tbuckley/cabot-search huggingface dataset:
Molecular screening for cancer treatment optimization (MOSCATO 01): A prospective molecular triage trial—Interim results.
Authors: Antoine Hollebecque, Christophe Massard, Thierry De Baere, Nathalie Auger, Ludovic Lacroix, Valerie Koubi-Pick, Philippe Vielh, Vladimir Lazar, Rastislav Bahleda, Maud Ngo-camus, Eric Angevin, Andrea Varga, Frederic Deschamps, Anas Gazzah, Clement Mazoyer, Catherine Richon, Gilles Vassal, Alexander M. Eggermont, Fabrice Andre, Jean-Charles Soria
Journal: Journal of Clinical Oncology (2013)

2512 Background: Characterization of the genomic alterations (GA) that could drive tumor growth of an individual patient (pt) is now critical to better select targeted therapies in phase I trials. Methods: Pts with advanced solid tumors, who failed at least one line of standard therapy, were offered an on-purpose tumor biopsy for molecular characterization. Biopsies were mainly obtained using 18G needles under CT or ultra-sound control, from metastatic or primary tumor sites. DNA extracted from fresh tumor biopsies was analyzed by CGH (Agilent platform) (if ≥ 50% tumor cells in the sample) and by sequencing for 30 target genes (if ≥ 30% tumor cells in the sample). An expert panel of scientists and clinicians reviewed results to determine the biological signification of the GA and match such pts to the most relevant targeted therapy available (mainly in early clinical trials). PFS using therapy based on GA was compared to the PFS for the most recent therapy on which the pt had just experienced progression (PFS ratio). Results: From December 2011 to august 2012, 129 heavily pretreated pts (median of 3 previous lines) were consented. Among them, 111 (86%) had a dedicated tumor biopsy. An actionable target was identified in 52 patients (40%). Among them, 25 pts (23% of biopsied pts) have been treated with a targeted therapy. The median time between biopsy and molecular results was 21 days [17 – 28]. GA of interest encompassed FGF ligand or receptor amplification (n=9), cyclin amplification or deletion (n=4), KRAS/BRAF/NRAS mutation (n=3), PI3K amplification or PTEN deletion (n=3), EGFR amplification or mutation (n=3) (outside lung cancer), HER2 amplification (n=2) (outside breast cancer), EML4/ALK translocation (n=1). Among the 25 pts treated according to their GA, we observed 5 PR (20%), 14 SD (56%) and 3 PD (12%). Three pts (12%) were not evaluable because of early discontinuation of the therapy. PFS ratio was &gt;1.3 among 9 out of 19 evaluable pt (47%). Conclusions: High throughput molecular analysis is feasible in daily practice. It allows enrichment of phase I trials with specific GA, and leads to promising anti-tumor activity (20% PR as compared to the classical 7-10% PR obtained in all comers phase I trials). Clinical trial information: NCT01566019.
A phase II study of perioperative S-1 combined with weekly docetaxel in patients with locally advanced gastric cancer: Clinical and pharmacogenetic results.
Authors: Sook Ryun Park, Young Woo Kim, Keun Won Ryu, Hyeong-Seok Lim, Jun Ho Lee, Sun-Young Kong, Mi-Jung Kim, Mihee Choi, Young Iee Park
Journal: Journal of Clinical Oncology (2013)

4114 Background: We conducted a phase II study to evaluate the efficacy and safety of perioperative S-1 + docetaxel (DS) in locally advanced gastric cancer (LAGC), and to investigate the association between CYP2A6 genotypes and treatment outcomes. Methods: Eligibility criteria included 18-70 yrs, PS 0-1, measurable lesion(s), and LAGC (clinical stage III-IV (M0) by Japanese staging system). Pts were given each 3 cycles of pre- and post-operative chemotherapy (S-1 40 mg/m 2 bid on D1-14, docetaxel 35 mg/m 2 iv on D1, 8 q 3 wks), and underwent surgery (≥D2). Results: From Oct 2006 to June 2008, 44 pts entered into the study, and 43 pts were eligible. Median age=53 yrs (range, 33-69); PS 0/1=2/41; M/F=29/14; and stage IIIA/IIIB/IV (M0)=20/18/5. All 43 eligible pts completed preoperative DS and 40 pts (93%) completed postoperative DS. The most common G3/4 toxicities during pre- and post-operative DS were neutropenia (28% vs. 65%), stomatitis (19% vs. 5%), and abdominal pain (5% vs. 18%). The clinical response rate was 74.4% (95% CI, 61.4-87.4%) with 1 CR (2.3%) and 31 (72.1%) PRs. R0 resection rate was 97.7%, major pathologic response rate was 48.8% with 1 CR, and pathologic stage was 0/1/2/3/4 (%) = 2.3/44.2/20.9/20.9/11.6. With a median follow-up of 66.6 months, 3-yr PFS and 5-yr OS was 62.8% and 69.6%, respectively. Survival differed according to clinical response, clinical downstaging, and CYP2A6 genotypes (Table). Pts with two CYP2A6 variant alleles (V/V) had higher C max (27.7±4.6 vs. 20.3±1.2; p=0.045) and AUC inf (220.4±43.1 vs. 172.5±12.5; p=0.187) of tegafur, and lower C max (1.4±0.2 vs. 1.8±0.1; p=0.178) and AUC inf (8.4±1.2 vs. 9.7±0.5; p=0.308) of 5-FU than those with no or one variant allele (W/W or W/V). Conclusions: DS is active with a manageable toxicity profile in the perioperative setting in pts with LAGC. CYP2A6 genotype may be predictive of efficacy (S-1 and docetaxel was provided by JEIL Pharm. Co., Ltd. and sanofi-aventis Korea Co., Ltd., respectively). Clinical trial information: NCT00587145. [Table: see text]
Relationship of cognitive function, quality of life (QOL), and neuroimaging in primary CNS lymphoma (PCNSL) survivors.
Authors: Nancy Diane Doolittle, Agnieszka Korfel, Meredith A. Lubow, Elisabeth Schorb, Uwe S. Schlegel, Sabine Rogowski, Rochelle Fu, Edit Dosa, Gerald Illerhaus, Dale F. Kraemer, Pasquale Calabrese, Nancy A. Hedrick, Leslie L. Muldoon, Leeza M. Maron, Kristoph Jahnke, Robert W. Butler, Edward A. Neuwelt
Journal: Journal of Clinical Oncology (2012)

2040 Background: Delayed treatment-related neurotoxicity in PCNSL is a significant problem since improved treatments have increased survival. The study purpose is to describe and correlate neuropsychologic (NP), QOL and neuroimaging outcomes as neurotoxicity indicators. Methods: Four centers in Germany and U.S. prospectively evaluated PCNSL patients (pts) in complete remission (CR) for 2 yrs or more, treated as shown in the Table. NP tests evaluated attention/executive function, verbal memory, motor skills, and QOL (Correa, Ann Oncol 2007). Brain MRI was obtained; the size of T2 abnormalities was determined using two perpendicular linear measurements where hyperintensities were largest and the sum of the measurements was calculated. Differences in total T2 among treatments were compared using analysis of variance; correlations between total T2 and NP or QOL results were assessed using Pearson’s correlation coefficient (r). Results: From Feb 2009 to Feb 2011, 80 pts were evaluated (43 male; median age, 59; median KPS, 80). Median follow-up from diagnosis to evaluation was 5.5 yrs. Total T2 abnormalities were significantly different among treatments (p = 0.0006). The mean area of total T2 in pts treated with WBRT was significantly higher and more than twice the mean of any of the other 3 treatments. Total T2 abnormalities were negatively associated with NP results ie. attention/executive function, r = -0.38 (p = 0.0006), verbal memory, r = -0.23 (p = 0.042), motor skills, r = -0.28 (p = 0.016), composite score, r = -0.34 (p = 0.002); and functional/global QOL (higher total T2 associated with lower QOL). Conclusions: This large PCNSL series in long-term (LT) CR reveals higher total T2 abnormalities in pts treated with WBRT, which are associated with poorer cognitive performance and lower QOL at LT follow-up. Enhanced chemotherapy results in exciting LT survival and function. [Table: see text]
DA-EPOCH-R Is an Effective Regimenin High Grade B-Cell Lymphoma Defined By Cell-of-Origin, Karyotype and BCL2/MYC/BCL6 Status and Expression
Authors: Grzegorz Rymkiewicz, Joanna Romejko-Jarosinska, Katarzyna Blachnio, Beata Grygalewicz, Magdalena Chechlinska, Ewa Paszkiewicz-Kozik, Katarzyna Domanska-Czyz, Beata Ostrowska, Anna Paulina Dabrowska-Iwanicka, Renata Woroniecka, Klaudia Borkowska, Beata Sledz-Gawronska, Michal Osowiecki, Lukasz Targonski, Zbyszek Bystydzienski, Kinga Sikorska-Mali, Lidia Poplawska, Iwona Wylezol, Marcin Szymanski, Monika Swierkowska-Czeneszew, Anna Borawska, Monika Prochorec-Sobieszek, Barbara Pienkowska-Grela, Jan Walewski
Journal: Blood (2016)
A retrospective analysis of the role of gefitinib in the definitive management of esophageal/gastroesophageal junction (E/GEJ) cancer.
Authors: Davendra Sohal, Thomas W. Rice, Lisa A. Rybicki, Cristina P. Rodriguez, Gregory M. M. Videtic, Jerrold P. Saxton, Sudish C. Murthy, David P. Mason, Brooke Elizabeth Phillips, Raymond R. Tubbs, Thomas Plesec, Michael J. McNamara, Denise I. Ives, Joanna Bodmann, David J. Adelstein
Journal: Journal of Clinical Oncology (2013)

e15000 Background: The role of epidermal growth factor receptor (EGFR) inhibition in resectable E/GEJ cancer is uncertain. We update and retrospectively compare results from two Cleveland Clinic trials of concurrent chemoradiotherapy (CCRT) and surgery; the second study differing only by the addition of gefitinib (G) to the treatment regimen. Methods: Eligibility required a diagnosis of E/GEJ squamous cell or adenocarcinoma (ACA), with an endoscopic ultrasound stage of at least T3, N1, or M1a (AJCC 6 th ). Patients (pts) in both trials received 5-FU (1000mg/m2/d) and cisplatin (20mg/m2/d) as continuous infusions over days 1-4 along with 30 Gy radiation at 1.5 Gy bid. Surgery followed in 4-6 weeks; identical CCRT was given 6-10 weeks later. The second trial added G, 250mg/d, on day 1 for 4 weeks, and again with postoperative CCRT for 2 years. Preliminary results and comparisons have been previously published. Results: Clinical characteristics were similar between the 80 pts on the G trial (2003-2006) and the 93 pts on the no-G trial (1999-2003): median age (58 vs. 59 years), male gender (91% vs. 86%), ACA (94% vs. 83%), and HER2 positivity (28% vs. 18%). Minimum follow-up for all pts was 5 years. Multivariable Cox analyses comparing the G vs. no-G pts and adjusting for statistically significant covariates demonstrated improved overall survival (HR 0.62, 95% CI 0.44-0.88, p=0.008), relapse-free survival (RFS) (HR 0.59, 95% CI 0.41-0.84, p=0.003), and distant metastatic recurrence (HR 0.64, 95% CI 0.43-0.96, p=0.03), but not locoregional recurrence. Further subgroup analyses demonstrated improved RFS with G in pts not experiencing a pathologic response (HR=0.59, 95% CI 0.38-0.92, p=0.021), with T4 or M1a disease at surgery (HR=0.33, 95% CI 0.13-0.87, p=0.024), or with HER2-negative tumors (HR=0.65, 95% CI 0.42-0.99, p=0.048). Conclusions: Although this retrospective comparison can only be considered exploratory, it suggests that gefitinib may improve clinical outcomes when combined with CCRT and surgery in the definitive treatment of E/GEJ cancer. Clinical benefit may be greatest in pts with a poor response to preoperative chemoradiation, and in those with HER2-negative tumors. Clinical trial information: NCT00258323.
A preliminary evaluation of the TrueNTH androgen deprivation therapy educational program.
Authors: Erik Wibowo, Richard J Wassersug, John W Robinson, Andrew Matthew, Deborah L McLeod, Shawn Wilyman, Lauren M Walker
Journal: Journal of Clinical Oncology (2017)

219 Background: Androgen deprivation therapy (ADT) is the most common systemic treatment for prostate cancer (PCa), but has many adverse effects that reduce patients’ quality of life and that of their partners. In 5 Canadian cities, we offer an educational program designed to help PCa patients and their partners manage ADT side effects as well as maintain a strong dyadic relationship despite changes that accompany ADT. Methods: Patients on or about to start ADT and their partners participate in a 1.5 hour educational session. Patients receive a copy of the 2014 book, Androgen Deprivation Therapy: An essential guide for men with prostate cancer and their partners (DEMOS Health, NY) which discusses how to manage ADT side effects and how to make effective lifestyle changes to maintain a good quality of life. To date, 358 patients and 220 partners have attended the ADT class. A subset (32%) of participants elected to complete questionnaires at baseline and again 2 to 3 months later to assess the program efficacy. Results: At the time of the ADT class, patients who have been on ADT for ≥ 2 months had more frequent side effects (e.g., hot flashes and breast tenderness), and were more bothered by hot flashes. They also reported worse self-efficacy for managing weight gain and diabetes than those who have been on ADT for &lt; 2 months. However, at 2 to 3 months after the class, patients’ self-efficacy for managing ADT side effects improved, despite experiencing more side effects and more bother associated with those side effects. Notably, patients who were on ADT for a shorter duration (&lt; 2 months), who have attended the class, had less bother associated with hot flashes and better self-efficacy for managing weight gain than those who had been on ADT longer before attending the class. Conclusions: The TrueNTH ADT Educational Program potentially dampens side effect bother and improves self-efficacy for two of the most troublesome adverse effects of ADT, hot flashes and weight gain respectively. The program is most beneficial when offered to patients just starting on ADT. Future analyses will focus on exercise behaviour and dyadic relationship to assess the program’s effectiveness in encouraging a healthy lifestyle and maintain strong dyadic bonds in the face of ADT.
Carboplatin (C), cetuximab (Cet), and everolimus (E) in recurrent or metastatic squamous cell carcinoma of the head and neck (RMSCCHN). Results of a phase Ib study.
Authors: Nabil F. Saba, Scott A Kono, Jennifer Robin Mendel, Selwyn J Hurwitz, Taofeek Kunle Owonikoko, Colleen Margaret Lewis, Donald Harvey, Jaqueline Willemann Rogerio, Zhengjia Chen, Trad Wadsworth, Mark El-Deiry, Amy Y. Chen, Kristin Higgins, Suresh S Ramalingam, Jonathan Jay Beitler, Dong M Shin, Fadlo Raja Khuri
Journal: Journal of Clinical Oncology (2013)

6083 Background: Platinum-based therapy in combination with Cet is the standard first line systemic therapy in RMSCCHN. Preclinical studies suggest that mTOR inhibitors may restore sensitivity to EGFR inhibitors in resistant cell lines, and that in combination with Cet may augment anti-tumor activity. We conducted a phase Ib trial of C, Cet and E for untreated RMSCCHN. Methods: Patients received C at AUC=2 on a 3 weeks on 1 off schedule with Cet weekly at a fixed dose and E at escalating dose levels of 2.5, 5.0, 7.5 and 10 mg daily using a 3+3 design. After 4 cycles of therapy patients without disease progression continued on maintenance Cet and E until disease progression or intolerable toxicity. Patients had previously untreated RMSCCHN not amenable to surgery or radiotherapy, age ≥ 18 years and an Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0-2. Results: After IRB approval, the study enrolled 18 patients with RMSCCHN between February 8, 2011 and Jan 25 2013. One patient was a screen failure. Four had an anaphylactic reaction to Cet and were excluded from the analysis. A total of 13 patients received E (M/F: 92%); median age 65 (44-75yrs). Two of six patients treated at dose level 1 (E-2.5 mg/day) experienced dose limiting toxicity (DLT) with grade 3 hyponatremia and nausea. Additional 7 patients were treated with de-escalated dose of E (2.5 mg QOD). No DLTs were observed at this dose level. Salient clinically relevant Grade &gt;2 toxicities included: leukopenia (23%), neutropenia (15%) hyponatremia (18%), hyperglycemia, nausea, rash, hypokalemia, urinary infection, bacteremia, (each 8%). Dose reductions of C were necessary for a total of 18/61 delivered cycles of therapy. A response rate (RR) of 62.5% with all responders having partial responses (PR) was observed. The PFS was 7.8 months. Conclusions: The MTD of E in combination with Cet and C is estimated at 2.5 mg QOD. Though this is less than the commonly utilized dose of E, the regimen was associated with encouraging response rate and PFS Clinical trial information: NCT01283334.
Randomized phase II study of two doses of pixantrone in patients with metastatic breast cancer (N1031, Alliance).
Authors: Kostandinos Sideras, Alvaro Moreno-Aspitia, Richard Charles Tenglin, Heshan Liu, Wilma L. Lingle, Monica Madden Reinholz, Kevin C Halling, Beiyun Chen, Gerald G. Gross, Rex Bradford Mowat, Shaker R. Dakhil, Edith A. Perez
Journal: Journal of Clinical Oncology (2012)

1083 Background: Pixantrone (Pix) is a novel aza-anthracenedione with structural similarities to mitoxantrone and promising activity against non-Hodgkin’s lymphoma. Due to the lack of iron binding it is theorized to exhibit less cardiotoxicity than the anthracyclines. Methods: N1031 is a phase II RCT of 2 schedules of Pix, in pts with MBC. Group A pts received 180mg/m2 IV q3 wks, and group B pts 85mg/m2 IV on days 1, 8, 15 q4 wks. Eligibility included prior exposure to anthracyclines and/or taxanes, and 1 to 3 regiments in the metastatic setting (minimum of 2 if no prior adjuvant therapy given). Due to lack of long term cardiac safety data no more than 12 cycles were allowed. Frequent cardiac imaging was performed per protocol. Primary endpoint was RR and secondary endpoints included PFS, OS, safety, and QOL. Planned sample size was 25 pts per group. Results: In total 46 pts were evaluable (23 per group), mean age 55.5 yrs (range 38-79), 37% PS 0, 52% PS 1, and 11% PS 2. 80% of pts had prior exposure to doxorubicin, 72% had prior (neo)-adjuvant therapy, 76% were ER+ and 57% received prior HT. Number of prior metastatic regiments was: 1 (28%), 2 (61%) and 3 (11%). Most common adverse events (%) of any grade were: alopecia (74), anemia (74), fatigue (85), nausea (67), ANC decrease (87), and skin disorder (41). Grade 3-4 adverse events (%) at least possibly attributed to Pix and occurring in at least 2 pts were: ANC decrease (57), fatigue (9), increased AST (4%). One pt from each group (4%) had a grade 3 decrease in EF. There were no major differences between the two groups except for more oral mucositis in group A (35% vs 4%). Median number of cycles was 3 in group A (range 1-12) and 2 in group B (range 1-8). There was only 1 confirmed tumor response per group (4%,95% CI: 0.1-22%) prompting early termination of the trial. The median PFS was 2.7 mo (95% CI: 1.8-3.8), and the median OS was 8.9 mo (95% CI: 7.5-N/A). Conclusions: Pixantrone has insufficient activity in patients with MBC exposed to prior anthracyclines and/or taxanes. Adverse events were similar to prior experience with Pix. There were no major differences between the 2 schedules of administration. There was no significant cardiac toxicity seen in this trial. Correlative studies are underway.
Micrometastasis volume in stage II colorectal cancer: A prospective study by Clinical Study Group of Osaka University (CSGO).
Authors: Kohei Murata, Hirofumi Yamamoto, Mutsumi Fukunaga, Tadashi Ohnishi, Shingo Noura, Yasuhiro Miyake, Masakazu Ikenaga, Takeshi Kato, Hidekazu Takahashi, Naotsugu Haraguchi, Junichi Nishimura, Taishi Hata, Tsunekazu Mizushima, Masataka Ikeda, Masayuki Ohue, Junichi Hasegawa, Mitsugu Sekimoto, Riichiro Nezu, Yuichiro Doki, Masaki Mori
Journal: Journal of Clinical Oncology (2017)

597 Background: We reported in a retrospective study that the presence of micrometastasis in lymph nodes (LNs), when assessed by CEA-specific RT-PCR, is a significant prognostic factor in stage II colorectal cancer (CRC). The aim of this study was to clarify the clinical value of micrometastasis in a prospective multicenter trial. Methods: From November 2001 to December 2005, a total of 419 CRC cases were preoperatively registered at a central data center. Of them, 315 node-negative stage II CRC were enrolled. After RNA quality check, 304 CRC cases were analyzed for CEA mRNA in LNs by both conventional RT-PCR (a band method) and quantitative RT-PCR. Long-term prognosis of the patients was determined by each method. Results: A positive band for CEA mRNA was detected in 73 (24.0%) of 304 patients. Post-operative adjuvant chemotherapy was applied in 31 CEA band-positive cases with an oral 5-FU derivative HCFU (1-hexylcarbamoyl-5-fluorouracil) for one year, while chemotherapy was not administered to CEA band-negative group. Multivariate Cox regression analyses revealed that a high micrometastasis volume (High-MMV, n = 95) was an independent poor prognostic factor for 5-year DFS ( P= 0.001) and 5-year OS ( P= 0.016). Conclusions: This prospective clinical trial demonstrates that micrometastasis volume is a useful marker in identifying patients who are at high or low risk for recurrence of stage II CRC.
Predicting late fecal incontinence risk after RT for prostate cancer: External independent validation.
Authors: Alessandro Cicchetti, Barbara Avuzzi, Federica Palorini, Tiziana Rancati, Claudio Stucchi, Giovanni Fellin, Pietro Gabriele, Vittorio Vavassori, Claudio Degli Esposti, Cesare Cozzarini, Claudio Fiorino, Riccardo Valdagni
Journal: Journal of Clinical Oncology (2017)

116 Background: To validating a predictive model for late fecal incontinence (FI) on a recent population (pop) of prostate cancer patients (pts) treated with radical radiotherapy. NTCP model was derived from literature. Methods: Pop included 267 pts treated with IMRT in 2010-2014. Prescribed dose was between 68 and 80 Gy with conventional and hypo-fractionated (HF, from 2.2 to 2.8 Gy) treatment. Rectal toxicity was scored using the LENT/SOMA. Follow-up (FU) was considered up to 2 years. We chose to validate a model for prediction of chronic FI through multiple measures during FU. Mean FI was defined as the average score during the FU period after RT (Mean incontinence &gt; 1). Literature based multivariate model included: mean rectal dose (Dmean), previous diseases of colon (COLO) and previous abdominal surgery (SURG). Dose distributions were corrected EQD in 2 Gy fractions. Results: 186 pts were available. Mean grade &gt; 1 FI was scored in 18 patients (〜10%). Univariate logistic analysis confirmed the risk factors reported in literature. Similar Odds Ratios (OR) were found for Dmean (1.04vs1.05) and SURG (1.90vs1.50). COLO was not a risk factor for this pop. As consequence, NTCP models including Dmean and Dmean+SURG were evaluated through calibration plot. The models showed a clear trend (increasing observed toxicity rates with predicted risk), but the observed toxicity rates were underestimated (slope〜3, R2〜0.7). Including HF (OR = 2.20, 8.6% vs 17.6%) as a variable into the previous model the calibrations improved significantly (slope〜1, R2〜0.9). Conclusions: The study confirms formerly published results on effect of abdominal surgery and dose to large rectal volumes as potential risk factors for late FI. The overfitting in calibrations could be due to an effect of HF, not included in previous models developed on normofractionated treatments. This effect goes beyond the applied standard correction using LQ model for late effects and also beyond the time recovery correction (slope〜2, R^2〜0.8). Probably we should found a more suitable alpha/beta value for the longitudinal definition (toxicity starting in acute phase and persisting during follow-up) instead of using the assumption settled on incidence of late peak events.