tbuckley/cabot-search huggingface dataset:
Clinical experience with neuroendocrine rectal tumors.
Authors: O. Derbel, S. Limem, L. Tassy, F. Desseigne, M. Rivoire, P. Meeus, P. Peyrat, M. Stella, I. Martel-Lafay, C. De La Fouchardiere
Journal: Journal of Clinical Oncology (2011)

611 Background: Carcinoids are heterogeneous neuroendocrine tumors with malignant potential. The rectum is the third most common location for gastrointestinal carcinoids after small bowel and colon. Due to their rarity, the characteristics and behavior of this unusual malignancy remain unclear. Methods: Retrospective review of the clinicopathologic features of patients treated for carcinoid tumors of the rectum. Results: A single institute's tumor registry was retrospectively queried, identifying nine patients with rectal carcinoid tumors over a 10-year period. The mean age at diagnosis was 57.6 years. Four of the nine patients were female. Presenting symptoms included abdominal pain in five patients, rectal bleeding in two patients and a change in bowel habits in one patient. As previously reported, no patient had symptoms consistent with carcinoid syndrome. The rectal tumor size was &gt; 2 cm in five patients. The rectal tumor was located in the lower third of the rectum in three cases (&lt; 5 cm from anal verge) whereas three were in the middle third (6-11 cm) and two in the upper third (11-15 cm). Four of the tumors were well differentiated tumors (grade 1), 1 was atypical carcinoid or moderately differentiated tumors (grade 2), and 4 were poorly differentiated tumors (grade 3) according to the SEER. Initially, 5/9 patients had distant metastasis. As an initial site of metastasis, the liver was the most common site (4/5 patients, 80%). Five patients underwent surgical treatment of their rectal tumor, two with endoscopic transanal resection whereas 3 patients had a low anterior resection (LAR). Three patients received chemotherapy treatment only in the metastatic setting and one patient received chemotherapy and radiotherapy as palliative treatment. Of the nine patients, five had progressive disease after initial treatment. With a median follow-up of 14 months, the overall survival of the entire population was 13.4 months. Conclusions: Neuroendocrine carcinomas of rectum are uncommon. Only small rectal carcinoids can be safely managed and surgery represents the treatment that can offer a greater chance of survival to these patients. Larger primary tumors have a high tendency to spread early. They are associated with aggressive behavior, resistance to chemotherapy and poor prognosis. No significant financial relationships to disclose.
A phase I study evaluating CC-4047 in patients with advanced solid tumors
Authors: C. J. Nock, M. M. Cooney, T. Mekhail, J. M. Brell, S. S. Krishnamurthi, J. A. Bokar, S. Sanborn, J. Samsa, N. J. Horvath, A. Dowlati
Journal: Journal of Clinical Oncology (2008)

3585 Background: CC-4047 is an IMiD™ compound with immunomodulatory properties and on an equimolar basis in vitro, displays equivalent anti-angiogenic properties; however, CC-4047 gives a greater stimulation of apoptosis, inhibition of COX-2 production, and inhibition of cellular TNF-alpha production relative to thalidomide. This phase I trial was undertaken to determine the maximal tolerated dose (MTD), dose-limiting toxicity (DLT), and to evaluate for any tumor response. Methods: To be eligible the patients had advanced solid tumors, ECOG performance status of 0 to 2, and adequate organ function. Patients received CC-4047 capsules once daily continuously from days 1 to 21 followed by a 7 day rest. Cycles were repeated every 28 days. DLT during cycle one was defined as any ≥ grade 3 non-hematologic toxicity, febrile neutropenia, grade 4 neutropenia, or platelet count ≤ 25,000/ul. Results: 11 patients, 6 male and 5 female, were enrolled. Patient tumor types included colon (3), prostate (2), and one each of adenocarcinoma unknown primary, breast, lung, melanoma, pancreas, and synovial cell sarcoma. Median age was 60 years (range 45 to 76). Median number of prior systemic therapies was 4 (range 2 to 7). Three patients received 5 mg daily of CC-4047 without any DLTs. The dose was increased to 10 mg of CC-4047 in the subsequent two patients and both had DLTs consisting of dyspnea. The attribution to therapy was complicated by disease progression in both these patients. The CC-4047 dose was then decreased to 7 mg daily and of the 6 patients enrolled at this 7 mg dose level one experienced a DLT of dyspnea. Grade 3 toxicities included neutropenia in 6 (55%) patients, leukocytopenia in 2 (18%) patients, and lymphopenia in 1 (9%). The median number of cycles completed is 2, (range 1 to 5). A patient with advanced, hormone and chemotherapy refractory prostate carcinoma, experienced a 48% decline in PSA and is currently on study for 5 + cycles. Conclusion: The recommended dose for further study in phase II trials of CC-4047 is 7 mg once daily for 21 consecutive days with 7 days off. Dyspnea and grade 3 neutropenia were observed. One patient with advanced prostate cancer experienced a significant decrease in his PSA. No significant financial relationships to disclose.
Developing and promoting evidence-based use of granulocyte colony stimulating factors (GCSF) in the palliative chemotherapy setting.
Authors: Aymen Elfiky, Marina Kaymakcalan, Sherri Stuver, Christopher Sweeney, Joseph O. Jacobson, Saul Weingart
Journal: Journal of Clinical Oncology (2013)

172 Background: National guidelines help define the standard for institutional clinical and insurance coverage policies, butdo not cover all chemo regimens or clinical scenarios. Given high utilization rates of primary granulocyte colony stimulating factors (GCSF) use in metastatic prostate cancer (CaP) patients treated with second-line cabazitaxel chemotherapy, we assessed indications and clinical rationale with goal of developing guidelines for appropriate use of GCSF in this population. Methods: We analyzed existing National Comprehensive Cancer Network (NCCN) and ASCO Myeloid Growth Factors supportive care guidelines as applied to specific chemo regimens, patient and laboratory risk factors (RF). We subsequently examined phase III TROPIC trial data for incidence of neutropenic events in CaP patients treated with cabazitaxel. Additionally, the medical records of the 25 Dana-Farber CaP patients treated with cabazitaxel from 1/2012 through 9/2012 who received primary GCSF prophylaxis were characterized by neutropenia/complications and their RF profiles using existing guidelines. Findings were presented to the genitourinary oncology providers with discussion culminating in consensusrecommendations for GCSF use. Results: Existing guidelines recommend 7 un-weighted factors to consider for GCSF use, in addition to febrile neutropenia (FN) risk &gt; 20% for any chemo regimen. Cabazitaxel is listed as intermediate FN risk (10-20%). Trial data report FN incidence as 7% without primary prophylaxis. The number of NCCN RF for evaluated Dana-Farber CaP patients is represented below. Conclusions: Group consensus considered any of the following to place patients at high risk of neutropenic events: ECOG ≥2; prior episode of FN with any-line chemo; prior neutropenia resulting in treatment delay; and previous radiation comprising &gt;25% bone marrow exposure. Final clinical consensus regarding high risk patients was to consider standard dose cabazitaxel (25mg/m2) with GCSF support versus dose reduced cabazitaxel (20mg/m2) without GCSF. In cases where provider posits there is no compromise of benefit to patient, initial consideration will be for dose reduction. [Table: see text]
Dasatinib efficacy by dosing schedule across individual baseline BCR-ABL mutations in chronic phase chronic myelogenous leukemia (CML-CP) after imatinib failure
Authors: A. Hochhaus, M. Mueller, J. E. Cortes, D. Kim, Y. Matlob, L. Ploughman, T. Hughes
Journal: Journal of Clinical Oncology (2008)

7014 Background: Dasatinib is 325-fold more potent than imatinib and 16-fold more potent than nilotinib against unmutated BCR- ABL in vitro and has demonstrated efficacy in CML-CP patients (pts) resistant or intolerant to imatinib. Dasatinib's current labeled dose of 100 mg once daily reflects findings of a randomized phase III dose optimization study showing similar efficacy and less-frequent key side effects compared with 3 other dosing schedules. Here, we analyze efficacy according to frequently occurring individual baseline BCR-ABL mutations in this study (CA180–034). Methods: The study design has been described previously. Pts were randomized using a 2x2 factorial design to 100 mg or 140 mg dasatinib per day and to a once-daily vs twice-daily schedule. Samples were tested for the presence of point mutations in BCR-ABL by direct sequencing. Results: 670 pts were randomized, of which 581 had a baseline mutation analysis and 1-year cytogenetic response data available. For the 100 mg QD, 70 mg BID, 140 mg QD, and 50 mg BID groups, the overall major cytogenetic response (MCyR) rates were 62%, 58%, 63%, and 56%, respectively (not significant). MCyR by individual baseline mutations observed in ≥15 pts is shown. Conclusions: Dasatinib 100 mg once daily leads to MCyR across individual baseline BCR-ABL mutations except T315I, including those occurring in the P-loop region, and the MCyR rate appears similar to the 3 other dosing schedules. MCyR, n/N (%) pts Mutation 100 mg QD N=147 70 mg BID N=146 140 mg QD N=139 50 mg BID N=149 M244V 3/6 1/5 4/7 2/2 G250E 3/5 3/10 3/9 2/7 E255K/V 1/3 2/2 1/2 2/8 Any P-loop (residues 248–256) 5/8 9/17 6/17 5/17 T315I 0/5 0/1 1/4 0/5 M351T 1/7 4/8 5/8 8/10 F359C/I/V 5/8 6/9 2/3 7/10 H396P/R 4/5 1/2 2/4 2/5 Any 26/49 (53) 21/46 (46) 29/51 (57) 26/61 (43) Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Bristol-Myers Squibb Bristol-Myers Squibb Bristol-Myers Squibb, Novartis Bristol-Myers Squibb, Innovive, Merck, Novartis, Wyeth
Re-induction with ipilimumab, gp100 peptide vaccine, or a combination of both from a phase III, randomized, double-blind, multicenter study of previously treated patients with unresectable stage III or IV melanoma.
Authors: F. S. Hodi, S. O'Day, D. F. McDermott, J. B. Haanen, C. Robert, X. Zhu, M. J. Yellin, R. A. Ibrahim, A. Hoos, J. D. Wolchok
Journal: Journal of Clinical Oncology (2010)

8509 Background: Ipilimumab, a fully human monoclonal antibody against cytotoxic T-lymphocyte antigen-4, has demonstrated clinical activity against advanced melanoma. In prior studies, gp100 vaccine showed immunological and clinical responses, and enhanced clinical activity when combined with other immunotherapy. Safety and efficacy of ipilimumab, ipilimumab + gp100 vaccine, and gp100 vaccine were evaluated in this study. Methods: Eligible patients were randomized 1:3:1, respectively, to receive an induction course of 4 doses of study drug: ipilimumab (3 mg/kg q3w × 4 doses) + placebo; ipilimumab + gp100 (peptides 209-217 [210M] and 280-288 [288V]); or gp100 (1 mg q3w × 4 doses) + placebo. Re-induction was allowed within 28 days of documented progression, provided the response to the initial cycle of therapy was SD lasting ≥3 months from week 12, CR, or PR. Patients were re-induced with 1 to 3 additional courses of the originally assigned regimen. Results: Of 643 patients initially treated, 32 were re-induced per protocol (8 with ipilimumab, 23 with combination therapy and 1 with gp100 [6.1%, 7.3%, and 0.8%, respectively, of the total who received initial therapy with each]) and their responses reassessed. Efficacy results are presented below. An acceptable safety profile was demonstrated in all 3 treatment arms and was similar to that of the initial induction treatment. Conclusions: In patients who progressed following an initial response to the induction course of therapy, the disease control rate in the ipilimumab arms was 65%-75% compared to 0% in the gp100 arm upon re-induction. These findings may have implications for the use of ipilimumab therapy in the long-term management of advanced melanoma. Induction, n Best overall response Ipilimumab + gp100 (n = 23*) Ipilimumab (n = 8) gp100 (n = 1) Total (n = 32) CR 0 0 0 0 PR 7 2 1 10 SD 15 6 0 21 Unknown 1 0 0 1 Re-induction, n (%) CR 0 1 (12.5) 0 1 (3.1) PR 4 (17.4) 2 (25.0) 0 6 (18.8) SD 11 (47.8) 3 (37.5) 0 14 (43.8) PD 8 (34.8) 2 (25.0) 1 (100.0) 11 (34.4) Unknown 0 0 0 0 * 5 additional pts were re-induced in error and are not part of the analysis. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Bristol-Myers Squibb, Medarex Bristol-Myers Squibb Bristol-Myers Squibb, Medarex Bristol-Myers Squibb Bristol-Myers Squibb, Medarex
FDG-PET scan after induction chemotherapy for esophageal squamous cell cancer (ESCC) to predict for outcomes after chemoradiation (chemoRT) and to guide salvage chemotherapy during RT.
Authors: Geoffrey Yuyat Ku, Yelena Yuriy Janjigian, Anuja Kriplani, Leonard Ong, Valerie W. Rusch, Manjit S. Bains, Nabil P. Rizk, Inderpal S. Sarkaria, Marinela Capanu, Karyn A. Goodman, David H. Ilson
Journal: Journal of Clinical Oncology (2014)

94 Background: Pre-operative or definitive chemoRT is accepted treatment for locally advanced (LA) ESCC. We have retrospectively shown that assessment by PET scan following induction chemo prior to chemoRT and surgery predicts outcomes in SCC Pts (Cancer 118:2820; 2012). Some Pts with progression on PET after induction chemo had long-term survival when changed to alternative chemo during RT. Methods: We retrospectively reviewed all Pts with LA ESCC who received induction chemo and chemoRT from 2002 to 2010; all Pts had PET scan before and after induction chemo. Results: 62 Pts were identified, median age 63, median Karnofsky performance status 80%, 75% with uN+ disease. 43 (69%) received induction chemo with platinum/irinotecan (CPT-11), 13 (21%) with platinum/paclitaxel and 6 (10%) with docetaxel/CPT-11 ± cisplatin. 38 Pts (61%) were PET responders (PETr; ≥35% decrease in mSUV of tumor) and 24 (39%) were PET non-responders (PETnr; &lt;35% decrease). All PETr received same chemo during RT. Of PETnr, 9 continued with same chemo during RT and 15 were changed to a different chemo with RT. 33/38 PETr (87%) achieved a clinical complete response (cCR) vs. 4/9 (44%) of PETnr/no chemo change vs. 11/15 (73%) of PETnr/chemo change (p=0.01 for PETr vs. PETnr/no chemo change; p=0.25 for PETr vs. PETnr/chemo change). 17 Pts had resection, all R0; 5/12 PETr (42%) had pathologic CR (pCR) while 0/3 PETnr/no chemo change Pts had pCR. Median disease-specific survival (not reached vs. 19 mos, p=0.002) and overall survival (OS; 69.6 vs. 17.4 mos, p=0.0056) were significantly better for PETr vs. PETnr. Median OS for PETnr/chemo change was 19.6 mos vs. 13.3 mos for PETnr/no chemo change (p=0.50); 6/15 PET nr who had different chemo with RT have extended survival, including 4 who are without disease at 2.8 – 9+ years. Conclusions: PET scan after induction chemo appears to predict for outcomes in ESCC Pts who received chemoRT. Long-term survival is possible in PETnr who switch to different chemo during RT. Such a strategy should be prospectively evaluated in a clinical trial.
Mammography-detected breast cancer over time among patients age 75 and older at a community-based cancer center: 1990-2008.
Authors: J. A. Malmgren, M. K. Atwood, H. G. Kaplan
Journal: Journal of Clinical Oncology (2011)

9086 Background: In 2009 the US Preventive Services Task Force reported insufficient current evidence to assess additional benefits and harms of screening mammography for women age 75+. Our aim is to evaluate mammography detected breast cancer characteristics and outcomes in this oldest age group. Methods: We conducted a prospective cohort study of all women presenting with primary breast cancer (BC), aged 50-75+, biopsy confirmed Stage 0-IV, 1990-2008, identified and tracked in our registry database (n=5,595). Clinical presentation characteristics including age, AJCC 6 TNM stage, and method of detection by patient (PtD), physician (PhysD) or mammography (MgD) were chart abstracted at time of diagnosis. Cases with unknown or other method of detection (n=89) were excluded. The Kaplan Meier method was used to compare disease specific survival (DSS) rates. Results: Women age 75+ comprised 17% of our cohort (n=950), mean age 79.77, range 75-94 with 63% MgD (n=596), 29% PtD (n=273), and 9% PhysD (n=81). Among patients age 75+, percent mammography detected BC averaged 52% from 1990-1998 and averaged 68% from 1999-2008 with a concurrent decline in PtD and PhysD BC over time (Pearson Chi-Square = 29.97, p <.001). Overall, 17% of MgD breast cancers were stage 0 and 62% were stage I with 3-4% stage 0 and 32-35% stage I among PtD and PhysD BCs (Pearson Chi-Square = 226.28, p<.001). Percentage stage 0 cases decreased with increasing age at diagnosis for MgD BC; age 50-59 = 25%, age 60-69 = 21%, age 70-74 = 14% and age 75+ = 17%. Percentage MgD stage I BC increased with age; age 50-59 = 50%, age 60-69 = 57%, age 70-74 = 61% and age 75+ = 62% (Pearson chi square 49.78, p<.001). 75+ MgD 5 year DSS was 98% with the 10 year rate = 92% compared to PtD 5 year DSS = 87% and 10 year DSS = 80% (log rank test = 20.95, p<.001). Conclusions: At our institution, the majority of breast cancer in women age 75+ is currently mammography detected with a lower rate of stage 0 disease and higher rate of stage I disease than women age 50-69. MgD BC in women 75+ presents primarily with disease treatable with options well tolerated by older adults and exhibits a low rate of DSS mortality.
Evaluation of the seventh TNM classification system in patients with esophageal cancer receiving chemoradiotherapy.
Authors: M. Nomura, T. Kodaira, A. Mizota, C. Kondoh, K. Shitara, T. Yokota, D. Takahari, T. Ura, S. Hatooka, K. Muro
Journal: Journal of Clinical Oncology (2011)

83 Background: The new 7th edition of the TNM classification system is based on pathologic data of esophageal cancer underwent surgery alone. No report is available on the prognostic evaluation of the new staging system in patients treated with chemoradiotherapy (CRT). The objective of this study was to evaluate the prognostic impact of the 7th edition of the TNM staging system in esophageal cancer patients treated with CRT. Methods: A retrospective review was performed of 301 consecutive patients who met the following inclusion criteria: (1) squamous cell carcinoma of thoracic esophagus; (2) total radiation dose ≥ 50 Gy; (3) concomitant chemotherapy consisting of 5-fluolouracil and platinum; (4) no previous thoracic radiotherapy or surgery. We compared the prognostic impact of the 6th and 7th editions of the TNM staging systems. Also, we compared the prognostic impact of stage group and prognostic group, which was newly defined in the 7th edition. Survival analysis was performed by using log-rank and Cox regression testing. Results: Patients with stage I/II/III/IV were 52/42/54/153 and 57/46/128/70 according to 6th and 7th edition, respectively. Eighty-four patients were shifted to a lower stage in 7th edition compared with 6th edition, and most of these were from stage IV to III (n = 74). There were significant differences among stages I to III (p &lt; 0.01, respectively) according to each edition. However, 7th edition poorly distinguishes between stages III and IV (p = 0.43). The survival curve of stage IV (lymph) almost completely overlapped with stage III (p = 0.69), although there were significant differences between stages IV (lymph) and IV (organ) (p = 0.04). Among the factors included in prognostic group in 7th edition, the histological grade and cancer site had no significant influence on patient survival, and T factor was only independent prognostic factors in multivariate analysis (p &lt; 0.01). Conclusions: Our study suggested several pitfalls in 7th TNM classification as prognostic factor in patients who received CRT. No significant financial relationships to disclose.
ProTat: A phase II trial of docetaxel (D), prednisolone (P) and thalidomide (T) in patients with androgen-independent prostate cancer (AIPC)
Authors: G. M. Marx, N. Pavlakis, S. McCowatt, S. Begbie, C. Underhill, A. Boyce, P. Katelaris
Journal: Journal of Clinical Oncology (2005)

4672 Background: The median survival of men with AIPC remains poor. Three weekly D and P improves survival, PSA response, symptom control and QOL over weekly D/P and mitoxantrone/P. Thalidomide inhibits angiogenesis, an important mechanism in the pathogenesis in AIPC. Weekly D and T are synergistic and have high response rates and median survivals, but the incidence of thromboembolism (TE) is substantial with this combination. Methods: Open label Phase II trial with PSA response as primary endpoint. Secondary endpoints included toxicity, QOL, duration of response, survival, identification of biologic predictors of response and identification of changes to the thrombotic cascade with this combination. Treatment included: Dexamethasone premedication. D 75mg/m2 Day 1 Q3 weekly. T 200mg po daily. P 5 mg po bd daily. Enoxaparin 40 mg sc daily, for TE prophylaxis. LHRH agonist therapy was continued. Results: Between May 2004 and Dec 2004 26 patients have been enrolled in this ongoing study. Twenty two patients are evaluable for response and 24 are evaluable for toxicity. The median age was 74 (range53–82). 24/26 patients had ECOG PS 0,1. The median number of cycles delivered was 4 (range 2–8). Dose reductions of T were required in 3 patients and D in 6 patients. A 50% reduction in PSA was seen in 17/22 (77%). 2/22 patients had stable disease and 3 progressed on treatment. On radiologic assessment of patients with measurable disease 5/13 (38%) had a response and 5/13 (38%) had stable disease. Grade 3 and 4 toxicities included febrile neutropenia in 5 patients and 1 patient had grade 3 nausea. No patients developed TE. Biologic markers have been collected but not yet analysed. Conclusions: The combination of D, T, P and E is safe, feasible and highly active in chemoniave men with AIPC. No significant financial relationships to disclose.