results: Of 455 participants, 120 did not have a history of anthracycline exposure, 1 was excluded for lack of echo data, and 17 were excluded due to poor genotyping quality control. Out of the remaining 317 participants, 41 had LV dysfunction. On initial testing, survivors with the rs2229774 variant were at lower risk for LV dysfunction (OR 0.14; 95% CI 0.02-0.99; p = 0.02), compared to survivors with other variants. Of note, the allele frequency in those without LV dysfunction was similar to reported studies and public data. In full gene analysis, those with a missense variant in ESPL1 (separase), within LD block but upstream of RARG, were at significantly increased risk of LV dysfunction (OR 5.61; 95% CI 1.48-21.3; p=0.005) compared to those without the ESPL1 variant. Conclusions: Based on these findings, rs2229774 RARG variant does not appear to confer genetic susceptibility to left ventricular dysfunction. ESPL1, a nearby candidate, may be the risk-conferring variant. Replication efforts are ongoing.
Role of HER3 expression and PTEN loss in patients with HER2-overexpressing metastatic breast cancer (MBC) patients who received taxane plus trastuzumab treatment.
Authors: Yeon Hee Park, Hyun Ae Jung, Won Jin Chang, Moon Ki Choi, Jung Yong Hong, Oh-Nam Ok, Jeong Ju Seo, Yoon-La Choi, Ingu Do, Jin Seok Ahn, Young-Hyuck Im
Journal: Journal of Clinical Oncology (2013)

637 Background: The HER3 receptor is a key member of ErbB family and preferentially signals through the PI3K pathway. Formation of dimers between HER3 and HER2 seems to be crucial for HER2-driven signals in HER2 overexpressing tumors. Given the fact that HER2-HER3 is considered the most active signalling dimer of the ErbB system, HER3 activity may contribute to the resistance of trastuzumab. PTEN plays a well-established role in the negative regulation of the PI3K pathway. Our aim of this study was to investigate the role of HER3 and PTEN expression in patients with HER2 overexpressed MBC. Methods: One-hundred twenty-five MBC patients who were treated with taxane plus trastuzumab chemotherapy as the first line therapy were included in this analysis. Immunohistochemical stainings (IHC) with HER3 and PTEN antibody were conducted retrospectively. Results: Median age was 48 years. HER3 IHC was graded from 0 to 3. PTEN IHC was scored as multiplication of intensity and proportion from 0 to 300. The patients who had negative HER3 stain showed better progression free survival (PFS) to taxane plus trastuzumab chemotherapy than those positive HER3 stain (p=0.001, median PFS 21 vs. 11 mo.). The patients who had PTEN score of more than 20 showed longer PFS than those PTEN score of 20 or less than 20 (p=0.006, median PFS 13 vs. 9 mo.). The patients who had PTEN score of more than 20 showed longer overall survival (OS) than those PTEN score of 20 or less than 20 (p=0.005, median OS 48 vs. 25 mo.). HER3 negativity and PTEN loss were identified as independent risk factors for PFS [Hazard Ratio (HR) 0.4 (95% CI 0.3-0.8 for HER3 negativity; HR 2.1 (95% CI 1.2-3.7) for PTEN loss]. However, PTEN loss (HR 3.1 [95% CI 1.6-6.3]) was identified as an independent risk factor for OS. Conclusions: HER3 and PTEN expression may be predictive markers for trastuzumab treatment in HER2-positive MBCs. PTEN expression may have a potential predictive and prognostic biomarker for trastuzumab treatment.
Clinical impact of first response evaluation (FRE) in metastatic colorectal cancer (mCRC) patients (pts) treated with a cetuximab-based regimen (C-R): Results of a mono-institutional experience.
Authors: Fabiola Lorena Rojas Llimpe, Francesca Di Fabio, Stefania Giaquinta, Sara Pini, Daniela Adua, Carmine Pinto
Journal: Journal of Clinical Oncology (2013)

e14717 Background: Some reports suggest positive impact from early tumor shrinkage in progression-free survival (PFS) and overall survival (OS) in mCRC pts receiving C-R. The aim was to evaluate the clinical impact of FRE in mCRC pts treated with a C-R in first-line (1 st -L) or after 1 st -L. Methods: Between May 2004 and Dec. 2012, 73 pts referred to our institution. The FRE was assessed 8-10 wks after the start of treatment by a CT-scan according to RECIST criteria 1.0. At the time of FRE, pts who achieved CR/PR were considered as responders (resp), and SD/PD as non-responders (non-resp). Were included KRAS wild-type (KRAS-wt) and KRAS undefined tumors (KRAS-ud). PFS and OS are reported in months. Results: Pt characteristics: 51M (70%) and 22F (30%); median age 62(27-80) yrs; 59 colon (80.8%) and 14 rectum (19.2%); median number of metastatic sites 2 (1-5); synchronous mts 47 (64.4%), metachronous mts 26 (35.6%); 46 (63%) KRAS-wt, 27 (37%) KRAS-ud. Twenty-nine (39.7%) pts were treated with C-R in 1 st -L (all KRAS-wt), and 44 (60.3%) after 1 st -L (17 KRAS-wt, 27 KRAS-ud). C was combined with FOLFIRI in 36 (49.3%) pts, irinotecan in 36 (49.3%), and was alone 1 (1.4%). At the time of FRE 26(35.6%) pts were resp: 13 1 st -L and 13 after 1 st -L; 47 (64.4%) were non-resp: 16 (34%) 1 st -L and 31 (66%) in after 1 st -L. In pts treated as 1 st -L, the PFS in resp vs non-resp was: 13 (95% CI 6-20) vs 5 (95% CI 4-5) (p=0.03); the OS was: 23 (95% CI 11-34) vs 11 (95% CI 9-13) (p=0.11). In pts treated after 1 st -L the PFS in resp vs non-resp was: 13 (95% CI 8-18) vs 5 (95% CI 0.4-9) (p&lt; 0.0001); the OS was: 17 (95% CI 12-21) vs 12 (95% CI 6-19) (p 0.67). In the KRAS-wt pts the PFS in resp vs non-resp was: 13 (95% CI 11-15) vs 5 (95% CI 4-6) (p 0.00); the OS was 23 (95% CI 16-30) vs 11 (95% CI 8-14) (p 0.02). In the KRAS-ud pts the PFS, in resp vs non-resp was: 9 (95% CI 0-20) vs 3 (95% CI 0-8) (p 0.00), the OS was: 18 (95% CI 1-36) vs 13 (95% CI 10-15) (p 0.03). A Cox regression model, including: sex, age, KRAS, line of therapy, FRE, skin rash grade, shows that the FRE was the main predictor of PFS (p&lt;0.0001) and OS (p=0.011). Conclusions: The FRE seems to predict the clinical outcome in pts receiving C-R as 1 st -L or after 1 st -L.
Randomized phase II trial of weekly squalamine, carboplatin, and paclitaxel as first line therapy for advanced non-small cell lung cancer
Authors: V. Rose, J. Schiller, A. Wood, E. Eskander, K. Holroyd, A. Desai, J. T. Lee, M. Ahmed, B. Kim
Journal: Journal of Clinical Oncology (2004)

7109 Background:Squalamine is an anti-angiogenic aminosterol that acts directly within activated endothelial cells and has acivity in cancer and eye angiogenesis models. Previously a Phase I/II trial in advanced non-small cell lung cancer (NSCLC) of a once every three weeks regimen of squalamine (given as a five day infusion at doses of 100 to 400 mg/m2/day) combined with carboplatin (AUC=6) and paclitaxel (225 mg/m2) was reported to give a response rate of 28% in 43 patients, with median survival of 10.0 months and one year survival of 40%. In the current study a weekly “metronomic” dosing approach of the squalamine, carboplatin, and paclitaxel regimen was evaluated. Methods:45 patients with Stage IIIB NSCLC with pleural effusion or Stage IV disease were enrolled. The drug regimen was a weekly three hour infusion of squalamine (patients randomly assigned 1:1 to a dose of 100 or 200 mg/m2)combined with weekly carboplatin (AUC=2) and paclitaxel (75 mg/m2), for 12 weeks. Patients were eligible to receive additional chemotherapy if tolerating therapy well and experiencing continued clinical benefit. Results:Two patients were withdrawn for intercurrent illness before receiving any study medication. Objective responses occurred in 23% of the patients (10 of 43; 1 complete and 9 partial responses), with five responses in each of the two dose groups. There were less serious adverse events than with the three weekly regimen. Survival data is maturing and will be available at the time of the presentation. Conclusions:The weekly regimen of squalamine combined with carboplatin and paclitaxel was better tolerated than the three week regimen, but this “metronomic” dosing approach did not improve efficacy. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Genaera Corp. Genaera Corp. Genaera Corp.
Longitudinal trajectory of cancer survivorship in patients with recurrent rectal cancer: Anatomy of recurrence in relation to quality of life and pain.
Authors: Tarik Sammour, Songphol Malakorn, George J. Chang, Miguel A. Rodriguez-Bigas, Brian Bednarski, Cathy Eng, Prajnan Das, John Michael Skibber, Y. Nancy You
Journal: Journal of Clinical Oncology (2017)

679 Background: Multiple treatment modalities are utilized for patients with recurrent rectal cancer (RRC). While recurrent pelvic tumor can be highly symptomatic, treatments often carry significant morbidity risks. Patient reported outcomes such as quality of life (QoL) and pain can supplement traditional clinical endpoints in assessing the effectiveness of salvage treatments, and thus aid in treatment decision making. We aimed to examine the longitudinal trajectory of cancer survivorship in RRC. Methods: A prospective protocol enrolled patients diagnosed with RRC between 2008 and 2015. Participants prospectively self-reported QoL (measured by the validated EORTC QLQ-C30 and EORTC QLQ-CR29) and pain (measured by the Brief Pain Inventory, BPI), at presentation, and then every 6 months for 5 years. After accounting for repeated measures, trajectory of mean scores over time was assessed for patients amenable to surgical salvage vs those who were not, using linear mixed-effects modeling. Results: A total of 104 patients were enrolled of which 73 (70.2%) were amenable to salvage surgery with curative intent. Surgical salvage was associated with 30 day morbidity of 68.5% (13.7% and 5.5%, Grade 3 and 4 respectively). Three year overall survival was 56.7% (68.5% in surgical and 29.0% in non-surgical patients). Mean baseline QoL scores did not differ between surgical vs nonsurgical patients but were significantly impacted by the anatomical site of recurrent disease (lowest scores in posterior pelvic recurrence; P=0.012). On longitudinal analysis with a median followup of 33 months, surgically salvaged patients showed gradual sustained improvement in QoL but not pain scores. Anatomy of initial recurrence had an ongoing impact on QoL long term with posterior recurrences having the worst scores. Both QoL and pain scores worsened in patients not amendable to surgical salvage. Conclusions: Disease anatomy determines QoL at baseline and long term in patients with RRC. Surgery improves QoL but not pain in selected resectable cases.
Survival impact of CAPOX versus FOLFOX in the adjuvant treatment of stage III colon cancer.
Authors: Jonathan M. Loree, Aaron Sha, Maryam Soleimani, Maria Yi Ho, Hagen F. Kennecke, Winson Y. Cheung, Karen E. Mulder, Shirin Abadi, Jennifer L. Spratlin, Sharlene Gill
Journal: Journal of Clinical Oncology (2017)

710 Background: CAPOX and FOLFOX are used interchangeably in the adjuvant treatment of colon cancer despite the lack of comparative phase III trials.We aimed to compare toxicities, relative dose intensity (RDI), disease free (DFS) and overall survival (OS) of these regimens in the real world. Methods: We identified consecutively treated patients (pts) with stage III colon cancer at two centers who received either CAPOX or mFOLFOX6 when either option was accessible to pts. RDI was defined as total dose received divided by the total intended dose if all cycles had been delivered. Dose limiting toxicities (DLTs) were toxicities that resulted in a dose reduction of an agent. Survival was compared with the log-rank test and Cox models that adjusted for age, gender, ECOG, T-stage, and N-stage. Results: Of 394 pts, 61.7% received FOLFOX. Age, gender, ECOG, T-stage, N-stage, and time between surgery and start of therapy did not differ between groups. However, RDI and toxicity profiles differed between treatment groups (see Table). With a median follow up of 45 months, there was no difference in OS (HR 0.73, 95%CI 0.45-1.22; P= 0.24); however, CAPOX was associated with a more favorable DFS (HR 0.61, 95% CI 0.40-0.93; P= 0.022). In multivariate analysis, treatment with CAPOX showed trends towards improved OS (HR 0.61, 95% CI 0.34-1.07; P= 0.086). A significant association with improved DFS (HR 0.53, 95% CI 0.33-0.87; P= 0.012) persisted. Exploratory analysis comparing outcomes stratified by the presence of any DLT, neutropenia, thrombocytopenia, and neuropathy failed to show an association with either OS or DFS. (See table.) Conclusions: Our findings suggest that the use of adjuvant CAPOX is associated with an improved DFS despite greater toxicity and lower RDI. Patient selection, the higher starting dose of oxaliplatin in CAPOX, or the metronomic nature of capecitabine may be contributing to improved efficacy of CAPOX. [Table: see text]