tbuckley/cabot-search huggingface dataset:
Gastrointestinal stromal tumor of the rectum and rectovaginal space: A retrospective review
Authors: C. Mussi, J. Jakob, E. Wardelmann, P. Reichardt, P. G. Casali, M. Fiore, P. Collini, A. Gronchi, P. Hohenberger
Journal: Journal of Clinical Oncology (2008)

10560 Background: The aim of the study was to assess the outcome of patients with gastrointestinal stromal tumors (GISTs) of the rectum and rectovaginal space. Methods: 575 patients affected by GISTs were treated over 20 years at two institutions and data gathered in prospective databases. Among these, we identified 39 patients who presented with primary or recurrent rectal/pararectal GISTs. All patients except one underwent surgery. Local and distant outcome, morbidity and response to combined treatments were analyzed (median follow-up: 43 months). Results: A male prevalence was noticed (M:F=2). Four patients had an initial diagnosis of rectal cancer and four of MPNST, leiomyosarcoma or leiomyoma. Twenty-five tumors were classified as high risk for malignant behavior, 7 as intermediate and 7 as low/very low risk. Thirty-three tumors originated in the rectum and 6 in the rectovaginal space. Anterior resection or abdominoperineal resection was performed in 19 patients and transanal/transperineal resection in the other cases. Thirteen patients received preoperative treatment with imatinib mesylate for variable periods (median 15 months). Eleven patients experienced PR or CR, one had SD and another one was operated in progression. Additional radiotherapy was delivered in 6 cases. In one patient radiotherapy resulted in disease stabilization after failure of imatinib therapy. Sixteen patients (42.1%) had local recurrences, 10 after extraperitoneal procedures and 6 after transabdominal resections. Six patients had more than one local relapse (range 2–5). Eleven patients (32.3%) developed distant metastases. Five-year local disease-free survival and disease-specific survival were 53.2% and 85.6% respectively. Among the five patients who received postoperative radiotherapy, only one developed a further recurrence. Conclusions: GIST needs to be considered in patients thought to suffer from rectal/pararectal tumors without clear diagnosis of adenocarcinoma. They have a high risk of local relapse if treated like rectal cancer. Function-preserving surgery is challenging. Preoperative treatment with imatinib results in substantial tumor shrinkage in most patients and facilitates radical and conservative surgery. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Novartis Novartis, Pfizer Novartis, Pfizer
Phase I study of topotecan and amrubicin in patients with chemo-naive extensive disease (ED) or relapsed small-cell lung cancer (SCLC)
Authors: M. Tabata, K. Hotta, S. Harita, Y. Segawa, T. Shibayama, K. Kiura, T. Shinkai, H. Ueoka, M. Tanimoto
Journal: Journal of Clinical Oncology (2005)

7340 Background: Combination chemotherapy of topotecan and amrubicin for ED or relapsed SCLC has not been fully evaluated. To determine the maximum-tolerated dose (MTD), a Phase I study in patients with ED or relapsed SCLC was conducted. Methods: Both relapsed patients with prior chemotherapy and chemo-naïve ED patients were enrolled in this study. Topotecan was administered through days 1 to 5, whereas amrubicin was administered on days 3 to 5. Courses were repeated every 3 weeks. The starting doses of topotecan and amrubicin were 0.75 and 30 mg/m2/day, respectively. Blood samples were obtained during the second and third days of the first cycle. Toxicities were graded according to the National Cancer Institute Common Toxicity Criteria (Ver2.0). Results: Patients with ED or relapsed SCLC (n = 9) were enrolled between April and November 2003, including 3 sensitive-relapsed cases. A total of 24 courses were assessable for safety. The principle toxicity was myelosuppression. In the first course of dose level 3, DLT was observed in all 3 patients (persistence of grade 4 neutropenia in 1 patient, grade 3 thrombocytopenia with platelet transfusion in 1 patient, plus persistence of grade 4 neutropenia and leukopenia and grade 3 febrile neutropenia in 1 patient). Thus, MTDs of topotecan and amrubicin were determined to be 0.75 and 40 mg/m2, respectively. Objective response was obtained in 7 patients (78%), including 4 relapsed patients. Cmax and AUC of amrubicinol were correlated to duration of grade 4 neutropenia (Spearman’s test, p=0.0239 and 0.0211). Additionally, the mean Cmax of topotecan on day 2 in 7 responders was significantly higher than that in 2 non-responders (22.9±3.6 and 10.9±0.4, respectively, Mann-Whitney U test, p=0.0404). Conclusions: This combination was well tolerated and produced a promising antitumor effect for ED or relapsed SCLC. Several pharmacokinetic factors may be predictive of toxicity and response. No significant financial relationships to disclose.
Expression of Bax and Bcl-2 in human rhabdomyosarcoma: Correlation with survival in 64 patients
Authors: D. M. Steinert, J. Salganick, M. Ballo, W. Zhang, M. Munsell, B. Raney, N. Jaffe, J. Koh, A. El-Naggar, J. Trent
Journal: Journal of Clinical Oncology (2005)

9041 Background: Rhabdomyosarcoma (RMS) is an aggressive soft-tissue sarcoma, the most common in children, but rare in adults. Understanding the expression of molecules involved in apoptosis in RMS tumors may lead to a better understanding of resistance to chemotherapy and identification of novel therapeutic targets. As yet, no study has correlated the expression of both Bax and Bcl-2 with survival (OS) or progression-free survival (PFS) in patients with RMS. Methods: We retrospectively reviewed the cases of 64 consecutive patients with RMS treated at our institution between 1980–2002 and who had paraffin-embedded tissue samples and clinical information available. Two reference pathologists reviewed all 64 cases to confirm the histologic diagnosis. A tissue microarray was constructed from the tissue samples with subsequent immunohistochemical evaluation of Bax and Bcl-2 expression. Clinicopathologic information was collected on all patients and analyzed for correlation with OS and PFS. The methods of Kaplan and Meier and Cox’s proportional hazards regression model were used for statistical analysis. Results: Bax and Bcl-2 were expressed in 62 of 64 (97%) and 12 of 64 (19%) tumor samples, respectively. With a median follow-up of 28 months, we observed improved median PFS in patients whose tumor expressed Bax vs. those that did not (PFS = 15 vs. 2 months, p <0.01). There was also a trend toward improved OS in patients whose tumor expressed Bax vs. those whose tumor did not (OS = 36 vs. 18 months, p= 0.10). Tumors expressing Bcl-2 showed no trend regarding survival, and the ratio of Bax/Bcl-2 did not show a trend in survival. Conclusions: Bcl-2 and Bax are expressed in human RMS tissue. Expression of Bax may be associated with improved OS and PFS in these patients, but our sample size limits definitive conclusions. No significant financial relationships to disclose.
Multimodality treatment with curative intent for early rectal carcinoma—Long term Clatterbridge(UK) experience
Authors: A. Sun Myint, V. S. Ramini, H. Wong, K. Perkins, R. Grieve, M. J. Hershman, C. Makin
Journal: Journal of Clinical Oncology (2008)

15018 Background: Local treatment of early rectal cancer with curative intent is highly controversial.The standard treatment for low rectal cancer is low anterior resection or APR.We present an update of our long-term results in patients treated with low rectal cancer using combined modality at Clatterbridge. Methods: From Jan’92 to July’07,local treatment was offered to 220 patients with low rectal cancer.Mean age 76 years (range 33–100). There were 129 males and 91 females. After MRI& EUS staging, patients with tumours <3cm had TEM or Papillon. Responders and those with R0 resection were watched closely. Larger tumours had CRT(45Gy/25/35) +5FU 1G/m2 or capecitabine 825mg/m2x5 wks. Papillon boost (80Gy)was offered to responders (90% regression). TEM was used to remove residual tumour for histology. Non responders (<25%regression) had radical immediate surgery,if they are fit. Delayed salvage surgery was offered to local recurrence with no metastatic spread. Results: Of 220 patients treated, 24(11%) had persistent residual disease and had immediate surgery. Twenty one patients were cured (87.5%)and 2 developed distant relapse. Out of 196 patients who responded well initially, 20 (10.2%) recurred. Delayed salvage with repeat Papillon or surgery was carried out on 9/11 patients with local recurrence alone and 7 were cured. Overall cure rate was 202/220 (92%)after salvage. Conclusions: Local treatment of early rectal cancer is a controversial and complex. Patients diagnosed with early rectal cancer is increasing and the ageing population is expanding. The demand for local treatment will increase as some of these patients will not be fit for radical surgery. It is important to balance the benefits of radical surgery (lower LR but increase in morbidity and mortality) against slightly higher LR (∼10 %) but much lower mortality and morbidity from conservative local treatment such as TEM or contact radiotherapy. Our study has shown that salvage surgery can be effectively carried out for recurrences after local treatment This can be offered for elderly patients with medical co morbidity and also for small number of younger patients who wish to avoid major surgery initially. We recommend a close follow up so that local recurrences can be detected early for salvage surgery. No significant financial relationships to disclose.
A meta-analysis of chemotherapy duration in metastatic breast cancer (MBC)
Authors: A. Gennari, M. Sormani, P. Bruzzi, N. Wilcken, O. Nanni, M. Fornier, M. R. Stockler
Journal: Journal of Clinical Oncology (2008)

1067 Background: Ten years ago, a systematic review of 4 randomised trials comparing longer with shorter chemotherapy duration in MBC showed a 20% reduction in the risk of death with more chemotherapy cycles, supporting the policy of prolonging treatment in the absence of progressive disease or unacceptable toxicity. Since this analysis, new studies on different chemotherapy durations have been reported, with conflicting results. With these premises, the aim of this study was to review all the available evidence on this subject. Methods: The criteria used to identify relevant studies, through literature search, were 1) randomised trials, 2) investigation of longer versus shorter chemotherapy duration, 3) overall survival data. Eight studies comprising 1,942 randomised patients were retrieved. Pooled estimates, based on published data, of overall survival HRs were obtained according to standard meta-analysis procedures. Sensitivity analyses were performed to examine whether the overall effect on survival was associated with study design (intermittent control arm vs not), number of chemotherapy cycles in the control arm (<4 vs >4) and co-administration of endocrine therapy. Results: Overall longer chemotherapy duration was associated with an 8% reduction in the risk of death (HR 0.92, CI 0.84–1.00; p 0.07). The magnitude of this effect was remarkably similar across groups of trials (table), suggesting its independence of study design, number of chemotherapy cycles in the control arm and concomitant endocrine therapy. Conclusions: The benefit associated with longer chemotherapy duration as first line treatment of MBC is, at best, marginal. Study subset Author, year HR 95% CI p Intermittent control arm Coates, 1987; Harris, 1990; Muss, 1991; Ejlertsen, 1993; French, 2000; Nooij, 2003 0.91 0.82–1.01 0.08 Nonintermittent control arm Gregory, 1997; Falkson, 1998; Gennari, 2006 0.94 0.76–1.16 0.56 Control arm < 4 cycles Coates, 1987; Harris, 1990; French, 2000 0.90 0.77–1.04 0.16 Control arm >4 cycles Muss,1991; Ejlertsen, 1993; Gregory,1997; Falkson,1998; Nooij, 2003; Gennari,2006; 0.93 0.83–1.05 0.22 Concomitant Tamoxifen Ejlertsen, 1993; Falkson,1998; Gennari,2006; 0.87 0.74–1.02 0.09 No concomitant Tamoxifen Coates, 1987; Harris, 1990; Muss, 1991; Gregory, 1997; French, 2000; Nooij, 2003 0.94 0.84–1.05 0.28 Overall All 0.92 0.84–1.00 0.07 No significant financial relationships to disclose.
Antitumor activity of the maytansinoid immunoconjugate B-B4 (B-B4-DM1) against CD138+multiple myeloma cells.
Authors: P Tassone, A Gozzini, Goldmacher, MA Shammas, HS Xie, L Catley, R Burgher, T Hayashi, T Hideshima, D Chauhan, N Munshi, KC Anderson
Journal: Blood (2003)
Phase II study of weekly paclitaxel in patients with advanced gastric cancer in Japan
Authors: H. Baba, Y. Emi, Y. Kakeji, E. Tokunaga, S. Ushiro, M. Watanabe, Y. Maehara
Journal: Journal of Clinical Oncology (2004)

4226 Background: Paclitaxel is an effective anticancer agent against gastric cancer. Phase II study of triweekly paclitaxel of 210 mg/m2 in Japan showed response rates of 23% and MST of 11 months. Recently, weekly administration has attracted attention with a higher response rate and less toxicity in breast cancer. In this study we evaluated the clinical effect and toxicity profile of weekly paclitaxel against advanced gastric cancer. Methods: The eligibility criteria were as follows; 1) histologically proven gastric cancer with measurable lesion, 2)PS 0–2, 3)age<75, 4) adequate bone marrow, liver, renal functions, 5) life expectancy of more than 3 months. Fifty-nine patients were treated with weekly 1h-infusion paclitaxel of 80mg/m2 with a short premedication for consecutive 3 weeks with one week rest as one course. Results: Patients characteristics were as follows: male/female; 44/15, mean age of 64, PS 0/1/2; 27/20/12, previous treatment (-)/(+); 11/48. Median treatment cycle was 3. Over all response rate was 22.2% and median survival time of 263 days. There were no treatmwnt-related deaths. Hematologic and nonhematologic toxicities more than grade 3 included leucopenia(15.3%), neutopenia(20.3%), fatigue(1.7%), and arthralgia(1.7%). An improvement in PS, food intake, pain, and ascites accumulation was recognized in 17.3%, 16.4%, 23.1%, and 47.6%, respectively. Conclusions: Weekly paclitaxel was active for both previously untreated and treated patients with advanced gastric cancer with a minimum toxicity profile, and can be useful to improve QOL and prolong survival time of patients. No significant financial relationships to disclose.
Prospective analysis of KRAS, BRAF, and PIK3CA mutational status and EGFR copy number in patients (pts) with locally advanced rectal cancer: A translational substudy of a clinical trial (SAKK 41/07) evaluating the effect of neoadjuvant chemoradiation (CRT) with or without panitumumab.
Authors: D. Koeberle, S. Bougel, J. Benhattar, F. Bosman, O. Gautschi, H. Sun, G. Bodoky, R. von Moos, D. Helbling
Journal: Journal of Clinical Oncology (2011)

3549 Background: The prevalence of possible prognostic and predictive markers is of great importance for future study designs and essential for the interpretation of clinical trials incorporating an EGFR-inhibitor. KRAS, BRAF and PIK3CA mutational status has not been prospectively assessed in rectal cancer patients. Methods: Macrodissection was performed on pretreatment formalin fixed paraffin embedded biopsy sections to increase the proportion of tumor cells. DNA was extracted with the Maxwell 16 FFPE Tissue LEV DNA purification kit. After PCR amplification, mutations were identified by pyrosequencing analysis. We prospectively analysed pretreatment biopsy material from 127 rectal cancer patients biopsies for KRAS (exon 2 codon 12 [2-12] and 13 [2-13], exon 3 codon 59 [3-5]) and 61 [3-61], codon 4 codon 117 [4-117] and 146 [4-146]). 68 patients (KRASwt exon 2, 3 only) were further analysed regarding BRAF (exon 15 codon 600) and PIC3CA (exon 20 codon 1043 [20-1043] and 1047 [20-1047]) mutations and EGFR copy number, which was measured by qPCR. To normalize the quantification of the EGFR copy number, we used KRAS copy number as a reference. The calculation was done on the basis of the two standard curves relative quantification method. Results: KRAS mutations: 29 pts (23%) with exon 2-12, 8 pts (6%) with exon 2-13, 1 pts (1%) with exon 3-59, 4 pts (3%) with exon 3-61, 4 pts (3%) with exon 4-117, 9 pts (7%) with exon 4-146. KRAS mutational rate (for all analysed exons/codons) 43%. One patient (1.5%) showed a BRAF mutation. 5 patients (7.4%) had a PIK3CA mutation (1 x Exon 20-1043, 4 x Exon 20-1047). The median EGFR copy number was 1.1. Conclusions: KRAS mutations appear equally common in rectal and in colon cancer. BRAF and PIK3CA mutations are rare in KRASwt rectal cancer patients. In KRASwt patients the EGFR copy number is not increased. Correlation analyses between molecular results and response data from neoadjuvant therapy trial is ongoing and will be presented at the meeting.
End-of-life decisions by adults with cancer: Role of religious practices and spiritual beliefs
Authors: R. M. Navari, L. M. Buckingham
Journal: Journal of Clinical Oncology (2007)

9067 Background: Religious practices and spiritual beliefs may affect end of life care decisions. Methods: Adult patients with advanced common cancers (Stages III, IV; lung, breast, prostate, colon) who were within one year of their diagnosis and were receiving active treatment in two community oncology practices, were interviewed (30 questions, 20–30 minutes) during an outpatient office visit to determine the major influences on end of life decisions. Specific attention was given to advance directives, influences on end of life decisions, discussions with family and physicians, and the role of religious practices and spiritual beliefs. 353 consecutive patients were invited to be interviewed and 339 patients (median age 66.2 yrs, 52.7% female, 57% married, 58% Caucasian, 30% African-American, 62% Christian, 61% high school education) completed the interview and were evaluable. Results: Fifty-one percent of the patients had an advance directive. The major influences on end of life decisions were family discussions (63%), quality of life (56%), personal experiences (50%), religious/spiritual beliefs (48%), financial burdens (41%), physician discussions (39%), and specific individuals (10%). Factors associated with having an advance directive were religious or spiritual affiliation, participating in regular religious or spiritual practices, and having discussed end of life decisions with their family or a physician. Patients had little knowledge of their religion's specific recommendations on end of life care and had few discussions with a religious professional on these issues. Conclusions: Health care providers need to recognize the influences on end of life decisions, as well as the role of patients’ religious practices and spiritual beliefs. No significant financial relationships to disclose.
Interim analysis of The Spanish Lung Cancer Group (SLCG) BRCA1-RAP80 Expression Customization (BREC) randomized phase III trial of customized therapy in advanced non-small-cell lung cancer (NSCLC) patients (p) (NCT00617656/GECP-BREC)
Authors: Teresa Moran, Manuel Cobo, Manuel Domine, Maria Sanchez-Ronco, Isabel Bover, Mariano Provencio, Bartomeu Massuti, Alain Vergnenegre, Guillermo Lopez-Vivanco, Gilles Robinet, Amelia Insa, Margarita Majem, Ramon De Las Penas, María Ángeles Sala, Dolores Isla, Nathalie Baize, Javier Garde, Imane Chaib, Carlos Camps, Rafael Rosell
Journal: Journal of Clinical Oncology (2013)

LBA8002 The full, final text of this abstract will be available at abstract.asco.org at 7:30 AM (EDT) on Monday, June 3, 2013, and in the Annual Meeting Proceedings online supplement to the June 20, 2013, issue of Journal of Clinical Oncology. Onsite at the Meeting, this abstract will be printed in the Monday edition of ASCO Daily News.
Diverse long-time progression-free survival (PFS) and overall survival (OS), based on metastasis location, in metastatic urothelial carcinoma (MUC) patients treated with pemetexed (P) in monotherapy: Results from a longer follow-up of Arco del Mediterraneo Group.
Authors: J. Cervera Grau, E. Gonzalez-Billalabeitia, A. Lopez, O. Juanidal, J. Satre, E. Barrajon, G. Esquerdo, C. Molins, S. Maciá, C. D. Rolfo
Journal: Journal of Clinical Oncology (2010)

e15120 Background: Patients with MUC relapsing after standard chemotherapy perioperative or after localy advanced or metastatic disease, have no good treatments. We report our series with high activity of P in monotherapy. Methods: Patients with locally advanced and/or MUC receiving pemetrexed 500 mg/m2 every 21 days with folic acid and vitamin B12 supplementation as first, second, third or fourth-line chemotherapy on a compassionate use were elegible. Results: At this moment 32 patients has been reported median, age 62 [41-82]. 5, 19, 8 and 1 patients received P as first, second, third, fourth respectively. A median of 3 courses were administered [1-12]. An objective ilness control was achieved in 15/32 (SD+PR+CR) for an overall control rate of 46.92%. At this moment,a median of 96 [17-606] days (PFS) and 133 [17-672] days (OS) has been reported for our 32 cases. It has not been hard to distinguish between 3 groups; 13 patients with extranodal metastasis reported a median of 103 [47-218] (OS) days and 51,5 [26-145] (PFS) days. 9 patients with nodal +visceral metastasis reported a median of 175 [40-560](OS) days and 128[40-510] (PFS) days.10 patients with nodal metastasis reported a median of 310 [66-672] (OS) days and 157[44-606] (PFS) days. Conclusions: Even with this short group, our longer follow-up show that P in monotherapy, as first, second, third, fourth line therapy in MUC, is associated with high activity and long- time survival specially in metastatic nodal MUC. Other associations and its effectiveness in chemotherapy-naïve patients would be studied. More patients will be reported. No significant financial relationships to disclose.
Multimodality management of borderline resectable pancreatic neuroendocrine tumors: Sentinel report of a single-institutional experience.
Authors: Chenwi Ambe, Phuong Nguyen, Barbara Centeno, Junsung Choi, Jonathan R. Strosberg, Larry K. Kvols, Pamela Joy Hodul, Sarah E. Hoffe, Mokenge Peter Malafa
Journal: Journal of Clinical Oncology (2015)

418 Background: Pancreatic neuroendocrine tumors (PNET) constitute about 3% of pancreatic neoplasms. In borderline resectable disease, there is a lack of data to support an optimal neoadjuvant approach for curative outcomes. We describe our institutional experience with a multimodality approach. Methods: We identified all patients with borderline resectable PNET, using NCCN criteria for adenocarcinoma of the pancreas, who received neoadjuvant therapy at our institution between 2000 and 2013. The reason for borderline status was noted. Neoadjuvant regimen, radiographic response, pathologic response, surgical margins, nodal harvest, number of positive nodes, and recurrence were all documented. Results: A total of 112 patients had undergone pancreatic resections for neuroendocrine tumors during the study period. Six patients had borderline resectable disease. The mean age was 55 years (24-70). They all received at least 1 cycle of Temodar and Xeloda. Three of the six patients also received concurrent 5-FU and radiation. There was radiographic evidence of treatment response in all patients. Five of six patients (83 %) had negative margin (R0) resection. Low volume miliary metastatic disease in the liver was detected in 1 patient at the time of surgery. The median number of lymph nodes harvested was 12. Half of the patients had node positive disease. On pathologic review, 4 patients had histologic evidence of a moderate response. All patients are alive and 5/6 are free of disease. Range of follow up is 3.0-4.32 years. The patient with metastatic disease has had no progression and is the only one who is currently receiving any form of treatment. Conclusions: Neoadjuvant Temodar and Xeloda ± radiation with 5-FU sensitization can lead to R0 resection with durable response in patients with borderline resectable PNET. To our knowledge, this is the first report of the use of multimodality therapy (neoadjuvant chemotherapy ± chemoradiation and surgery) in the treatment of borderline resectable PNET.