tbuckley/cabot-search huggingface dataset:
Treatment patterns and outcome among patients with multiple myeloma relapsing and or refractory to bortezomib and immunomodulatory drugs: A multicenter International Myeloma Working Group study.
Authors: S. Kumar, J. Crowley, S. K. Klein, J. J. Lahuerta, J. Lee, P. Moreau, G. Morgan, P. G. Richardson, D. S. Siegel, B. G. Durie
Journal: Journal of Clinical Oncology (2010)

8125 Background: Outcome of patients (pts) with multiple myeloma (MM) has improved with the introduction of the immunomodulatory drugs (IMiD; thalidomide, lenalidomide) and the proteasome inhibitor bortezomib (Bz). However, MM remains incurable and new therapies are needed. Improvement with upcoming therapies needs to be measured in the context of outcome with the current therapies. Moreover, the natural history of MM with the newer therapies used currently remains unclear. Methods: We designed a multicenter, retrospective study that enrolled 270 pts with relapsed MM, from 8 sites in US, 5 in Europe and 1 in Asia. Pts were refractory to Bz, defined as no response to prior Bz-containing regimen or disease progression within 60 days of a Bz-containing regimen. Pts also had to be relapsed, refractory, intolerant, and/or ineligible, to an IMiD. Clinical and lab data from diagnosis and individual relapses were collected. The date pts satisfied the above entry criteria was defined as time zero (T0). Results: The median age at diagnosis was 58 years (range, 31-86) and median time from diagnosis to T0 was 32 months (mos) and 32% had ≥ 3 prior regimens, including a transplant (SCT) in 60%. Following T0, 192 (71%) pts had a treatment recorded, including an SCT in 34 (13%). Various regimens were utilized after T0 (median=1; range 0-8). The first regimen following T0 contained Bz in 52 (27%) pts and an IMiD in 63 (33%) pts. An MR or better was seen to at least one therapy after T0 in 87 (45%) including ≥ PR in 65 (34%) and ≥ VGPR in 18 (9%). The probability of achieving a PR or better was higher for younger patients, those with a VGPR or better before T0 and those who received an SCT after T0. The median overall survival (OS) and event free survival (EFS) were 8 mos (95% CI; 6,10) and 5 mos (95% CI; 4,5 mos) respectively. Conclusions: This study confirms the poor outcome of pts once they relapse and become refractory to novel agents. This observational dataset will provide context for interpreting ongoing clinical trials of new drugs for MM. SCT results in higher response rates, especially in those receiving it for the first time, and should be taken into account when defining populations for studies of new drugs. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Celgene, Merck, Millennium Bayer, Celgene, Genzyme, Millennium, Novartis
Rituximab Maintenenance Therapy Prolongs Event Free Survival in Patients with CD20+ B-Cell Non-Hodgkin-Lymphoma.
Authors: Mathias Witzens-Harig, Manfred Hensel, Johann W. Schmier, Kai Neben, Axel Benner, Peter Dreger, Christian Kuhn, Ingo Schmidt-Wolf, Alwin Kraemer, Anthony D. Ho
Journal: Blood (2007)
Prognostic significance of lymph node sampling in node-negative appendiceal carcinoids.
Authors: Mustafa Raoof, Sinziana Dumitra, Gagandeep Singh, Yuman Fong, Byrne Lee
Journal: Journal of Clinical Oncology (2016)

678 Background: Surgical resection is the primary therapy for local and locally advanced carcinoid tumors of the appendix. The extent of surgery is largely dictated by the size of the tumor. Tumors &gt;2 cm require a right hemicolectomy with associated mesenteric lymphadenectomy. What constitutes an adequate mesenteric lymphadenectomy is not known. Methods: This is a study of a contemporary cohort from NCI’s SEER database (Jan, 2004- Nov, 2012). Patients with non-metastatic appendiceal carcinoid tumors were included. Surgical extent was defined as limited (appendectomy or illeocecectomy) or extended (hemicolectomy). Primary outcome was overall survival (OS). Survival analysis was performed using the Kaplan-Meier and Cox-proportional hazards model. Results: Of the total 1,104 patients that met the inclusion criteria, 52% were female, 88% were white and majority were middle aged (40-60y) 45%. Majority of the tumors were &lt;2 cm (49.3%) and lymph node(LN) negative 85%. Median LN retrieved were 10 (IQR 0-17). Median follow-up was 32 months (IQR 10-61). A multivariate Cox-proportional hazard model demonstrated that increasing age, tumor size &gt; 3cm, tumor spread to contiguous organs, LN positivity and LN count &lt;11 (HR 1.78: 95%CI 1.17-2.69; p=0.006) are associated with worse OS. Five-year overall survival increased with the number of LN retrieved (LN 1-10, 81.4%; LN &gt;10, 85.9%, p=0.035). Stratified analysis by LN status demonstrated that LN count &lt;11 was an independent predictor of worse OS in node negative patients (HR 2.10: 95%CI 1.25-3.53; p=0.005) but not node positive patients (p=0.65). Subset analysis by tumors size demonstrated that prognostic value of LN count &lt;11 was only significant for tumors greater than 3 cm (HR 2.32: 95%CI 1.15-2.03; p=0.018). Conclusions: This is the largest study to date that looks at prognostic significance of LN count for appendiceal carcinoids. The number of LNs evaluated is an independent prognostic factor in pathologic node-negative, appendiceal carcinoid tumors measuring greater than 3 cm. This data supports performing a formal lymphadenectomy (&gt;10 LN) even if no mesenteric disease is visible for adequate staging.
Medical Savings Accounts
Authors: American College of Physicians
Journal: Annals of Internal Medicine (1996)

This position paper examines medical savings accounts (MSAs) as a supplemental mechanism for financing health care services.Although federal legislation to encourage MSAs did not pass in 1995 and is not likely to pass in 1996, MSAs will continue to be seriously considered by public policymakers. Individual retirement accounts accumulate funds for retirement; MSAs could be used to accumulate funds for health care expenditures.Changes in the federal tax code would be required to permit tax-deductible contributions and tax-free earnings to individual MSAs. To be withdrawn without penalty, funds from an MSA could only be used to pay for approved medical or health insurance expenses. Each person would own and control his or her account, regardless of changes in employment. Coupled with high-deductible health insurance, MSAs could empower cost-conscious patients in health care decision making, increasing competitive pressure to reduce health care costs. Administrative costs and paperwork associated with health insurance might also be reduced, and some people who currently do not have health insurance might be able to obtain some financial protection. Medical savings accounts may not help unemployed persons or low-and middle-income persons who cannot afford to contribute to such accounts. These accounts may result in reduced health insurance protection and greater out-of-pocket expenses for those most in need of health care. Problems of adverse risk selection could arise if healthy persons choose insurance options involving MSAs; this choice would cause premiums to increase for persons who desire traditional health insurance. *This paper was written by Jack A. Ginsburg, MPE, and was developed for the Health and Public Policy Committee of the American College of Physicians: Whitney Addington, MD, Chair; Philip D. Bertram, MD, vicechair; Philip Altus, MD; Robert A. Berenson, MD; William M. Fogarty, MD; Nancy E. Gary, MD; David J. Gullen, MD; Janice Herbert-Carter, MD; Richard Honsiger Jr., MD; Derrick L. Latos, MD; Risa J. Lavizzo-Mourey, MD; Angela McLean, MD; and James Webster Jr., MD. Approved by the Board of Regents on 15 July 1995.
Postoperative adjuvant chemoradiation in gastric carcinoma: Results of a retrospective analysis.
Authors: H. Abahssain, I. Lalya, F. A. Zakkouri, m. A. Tazi, H. Mrabti, T. Kebdani, M. Ichou, N. Benjaafar, H. Errihani
Journal: Journal of Clinical Oncology (2011)

e14533 Background: Postoperative chemoradiation as per the Intergroup 116 trial demonstrated a superior survival for completely resected high-risk gastric cancer. To investigate the tolerability and survival of this regimen in clinical practice setting, we analyzed retrospective data in a single Institution of Oncology in Morocco. Methods: Patients with resected gastric adenocarcinoma were treated with postoperative concomitant chemoradiotherapy. Inclusion criteria were T3, T4 disease or positive regional lymph nodes. Adjuvant treatment consisted of 425 mg/m2 of fluorouracil plus 20 mg/m2 of leucovorin for 5 days, followed by 45 Gy of radiotherapy for 5 weeks, with fluorouracil and leucovorin on the first 4 and the last 3 days of radiotherapy. Two 5-day cycles of fluorouracil and leucovorin were given 4 weeks after the completion of radiotherapy. Toxicity was recorded according to RTOG criteria. Overall and disease free survival rates were calculated using the Kaplan-Meier method. Results: Between 2006 and 2009,680 patients were diagnosed with stomach cancer. Thirty-one patients with resected gastric adenocarcinoma were treated with postoperative concomitant chemoradiation ; 71% were male and median age was 54 years (range, 38-71); 77.5% had T>3 tumors and 90.3% had N+ disease; 83.9% had R0 resection; 17 patients (56.7%) completed the whole course of chemoradiation. Reasons for cessation treatment was toxicity ; Nineteen patients (61.3%) experienced grade > 2 acute toxicity. Fifteen patients (48.4%) had gastrointestinal toxicity and thirteen (41.9%) had hematological toxicity. Grade 3 or above toxic effects occurred in 32.3% of the patients. With a median follow-up of 21 months (range: 7.4- 46.8 months), 45.2% patients had died, and 67.7% were free of disease. Median disease-free survival is 33.6 months and median overall survival is 27.4 months. Cox regression analysis showed that positive margin was significantly associated with poorer survival (HR = 3.58, 95% CI = 1.05-12.21, p < 0.04). Conclusions: A postoperative regimen of concomitant chemoradiation therapy as per Intergroup 116 was tolerated and seems to be efficacy. Positive margin resection was the only significant prognostic factor for survival.
TEMOBIC: A ANOCEF phase II study of BCNU and temozolomide (TMZ) combination prior to radiotherapy (RT) in anaplasic oligodendroglial gliomas (AOG).
Authors: O. L. Chinot, K. Hoang-Xuan, M. Fabbro, L. Taillandier, J. Honnorat, M. Barrie, M. Sanson, C. Kerr, P. Beauchesne, S. Cartalat-Carel, D. Autran, A. Loundou, R. Guillevin, K. Mokhtari, D. Figarella-Branger, J. Delattre
Journal: Journal of Clinical Oncology (2011)

2034 Background: Despite demonstrated chemosensitivity with PCV and TMZ, improvement of chemotherapy regimen need to be explored in AOG. Promising activity of BCNU and TMZ combination has been reported in GBM. We conducted a phase II study to evaluate safety and efficacy of BCNU-TMZ prior to RT in newly diagnosed AOG. Methods: This single arm multicenter phase II study assessed efficacy and safety of BCNU (150 mg/m2, day 1) and TMZ (110 mg/m2, D1-D5), every 6 weeks, up to 6 cycles, before conventional RT (60 Gy/30f). Eligibility criteria included histology of WHO 2000 grade 3 oligodendroglioma (AO) and mixed oligoastrocytoma (AOA), measurable contrast enhancing disease after initial surgery, no prior RT or CT. Histologic and MRI review were centrally performed. IDH1 mutation, internexin α (INA), p53 and MGMT expression were assed by IHC. Primary end point was response rate (RR). Secondary end-points included PFS and OS. Results: From 12/2005 to 9/2009, 54 pts were included and define the intend to treat population (ITTP). Median age was 53.3y. Surgery consists of biopsy in 37 pts and partial surgery in 17 pts. After central review, 43 patients constituted the per-protocol population (PPP) including AO n=14 and AOA n=29. In ITTP, RR was 38.5% including 7 (13.5%) CR and 13 (25%) PR. Median PFS was 15 mo (95% CI, 2 to 28.2) and 15.4 mo (95% CI, 3 to 27.6) in the ITTP and PPP respectively. Median PFS was 2.4, 14, 18.6 mo in case of PD, SD, and PR. Median OS was 25 mo (95% CI, 17.6 to 32.4). R132H mutated IDHI, INA and MGMT were expressed in 26/ 49 (53%), 12/50 (24%) and 8/44 (18%). In ITTP and PPP, IDH1, INA and MGMT strongly impact PFS and OS. Grade 3-4 toxicities included thrombopenia n=20, neutropenia n=13, elevated transaminases n=5. Treatment discontinuation for toxicity concerned 4 pts. 3 treatment possibly related deaths were reported (1 thrombopenia, 1 pulmonary fibrosis, 1 acute leukaemia). Conclusions: BCNU and TMZ combination is effective in this AOG population, despite pejorative prognostic characteristics, and is associated with prolonged tumor control in pts with negative INA. However, significant toxicity of the combination should be taken into account for further development.
Study on malignancy, staging, and grading for gastrointestinal stromal tumors
Authors: Y. Hou, X. Zhu, S. Lu, Y. Zhou, J. Xu, Y. Ji, J. Hou, W. Qi, Y. Shi, Y. Tan
Journal: Journal of Clinical Oncology (2008)

21521 Background: The biologic behavior spectrum of gastrointestinal stromal tumors (GISTs) exhibit from indolent to highly aggressive. Although risk stratification was proposed by the NIH criteria according to tumor size and mitoses, limitations of the criteria exist, and better risk factors are needed. Methods: A retrospective review was conducted in 840 patients who had undergone surgical resection of primary GISTs from 12 hospitals. GISTs were classified as malignant according to gross spread including liver metastasis, peritoneal dissemination as well as microscopic spread including lymph node metastasis, vascular, fatty, nerve and mucosa infiltrating, or death, the left recorded as biologic behavior uncertain. Results: Significantly different factors for malignancy identified in the two groups were 5 morphological parameters including mitotic count≥10 per 50HPF (P=0.000), muscularis propria infiltrating (P=0.000), coagulative necrosis (P=0.002), ancient-coin-like growth pattern (P=0.006), and nuclear severe atypia (P=0.029). A new classification system based on a combination of these 2 gross spread, 5 microscopic spread and 5 parameters in situ were developed. Among 840 patients, 485 were malignant, 355 were benign-borderline. The disease free survival (DFS) showed significant difference between borderline and malignant GISTs, between presence and absence of gross spread, between presence and absence of microscopic spread, DFS was associated with the number of parameters predictive of malignancy in GISTs without gross spread. Conclusions: Twelve parameters were predictive of malignancy, malignant GISTs could be divided into clinical stage II and I, pathological stage II and I according to presence or absence of gross and microscopic spread, malignant degree could be graded according to the number of malignant parameters. The clinical stage, grade, mitotic count ≥10/50HPF were the most important prognostic parameters in malignant GISTs. It is expected, the new approach and results will be of value in imatinib therapy. No significant financial relationships to disclose.
Looking for synergy or additivity between <sup>188</sup>Re and sorafenib on hepatoma cell lines.
Authors: Marc Pracht, Nicolas Lepareur, Julien Edeline, Laurence Lenoir, Valerie Ardisson, Bruno Clement, Jean Luc Raoul, Eveline Boucher, Etienne Garin
Journal: Journal of Clinical Oncology (2012)

247 Background: In case of non resectable HCC, radioembolization and sorafenib (S) are therapeutic options respectively for intermediate and advanced stages. In some other cancers, there is an increase of efficacy when external beam radiotherapy is done concomitantly with systemic chemotherapy or targeted therapies. So we wondered if there could be a synergistic or an additive activity when S is combined with a radionuclide. Methods: Hepatoma cell lines N1S1 (murine HCC), HepG2 (human hepatoblastoma) and HepaRG (human HCC) were treated with increasing concentrations of rhenium-188 ( 188 Re) or S. On each cell line, we have studied the cellular toxicities of S and 188 Re using Tetrazolium dye test, extra-cellular medium LDH level and morphologic analysis. This was done for different dosage of S and 188 Re. We measured the lethal concentration killing 25% of cells (LC25) with the results of the Tetrazolium dye test. Secondly, we looked for synergy or additivity on cellular toxicity of these two compounds according to cell lines by combined treatment. Synergy or additivity was estimated with the combination index (CI) method (synergy if CI lower than 1, additivity if CI = 1, antagonism if CI upper to 1) based on the Tetrazolium dye test’s results. Results: Monotherapy dose-dependent toxicities were observed for all three cell lines with 188 Re and for the N1S1 and HepG2 cell lines only with S. Combined treatment with 188 Re and S showed synergy on HepaRG and N1S1 cell lines and additivity on the HepG2 cell line. Conclusions: The additive, and even synergistic, interest of a combined treatment with 188 Re and S is demonstrated in vitro (for the first time to our knowledge) on hepatoma cell lines. This results, in particular for the HepaRG cell line (human HCC), could be explained by the down-regulation of the hepatic drug transporters which are responsible for the Sorafenib efflux in case of simultaneous DNA damages due to a radionuclide exposition. This promising approach now needs to be confirmed in vivo. [Table: see text]
The impact of tumor histology on survival among elderly chemotherapy-treated patients with stage IIIB/IV NSCLC
Authors: K. Clements, M. D. Marciniak, D. Faries, K. Lang, J. Nyambose, C. C. Earle, K. Sugarman, D. Taylor
Journal: Journal of Clinical Oncology (2008)

19067 Background: Data regarding the impact of tumor histology on survival in patients receiving chemotherapy treatment for advanced-staged NSCLC is lacking. The purpose of this analysis was to assess the impact of tumor histology on survival among elderly patients with Stage IIIB/IV NSCLC. Methods: Patients aged 65 years and older diagnosed with Stage IIIB/IV NSCLC in a SEER cancer registry between 1997 and 2002 were identified retrospectively and followed in the SEER-Medicare database. Log-rank tests were used to test the significance of difference in survival by histology. A multivariate Cox-proportional hazards model of survival was employed to account for confounding factors. The model included a treatment-by-histology interaction term to formally test whether the association between treatment and survival differs by histology. Results: Among elderly Stage IIIB/IV NSCLC patients, median survival was 4.0 months among patients with non-squamous cell carcinoma and 4.2 months among patients with squamous cell carcinoma (p = < 0.0001). In multivariate analysis, non-squamous cell carcinoma was also associated with poorer survival (hazard ratio [CI]) 1.10[1.04–1.16]. Primary treatment was a significant independent predictor of improved survival. Those patients receiving any chemotherapy 0.60[0.56–0.64], other treatment 0.78[0.73–0.84] compared to those who received no treatment had better survival outcomes. The treatment-histology interaction term did not provide evidence that the association between treatment and survival differed by histology. Conclusions: Several factors were found to be associated with survival in patients with Stage IIIB/IV NSCLC, including primary treatment and the presence of non-squamous carcinoma. There is no evidence that histology changes the association between treatment and survival. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Eli Lilly Eli Lilly Eli Lilly Eli Lilly
Clinical efficacy of 2-day versus 5-day accelerated partial breast irradiation delivered via balloon-based brachytherapy: Results of a matched pair analysis.
Authors: Peter Y. Chen, Chirag Shah, John Ben Wilkinson, Michelle Wallace, Hong Ye, Ashley Fowler, Nayana Dekhne, Pamela Benitez, Alvaro A. Martinez, Frank Vicini
Journal: Journal of Clinical Oncology (2012)

148 Background: This analysis compares the efficacy of a 2-day vs. 5-day accelerated partial breast irradiation (APBI) schedule in treatment of early-stage breast cancer. Methods: Patients were treated between 6/2000 and 1/2011 with balloon-based brachytherapy using a 2-day (700 cGy x 4 BID) or a 5-day (340 cGy x 10 BID) fractionation. The CTV was a 1cm expansion from the balloon surface with a single-lumen device used in all cases. To compare efficacy between the two treatment groups, a matched-pair analysis was performed using a 1:2 ratio which paired 38 two-day with 76 five-day patients. Match criteria included minimal follow-up (FU) &gt; 1.0 yr, clinical stage, age (+/- 3 yrs), and ER status. Clinical outcomes analyzed include local-regional recurrence [LR, RR] distant metastases (DM), disease-free, cause-specific and overall survival [DFS, CSS, and OS]. Results: No significant differences were noted for age (p=0.838), clinical stage (p=1.000), ER (p=1.000), tumor size (p=0.236), margin status (p=0.556), nodal stage (p=0.381), PR (p=0.749), use of chemotherapy (p=0.927) or endocrine therapy (p=0.129). Per the ASTRO Consensus Guidelines, no differences were noted in the clinical groups between the 2-and 5-day treatments with the majority categorized as suitable or cautionary (2-day: 92% vs. 5-day: 87% p=0.436). With a mean FU of 4.7 yrs (4.9 yrs for 2-day vs. 4.5 yrs for 5-day, p=0.279), no differences were seen in the 5-year actuarial rates of LR (0.0% vs. 2.6%, p=0.359), DFS (94.4% vs. 96.1%, p=0.618), CSS (100% vs. 94.9 %, p=0.207), or OS (97.3% vs. 92.5%, p=0.811) between the 2-and 5-day groups, respectively. There was no RR in either group. DM rates were similar for both (5.6% vs. 1.3 %, p=0.456). Conclusions: With near 5-year FU for the 2-day schedule, APBI with the 2-day regimen yielded outcomes equivalent to the 5-day schema. Reduced on-treatment days by such hypofractionation offers flexibility in clinical and patient scheduling. Further FU and more patients will be needed to substantiate equivalence of hypofractionated APBI. An HIC-approved protocol randomizing patients between the 2 vs. 5-day treatments is currently open for accrual at our institution.
The yin and yang of idiopathic pulmonary fibrosis
Authors: Michael Kreuter, Vincent Cottin
Journal: European Respiratory Journal (2017)

125 years ago, Osler [1] summarised in his medical textbook for the first time the knowledge at that time on "chronic interstitial pneumonia" as pulmonary diseases with fibroid changes, easy to diagnose but difficult to classify. In his very detailed report (recommended reading for everyone interested in interstitial lung diseases (ILDs), although it probably did not correspond to idiopathic pulmonary fibrosis (IPF), as discussed elsewhere [2]), he mentioned aetiology, histopathology and clinical characteristics, and finally about treatment stated that "nothing can be done for the condition itself ". Typical for this time, information for this interesting chapter was gathered mainly from reports by pathologists and from clinical observations by Osler himself and his colleagues. It took decades until further descriptions on these diseases became available, first in the report by Hamman and Rich [3] on patients with fatal outcomes of unexplained interstitial pneumonias, and then in the diverse classifications of ILDs beginning in the 1960s [4–6]. Almost every piece of information on clinical aspects of patients with ILDs (mainly with IPF) gathered until then and even until almost the end of the last century came from clinical observational reports, i.e. casuistics or case series, or from retrospective analyses [6]. IPF registries and clinical trial data complement each other <http://ow.ly/Te9C307KonP>