tbuckley/cabot-search huggingface dataset:
Does the Oncotype DCIS score impact treatment decisions?
Authors: Sarah Patricia Cate, Alyssa Gillego, Manjeet Chadha, John Rescigno, Paul R. Gliedman, Ilana Kats, Susan K. Boolbol
Journal: Journal of Clinical Oncology (2013)

91 Background: The Oncotype Dx DCIS Score has been developed and validated for risk recurrence in ductal carcinoma in situ. It is a 12 gene assay performed on an individual patient’s tumor. The results give information about the 10 year risk of any in-breast event and the 10 year risk of an invasive breast cancer. The clinical validation study was based on patients enrolled in ECOG 5194. The purpose of our study was to evaluate the impact of the DCIS Score on recommendations for adjuvant radiation therapy. Methods: In this IRB approved study, 27 patients at our institution underwent evaluation with the DCIS Score from April 2012 to February 2013. All patients had specimens submitted for DCIS Scores. 14 patients had margins of 3 mm or greater. 12 patients had margins of 1 mm to 2.5 mm, and 1 patient had margins that were less than 1 mm from the DCIS. The mean age was 56.8 years, with a range of 40-79 years old. The DCIS Score is reported on a scale of 0-100. All patients underwent consultation with radiation oncology. The radiation oncologists formulated their preliminary recommendation prior to reviewing the patients’ DCIS Scores. The final recommendation for radiation treatment was rendered after reviewing the DCIS Score. We then compared the pre-DCIS Score and post-DCIS score treatment recommendations. Results: 21 patients (78%) were advised to have adjuvant radiation therapy. 6 patients (22%) were advised not to undergo adjuvant radiation based on their clinical and pathologic features. Although the DCIS Score did not change treatment recommendations for any patient in this study group, it did confirm initial treatment recommendations. For the patients who were advised not to have radiation, their DCIS Scores were 0-31. Conclusions: The DCIS Score is a validated tool to assess the local risk of recurrence for ductal carcinoma in situ. In our study population, the results of the DCIS Score did not alter treatment in any patient. It is important to note that in the 6 patients who were advised not to have radiation, the low DCIS Score confirmed the radiation oncologist’s perceived low risk of recurrence. In order to increase confidence in results of the DCIS Score, further studies need to be performed.
Retrospective study of non-mucinous appendiceal adenocarcinomas: Role of systemic chemotherapy and cytoreductive surgery.
Authors: Marc Isamu Uemura, Wei Qiao, Keith F. Fournier, Jeffrey Morris, Paul F. Mansfield, Cathy Eng, Richard Eldon Royal, Robert A. Wolff, Kanwal Pratap Singh Raghav, Michael J. Overman
Journal: Journal of Clinical Oncology (2016)

263 Background: The majority of studies evaluating appendiceal epithelial neoplasms have focused on those with mucinous histology. Few studies have reported on non-mucinous appendiceal adenocarcinomas. We performed the largest single-center study to investigate this histologic subtype, in order to describe the natural history and impact of both cytoreductive surgery (CRS) and systemic chemotherapy. Methods: We retrospectively reviewed 172 pts with non-mucinous appendiceal adenocarcinoma evaluated at the UT-MD Anderson Cancer Center between 1990 and 2015. Patient demographics, tumor characteristics, therapy received, and outcomes were recorded. Response assessment was semi-quantitative (response vs. no response) according to the treating physician. Overall survival (OS) and time to progression (TTP) were calculated using Kaplan Meier product-limit method and survival rates compared using the log rank test. Results: Median age at diagnosis was 52.9 yrs (M:F 1:1). Most pts presented with advanced stage: stage I (1.7%), stage II (32.5%), stage III (14.5%), and stage IV (51.2%). No patient had well-differentiated histology. 56% had moderate and 44% poor histology. Median OS by stage was 90.9m [95% CI: 70.8 to 172.9] for stage II, 52.1m [95% CI: 28.9 to NA] for stage III and 28.3m [95% CI: 22.9 to 31.9] for stage IV, (p &lt; 0.0001). In pts with metastatic disease (n = 128) CRS was attempted in 20 (15.6%) and was complete (CCS 0/1) in 12. The median OS for pts achieving complete CRS was 48.6m. Systemic chemotherapy was administered to 92% (118/128) of metastatic pts. The median TTP was 9.4m [95% CI: 8.0 to 11.5] and semi-quantitative response rate was 54%. The majority of pts received either oxaliplatin-based, 57%, or irinotecan-based, 23%, first-line chemotherapy regimens. No statistical difference in TTP (p = 0.9) or OS (p = 0.07) between different chemotherapies was seen. Conclusions: In contrast to mucinous appendiceal neoplasms, non-mucinous appendiceal adenocarcinomas rarely present with low-grade (well-differentiated) histology. Treatment approaches appear more akin to colorectal cancer with most metastatic pts undergoing systemic chemotherapy and a minority undergoing CRS.
Did TC contribute to the prolonged survival of ovarian clear cell carcinoma patients?
Authors: H. Kajiyama, K. Fumitaka
Journal: Journal of Clinical Oncology (2008)

16537 Background: The aim of this study was to estimate the survival impact of front-line paclitaxel- carboplatin (TC)- compared to conventional cisplatin (CDDP)-based regimens in 202 patients with clear-cell carcinoma (CCC) of the ovary. Methods: Clinicopathologic information of 202 CCC patients was obtained from the Tokai Ovarian Tumor Study Group between 1986 and 2005. Survival curves were calculated using Kaplan-Meier methods. The significance of differences in survival rates was analyzed using the log- rank test. Results: The median age at the time of initial treatment was 53 years, and ranged from 30 to 72. One hundred and two (50.5%) patients received TC, and 100 patients undewent other CDDP-based chemotherapy after initial debulking surgery. There was no significant difference in age, FIGO stage, preoperative CA125 values, the rate of positive peritoneal cytology, volume of ascites, and surgical procedure between TC- and CDDP-based groups. Three-year progression-free survival (PFS) rated of TC- and CDDP-based groups were 71.4% and 65.9%, respectively. In addition, 5-year overall survival (OS) rates of TC- and CDDP-based groups were 71.0% and 67.5%, respectively. There was no difference in PFS and OS between both groups (p=0.286, and p=0.291, respectively). Conclusions: Our retrospective data demonstrated that the chemotherapy regimen was not significantly associated with PFS and OS in CCC patients. No significant financial relationships to disclose.
Impact of G-CSF prophylaxis on the occurrence of neutropenia in patients with metastatic castration-resistant prostate cancer (mCRPC) receiving cabazitaxel.
Authors: M. Ozguroglu, S. Oudard, A. O. Sartor, S. Hansen, J. H. Machiels, L. Shen, J. S. De Bono
Journal: Journal of Clinical Oncology (2011)

e15131^ Background: The Phase III TROPIC trial demonstrated that cabazitaxel plus prednisone (CbzP) improved overall survival compared with mitoxantrone plus prednisone (MP) in patients with mCRPC who progressed during or after docetaxel-based therapy (HR 0.70; p < 0.0001) (Lancet 2010; 376:1147–54). A higher proportion of men in the CbzP group had Grade ≥ 3 neutropenia (82% vs. 58%) and febrile neutropenia (FN) (8% vs. 1%) compared with MP. In patients clinically predisposed to neutropenia, ASCO guidelines recommend prophylaxis with granulocyte-colony stimulating factor (G-CSF) and/or dose reductions. We analyzed the effect of G-CSF use on neutropenia in TROPIC. Methods: Men with mCRPC (n=755) who progressed during or after docetaxel were randomized to receive CbzP (n=378) or MP (n=377). Primary prophylaxis with G-CSF for neutropenia was not allowed in cycle 1, but G-CSF use was permitted from cycle 2 onward following a first occurrence of neutropenia with protocol-defined complications. G-CSF use was classified as prophylactic if administered within 3 days of chemotherapy dose or therapeutic if administered > 3 days after chemotherapy dose. Results: From cycle 2 onward, a total of 3246 chemotherapy cycles were administered, 2322 (72%) without G-CSF and 924 (28%) with G-CSF. In cycles 2–10 (in which prophylactic G-CSF was allowed), the percentages of cycles with Grade ≥ 3 neutropenia were similar between treatment groups (39% CbzP; 36% MP). The percentage of CbzP cycles in which Grade ≥ 3 neutropenia was observed was lower when G-CSF was used as prophylaxis versus therapeutically (25% vs. 58%; p < 0.0001). Of the 17 patients in the CbzP group who had FN during the first cycle, 9 did not use G-CSF and 8 received therapeutic G-CSF. In the 11 patients who had FN in cycles 2–10, 3 received G-CSF prophylaxis, 4 received therapeutic G-CSF, and 4 received no G-CSF. Conclusions: G-CSF use reduced the incidence and severity of neutropenia in men receiving CbzP for mCRPC. The most pronounced effects were noted when it was given as prophylaxis. Patients with mCRPC at risk of this predictable side effect should receive G-CSF prophylaxis as recommended by current treatment guidelines.
Report of a phase II study of sphingosomal vincristine (SV) in patients with relapsed or refractory Hodgkin’s disease
Authors: L. Fayad, J. Romaguera, S. Hart, A. Younes, B. Pro, F. Hagemeister, P. McLaughlin, N. Dang, A. Pretti, A. Sarris, F. Gil
Journal: Journal of Clinical Oncology (2005)

6624 Background: Combination therapy is often not an option for multiple relapsed/refractory Hodgkin’s disease patients particularly after salvage high-dose chemotherapy and transplant. Vincristine is a cell cycle-specific anticancer drug, with established activity in Hodgkin’s disease. Sphingosomal vincristine (SV) is a novel sphingosome encapsulated formulation of vincristine, which presents several advantages over regular vincristine. SV has a longer half-life (15 hours versus 15 minutes), can be given uncapped, and shows accumulation in tumor sites in experimental models, providing a rationale for this cell-cycle specific agent. Methods: : SV was evaluated as a single agent for the treatment of patients with relapsed or refractory Hodgkin’s disease including those who failed auto or allogeneic transplantation. SV was administered at 2 mg/m2 (no dose capping) IV over 1 hour every 14 days. Patients were restaged every two cycles, responders continued two cycles beyond their best response to a maximum of 12 cycles. Results: Data is reported on 29 patients, 16 males and 13 females; median age was 32 years (range 19–58). Patients had a median of 4 prior chemotherapy regimens (range 2–10), 20 patients had also received prior radiation therapy and 22/29 pts (76%) failed prior transplant. Patients received a median of 4 cycles of SV (range 1–12). Among 27 patients evaluable, 8 responded with 2 CR, 2 CRu, and 4 PR for an overall response rate (ORR) of 30%. Other patients had stable disease (10 pts) or progression (9 pts). Among the responders the median number of prior therapy was 3 (range 2–6), 6/8 responders failed prior auto transplant. Grade 3 toxicity included: sensory neuropathy (2 pts), constipation (2 pts), pain/myalgia (2 pts), fatigue (2 pts), fever (w/o neutropenia) (1 pt). There was no grade 4 toxicity. Conclusions: SV is a promising agent for the treatment of relapsed/refractory Hodgkin’s disease with a 30% ORR in a heavily pretreated population. This therapy was well tolerated with mostly mild to moderate toxicities reported and few grade 3 toxicities despite the number of prior therapies. The ORR and manageable toxicity observed in this study supports further investigation of SV in this disease. No significant financial relationships to disclose.
Cardiovascular safety profile of VT-464 in patients (pts) with castrate-resistant prostate cancer (CRPC).
Authors: Michael R Kurman, Philip Sager, Marc S. Rudoltz, Joel Eisner, Daniel Goodman, Eugene Heyman, Daniel Salvail, Caroline Bell, William R. Moore
Journal: Journal of Clinical Oncology (2016)

198 Background: VT-464 is a dual selective inhibitor of CYP17,20 lyase and an androgen receptor antagonist in development for the treatment of CRPC. In early clinical testing, several pts receiving VT-464 in 28-day cycles were noted to have syncopal, pre-syncopal or vaso-vagal episodes with typical prodromes. To further evaluate these events, Holter monitoring (HM) was performed in pts enrolled in two clinical studies. Methods: Continuous HM was performed at Screening, after the first dose of VT-464 C1D8, and C2D1 for study INO-VT-464-CL-001; and at Screening, after the first dose of VT-464, and C2D1 for study INO-VT-464-CL-004. The Screening visit HM data was considered the baseline. Plasma levels of VT-464 (in selected pts) and 12-lead ECGs of 10-seconds duration were extracted in triplicate for each pt from the HM data at Baseline, Day 1 and C2D1 at multiple time points. Results: 57 pt screened for VT-464 treatment, underwent HM. Nonsustained ventricular tachycardia (NSVT) was seen in 6 pts (11%) prior to VT-464, providing a background estimate in this population. 37 pts were treated with VT-464 and had &gt; 1 post-screen HM; 4 pts (11%; all with cardiac disorders) had post-treatment NSVT (all &lt; 5 beats); no episodes of sustained VT were seen. 28 pts had ECG data extracted from HMs that coincided with peak plasma levels of VT-464. There was no QTcF or QRS prolongation; increases in the HR (mean 13.1-19.5 BPM but with a non-significant VT-464 concentration/HR relationship) and small PR increases (mean 32.9 ms; partially driven by several pts) without second degree AV block were observed. Conclusions: VT -464 did not prolong QTcF or QRS intervals and the lack of a significant exposure response HR analysis suggests that the HR increases may not be drug related. The PR prolongation is unlikely to be clinical significance. HM showed a frequency of NSVT consistent with background frequency for this pt population.A detailed examination of study pts experiencing syncope or presyncope revealed these to likely be vasovagal in nature, consistent with the increased vagal tone observed in nonclinical testing. There does not appear to be a pro-arrhythmogenic potential of VT-464 based on data from both nonclinical and clinical assessments. Clinical trial information: NCT02361086.
Association of the immune checkpoint molecule expression with neutrophil-lymphocyte ratio in patients with gastric cancer: A retrospective study.
Authors: Hiroaki Tanaka, Tatsuro Tamura, Kenjiro Kimura, Katsunobu Sakurai, Takahiro Toyokawa, Ryosuke Amano, Naoshi Kubo, Kazuya Muguruma, Masaichi Ohira, Kosei Hirakawa
Journal: Journal of Clinical Oncology (2016)

48 Background: Programmed cell death (PD) -1, one of immune checkpoint molecules, expresses on T cells and induces immune tolerances in tumor microenvironment by binding to the ligand PDL-1 on the cancer cells. The clinical effect of immune checkpoint inhibitors such as anti-PD-1/PDL-1 antibody was demonstrated in various cancer including malignant melanoma, lung cancer and gastric cancer. The development of biomarkers for case selection that these inhibitors are effective will be in urgent need. We previously showed that neutrophil-lymphocyte ratio (NLR), a marker for general immune response, was related with postoperative recurrence and advanced stage of gastric cancer. In this study, we report the association of pretreatment NLR with PD-1/PDL-1 expression in the primary tumor of gastric cancer. Methods: Using immunohistochemistry, we retrospectively examined the expression of PDL-1 and infiltration of PD-1 + cells in primary tumor from 180 patients who had undergone surgery for gastric cancer between 2007 and 2010 at the Department of Surgical Oncology of Osaka City University. Results: Positive expression of PDL-1 was observed in 78 (43%) patients. PDL-1 expression was correlated with tumor infiltrated PD-1 + cells and related poor prognosis of the patients with Stage II/III. NLR was correlated with pathological stage and lymph node metastasis. In the positive PDL-1 group, NLR was significantly increased compared with negative group. However, the number of infiltrated PD-1+ cells was not correlated with NLR. Conclusions: PDL-1 expression in gastric cancer tissues was associated with pretreatment NLR, indicating that local immune suppression could be reflected in the systemic immune responses. Our data also suggested that NLR might be one of surrogate marker for PD-1/PDL-1 blockade therapy for gastric cancer.
Clinical Significance of Addition of Cytarabine or Thiotepa to TBI/CY Regimen.
Authors: Takayoshi Tachibana, Masatsugu Tanaka, Maki Hagihara, Rika Ohshima, Etsuko Yamazaki, Hideyuki Koharazawa, Jun Taguchi, Naoto Tomita, Katsumichi Fujimaki, Rika Sakai, Hiroyuki Fujita, Shin Fujisawa, Atsuo Maruta, Yoshiaki Ishigatsubo, Heiwa Kanamori
Journal: Blood (2012)
Discerning Malignant and Benign New Nodules at Incidence Rounds of CT Lung Cancer Screening: The Role of Volume and Predicted Volume Doubling Time
Authors: Joan E. Walter, Marjolein A. Heuvelmans, Geertruida H. De Bock, Pim A. De Jong, Rozemarijn Vliegenthart, Matthijs Oudkerk
Journal: Journal of Thoracic Oncology (2015)
Continued Improvement in Survival in Multiple Myeloma and the Impact of Novel Agents
Authors: Shaji K. Kumar, Angela Dispenzieri, Morie A Gertz, Martha Q Lacy, John A Lust, Suzanne R Hayman, Francis K Buadi, David Dingli, Steven R Zeldenrust, Stephen Russell, Prashant Kapoor, Yi Lin, Lisa Hwa, Dirk Larson, Colin L. Colby, Joanne T Benson, Robert A. Kyle, S. Vincent Rajkumar
Journal: Blood (2012)
Concurrent chemoradiotherapy for unresectable hilar choloangiocarcinoma: A single-institution experience.
Authors: P. Hunag, Y. Chao, C. Li, R. Lee, L. Wang, S. Yen
Journal: Journal of Clinical Oncology (2011)

326 Background: Hilar cholangiocarinoma (Klatskin tumor) is a rare malignancy which is best managed with surgical resection. The majority of patients, however, is unresectable at the time of diagnosis and generally has a poor outcome. The purpose of this study was to retrospectively evaluate the role of chemoradiotherapy (CCRT) for patients with unresectable hilar choloangiocarcinoma at a single institution. Methods: Between 2001 and 2008, a total of 33 patients with unresectable, nonmetastatic hilar cholangiocarcinoma treated at Taipei Veterans General Hospital were reviewed. All patients were to receive 3D-CRT with a median dose of 50.4 Gy (range, 39.6- 60) at 1.8-2 Gy per fraction per day. Sixteen patients also received bolus 5-fluorouracil (5-FU) CCRT (500 mg/m 2 /d for 3 days repeated every 2 weeks during radiotherapy for 6 weeks). Survivals were estimated by the Kaplan-Meier method and compared by log-rank test. Results: There were 21 males and 12 females, with a median age of 71 years (range, 29 - 81). The median follow-up time was 10.4 months (range, 1 – 42.3) for all patients with the 1- and 2-year survival rates of 45% and 12%, respectively. The median overall survival (OS) and progression-free survival (PFS) were 13.5 months and 10.2 months for the CCRT group, and 10.4 months and 6.5 months for the RT alone group (p = 0.36 and p = 0.28, respectively). Adverse events were similar in thetwo groups with 14 patients (42%) developed grade 1-2 gastrointestinal toxicity during RT. Locoregional progression was observed in 26 patients (79%) and distant metastases in 9 patients (27%). All patients experienced disease progression and had died at time of analysis. Conclusions: The outcome remains poor for unresectable hilar cholangiocarcinoma despite aggressive combined modality treatment. Although not statistically significant, our data showed CCRT provides longer OS and PFS in patients with unresectable hilar cholangiocarcinoma compared to RT alone. Locoregional progression is the main problem for this disease and the efficacy of adding chemotherapy or biologic agents needs to be further investigated. No significant financial relationships to disclose.
Long-term results of the International Adjuvant Lung Cancer Trial (IALT) evaluating adjuvant cisplatin-based chemotherapy in resected non-small cell lung cancer (NSCLC)
Authors: T. Le Chevalier, A. Dunant, R. Arriagada, B. Bergman, M. Chabowski, C. LePechoux, M. Kozlowski, M. Tarayre, J. P. Pignon
Journal: Journal of Clinical Oncology (2008)

7507 Background: Based on 4 to 5-year follow-up data in recent randomized trials, adjuvant cisplatin-based chemotherapy is now generally recommended after complete surgical resection for patients with non-small-cell lung cancer. We evaluated the results of the IALT study, initially reported with a 4.7 year follow-up (ASCO 2003), with three additional years of follow-up. Methods: Patients with completely resected NSCLC were randomly assigned to three or four cycles of cisplatin-based chemotherapy or to observation. The dose of cisplatin (total 300–400 mg/m2), the drug to be combined with cisplatin (etoposide or vinorelbine or vindesine or vinblastin) and the use of adjuvant radiotherapy were predefined at each center. Cox models were used to evaluate treatment effect according to follow-up duration. Results: Between February 1995 and December 2000, there were 1,867 patients included. Median follow-up was 7.5 years at the cut-off date of September 1, 2005. The survival status was known for 1,807 patients. Results showed a beneficial effect of adjuvant chemotherapy on overall survival (HR: 0.91; 95% CI: 0.81–1.02, p= 0.10) and on disease-free survival (HR: 0.88; 95% CI: 0.78–0.98, p= 0.02). However, there was a significant difference between the results of overall survival before and after 5 years (HR: 0.86; CI: 0.76–0.97, p = 0.01 versus HR: 1.45; CI: 1.02–2.07, p =0.04); p-value for interaction was 0.006. Disease-free survival benefit was also different according to the follow-up duration (p-value for interaction: 0.04; global, first 5 years, HR=0.85, p=0.006; after five year, HR=1.33, p=0.16). The analysis of non-lung cancer deaths for the whole period showed a HR of 1.34 (CI: 0.99–1.81; p=0.06). Conclusions: These results confirm the efficacy of chemotherapy for the first 5 years after surgery. The difference in results between less than and more than 5 years of follow-up may suggest possible late adjuvant chemotherapy-related over-mortality. This potential effect underscores the need for the long-term follow-up of adjuvant lung cancer trials in order to evaluate results in terms of treatment benefits and long-term hazards. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration GlaxoSmithKline