bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cisplatin (C) based chemoradiation (CXRT) for locally advanced squamous cell carcinoma (SCCA) of the anal canal (AC): A 20-year perspective.
Authors: Eng C. , Xing Y. , You Y. N. , Chang G. J. , Das P. , Phillips J. , Wolff R. A. , Rodriguez-Bigas M. A. , Ohinata A. , Crane C. H. 
Published: February 2017

482 Background: The standard of care for locally advanced SCCA of the AC is 5-fluorouracil (5-FU)/mitomycin C (MMC) with concurrent XRT. C was evaluated with 5-FU in 2 large phase III studies (RTOG 98-11 and ACT II) to establish superiority over 5-FU/MMC. Neither study showed significant differences for disease-free survival (DFS) or overall survival (OS). RTOG 98-11 reported reduced colostomy-free survival (CFS) in the C-induction arm; no differences were noted in the ACT II study. We present our 20-year experience with C for locally advanced SCCA of the AC which has been adopted as the standard unless contraindicated. Methods: A retrospective, single institution analysis for locally advanced SCCA of the AC was completed in patients (pts) that received concurrent 5-FU/C/XRT from 1989-2009. Medical records were reviewed for history of STDs, chronic immunosuppression, stage, dose of XRT, toxicity, clinical response (CR), recurrence, and OS. Multidisciplinary management included surgical, radiation, and medical oncologists. OS, DFS, and CFS were calculated using the K-M method. The log-rank test was used to compare OS among these subgroups. Results: 185 pts were identified (51 M:134 F). The median age was 56 (35-83 y.o.). AJCC stage was I (n = 25); II (n = 76); IIIA (n = 36); and IIIB (n = 48). The median XRT dose was 55 Gy in 30 fractions. 181 pts were evaluable for response; 4 were lost to follow up. Complete CR (cCR) was noted in 169 pts (93%); partial response (n = 12); 6 pts received an APR. After a median follow up of 8.6 years, 14 pts (8%) developed local recurrence; 11 received salvage surgery. 16 pts (9%) developed distant metastases (DM). The 5-yr DFS = 81%, 5-yr OS = 85% and 5-yr CFS was 88%. By univariate analysis, N-stage was a poor prognostic indicator for 5-yr DFS (p = 0.02) and DM (p = 0.046) but not OS or CFS. Increased T-stage correlated with salvage surgery (p = 0.005). Conclusions: Cisplatin-based chemoradiation for locally advanced SCCA of the anal canal resulted in favorable DFS, OS, and CFS compared to historical data and phase III studies. Platinum-based therapy for anal cancer appears to be an acceptable alternative to MMC and should be considered as a standard option for locally advanced disease. No significant financial relationships to disclose.
Geriatric subgroup of AGITG MAX trial: International randomized phase III trial of capecitabine (C), bevacizumab (B), and mitomycin C (M) in first-line metastatic colorectal cancer (CRC).
Authors: Price T. J. , Zannino D. , Wilson K. , Simes J. , Van Hazel G. A. , Robinson B. A. , Broad A. , Ganju V. , Ackland S. P. , Tebbutt N. C. 
Published: February 2017

510 Background: In an aging population a greater proportion of geriatric patients will be considered for systemic chemotherapy. CRC is a common cancer and will be a major health issue in geriatrics. Methods: MAX, a three arm study of C v CB v CBM, found an improvement in PFS with addition of B (± MMC) to C (Tebbutt NC et al. JCO 2010; 28(19): 3191–3198). This analysis assesses effect of adding B (± MMC) to C on PFS, OS, RR and toxicity in geriatric patients (age >75y). Results: 99 patients (21%) were >75y. Number/Median age: C 37/78.5y (75.2–86), CB 32/78.7y (75.2–84.9), CBM 30/80.2y (75.2–83.4). Baseline characteristics were well balanced. 88% commenced C dose of 2000mg/m2/day, d1–14, q21 (61% for <75y). ECOG 0–1 for 88%. Comorbidities were: (%) Ex/smoker 13/2, diabetes 15, HT 56, IHD 15, CVA/TIA 10. These are similar to reported rates ( http://www.aihw.gov.au/cdarf/data_pages/incidence_prevalence/index.cfm ) in this population. Proportion receiving all three chemotherapy drugs at some time (5FU/oxaliplatin/irinotecan) was 10% >75y v 20% <75y. RR, median PFS & OS reported in Table. Interaction test for OS, RR and PFS revealed no impact of age. Gd 3-4 tox for >75y C/CB/CBM respectively was (%); vomiting 5/13/3, diarrhea 19/22/20, stomatitis 3/0/3, HT 0/3/3, thrombosis/thrombus/embolism 5/6/13, cardiac 0/6 (3 Gd5)/3. There was one perforation (Gd5) in C. Grade 2/3 HFS (%) was 38/59/53. One Gd 3-4 neutropenia episode in CB, no Gd 3-4 thrombocytopenia. Overall, toxicity rate similar to <75 y. Conclusions: Significant improvement in PFS with addition of B to C was seen in this geriatric population, similar to results of ITT group and those <75yrs. Treatment was well tolerated with no signal of increased toxicity when compared to those <75yrs, including VTE/ATE. [Table: see text] [Table: see text]
Patterns of care and survival trends in elderly metastatic colorectal cancer patients: A SEER-Medicare analysis.
Authors: Shankaran V. , Beck S. J. , Blough D. K. , Yim Y. , Yu E. , Ramsey S. D. 
Published: February 2017

520 Background: Over the last decade, the treatment of metastatic colorectal cancer (mCRC) has changed dramatically as new drugs and hepatic resection have been incorporated into practice. The goal of this study is to examine treatment patterns and survival trends for older patients (pts) with mCRC. Methods: Pts ≥ age 65 with mCRC diagnosed (dx) 2001-2005 were identified from the SEER-Medicare database. Pts were excluded for lack of Medicare parts A and B in the year prior to dx, second malignancy, or non- adenocarcinoma histology. First-line (1L) chemotherapy (CTx) use was identified by claims within 3 months of dx. Metastatectomy was identified by various claims for liver resection. Comorbidity was assessed by Klabunde index. A Cox proportional hazards regression model was used to assess the effect of demographic and treatment factors on survival. Results: A total of 5,725 pts (median age 77) met inclusion criteria. 274 pts (5%) underwent hepatic resection and 2,647 (46%) received CTx. From 2001-2003, 43% of pts received 1L CTx (34% and 1% with regimens containing irinotecan (Iri) and oxaliplatin (Ox) and 49% with 5-FU/cap alone). From 2004-2005, 51% of pts received 1L CTx (25%, 14%, and 37% with regimens containing bevacizumab (Bv), Iri, and Ox and 40% with 5-FU/cap alone). In the multivariate analysis using the Cox proportional hazards model, survival was significantly improved in pts receiving CTx or hepatic resection and in pts dx 2004-2005 (Table). Conclusions: In an older mCRC population, hepatic resection, CTx use, and mCRC dx in 2004-2005 are associated with improved survival. Improved survival of pts dx in 2004-2005 coincides with the 2004 approval dates and uptake of Bv and Ox, and may be associated with the use of these therapies. Further analysis will examine the associations between specific Ctx regimens, Bv, and survival and will include pts dx through 2007. [Table: see text] [Table: see text]
Role of L1 cell adhesion molecule in gastric carcinoma.
Authors: Ito T. , Kodera Y. , Tanaka C. , Ohashi N. , Nakayama G. , Koike M. , Fujiwara M. , Nakanishi H. , Nakao A. 
Published: February 2017

56 Background: L1 cell adhesion molecule (L1) is a 200-220 kDa transmembrane glycoprotein of the immunoglobulin super family initially identified in neural cells. L1 was detected in ovarian cancer in a stage-dependent manner, was found exclusively in the invasion front of colorectal cancer, and has been considered a stem cell marker in glioma. The authors have shown that mRNA expression of L1 was a significant prognostic factor in gastric cancer (Kodera et al. Gastrointestinal Cancer Symposium 2009, abst 37). Its role in gastric cancer was further investigated. Methods: Expression of L1 was observed by immunostaining in 72 surgically resected pT4A-stage gastric cancer specimens. The association of L1 with peritoneal seeding and prognosis was elucidated. mRNA expression of L1-expressing gastric cancer cell line, KATO3, was suppressed using siRNA (KATO3 L1-). Microarray was used to indentify molecules that differ in expression between KATO3 L1- and the parental cell line. Results: L1 was scarcely stained in non-cancerous epithelial cells and intestinal metaplastic cells. L1 was detected mainly in the cell surface membrane of cancer cells in 15 of 72 specimens, more often in the intestinal type cancer. No correlation was found between L1 expression and detection of cancer cells in the peritoneal washes or development of peritoneal carcinomatosis. Nevertheless, the prognosis of L1-positive cancer was significantly inferior (p = 0.024). Prognosis was particularly poor among 6 cases where L1 was expressed in cancer cells at the invasive front (median survival time 149 days). Of 40,000 genes evaluated in the microarray, mRNA expression of 50 genes were amplified by > 4-fold whereas the expression of 20 genes were attenuated to less than 1/4. Of these, expression of DYRK1A that induces apoptosis in conjunction with p53 was markedly suppressed to less than 1/8. Suppression of DYRK1A in the KATO3 L1- in comparison with the parental cell line was confirmed by RT-PCR. Conclusions: L1 affects prognosis of gastric cancer, particularly when it is expressed in cancer cells at the invasion front. Its role in the biology of gastric cancer has began to be elucidated. No significant financial relationships to disclose.
Sites of gastric cancer recurrence after adjuvant chemoradiotherapy.
Authors: Conrad T. , MacLellan S. , Kassam Z. , Mackay H. , Khalili I. , Jacks L. M. , Okrainec A. , Ringash J. 
Published: February 2017

68 Background: Since the Intergroup 0116 study in 2000, adjuvant post-operative chemoradiotherapy (CRT) has been offered routinely to similar patients with resected gastric cancer at Princess Margaret Hospital (PMH) using CT-planned and 3D conformal/intensity modulated radiotherapy (RT). The objective of this study was to analyze patterns of recurrence with respect to RT treatment volumes. Methods: Date and site (local, locoregional or distant) of first recurrence data was obtained from chart review for all patients treated at PMH with adjuvant CRT for resected gastric adenocarcinoma (Jan. 1, 2000-Nov. 30, 2009). Patients whose recurrences were limited to local (gastric remnant, duodenal margin, gastric bed recurrence) and/or regional sites (regional lymph node recurrence) were selected for analysis. When available, diagnostic imaging of recurrence site was registered to the original planning RT dataset. The center of mass for each recurrence was identified as a point and its location categorized according to the isodose encompassing it; in-field (≥ 90%), marginal (50%-89%), and out-of-field (< 50%). Results: Three-year OS, and RFS were 66% (95% CI: 58-73) and 58% (50-60), respectively. Of 203 patients treated, 75 recurrences were identified (Table). Of the 13 local/locoregional recurrences, 4 were in-field, 1 marginal, 1 could not be registered due to change in body habitus, and 7 did not have an available original dataset. Conclusions: Rates of isolated local and/or regional recurrence in this study were low. This represents a change in the pattern seen with surgery alone suggesting the addition of CRT results in decreased isolated local and/or regional recurrence. Of the small number of local and/or regional recurrences available for analysis, all were in-field or marginal. Further studies involving a larger cohort of patients might allow for more meaningful analysis of trends in recurrence site with evolving RT techniques. [Table: see text] No significant financial relationships to disclose.
Feasibility study of neoadjuvant chemotherapy with docetaxel, cisplatin, and fluorouracil (DCF) for clinical stage II/III esophageal squamous cell carcinoma.
Authors: Kato K. , Hara H. , Daiko H. , Igaki H. , Hamamoto Y. , Nagase M. , Kadowaki S. , Tahara M. 
Published: February 2017

95 Background: In JCOG 9907, neoadjuvant chemotherapy with cisplatin and 5-fluorouracil (CF) improved overall survival without additional serious adverse events in treating stage II/III esophageal squamous cell carcinoma (ESCC). However, ESCC patient survival remains unsatisfactory. We conducted a feasibility study of neoadjuvant chemotherapy with docetaxel plus CF (DCF) for clinical stage II/III ESCC. Methods: Eligibility criteria included clinical stage II/III (non-T4) ESCC, PS 0–1, and age 20–70 years. Chemotherapy consisted of a 1-h infusion of docetaxel at 70 mg/m2 and 2-h infusion of cisplatin at 70 mg/m2 (day 1), and continuous infusion of 5-FU 750 mg/m2 (days 1 to 5). Antibiotic prophylaxis on days 5 to 15 was mandatory. This regimen was repeated every 3 weeks (maximum 3 cycles) until unacceptable toxicity, patient refusal, or disease progression was observed. After chemotherapy completion, transthoracic esophagectomy with extended (> D2) lymphadenectomy was performed. The primary endpoint was the completion rate of protocol treatment. Results: From July 2009 to Feb 2010, 34 patients were enrolled, including 2 ineligibles. The 32 eligibles had a median age of 61 (range 36–70; male/female: 30/2), with PS0/1 of 20/12 and cStage IIA/IIB/III of 6/8/18. During chemotherapy, the most common grade-3 or -4 toxicities were neutropenia (88%), febrile neutropenia (3%), anorexia (9%), and stomatitis (6%). Thirty-one (97%) patients underwent surgery. The protocol completion rate was 87.5% (28/32). No treatment-related death was observed, and the operative morbidity incidence was comparable to those in previous studies. According to RECIST, the overall response rate was 61.5% after DCF completion. Primary-lesion pathological complete response was achieved in 26% of patients (8/31) who underwent esophagectomy. Conclusions: Neoadjuvant DCF was well tolerated. Although these data are preliminary, the protocol is highly promising and warrants further investigation. No significant financial relationships to disclose.
Multiplex panel of metabolomic markers for early detection of prostate cancer.
Authors: Vareed S. K. , Siddiqui J. , Putluri V. , Putluri N. , Rajendiran T. M. , Wei J. T. , Terris M. K. , Chinnaiyan A. , Michailidis G. , Sreekumar A. 
Published: February 2017

13 Background: Prostate cancer (PCa) is the second leading cause of cancer deaths among men in US. Prostate specific antigen (PSA) the clinical standard for early detection of PCa is not specific for the disease necessitating development of additional markers. Metabolites are stable, measurable in biological fluids and function as physiological indicators of the individual. Earlier we described the metabolomic alteration in PCa and nominated sarcosine as a tissue marker for PCa progression. Further, elevated sarcosine levels were seen in cancer urine. The current study describes a multiplex panel of metabolomic markers in urine that include sarcosine, for early detection of PCa. Methods: A sensitive liquid chromatography- mass spectrometry based assay was used to quantify relative levels of tissue specific metabolites in urine of PCa patients. The urine specimens examined in this study were collected at University of Michigan from post DRE and pre-biopsy from clinically challenging patients with PSA between 4-10 ng/mL where biopsy was either positive or negative for tumor. The urine supernatants were recovered post-centrifugation, adjusted to have an osmolarity between 350-400 mOsm/kg, spiked with defined amount of internal standards and evaluated by multiple reaction monitoring (MRM) using a triple quadrupole mass spectrometer. The MRM data was examined using random-forest (RF)-to generate a panel of discriminatory compounds that were validated in an independent test set. Results: A panel of 11 metabolites (glutamic acid, sarcosine, spermidine, histidine, methionine, adenosine, inosine, thymine, hydroxyphenyl lactic acid, acetyl valine and lauric acid) when employed in a RF-based 2-stage training model (n=63) delineated PCa and benign with a cross-validated (out-of-bag validation based on 20000 decision trees) accuracy of 76 %. When applied to an independent set of test samples (n=98) from the same cohort the accuracy, sensitivity, specificity, positive predictive value and negative predictive values were 72 %, 77.5 %, 62.5 %, 67.8 % and 73.2 % respectively. Conclusions: The study describes a first-generation multiplex panel of metabolic markers for early detection of PCa in urine supernatants. No significant financial relationships to disclose.
Phase II trial of bevacizumab (A), lenalidomide (R), docetaxel (D), and prednisone (P) in patients (pts) with metastatic castration-resistant prostate cancer (mCRPC).
Authors: Huang X. , Ning Y. M. , Gulley J. L. , Kluetz P. G. , Adelberg D. , Mulquin M. , Madan R. A. , Bassim C. , Figg W. D. , Dahut W. L. 
Published: February 2017

138 Background: Angiogenesis appears to play critical role in the progression of mCRPC. Previously we have shown anti-tumor activity in mCRPC with the combination of D, thalidomide (T), A and P (Ning JCO 2010). We hypothesized that combining R, an analogue of T, with A, D and P would have a more favorable toxicity profile and similar anti-tumor activity. Methods: All pts had chemotherapy-naïve progressive mCRPC. 6 pts were treated with R at 15 and 20 mg prior to doses at 25 mg. Treatment is 75 mg/m2 D, 15 mg/kg A every 21 days as one cycle (C), plus 25 mg R for 14 days with daily 10 mg P and enoxaparin. After grade 3 neutropenia was seen in > 80% of pts in all cohorts, the protocol was amended to include prophylactic pegfilgrastim. PSA is tested each C with imaging after C2 and then every 3C. Dental exams with mandible CT's are at baseline, after C5, and then every 6C or earlier if needed. Results: 28 of a planned 51 pts have been enrolled. Pt characteristics include: median age 65.5 [51-78], Gleason score 8 [67.9% 8-10, 32.1% 6-7], on-study PSA 94.3 ng/mL [9.2-3520], and pre-study PSA doubling time 1.43 months [0.52-4.07]. Median C number was 8 [1-21]. 2/28 pts were off study due to clinical or radiographic progression. 26 pts remain on study. 22/24 (91.7%) and 20/24 (83.3%) pts who have completed ≥ 4C had PSA- decline of ≥ 50% and ≥ 75%, respectively. 14 pts with measurable disease were evaluable with 2 CRs (1 unconfirmed), 9 PRs (2 unconfirmed), and 3 SDs (a 78.6% overall RR). Grade ≥ 3 toxicities include neutropenia (16/28), anemia (6/28), thrombocytopenia (3/28), hypertension (1/28), and infection (2/28). 1/28 pts had febrile neutropenia. 8/28 pts (28.6%) developed grade 2 osteonecrosis of the jaw (ONJ), defined as bone death on dental exam, higher than 18.3% as reported by Ning. 5/8 had concomitant and 2/8 pts had history of bisphosphonate use. Conclusions: Combined therapy with anti-angiogenic agents R and A, plus D and P is associated with high response rates, 91.7% in PSA and 78.6% in measurable disease in mCRPC pts, with manageable toxicities. Further study is underway to characterize the activity and to explore the high incidence of ONJ, including the possibility of ascertainment bias. No significant financial relationships to disclose.
A phase II study of sunitinib (SU) for maintenance therapy in metastatic castration-resistant prostate cancer (mCRPC) after response to docetaxel (D).
Authors: Eigl B. J. , Trudeau M. G. , Winquist E. , Chi K. N. , Eliasziw M. , North S. 
Published: February 2017

151 Background: After treatment with D based chemotherapy, there is currently no standard therapy although new options are emerging. Due to its mechanism of action, acceptable toxicity profile and simple administration, SU has potential for therapeutic activity in the setting of maintenance therapy for patients with mCRPC who have responded to D based chemotherapy. Methods: Patients with mCRPC who had evidence of responding or stable disease at completion of D treatment were enrolled in this phase II multicentre trial. Patients received 50mg of SU daily on 4 week on/2 week off cycles. The primary endpoint was effect of SU maintenance on PFS. Because of potential effects of SU on PSA kinetics, clinical progression was defined independent of PSA. PSA response rate was a secondary endpoint. PSA-progression (PSA-P) was defined as a 25% PSA increase over baseline. Results: Thirteen patients have been enrolled and treated to date. Mean age was 63 years (47-76). ECOG scores of 0, 1, and 2 were reported for 4, 8 and 1 patients respectively. Mean number of prior cycles of D given was 9.5. A total of 28 cycles of SU were administered. A total of 291 adverse events (AEs) were recorded, of which 66%, 27%, and 7% were classified as Grades 1, 2, and 3, respectively. No Grade 4 AEs were seen. AEs were of a type and severity expected for SU. The most frequent grade 3 AEs were fatigue (n=3) and hand foot syndrome (n=3). No PSA responses have been documented. Most patients had immediate PSA increases without evidence of clinical progression. The mean PSAs increased by 159%, 396%, and 853% in Cycles 1, 2, and 3, respectively, corresponding to p-values of 0.18, 0.03, and 0.01 when compared to the PSA-P threshold of 25%. The trial will continue to complete its planned accrual of 26 evaluable patients and updated results, along with PFS, will be presented at the meeting. Conclusions: SU is well tolerated as maintenance therapy after D in men with mCRPC, with a predictable side-effect profile. PSA values after treatment with SU may not reflect progression in patients with mCRPCas significant increases were observed as early as Cycle 2 without clinical evidence of worsening disease. [Table: see text]
Prostate-specific membrane antigen antibody drug conjugate (PSMA ADC): A phase I trial in taxane-refractory prostate cancer.
Authors: Petrylak D. P. , Kantoff P. W. , Rotshteyn Y. , Israel R. J. , Olson W. C. , Ramakrishna T. , Morris S. 
Published: February 2017

158 Background: The unique expression of PSMA type II transmembrane glycoprotein on prostate cancer cells provides a potentially attractive target for antibody therapy. PSMA ADC, a fully humanized antibody to PSMA linked to the potent antitubulin agent monomethyl auristatin E (MMAE), binds PSMA and is internalized within the prostate cancer cell where cleavage and release of free MMAE occur, causing cell cycle arrest and apoptosis. We report results from an ongoing phase I dose escalation study of PSMA ADC in patients (pts) with taxane refractory metastatic prostate cancer (metCRPC). Methods: Eligibility requirements included pts ≥18 years with metCRPC after failure of a taxane- containing regimen and ECOG status of 0 or 1. PSMA ADC is administered by IV infusion Q3W for up to 4 cycles. Adverse events, PK, PSA, circulating tumor cells, clinical disease progression and immunogenic response to PSMA ADC continue to be assessed. Serum concentrations of PSMA ADC and total antibody are measured by an enzyme-linked immunosorbent assay (ELISA) method, and free MMAE is measured by liquid chromatography/mass spectrometry/mass spectrometry (LC/MS/MS) method. Dosing cohorts ranged from 0.4 mg/kg to 1.8 mg/kg. Results: The demographics of 15 subjects enrolled in the four dosing cohorts (0.4, 0.7, 1.1 and 1.8 mg/kg) were similar. Treatment has to date been generally well tolerated and the most common laboratory abnormalities were reversible changes in liver and hematological parameters. Exposure to PSMA ADC and serum half life (t1/2) increased in a dose-proportional manner. Similar PK metrics were observed after the first and third doses. Exposure to free MMAE was also dose proportional and approximately <0.1% of PSMA ADC. Conclusions: In this first-in-human evaluation, PSMA ADC appears to exhibit dose-proportional PK and limited release of free MMAE. Ongoing enrollment allows for assessment of potential clinical utility of this unique potential treatment of metCRPC. [Table: see text]