tbuckley/cabot-search huggingface dataset:
Potentiating the effect of chemotherapy with low-dose fractionated radiation (LDFRT) in locally advanced squamous cell carcinoma of the head and neck (SCCHN)
Authors: S. M. Arnold, M. Kudrimoti, J. Valentino, P. Spring, M. Ahmed, W. Regine, D. Kenady, C. Given, M. Mohiuddin
Journal: Journal of Clinical Oncology (2005)

3184 Background: LDRT induces more effective cell killing than predicted by the linear quadratic model in preclinical studies, through hyper-radiation sensitivity (HRS) and potentiates the effect of chemotherapy. We report the results of our second clinical investigation of LDFRT, as a potentiator of Carboplatin (C) and Paclitaxel (P) in locally advanced SCCHN. Methods: Two cycles of induction therapy were given every 21 days as follows: P (75mg/m2) given on D1, 8, 15; C (AUC 6) given D1; and LDFRT 50 cGy fractions (two each on Day 1, 2, 8 & 15). The primary endpoint was primary site CR rate, secondary endpoints were overall RR and toxicity. Response was assessed radiographically and by endoscopy, using RECIST criteria. Results: 25 patients were enrolled (23 males, 2 females, median age 55). Primary sites were: OP 14 (56%), OC 4 (16%), L 5 (20%)and HP 2 (8%). Seven patients (28%) had stage III, 13 (52%) stage IVa and five (20%) stage IVb. All patients were evaluable for response with median follow-up of 11 months. Three patients required dose reductions in induction chemotherapy and 3 patients required 1 week delays in definitive therapy secondary to cytopenias. Grade 3 or greater toxicities include: neutropenia (20%), leukopenia (32%), dehydration and hypotension (8%), anemia (4%), infection (4%), pulmonary (4%) and allergic rhinitis (4%) and diarrhea (4%). No treatment related deaths occurred. Primary site RR was 23/25 (92%): 15/25 (60%) had CR, 8/25 (32%) had PR, and 2/25 (8%) had SD. Overall RR (primary and nodal) was 22/25 (88%) with 9/25 (36%) CR, 13/25 (52%) PR and 3/25 (12%) SD. Conclusions: Chemopotentiating LDFRT combined with weekly P and C is effective in SCCHN and provided a RR of 88%. Most striking was the improvement in the primary site CR rate to 60% (from 28% in the previously trial of LDFRT, C and P). This is comparable to the highest primary site CR rates reported for induction therapy in SCCHN. LDFRT P, and C caused fewer grade 3 and 4 toxicities than more intensive induction regimens using chemotherapy alone. This is the second innovative trial utilizing LDFRT as a potentiator of chemotherapy and further investigation of this concept in a randomized trial is warranted. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Bristol-Myers Squibb
Safety, early efficacy, and demographic data from a phase I study of a replication selective adenovirus in patients with solid tumors
Authors: S. M. Shelby, D. Ichimaru, H. Kawamura, K. Nagai, A. Tong, J. J. Nemunaitis, N. N. Senzer, T. Fujiwara, Y. Urata
Journal: Journal of Clinical Oncology (2008)

14526 Background: Telomelysin (OBP-301) is a human telomerase reverse transcriptase gene (hTERT), in a promoter- regulated, replication-competent adenovirus derived from adenovirus serotype 5. Expression of hTERT is transcriptionally upregulated in about 80% of cancer cells (Cong, Y.S., Wright, W.E., and Shay, J.W. Microbiol Mol Biol Rev. 66(3): 407–25 (2002)). The strength of this lytic vector lies in the hTERT promoter’s ability to differentiate between normal and cancerous cells. Telomelysin uses the adenovirus’ intrinsic cytolytic ability to infect, manufacture DNA, and lyse human tumor cells. Methods: A phase I dose-escalation trial was conducted in patients with histologically-confirmed solid tumors. Telomelysin was injected directly into an index tumor <25cm2 and >1cm2 at single, ascending doses of 1 × 1010, 1 × 1011, and 1× 1012 viral particles/tumor. The primary objective was safety, and the secondary objectives were PK/PD, tumoral immune response, and antitumor activity. All patients had failed standard chemo and radiotherapy. Results: 3 patients per cohort were treated (n=9). The primary tumor types were head and neck (n=2), breast (n=1), soft tissue (n=1), melanoma, and others (n=5). Mild to moderate fatigue(56%), injection site pain (44%), sinus congestion (33%) headache (33%), pain (33%) are the most common adverse events, also injection site erythema (33%) and bruising (22%). OBP-301 was well-tolerated, and all reported events were grade 1 or grade 2 in severity. A post injection decrease in the percentage of lymphocytes (plasma) had a median of − 30.9% (p=0.0078, −70.6%, 2.6% min, max). The dip in lymphocytes, a known class effect and presumably pharmacodynamic, reversed by day 7. Viral genome was detected in the plasma within 24 hours after injection in all patients but one. All patients experienced stable disease at day 28’s visit. A decrease in tumor size from baseline was measured in some patients by day 28 (median percentage −2.6, min −15.5%, max 9.2%). Conclusions: No dose-limiting toxicities, or maximally tolerated dose were identified. Telomelysin was quite well- tolerated at doses resulting in infection, showed some early antitumoral activity, and is an excellent candidate to further explore. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Oncolys BioPharma, Inc. Oncolys BioPharma, Inc.
The impact of prostate cancer on overall cancer stage migration over time.
Authors: Jay P. Ciezki, Chandana A. Reddy, Eric A. Klein
Journal: Journal of Clinical Oncology (2016)

35 Background: To define cancer stage migration according to year of diagnosis and type of cancer diagnosis. Methods: Cancer stage, site, and year of diagnosis information were retrieved from an academic radiation oncology center's database. The Jonckheere-Terpstra test was used to assess changes over time. Results: From 2005 to 2014, 12,807 newly diagnosed patients (pts) were seen. The distribution of pts by stage was 2% stage 0, 17% stage I, 33% stage II, 16% stage III, and 32% stage IV. The pattern of stage distribution significantly changed over time as seen in the table (p = 0.0016). For 4 of the 5 most commonly seen cancers, (female breast, lung, esophagus, head and neck, and prostate (CaP)) over time fewer late stage cancers were diagnosed or had no change in stage. The only exception was CaP, the largest number of pts (26.5% of total). In 2005, 10.76% of new CaP cases presented with stage IV disease, dipped to 4.6% in 2011, and rose to 8.47% in 2014 (p &lt; 0.0001). The changes in stage I definition accounted for the increase seen in stage I disease, but could not account for the dip and subsequent increase in stage IV disease. Conclusions: The presentation of cancer by stage has changed over time, and it was predominately driven by CaP. The changes seen in stage IV CaP incidence in which it fell and then rose over the study period suggests that global practice changes may be present. An increased preference for active surveillance, recommendations against PSA screening, and increasing insurance deductibles may have favored a delay in treating/diagnosing CaP pts in the recent past. [Table: see text]
A phase II study of oxaliplatin (O) and gemcitabine (G) first line chemotherapy in patients with advanced biliary tract cancers
Authors: N. Gebbia, F. Verderame, R. Di Leo, D. Santangelo, G. Cicero, M. R. Valerio, C. Arcara, G. Badalamenti, F. Fulfaro, I. Carreca
Journal: Journal of Clinical Oncology (2005)

4132 Background: Biliary tract cancers are uncommon tumors with a poor prognosis and most patients (pts) present with invasive and inoperable disease at diagnosis. Chemotherapy represents a palliative treatment, but single or combination-drug schedules have demonstrated poor response rates with a median survival less than 6 months. Recently O and G have showed an interesting activity as single agents in this group of pts. Methods: We carried out a multicenter phase II study to evaluate the efficacy and safety of combined O and G in locally advanced and metastatic biliary tract carcinoma. The schedule of chemotherapy included O 100 mg/m2 on day 1 and G 1000 mg/m2 on days 1 and 8, every 21 days. Inclusion Criteria were: histological diagnosis of biliary tract carcinoma, age <75, Performance Status (PS)<=2, normal kidney and liver function, absence of brain symptomatic metastases, informed consent.Median patient age was 68 years (range 59 -73). At present 24 pts, 15 males and 9 females, have been enrolled. Nine pts had carcinoma of the gallbladder, 7 cholangiocarcinoma and 8 extrahepatic biliary system disease. Locally advanced 14 pts, metastatic 10 pts. Thirteen pts had a PS =0, 7 pts had a PS=1, 4 pts had a PS=2. Results: All the 24 pts were evaluable for response and toxicity. According RECIST criteria we observed 1 CR and 11 PR for an overall response rate of 50%. Five SD and 7 PD also occurred. The responders (PR+CR) demonstrated a TTP of 10 months (range 6–24) and an overall survival of 14 months (range 6 - 28), while the overall survival for all the pts on study was 10 months (range 2–28). According WHO criteria, 6 pts (25%) suffered grade 2–3 neutropenia, and 3 pts (12.5%) grade 2 thrombocytopenia. One third of pts developed grade 1–2- peripheral neuropathy, only 2 pts (8%) suffered grade 3 neuropathy. Nausea & vomiting G1–2 was present in 6 pts (25%). Conclusions: From these preliminary data O and G combination seems to be effective with a favorable safety profile in first line chemotherapy of advanced biliary tract cancers. No significant financial relationships to disclose.
The impact of HER2 positivity on survival in metastatic gastric and GEJ cancer.
Authors: Aalok Kumar, Chen Zhou, David Huntsman, Christian K. Kollmannsberger, Sharlene Gill, Howard John Lim
Journal: Journal of Clinical Oncology (2012)

17 Background: HER2 positive (+) gastric (GC) and GEJ adenocarcinoma (AC) has been associated with a worse survival outcome. This study examines the survival rate of patients (pts) with metastatic HER2 (+) GC and GEJ AC in the province of BC. Methods: Formalin fixed embedded tissue from pts with resected GC or GEJ AC from 2004−2011 were identified retrospectively through the BC Cancer Agency registry and prospectively for pts with a new diagnosis of advanced disease. Biopsies and resection samples were analyzed via previously validated methods. IHC scores of 3 were considered (+), 2 were equivocal and 0/1 were negative (−). 10% cut-off was used to determine (+) samples. Equivocal staining was considered (+) via FISH or SISH with a ratio of &gt; 2.2 considered amplified. Pt characteristics were abstracted to an anonymized database. Kaplan meier curves were calculated to evaluate overall survival from time of diagnosis or relapse to death for pts with Her 2 (+) or (-) disease. Results: 164 of 294 pts were identified with metastatic or relapsed GC (49%) or GEJ (51%) AC without traztumumab treatment. 21 (13%) of pts were HER2 (+) either by IHC, FISH or SISH. See Table for pt characteristics. The HER2 (+) group was older (median age 68 yrs vs 60), more GEJ (62% vs 49% p=1.23), and a higher number of pts that did not receive treatment (52% vs. 27% p=5.09). Median survival was not significantly different among HER2 (+) and (−) disease (4.0 mo vs. 7.3 mo, p=0.089). Conclusions: The rate of HER2 positivity is similar to that seen in trial data. HER2 positivity trends to a worse prognosis but was not significant in this study. [Table: see text]
PROMs from hospital to hospice.
Authors: Saskia cornelia Teunissen, Alexander De Graeff
Journal: Journal of Clinical Oncology (2014)

209 Background: Symptom burden in advanced cancer patients (pts) influences quality of life (QoL) and should be leading in advanced care planning for both hospital and hospice populations. The objective is to describe the course of symptomburden in those patients over time. Methods: Symptoms were biweekly assessed with the self-assessment tool Edmonton Symptom Assessment System (ESAS; Dutch translation) in a prospective longitudinal study of hospitalized patients and patients admitted to a hospice. Prevalence and intensity data were entered in a web-based database by distinguishing patients into 3 groups regarding the aim of palliative care: tumor palliation, symptom palliation and terminal care. Results: 808 pts included, mean age 65 (18-93), 57% female; 224 (30%) pts admitted in the hospice-setting, 584 (70%) in a medical oncology ward. The care aimed 36 % tumor palliation, 59% symptom management, 4% terminal care. Most prevalent symptoms were similar in hospital and hospice: fatigue, anorexia, dry mouth, pain, constipation. The highest clinical relevance (score &gt; 4 on NRS 0-10; 0 = no symptom, 10 = worst symptom) was found in hospital for fatigue (56%), anorexia (54%), constipation (48%), dry mouth (44%), pain (33%). In hospice patients fatigue (88%), dry mouth (66%), anorexia (63%), pain (4%), constipation (40%). In both care settings same national guidelines for symptom management are used as bottom line for interventions. 48% hospital patients scored &gt; 4 for overall wellbeing (0= very good, 10 = very bad) vs 68% in hospice. In the hospice cohort pts are discriminated by prognosis, symptomburden, QoL: &gt; 3 months survival, 2 – 12 weeks, &lt; 2 weeks. Analysis is ongoing, data will be presented at the conference. Conclusions: The course of symptom intensity in advanced cancer populations in hospital and hospice setting is quite similar. A combination of general, specialized and expert palliative care competencies are needed during the cancer continuum. Prospective monitoring of patients during the continuum is a methodological and practical challenge.
Avoidance of fulminant liver failure from hepatitis B reactivation with chemotherapy and immunotherapy: A value-based approach.
Authors: Kevin B. Knopf, Samantha Siegel, Charles L. Bennett
Journal: Journal of Clinical Oncology (2014)

134 Background: Fulminant liver failure (FLF) is a potentially fatal complication of hepatitis B reactivation in patients who receive rituximab and cytotoxic chemotherapy. Often patients receiving these regimens are treated with curative intent (e.g. diffuse large cell Non Hodgkin’s lymphoma, adjuvant chemotherapy for breast cancer) and thus avoidance of this complication is desirable. The only known treatment for fulminant liver failure is orthotropic liver transplant. We have developed a cost-effective approach to avoiding FLF. Methods: NCCN recommends screening for hepatitis B serologies in any patient who is to receive Rituximab therapy. Review of the literature regarding fulminant liver failure and cytotoxic chemotherapy revealed that the regimens most strongly associated with reactivation of HepB and fulminant liver failure included doxorubicin and high dose of cyclophosphamide—we have targeted Hepatitis B screening to patients receiving these two chemotherapy drugs. We target patients either felt to have a high probability of occult hepatitis B are screened—these include patients who have had a blood transfusion in a foreign country, those with a transfusion more than 20 years ago, and those patients where Hepatitis B can be passed vertically—including first and second generation Asian American immigrants. Patients deemed at high risk are checked for Hepatitis B surface Antigen and Hepatitis B Core antibodies. No routine imaging is performed. Patients who are HepBSag or HepBCoreAb positive who are to receive high risk chemo/immunotherapy are then started on entecavir 0.5 mg/d two weeks before starting therapy and this is continued for 6 months after completion of therapy. Patients who are HepBAg- and HepBCab+ are monitored with HBV DNA levels monthly during therapy with initiation of entecavir if HBV DNA becomes detectable. Results: Patients receiving chemo/immunotherapy associated with Hep B reactivation can be safely identified and given prophylactgic entecavir treatment. Conclusions: We have created a value-driven cost effective approach to minimizing FLF in patients receiving chemo/immunotherapy. Cost estimates based on US pricing will be presented.
A pre-cystectomy decision model to predict pathologic upstaging and oncologic outcomes in clinical stage T2 bladder cancer.
Authors: Siamak Daneshmand, Eila C Skinner, Gus Miranda, Anirban Pradip Mitra
Journal: Journal of Clinical Oncology (2012)

4578 Background: Neoadjuvant chemotherapy is the standard for advanced bladder cancer (BC), although its benefit in lower risk clinically organ-confined muscle-invasive (cT2N0M0) BC is uncertain. This study aimed to define pre-cystectomy factors in cT2N0M0 BC that could predict pathological upstaging at cystectomy and oncological outcomes. Methods: 1,964 institutional BC patients were reviewed. Neoadjuvant chemotherapy-naïve cT2N0M0 patients who underwent cystectomy were included. A multivariate classification and regression decision tree was used to assess hierarchical interactions of univariately significant variables, thereby identifying patients at greatest risk for upstaging and poor outcome. Results: 948 cT2N0M0 patients were identified; 512 (54%) were upstaged at cystectomy. Pathological upstaging was associated with poor RFS and overall survival (OS) (both p &lt; 0.001). Age, lymphovascular invasion (both P = 0.01), multifocality (p = 0.004), deep muscle invasion, tumor growth pattern and hydronephrosis (all p &lt; 0.001) were associated with upstaging. When these factors were included in a multivariate decision tree model, 71% of patients with hydronephrosis were upstaged and had the worst outcome (p &lt; 0.001). In patients without hydronephrosis, tumor growth pattern was a second-tier discriminator; only 37% of patients with papillary tumors were upstaged. In patients with non-papillary tumors, deep muscle invasion was a third-tier discriminator; 70% of patients with invasion were upstaged. Age was a third-tier discriminator in patients with papillary + non-papillary features; 33% of patients ≤65 years were upstaged compared to 47% of patients &gt;65 years. The decision tree was cross-validated and resulted in 3 risk groups – 5 year RFS/OS for low risk patients was 66%/48% versus 46%/27% for high risk patients (p &lt; 0.001). Conclusions: This study identified pre-cystectomy variables that predict upstaging and poor outcomes in cT2N0M0 BC. The decision tree approach highlighted the most crucial prognostic variables, and can aid in identifying low risk patients in a stepwise fashion who have lower probability of upstaging and better outcomes.
Comprehensive CYP2D6 genotyping in a multiracial U.S. breast cancer population
Authors: W. J. Irvin, L. A. Carey, O. Olajide, E. C. Dees, J. Peppercorn, W. K. Chiu, C. M. Walko, H. L. McLeod, J. P. Evans, K. E. Weck
Journal: Journal of Clinical Oncology (2009)

553 Background: CYP2D6 genotyping has been suggested to avoid suboptimal responses to tamoxifen (T). Most studies to date are in white patients (pts) and focus on a limited number of genetic variants. In this clinical trial, we comprehensively examined CYP2D6 allele frequencies in women of heterogenous ethnicity taking tamoxifen (T). Methods: In LCCC 0801, pts on T ≥ 4 months and not on potent CYP2D6 inhibiting medications were genotyped using the CYP450 AmpliChip for 2D6 alleles: *1-*11, *15, *17, *19, *20, *29, *35, *36, *40, *41, *1XN, *2XN, *4XN, *10XN, *17XN, *35XN and *41XN. T dose was increased in pts with any intermediate or poor metabolizing (IM or PM) alleles [but not in pts homozygous for extensive metabolizing (EM) alleles]. Serial T metabolite levels are being assessed. Here we report the allele frequency data from this study compared to previously published cohorts. Results: 108 pts participated in the study: 24 (22%) African-Americans (AA), 76 (70%) non-Hispanic whites, 4 Asians, 3 Hispanics and 1 Spanish European. Genotyping revealed 28 (26%) EM/EM, 1 EM/UM (ultra-rapid), 29 (27%) EM/IM, 22 (20%) EM/PM, 8 (7%) IM/IM, 10 (9%) IM/PM, 9 (8%) PM/PM and 1 unknown. Conclusions: Pts in this trial had a similar frequency of PM alleles to previous reports, however a high proportion of pts have IM alleles. In particular, the majority (79%) of AA pts possess at least one variant allele. Since PM and IM genotypes have been associated with reduced T metabolism, this may have implications for T efficacy and emphasizes the importance of trials examining CYP2D6 genotyping as a determinant of T use. (Supported by Laboratory Corporation of America, Roche Diagnostics, NC UCRF, NCI SPORE.) [Table: see text] [Table: see text]
Prognostic significance of serum thymidine kinase activity (TK1) level in patients with metastatic non-small cell lung cancer (NSCLC).
Authors: T. Korkmaz, S. Seber, G. Basaran, P. F. Yumuk, F. Dane, K. Okutur, M. Kanitez, M. Kocar, F. Telli, G. Demir, N. S. Turhal
Journal: Journal of Clinical Oncology (2011)

e18010 Background: TK is an enzyme supporting DNA synthesis under conditions of increased cell proliferation. The prognostic significance of TK1 activity in hematological malignancies and early stage solid cancers are well studied but little is known about the prognostic significance of TK1 activity in metastatic NSCL cancer. Methods: TK1 activity was measured by means of novel high sensitive non radioactive DIVITUM assay. We prospectively measured serum TK1 activity immediately before the first and second cycle of the treatment in 48 consecutive metastatic NSCL cancer patients. 10 healthy volunteers were also included as a control group. We aimed to evaluate the value of prognostic significance of TK1 activity. In addition, the clinical significance of the difference between the two serum TK1 activity levels was also assessed. Results: The mean TK1 level in the study group was significantly higher than the controls (respectively 325.6±63.46 vs. 32.97±7.307; p<0.0001). TK1 levels were positively correlated with weight loss (p=0.039). TK1 activity levels in the squamous subtype were higher than the adenocarcinoma but this difference was not significant. (respectively 444.2 ± 143.4 vs. 225.1 ± 59.77; p=0.108). A cut off value of 156 Du/l (AUC 0.77 %95 CI 0.62-0.92; sensitivity %56,1-specifity %14) was determined by ROC curve analysis. High TK1 values were associated with decreased PFS and OS. In multivariate analysis TK1 levels continued to be an independent prognostic factor for patients with metastatic NSCLC (p value for OS was found to be 0.02). Although the difference was not clinically significant, the mean TK1 levels before second cycle of chemotherapy was higher than baseline TK1 levels before the start of chemotherapy (respectively 620±35.3Du/L vs. 325.6±63.46 Du/l p). Conclusions: TK1 levels serve as a good independent prognostic factor in the metastatic setting for NSCLC. Early evaluation of TK1 levels during chemotherapy can not be used for monitoring treatment response. In addition TK1 can be a valuable molecular molecular therapeutic target for metastatic NSCLC.