tbuckley/cabot-search huggingface dataset:
Prognostic value of stringent complete response (sCR) post-autologous stem cell transplant (SCT) in multiple myeloma (MM)
Authors: P. Kapoor, S. Kumar, A. Dispenzieri, M. Q. Lacy, S. R. Hayman, F. K. Buadi, D. Dingli, P. R. Greipp, S. V. Rajkumar, M. A. Gertz
Journal: Journal of Clinical Oncology (2009)

8587 Background: The measurement of serum immunoglobulin free light chains (FLC) has diagnostic and prognostic utility in MM. Normalization of the FLC ratio may define a deeper complete response after therapy than by standard criteria of CR. A sCR requires normalization of the FLC ratio and absence of clonal plasma cells in the bone marrow (BM) in addition to the standard criteria for CR. The objective of our study was to evaluate the impact of specific types of CR [sCR, CR or near CR (nCR/ immunofixation positive CR)] post-SCT on time to progression (TTP) and overall survival (OS). Methods: 468 MM patients who had achieved at least a partial response post-SCT were studied. The results of serum and urine protein studies, serum FLC assay, and BM evaluation, including measurement of marrow plasma cell clonality by immunohistochemistry obtained ≥60 days after SCT were used to determine the best response. TTP was defined as the time from SCT to progression, with non-myeloma related deaths censored. Results: 179 patients achieved varying degrees of CR as their best response. 39, 35 and 105 patients achieved nCR, CR and sCR, respectively. The median estimated follow-up for the entire cohort was 52 months from the diagnosis and 41 months from SCT. The median TTP was 15, 29 and 35 months for patients achieving nCR, CR and sCR, respectively (P&lt;0.0001). The median OS for patients achieving nCR was 53 months from the diagnosis, but not reached for those with a CR or sCR (P=0.0009). The 5-year OS was 80% and 79% for patients with CR and sCR, respectively (P=NS). Similarly, OS from SCT was significantly shorter in patients achieving nCR (42 months vs. not reached for patients in CR and sCR; P&lt;0.001). Conclusions: Achievement of a sCR represents a deeper response state compared to conventional CR, translating to a longer response duration post SCT, validating its inclusion in the modified uniform response criteria. While we did not see a significant improvement in OS with sCR compared to CR in this group, this question needs to be addressed in a larger study. The step wise improvement in the response duration across nCR, CR and sCR highlights the contribution of immunofixation studies, marrow assessment of clonality and FLC estimates. [Table: see text]
Adjuvant chemotherapy and outcomes in esophageal carcinoma.
Authors: Nadia Saeed, Eric Albert Mellon, Kenneth L Meredith, Sarah E. Hoffe, Ravi Shridhar, Jessica M. Frakes, Jacques-Pierre Fontaine, Jose Mario Pimiento, Nishi Kothari, Khaldoun Almhanna
Journal: Journal of Clinical Oncology (2017)

181 Background: Neoadjuvant chemoradiation (NCRT) and surgery is standard treatment for esophageal cancer (EC) in the U.S. The role of adjuvant chemotherapy (ACT) is unclear. Providers assign ACT inconsistently, and both its rationales and benefits have yet to be clearly defined. We sought to evaluate rationales and benefits for ACT in EC. Methods: This single institution retrospective review included 382 patients (pts) with EC who were treated at our tertiary referral center. All pts received NCRT and 46 received ACT. We reviewed medical records to obtain demographic and clinical information. Survival outcomes were analyzed with Kaplan-Meier method from date of death or last follow up and log-rank analysis. Case-control analysis was performed using a 2:1 nearest neighbor propensity score matching algorithm, and included 113 pts, 41 of which received ACT. Results: 46 of the 382 pts in our study who received NCRT and surgery for EC also underwent ACT; two pts had single agent paclitaxel, 9 had 5-F/U and leucovorin, 7 had 5-F/U and cisplatin, 5 had carboplatin and paclitaxel, 2 had carboplatin alone, and the remainder had other combinations. Pts who received ACT were younger (med. age = 60.2 v 63.8 yr, p = 0.047), more likely to have adenocarcinoma (91.3% v 85.1%, p = 0.034), and less likely to have positive LNs on pre-treatment EUS (60.1% v 77.4%, p = 0.018). Pts with pCR were less likely to receive further treatment (6.5% v 45.8%, p &lt; 0.001), and pts with R1 resection were more likely to do so (15.2% v 4.2%, p = 0.007). With case-control analysis, no variables were significantly different between the two groups. The median follow-up times for the entire cohort and case-control analysis were 7.98 years and 8.89 years, respectively. There were no significant differences in overall (p = 0.975) or recurrence-free (p = 0.824) survival associated with ACT in either analysis. Conclusions: The role of CT following NCRT and surgical resection in pts with locally advanced ECis unclear. In the largest series to date, our single institution retrospective review found no significant difference in survival in pts who received ACT and those who did not. Prospective studies are needed to further identify the rationales for delivery of ACT, and to investigate any potential survival benefits.
A prospective, randomized trial of stem cell mobilization with VP-16 + G-CSF with or without rituximab for B-cell lymphoid malignancies
Authors: B. J. Bolwell, M. Kalaycio, R. M. Sobecks, S. Andresen, L. Rybicki, E. Kuczkowski, A. West, L. Bernhard, K. Cherni, B. Pohlman
Journal: Journal of Clinical Oncology (2004)

6640 Background: Rituximab has significant clinical activity against B- cell lymphoid malignancies. The use of rituximab immediately prior to peripheral stem cell (PSC) collection might serve as an in-vivo purge to purify a collected stem cell product. It is unknown, however, whether the use of rituximab at the time of PSC mobilization will alter the ability to collect adequate numbers of CD34+ cells, or have a beneficial effect on long term survival. To study this issue, we conducted a prospective randomized trial of PSC mobilization with or without rituximab. Methods: All patients had B-cell NHL and were eligible for autologous transplantation. The treatment plan consisted of VP-16 (2 gm/m2) + G-CSF, with peripheral blood stem cell mobilization beginning upon WBC recovery. Patients were randomized to receive either VP+G alone or rituximab 375 mg/m2 weekly for 3 doses prior to VP-16 administration (VP-G-R). 41 patients have been enrolled to date, 21 in the VP-R-G arm. 68% had diffuse large B-cell lymphoma, 27% had follicular lymphomas, and 5% had high grade lymphoma. The groups were balanced with respect to number of courses of prior chemotherapy, prior radiation therapy, disease status at transplant, LDH at transplant, and bone marrow involvement. Patients were pheresed for 5 days to a minimum 2.0 x 106 CD34+ cells/kg, or until 7 x 106 CD34+ cells/kg were collected, whichever came first. Results: There was no difference in CD34+ yield between the two groups : patients receiving VP-G-R collected a median total 10.4 x 106 CD34+ cells/kg vs. 8.2 x 106 CD34+ cells/kg in the VP-G group (p=0.29). Engraftment was identical between the two treatment groups. Median follow-up for surviving patients is 17 months after autologous transplant. There is no statistical difference to date in overall survival or relapse-free survival post- transplant between the two groups. Conclusions: We conclude that rituximab can be given immediately prior to stem cell mobilization without short-term toxicities or a negative effect on CD34+ cell yield. Whether there is long-term benefit using rituximab in the peri-mobilization period requires further follow-up. No significant financial relationships to disclose.
Phase I and pharmacodynamic study of the histone deacetylase (HDAC) inhibitor romidepsin plus erlotinib in previously treated advanced non-small cell lung cancer (NSCLC).
Authors: David E. Gerber, Rachael Skelton, Ying Dong, Laurin Loudat, Jonathan Dowell, David A. Boothman, Venetia Sarode, Wei Zhang, Yang Xie, Adi Gazdar, Eugene P. Frenkel, Joan H. Schiller
Journal: Journal of Clinical Oncology (2013)

8088^ Background: Preclinical studies have demonstrated anti-tumor efficacy of the combination of the HDAC inhibitor romidepsin plus erlotinib in NSCLC models insensitive to erlotinib monotherapy (eg, KRAS mutation, EGFR resistance mutation, EGFR wild type). Methods: This phase I study evaluated safety, pharmacodynamics, and preliminary activity of romidepsin (8-10 mg/m 2 ) given IV days 1, 8, and 15 every 28 days plus erlotinib 150 mg PO daily in previously treated advanced NSCLC. In Cycle 1, erlotinib was initiated on Day 3, permitting pharmacodynamic analysis of romidepsin alone and in combination. Results: As of January 31, 2013, 15 patients (pts) have been treated: median age 60 years; 7 F, 8 M; all former or current smokers; 6 had prior erlotinib exposure; 8 adenocarcinoma, 6 squamous, 1 large cell; 5 EGFR wild type 1 KRAS mutation, 9 unknown mutation status. Most common related AEs regardless of grade were nausea (87%), vomiting (73%), fatigue (60%), diarrhea and rash (both 53%), and decreased appetite (47%). Grade 3-4 AEs (all grade 3) included nausea and vomiting (both 20%); decreased appetite, diarrhea, fatigue (each 13%). Dose-limiting nausea and vomiting occurred at romidepsin 10 mg/m 2 level despite aggressive antiemetic prophylaxis and treatment. At romidepsin 8 mg/m 2 , related grade 3 AEs included fatigue (n=1) and diarrhea (n=1), with no grade 3 nausea or vomiting. 9 pts were evaluable by RECIST; best response SD (n=6), PD (n=3). Median PFS was 3.3 months (range 1.4-16.5 months). At romidepsin 8 mg/m 2 , PFS range 2.0-16.5 months. At both dose levels, romidepsin inhibited HDAC activity and increased histone H3 and H4 acetylation status in peripheral blood mononuclear cells. Romidepsin also inhibited EGFR phosphorylation and, in 60% of pts, MAPK phosphorylation in skin biopsies. Conclusions: Romidepsin 8 mg/m 2 plus erlotinib appears well tolerated, has encouraging evidence of disease control, and exhibits effects on relevant molecular targets in an unselected advanced NSCLC population. Further studies are underway. Clinical trial information: NCT01302808.
Mortality risk factors and survival of colon cancer patient.
Authors: Runhua Shi, Manga Devi Kodali, Stephani Chang Wang, Kalyana C Lavu, Lihong Liu, Joseph Ryan Shows, Glenn Morris Mills
Journal: Journal of Clinical Oncology (2013)

e14653 Background: It is estimated that 142,820 people will be diagnosed and 50,830 will die from colon cancer in U.S. in 2013. The known risk factors include age (&gt;50 years old), personal history of colon polyp(s) and Inflammatory bowel disease, family history of colon cancer, hereditary syndromes, Black race, type II Diabetes Mellitus, obesity, physical inactivity, smoking and alcohol use. In order to improve colon cancer survivorship, current study explores factors that affect it. Methods: Data of 524,613 colon cancer patients between 1973 and 2009 was obtained from the Surveillance Epidemiology and End Results (SEER) program. Factors evaluated in this study were age at diagnosis, gender, race, annual household income, education, unemployment, and smoking. Clinical factors evaluated include SEER historic stage and treatments received. The definition of these factors was based on the SEER data dictionary. Kaplan-Meier method and log rank test was used to estimate and compare survivals. Cox regressions were used to identify risk factors that affect survival. Results: Characteristics of this half millions colon cancer patients were 51.3% of males, 84.4% of whites, and 70% of adjusted household income &lt;$50,000. Primary site: Sigmoid Colon (30.84%), Cecum (22.7%), Ascending Colon (9.42%), and others (9.42%). Stage: Localized (37%), Regional (36.26%), Distant (20.01%), and Unstaged (6.63%). In multivariate analysis, adjusting for other factors, age (≤49 vs. 60-69, HR=0.57), female gender (HR=0.87), stage (localized vs. distant stage, HR= 0.15) and race (Black HR=1.38, vs. Asian) are significant factors in colon cancer survival. People living in areas with a high percentage of smokers have increased risk by 8%. People living in areas of higher unemployment have 6% increased risk. Household income and education level have relatively less effect on colon cancer survival (40-55k vs. 0-40k, HR=1.02). Conclusions: We conclude that in a large database, age, race, stage, smoking, and unemployment have significant impact on colon cancer survival. Other factors such as insurance status, detailed treatments, screening effect, individual life styles and etc. need further investigation.
Safety and activity of the investigational agent orteronel (ortl) without prednisone in men with nonmetastatic castration-resistant prostate cancer (nmCRPC) and rising prostate-specific antigen (PSA): Updated results of a phase II study.
Authors: Daniel J. George, Paul G. Corn, M. Dror Michaelson, Hans J. Hammers, Joshi J. Alumkal, Charles J. Ryan, Justine Yang Bruce, Susan Moran, Shih-Yuan Lee, Peter Mortimer, Maha Hussain
Journal: Journal of Clinical Oncology (2012)

4549 Background: Ortl is an investigational, oral, non-steroidal selective 17,20-lyase inhibitor that suppresses androgen production. Ortl affects cortisol synthesis less than similar agents due to limited inhibition of 17α-hydroxylase, and may permit steroid-free dosing. Ortl 300 mg BID was examined in patients (pts) with nmCRPC and rising PSA. Methods: Eligible pts had nmCRPC with PSA ≥2 ng/mL (PSA ≥8 ng/mL if doubling time &gt;8 mo), and surgical/medical castration, with testosterone (T) &lt;50 ng/dL. Prior chemotherapy, ketoconazole, or concomitant corticosteroids were excluded. Starting dose of ortl was 300 mg BID and continued until PSA progression, metastases, or unacceptable toxicity. The primary endpoint was the percentage of pts with PSA ≤0.2 ng/mL after 3 mo. Secondary endpoints included safety, PSA kinetics, time to metastases, changes in endocrine markers and circulating tumor cells (CTCs). Results: 39 pts were enrolled with baseline demographics including median age 71 y, ECOG PS ≤1, median PSA 12.1 ng/mL (range 2.6-67.8), T 7.9 ng/dL (1.4–17.3), and ACTH 19 ng/L (n=33; 0-47); 3 pts had dose reduction due to adverse events (AEs). Gr ≥3 AEs occurred in 16 pts (drug-related in 14); Gr ≥3 AEs ≥5% were dyspnea (8%), hypertension (13%), fatigue, hypokalemia, pneumonitis (5% ea). 7 pts (18%) had serious AEs; most common was pneumonitis (2=Gr 3, 1=Gr 2). 8 pts discontinued due to AEs; 2 pts required corticosteroids. At 3 mo, 6 pts (16%) achieved PSA ≤0.2 ng/mL; PSA50 and PSA90 rates were 76% and 32%, respectively; median PSA declined by 83% (n=34); median T declined by 89% to 0.78 ng/dL (n=31), and median ACTH increased by 171% to 43 ng/L; median cortisol declined by 21%. At 6 mo, PSA50 and PSA90 rates were 45% and 21%, respectively. Median time to PSA progression was 14.8 mo. 17 pts (44%) were on treatment &gt;6 mo. Of 37 pts with baseline CTC/7.5 mL assessed, only 1 had CTC ≥5 and converted to &lt;5; 6 had 1–4 CTCs at baseline, none converted to ≥5 during treatment. Conclusions: Ortl without steroids produces marked and durable declines in T and PSA, has manageable toxicities, and is feasible in men with nmCRPC.
Survival analysis of maintenance therapy with capecitabine (Cape) in patients with resected pancreatic adenocarcinoma (PAC) after adjuvant therapy: A retrospective cohort study.
Authors: Xuezhong Yang, Benjamin Weinberg, Jimmy J. Hwang, Christina Sing-Ying Wu, Madeeha Akram, Michael J. Pishvaian, Aiwu Ruth He, John Marshall
Journal: Journal of Clinical Oncology (2012)

e14658 Background: The 5-year survival of PAC with surgery alone is below 10%, and with adjuvant chemotherapy increases to about 20%. The original GITSG adjuvant study demonstrating a survival benefit compared to surgery could be attributed to the use of 2-years of weekly IV bolus 5FU, and not only chemoradiation. In theory, the prolonged exposure to therapy could maintain pressure on dormant cancer cells that may remain in G0 arrest, by attacking them as they infrequently enter G1/S phase. To evaluate this hypothesis, we retrospectively evaluated our pts who were treated with or without maintenance Cape. Methods: Pts in the Georgetown/Lombardi Cancer Center EMR since Oct 2007 were sought for PAC that was resected with curative intent, received standard adjuvant chemotherapy with or without chemoradiation. The study group received maintenance cape for at least 2 months, and the control group was monitored until disease recurrence. Only pts with complete follow-up survival data were analyzed. Results: 20 pts met the criteria as study group, and 58 pts as the control group. In the study group, cape was usually given 1000mg orally twice a day, Monday through Friday following adjuvant therapy, for an indefinite period, up to 2 years. Pts received cape for median duration of 12.5 months (2 to 24 months), and the median follow-up duration was 33 months (16 to 78 months). The median overall survival (OS) for the study group was 48 months. The 2 year OS was 94%, and 5 year OS was 40%. The median recurrence free survival (RFS) was 39 months. The 2 year RFS was 67%, and the 5 year RFS was 25%. Common toxicities were mild hand-and-foot syndrome and fatigue. 4 pts discontinued cape due to toxicities: febrile neutropenia, severe fatigue, weight loss and diarrhea. The control group was of comparable staging, and the median OS was 22 months, 5 year OS rate was 16%, median RFS was 13 months, 2 year RFS was 19%. Conclusions: In this single institute retrospective controlled cohort study, Cape maintenance therapy following adjuvant therapy in resected PAC is associated with a significantly (p&lt;0.05) higher OS and PFS compared to the control group. This approach should be studied in a RCT.
Imatinib in locally advanced dermatofibrosarcoma protuberans (DFSP): A phase II trial of the Dermatologic Cooperative Oncology Group (DeCOG)
Authors: S. Ugurel, J. Utikal, P. Mohr, P. Helmbold, C. Pfoehler, M. Schiller, I. Kellner, D. Schadendorf
Journal: Journal of Clinical Oncology (2006)

9561 Background: DFSP is known for its low metastatic potential but locally infiltrative growth, hereby enforcing extensive and often multiple surgical procedures. DFSP cells were recently shown to display chromosomal translocations of the regions 17q22 and 22q13, resulting in an autocrine growth stimulation loop via the platelet-derived growth factor (PDGF) pathway. The tyrosine kinase inhibitor imatinib blocks PDGF signal transduction, thus offering a new therapeutic option for DFSP patients. This multicenter phase II trial was aimed to investigate the efficacy of imatinib in locally advanced DFSP. Methods: The primary study endpoint was objective response, secondary endpoints were safety and relapse-free survival. Patients with histological proof of locally advanced primary or relapsed DFSP, measurable tumor parameters according to RECIST, and no evidence of distant metastases were eligible. Patients received imatinib 600 mg/d PO. Tumor measurements were performed at week 6 and 12, and every 8 weeks thereafter. At the end of imatinib treatment, at the earliest after week 12, residual tumors were surgically excised with histological proof of tumor-free margins. Results: By January 2006, nine out of 13 recruited patients were evaluable for response (per protocol, PP), three are still on treatment and one stopped treatment after 12 days due to side effects. Among the nine PP patients, seven partial responses, one stabilization, and one progression were observed. Five responders showed an ongoing tumor shrinkage until complete surgical excision, whereas two patients revealed an initial response at 6 weeks, followed by a disease progression at 12 weeks. None of the patients developed distant metastases under treatment or thereafter. Side effects were mostly mild to moderate (CTC grade 1–2). Severe side effects (CTC grade 3–4), reversible angina pectoris and septicemia, respectively, were observed in two patients. Conclusions: The study results indicate imatinib as a potent systemic treatment option in locally advanced DFSP. However, a subset of DFSP patients appeared resistant to imatinib, either primarily after treatment onset, or secondarily after showing an initial response. No significant financial relationships to disclose.
Efficacy of intralesional Rose Bengal in patients receiving injection of all existing melanoma in phase II study PV-10-MM-02.
Authors: Sanjiv S. Agarwala, John F Thompson, B Mark Smithers, Merrick I. Ross, Charles Raben Scoggins, Brendon J Coventry, Susan J Neuhaus, David R. Minor, Jamie M Singer, Eric Andrew Wachter
Journal: Journal of Clinical Oncology (2014)

9027 Background: The safety and efficacy of intralesional (IL) treatment of refractory cutaneous melanoma with rose bengal disodium (PV-10) was evaluated in an 80 patient international, multicenter, single arm phase II trial (NCT00521053). Overall, PV-10 was well tolerated and 41 of 80 ITT patients (pts) met the primary endpoint of objective response (CR+PR) in their injected target lesions (51% ORR CI 40-63%, 26% CR). Methods: Refractory pts (median of 6 previous interventions, 6.3 cm median sum lesion diameter in biopsy confirmed melanoma) received PV-10 into up to 20 cutaneous and subcutaneous lesions up to 4 times over a 16-week period and were followed for 52 weeks. Best overall response rate (BORR) was assessed by RECIST in up to 10 injected target lesions. Secondary endpoints included assessment of duration of response, BORR of untreated bystander lesions, overall survival and adverse events.Confidence intervals for response rates were based on the exact cumulative probabilities of the binomial distribution (95% confidence intervals). Results: In the subgroup of 28 pts who received PV-10 into all existing melanoma lesions (i.e., no uninjected lesions), ORR by-patient was 71% (CI 51-87%) with 50% CR (CI 31-69%). In these pts with all disease injected plus 26 pts with uninjected disease limited to bystanders (i.e. 54 pts with all disease monitored), CR was achieved in 232 of the 363 injected lesions (64% CR): 121 lesions required a single injection for CR, 84 required 2 injections, 22 required 3 injections and 5 required 4 injections. Additionally, 10 of 28 uninjected bystander lesions achieved CR. Conclusions: Recurrent locoregional melanoma can be a source of persistent morbidity, including disfigurement frequently accompanied with pain, ulceration, bleeding and infection. The high rate of symptom control in refractory patients, manifest in CR of injected lesions after minimal intervention, is the basis for a breakthrough therapy application based on the 28 patient "all treated" subgroup. Although the primary ablative effect is responsible for CR in injected tumors, durability of response and bystander response implicate an immunologic mechanism of action secondary to ablation. Clinical trial information: NCT00521053.