tbuckley/cabot-search huggingface dataset:
Ipilimumab in acral melanoma: A retrospective review.
Authors: Douglas Buckner Johnson, Chengwei Peng, Richard Glenn Abramson, Jedd D. Wolchok, Jeffrey Alan Sosman, Richard D. Carvajal, Charlotte Eielson Ariyan
Journal: Journal of Clinical Oncology (2014)

9056 Background: Ipilimumab (Ipi) improves overall survival (OS) in advanced melanoma. Retrospective studies suggest inferior outcomes for Ipi in atypical cohorts of melanoma (uveal, mucosal) compared to unselected populations. Acral melanoma (AM) is an uncommon subtype of melanoma with a poor prognosis. The clinical activity of Ipi has not been well defined in advanced AM. Methods: To assess the activity of Ipi in this cohort, we retrospectively reviewed the demographics, treatment history, and clinical outcomes for all patients (pts) with AM treated with Ipi from two centers between February 2006 and June 2013. Using Cox proportional hazards models, we assessed for factors that correlated with OS. Results: Of 35 patients with advanced AM who received Ipi, 28 were Caucasian, 6 were black, and 1 was Hispanic. Primary tumors arose on the volar surfaces in 28 and subungual sites in 7. Of 31 genotyped patients, 3 had mutations in BRAFV600E, 2 in NRAS, and 4 in CKIT. Stage IVc disease was present in 19 pts, IVb in 6, IVa in 5, and III in 5; 45% had elevated LDH. Median number of prior therapies was 1 (range 0-3) including targeted agents in 6 pts and immune-based therapies in 5. The median number of Ipi doses received was 4 (33 pts with 3mg/kg dosing and 2 with 10mg/kg). Best response by immune-related response criteria (irRC) was complete response in 1 pt, partial response in 3, and stable disease (SD) in 5 for an objective response rate (ORR) of 11.4% and clinical benefit (ORR + SD) at 24 weeks of 25.7%. Median progression-free survival (PFS) from initiation of Ipi was 2.6 months (mo) (95% CI 2.2-3 mo); median OS was 16.7 mo (95% CI 11-22.5 mo). Normal LDH and absolute lymphocyte count ≥1000 at 7 weeks predicted longer OS; metastatic stage, and timing or site of initial recurrence did not influence OS. Toxicities were similar to previous Ipi trials; 16 pts had an immune-related adverse event (irAE) and 7 pts had grade 3 irAEs (colitis in 2, hypophysitis in 3, and hepatitis and dermatitis in 1 each). Conclusions: Ipi induced clinical responses in pts with AM with similar ORR, PFS, and OS compared to unselected populations. Treatment was generally well-tolerated with a comparable toxicity profile to previous trials. Ipi remains an appropriate therapy option for pts with advanced AM.
A phase I study of HM781-36B, a novel pan-HER inhibitor, in patients (pts) with advanced solid tumors.
Authors: Tae Min Kim, Keun-Wook Lee, Do-Youn Oh, Jong-Seok Lee, Seock-Ah Im, Dong-Wan Kim, Sae-Won Han, Yu Jung Kim, Tae-You Kim, Jee Hyun Kim, Kyung-Mi Park, Jeewoong Son, Yung-Jue Bang
Journal: Journal of Clinical Oncology (2012)

3076 Background: HM781-36B is a pan-HER tyrosine kinase inhibitor, which showed a potent activity against the gefitinib- or erlotinib-resistant, EGFR L858R/T790M double mutant cells. A phase I study was conducted to determine the MTD, pharmacokinetics, and antitumor activity. Methods: Eligible pts had advanced malignancies refractory to standard therapies. Standard 3+3 scheme was used in the dose escalation part, and additional 12 pts were enrolled in the expansion cohort of molecular enrichment. Results: In dose-escalation part, 43 pts (median age: 55 yrs (range 25-82), M:F=25:18, ECOG PS 0/1/2/3: 23/17/2/1, median prior chemotherapy: 4) were treated. DLTs were G3 diarrheas in 5 pts, one at 12 mg, 16 mg, 24 mg, and two at 32 mg. The MTD was determined as 24mg. The most common drug-related adverse events were diarrhea, stomatitis, rash, pruritus, and anorexia. Among 41 evaluable pts, 4 pts achieved PR (1 unconfirmed, duration of response: 11.9 mo, 7.07 mo+, 4.5 mo+), and 19 pts had SD. Two of 4 PR pts were Her2-positive breast cancer pts. The median duration of treatment in pts with PR or SD was 3.87 (2.47- 15.17) months. In the dose range of 0.5 to 24 mg, it showed linear pharmacokinetics proportional to dose-escalation, relatively short half-life, and little accumulation. Additional 12 pts in the expansion cohort are under treatment at 24 mg (6 pts: EGFR-mutant NSCLC, 3 pts: Her2-positive gastric cancer, 2 pts: Her2-positive breast cancer, 1 pt: rectal cancer). Conclusions: HM781-36B was safe and well tolerable in advanced solid tumors. Preliminary evidence of anticancer activity has been observed. Updated data will be presented at the meeting.
Phase II trial of S-1 plus leucovorin in patients with advanced gastric cancer and clinical prediction by S-1 pharmacogenetic pathway.
Authors: Ming-ming He, Rui-hua Xu, Dong-sheng Zhang, Feng Wang
Journal: Journal of Clinical Oncology (2015)

e15028 Background: As the first phase II trial, it aimed to evaluate and predict the efficacy and safety of S-1 plus oral leucovorin (S-1/LV) as first-line chemotherapy for patients with advanced gastric cancer (AGC), using S-1 pharmacogenetic pathway approach. Methods: 39 patients orally took S-1 at conventional dose and LV simultaneously at a dose of 25 mg twice daily for a week, within a 2-week cycle. The primary endpoint was overall response rate (ORR), and the secondary endpoints were progression-free survival (PFS), overall survival (OS), disease control rate (DCR), and adverse events (AEs). Peripheral blood was sampled prospectively for baseline plasmic expression of dihydropyrimidine dehydrogenase (DPD), orotate phosphoribosyltransferase (OPRT), thymidine phosphorylase (TP), and thymidylate synthase (TS), CYP2A6 gene polymorphisms, and 5-FU pharmacokinetic parameters. Results: The ORR and the DCR was 41.0% and 76.9%, respectively. The median PFS and median OS was 4.13 (95% conﬁdence interval (CI), 3.44-4.83) and 11.40 (7.76-15.05) months, respectively. Grade 3~4 AEs occurred in only 13 patients. High OPRT/TS ( > 1.246 vs ≤ 1.246, Odd Ratio (OR) 16.962, 95% CI 1.781-161.581, P = 0.014) and peritoneal metastasis (vs liver metastasis, OR 25.604 (1.852-353.979), P = 0.016) were independently associated with responding. High OPRT/DPD ( > 0.754 vs ≤ 0.754, OR 15.566 (1.490-162.605), P = 0.022) was independently associated with grade 3~4 AEs. Response to S-1/LV (yes vs no, Hazards Ratio (HR) 0.275, 95% CI 0.124-0.609, P = 0.001), and high AUC0-24h of 5-FU ( > 1281.800 vs ≤ 1281.800, HR 0.272 (0.114-0.645), P = 0.003) were significantly independent predictors of prolonged PFS. Low baseline plasmic DPD ( ≤ 119.200 vs > 119.200, HR 2.726 (1.045-7.113), P = 0.040), and second-line treatment (yes vs no, HR 0.259 (0.091-0.736), P = 0.011) were significantly independent predictors of prolonged OS. Conclusions: S-1/LV regimen showed promising efficacy and safety for AGC. S-1 pharmacogenetic pathway prediction was used for the first time and found an optimal subset of AGC patients with high OPRT/TS, high AUC0-24h of 5-FU, low DPD and second-line chemotherapy that may benefit most from S-1/LV. Clinical trial information: NCT02090153.
The relationship between quantitative HER2 gene expression by the 21-gene RT-PCR assay and adjuvant trastuzumab (H) benefit in NCCTG (Alliance) N9831.
Authors: Edith A. Perez, Steven M Butler, Amylou C. Dueck, Frederick L. Baehner, Farid Jamshidian, Diana B. Cherbavaz, E Aubrey Thompson, Steven Shak, Peter Andrew Kaufman, Nancy E. Davidson, Julie Gralow, Yan W Asmann, Karla V. Ballman
Journal: Journal of Clinical Oncology (2013)

520 Background: There is considerable interest in developing HER2 testing criteria for adjuvant H. We used the 21-gene assay to examine the relationship of HER2 mRNA to benefit from H. Methods: N9831 compared adjuvant chemotherapy AC-T to concurrent chemotherapy-trastuzumab AC-TH in stage I-III HER2+ breast cancer. Recurrence Score (RS) and HER2 mRNA expression were determined by Oncotype DX (neg&lt;10.7, equiv 10.7 to &lt;11.5, and pos ≥11.5 log 2 expression units). Cox regression was used to assess the association of HER2 expression with H benefit for distant recurrence. Results: Median follow-up: 7.4 yrs. Of 1,940 total pts, 901 had consent and sufficient tissue. HER2 by RT-PCR was neg in 130 (14%), equiv in 85 (9%), and pos in 686 (76%) pts. Concordance between HER2 assessments was 95% for RT-PCR vs central IHC (&gt;10% + cells = +), 91% for RT-PCR vs central FISH (≥2.0 = pos) and 94% for central IHC vs central FISH. In the primary analysis, the association of HER2 expression with H benefit was marginally non-significant (P=0.057). In hormone receptor pos pts (local IHC) the association was significant (P=0.002). The association was nonlinear with the greatest estimated benefit at lower and higher HER2 mRNA expression levels. The observed treatment benefit in low HER2 pts was not due to imbalance between arms in RS and individual gene expression values. Conclusions: Concordance among HER2 assessments by central IHC, FISH, and RT-PCR was high. Association of HER2 mRNA expression with H benefit was marginally non-significant. A consistent benefit of trastuzumab irrespective of mHER2 levels was observed in the pts with either IHC+ or FISH+ tumors. Benefit was observed in pts with high HER2 by RT-PCR but also observed for the small groups of pts with negative results by quantitative RT-PCR or FISH (Table). Plausible mechanisms for this observation will be discussed. [Table: see text]
Adjuvant radiotherapy (adj RT) for extremity and trunk wall atypical lipomatous tumor/well-differentiated LPS (ALT/WD-LPS): A French Sarcoma Group (GSF-GETO) study.
Authors: Philippe Alexandre Cassier, Guy Kantor, Sylvie Bonvalot, Emilie Lavergne, Eberhard Stoeckle, Cécile Le Pechoux, Pierre Meeus, Marie-Pierre Sunyach, Jean-Michel Coindre, Thomas Dubergé, Alain Labib, Jean-Leon Lagrange, Claude Linassier, Corinne Delcambre, Jacques-Olivier Bay, Serge Leyvraz, Nicolas Penel, Sylvie Chabaud, Aude Duret, Jean-Yves Blay
Journal: Journal of Clinical Oncology (2013)

10582 Background: The role of adj RT in the management of ALT/WD-LPS remains controversial. Methods: 284 patients (pts) with operable ALT/WD-LPS, no history of previous cancer, CT or RT, treated between 1984 and 2011 and registered in the Conticabase database were included and described. Overall (OS) and local relapse free (LRF) survival were evaluated from the time of first treatment (trt). Their distributions were estimated by Kaplan-Meier method and compared between RT groups using Log-Rank test. Independent prognostic factors and adj RT, were explored with Cox model. Results: Among the 20 centers, 3 enrolled 58% of the pts. Median age at diagnosis was 61 (range 25-94), 146 pts (51%) were males, 223 (79%) pts had distal tumors while 35 (12%) and 26 (9%) had tumors involving the girdle and the trunk wall. The median size of primary tumors was 17 cm (range 2-48), 272 (96%) lesions were deep seated, 24 (9%) were multifocal within the same anatomical area. Surgery quality was unknown for 42 pts. Among the remaining pts, 102 (43%) were R0, 130 (54%) R1 and 8 (3%) R2. Adj RT was given to 129 pts (45%). Pts who received adj RT had larger tumors (p=0.034), involving more often the distal limbs (p&lt;0.001) and were more often multifocal in the same anatomical area (p=0.009). The use of adj RT varied across centers and along the study period. Other characteristics, including margin resection, were balanced between RT groups. Median follow-up for the whole population was 38.6 months (mo) (CI 95% [34.0-47.6]): 51.9 mo [43.0-62.3] for the RT group and 30.7 mo [23.3-37.8] for the surveillance group (Surv). None of the pts developed metastasis during follow-up. With 23 LR, 4 in the RT group and 19 in the Surv group, 3-years LRF rates were 98.8% [91.8-99.8] vs 90.4% [82.3-95.0] with and without adj RT (p&lt;0.001). Once stratified on time period (before/after 2003), adj RT, age and margin resection (R0 vsother) were independently associated with LRFS. No OS difference was observed (p=0.151). Conclusions: In this study, adj RT following resection of ALT/WD-LPS was associated with a reduction of local recurrence risk. More prolonged and homogeneous follow-up is required to confirm these results.
What do social media savvy cancer survivors tell us about the state of survivorship programs?
Authors: Diane Mary Radford, Alicia C. Staley, Jeffrey Landercasper, Leah L. Dietrich, Choua A Vang, Andrew Borgert, Deanna J. Attai
Journal: Journal of Clinical Oncology (2017)

57 Background: Patients treated for cancer are surviving their disease in increasing numbers. The 2005 Institute of Medicine (IOM) report From Cancer Patient to Cancer Survivor - Lost in Transition resulted in a call to develop survivorship programs. The Commission on Cancer (CoC) standard 3.3 became effective in 1/2015 requiring the delivery of a survivorship care plan (SCP) at the completion of treatment. Many cancer patients use social media (SM) as a way to obtain support and information. We sought to determine if SM savvy patients have received a SCP. Methods: An IRB-approved survey was conducted via the online tool SurveyMonkey between 3/21/2016 and 4/2/2016. Patients were invited to participate via SM outlets reaching cancer-related communities including Twitter chats, Facebook groups, blogs, and targeted emails. Cochran-Armitage Trend test, exact version, was performed by year for % of survivors receiving a SCP. Results: A total of 312 patients responded. 63% had completed their treatment (excluding endocrine therapy). Of a total of 194 individuals only 11.8% (23) were given a SCP at the end of treatment. A breakdown by treatment completion year is given below. Of those who did not receive a care plan 65% (112/172) answered that it would still be helpful to receive one. Most SCPs (86%) were supplied in paper form. However, patient-reported preferences for SCP delivery were paper (50%), online patient portal (41%), and email (9%). Conclusions: Despite the IOM report and CoC standard 3.3, the majority of SM savvy cancer survivors (88.2%) do not receive SCPs. In the respondents to this survey, there was no significant increase from 2015 onwards, p = 0.11, confirming an Advisory Board survey that just over 1/3 of programs felt confident that they could implement 3.3 by 2015. The CoC has updated its standard such that 25% of eligible patients should receive a plan by 12/31/2016. According to these data, that goal of 25% may not be achieved. [Table: see text]
Germline ATM mutations in families with early-onset and familial gastroesophageal and colorectal cancers.
Authors: Michael J. Hall, Olufunmilayo I. Olopade, Mary Beryl Daly, Sonia Kupfer
Journal: Journal of Clinical Oncology (2017)

11 Background: ATM is involved in repair of DNA damage due to radiation and environmental toxins via downstream interaction with CHEK2, BRCA1, and other proteins involved in double strand break repair. Mutations in ATM (Ataxia-Telangiectasia Mutated, 11q22) are among the most common hereditary cancer risk mutations in the general population (0.5-1.0% carrier rate), yet beyond risks of breast (BC) and pancreatic cancer (PC), the spectrum of clinically relevant cancer risks in ATM+ individuals remains uncertain. Thompson (JNCI 2005) previously reported possible risk of colorectal (CRC) (RR 2.54; 1.06-6.09) and gastric cancer (GC)(RR 3.39; 0.86-13.4) in ATM+ individuals, while more recently Hansford (JAMA Onc 2015) performed panel gene testing including CDH1 in patients meeting criteria for hereditary diffuse gastric cancer, and found possibly pathogenic ATM mutations in 3/144 (2%) CDH1-negative probands. In addition to GC, families contained multiple cases of BC, PC and CRC (5 cases, 2 &lt; 50). To further describe the frequency of upper and lower GI cancer in ATM+ families, we reviewed pedigrees from 20 families seen for risk assessment in two high-risk clinics and found to have germline ATM mutations. Methods: Pedigrees from ATM+ families evaluated at Fox Chase Cancer Center and the University of Chicago are included in this analysis. Cancer type, age at diagnosis, number of genes clinically tested, and ATM mutation were collected. Cancers &lt; 50 yrs are considered early-onset. Results: Among 20 total ATM+ families, 22 GI cancers were reported, with 5 families containing 16/22 (73%) of all GI cancers (see Table). Early-onset GI cancers were common in the 5 families (7/16, 44%), including 2/6 (33%) cases of GC, a 23 yr old man and his 45 yr old father both with GEJxn cancer (2/2, 100%), and 3/6 (50%) cases of CRC all from one large family. Conclusions: Our data lend evidence to support the need for early CRC and GC screening in ATM+ patients. [Table: see text]
Can we expect long-term survival in patients with extrahepatic metastasis of hepatocellular carcinoma?
Authors: Kangpyo Kim, Jinsil Seong
Journal: Journal of Clinical Oncology (2017)

251 Background: Hepatocellular carcinoma presenting metastases has been considered detrimental situation. However, it is not infrequent observing long term survivors following active therapeutic intervention in selected patients. In this study, we investigated whether long term survival could be real as well as its common clinical features. Methods: From november 2005 to december 2014, among 1020 HCC patients with extrahepatic metastasis, 75 patients survived over 2 years. The patient and tumor characteristics were examined involving the site, number of metastatic lesions, liver function, and other factors. Treatment methods for liver and metastatic lesions were also reviewed with subgroup survival analysis according to the treatment strategies. Results: We observed survival over 2 years in 7.3 % with median survival of 41 months. The most common sites of extrahepatic metastasis were lung, bone, adrenal gland and lymph nodes in order of frequency. Of 75 survivors, 72 (96%) had single organ metastasis, and 46 (64%) had four or less countable metastatic lesions. Child-Pugh score was within 5 to 7 points for 71 patients when extrahepatic metastasis first occurred. More than two-thirds of patients (52 patients, 69.3%) received local treatments such as surgery or radiotherapy showing significantly higher survival than systemic treatment only (23 patients, 30.7 %) group; 3 year survival 65.7 % versus 21.7 % for the group with and without local treatment respectively (p = 0.001). For patients with a viable tumor in the liver, the application of local treatments such as transarterial treatment or radiotherapy showed a significant survival benefit (3-year survival 46.6 % versus 31.3%, p = 0.045). Conclusions: The long-term survivors presented limited number of extrahepatic metastasis (oligometastasis) and received local treatment for their metastatic lesions. Local treatments to metastatic lesions will increase the survival of advanced HCC patients who have proper liver function and a small number of metastases in a single organ. This study suggests the application of individually tailored therapeutic strategies for advanced HCC patients with extrahepatic metastasis.
Physician participation and compliance with cancer clinical care pathways: A successful model of collaboration between payers and providers.
Authors: Thomas Ruane, Philip J. Stella, Jeffrey A. Scott, Bruce A. Feinberg, Joseph Cooper
Journal: Journal of Clinical Oncology (2012)

e16552 Background: Blue Cross Blue Shield of Michigan (BCBSM), Physician Resource Management (PRM), and Cardinal Health Specialty Solutions (CHSS), partnered to develop a clinical pathway program that would benefit all parties by improving the consistency and quality of patient care while reducing costs. A major obstacle to clinical pathway adoption is physician participation and compliance. Incentives were provided to physicians to join and comply with this clinical pathways program. We report the rates of physician participation and compliance after 1 year. Methods: In 2009, treatment and supportive cancer care clinical pathways moderated by PRM and CHSS chief medical officers were developed by a 12-member steering committee of BCBSM network oncologists. The non-steering committee physicians within the BCBSM network then provided input and review prior to implementation. Physician financial incentives were provided by BCBSM to encourage adoption of the cancer pathways: (1)$5,000 (2) an increased reimbursement rate for certain generic therapies associated with the pathways (3) a share of the savings realized in expenditures for chemotherapy and supportive medications directly attributable to pathways. Rates of participation and compliance by physicians were evaluated after the first year. Compliance was measured using insurance claims data from BCBSM and a proprietary CHSS claims management software tool. Results: Out of 228 Michigan private practice medical oncologists, 187 (82%) participated in the first year of BCBSM’s cancer pathways program. Average compliance rates for the cancer treatment and supportive care pathways over the year 2010 were 96% and 92.5% respectively. Conclusions: Effective clinical care pathway programs require robust physician participation and compliance. Involving physicians in the pathway development process and providing financial incentives led to high rates of physician involvement and “buy-in”, a crucial step in developing our successful clinical care pathway program.
A Phase IIa, Open-Label, Multicenter Study of Single-Agent MOR00208, an Fc-Optimized Anti-CD19 Antibody, in Patients with Relapsed or Refractory B-Cell Non-Hodgkin’s Lymphoma
Authors: Kristie A. Blum, Kami Maddocks, Zsolt Nagy, Pier Luigi Zinzani, Andre Goy, Mariano Provencio, Tadeusz Robak, Christian Buske, Roman Pawel Korolkiewicz, Mark Winderlich, Wojciech Jurczak
Journal: Blood (2014)
Effect of subsequent chemotherapy on overall survival in first-line chemotherapy with targeted agents for patients with metastatic colorectal cancer: Systematic review and meta-analysis of randomized control trials.
Authors: Daisuke Sakai, Toshihiro Kudo, Aya Kato, Toshinori Sueda, Hidekazu Takahashi, Naotsugu Haraguchi, Junichi Nishimura, Taishi Hata, Chu Matsuda, Tsunekazu Mizushima, Yuichiro Doki, Masaki Mori, Taroh Satoh
Journal: Journal of Clinical Oncology (2017)

782 Background: One of recent standard first line chemotherapies for metastatic colorectal cancer is doublet of cytotoxic agents, fluorouracil and oxaliplatin or irinotecan, in combination with target agent, bevacizumab, or anti-EGFR antibody as cetuximab or panitumumab for KRAS or RAS wild type (WT). In this decade, nevertheless progression free survival (PFS) of clinical trials was little improved, overall survival (OS) had been increased. Methods: We analyzed data from 14 recently published phase III randomized clinical trials in mCRC to correlate the percentage of patients receiving subsequent chemotherapy with the reported OS. Results: Median PFS and OS were 10.3 and 25.0 months, respectively. In all comer trials, median OS is significantly correlated with the percentage of patients who received subsequent chemotherapy after first line chemotherapy of their disease [regression coefficient (R2) = 0.85 p = 0.0018]. In trials with KRAS WT, a correlation between OS and the rate of subsequent therapy was modest [r2 = 0.605, p = 0.0637]. Median PFS and RR were not correlated with median OS. Conclusions: Our results support the strategy of making salvage chemotherapy available to all patients with advanced CRC to maximize OS. In addition, our findings suggest that, with the availability of effective salvage options, PFS might no longer be regarded as the appropriate surrogate end point of OS by which to assess the efficacy of a palliative first-line treatment in CRC.
The metastatic phenotype of inflammatory breast cancer is associated with ALDH1 positive cells
Authors: E Charaffe-Jauffret, C Ginestier, F Iovino, C Tarpin, B Estreni, J Jacquemier, L Xerri, Gabriela Dontu, D Birnbaum, P Viens, M Wicha
Journal: Clinical Cancer Research (2009)