Academic literature on the topic 'BR 20.5 UL 2009'

Introduction: Chronic lymphocytic leukemia (CLL) is incurable with standard therapy. With first-line chemotherapy, some patients (pts) may achieve durable remissions of many months/years. Lenalidomide (LEN) has improved progression-free survival (PFS) when given as maintenance (MNT) therapy after front-line chemotherapy (CALGB10404, CLLM1). The combination of LEN + rituximab (LR) has activity in relapsed CLL, hypothesizing benefit as MNT therapy after first-line chemotherapy. Methods: Adult pts ≥18 years with previously untreated CLL received induction bendamustine (B) 90 mg/m2 IV days 1 & 2 and rituximab (R) IV day 1 (375 mg/m2 cycle 1, then 500 mg/m2 cycles 2-6) for 6 treatment cycles (as few as 4 cycles allowed). MNT therapy with LR was initiated within 12 weeks after cycle 6, day 1 of BR. Criteria to start LR MNT included: neutrophils ≥1000/microliter (uL), platelets ≥75 K/uL, and creatinine clearance ≥40 mL/min. LEN was administered in 28-day cycles for 24 cycles, initially 5-10 mg daily continuous dosing, later modified to 5-10 mg on days 1-21 of each 28-day cycle in 6/2018 due to neutropenia and second malignancy risk. LEN was reduced to 5 mg every other day for toxicities at 5 mg/day. R 375 mg/m2 IV was given every odd cycle (total of 12 doses). Patients discontinuing LEN for any reason were allowed to continue R MNT per protocol. The primary endpoint is PFS with LR MNT therapy, calculated from the first day of MNT therapy until progressive disease (PD), death, or start of a new therapy. Secondary endpoints are response rate and overall survival. Results: Thirty-four pts have enrolled beginning 11/2013, with follow-up through 6/2019. Median age is 64 years, with 8 pts ≥70 years; 8 women and 26 men. CLL FISH panel is available on all pts: 14 with 13q (as sole abnormality), 9 with 11q deletion, 6 with trisomy 12, 4 with normal FISH panel and 1 with 17p deletion. Heavy chain mutation analysis is available on 11 pts: 8 unmutated, 2 mutated, 1 indeterminate. Thirty-one pts completed 4 (n=2) or 6 cycles of induction BR; 3 pts are receiving induction BR. Twenty-four pts have received MNT LR; 7 did not receive LR for reasons of PD during induction (n=2), infection (n=1), pt preference (n=2), renal insufficiency (n=1), and new carcinoma (n=1). MNT LR was completed in 7 pts; 9 pts are still receiving LR. Fourteen subjects have discontinued protocol therapy, 3 during induction due to PD (n=2) and infection (n=1), and 8 during MNT. Toxicities that led to discontinuation of LR were recurrent infections in 7 pts, including 2 events of PJP pneumonia; 4 pts had recurrent neutropenia with infections; 1 pt had neutropenia without infections. Response is assessable in 31 patients using the International Working Group Consensus Criteria. Best responses to treatment were: partial response 65% (22/34), complete response (CR)/unconfirmed CR 24% (8/34). The median number of MNT cycles received is 16. The dose intensity of LEN across total cycles received (n=278): 5 mg every other day (52.5%), 5 mg/day (43.9%), and 10 mg/day (3.6%). The most common reason for dose reduction or dose holding was neutropenia. Most common Gr 3/4 toxicities (reported as events Gr3/Gr4) during MNT therapy were: neutropenia (20/20), leukopenia (19/4), febrile neutropenia (3/1), and infections (11/-). The majority of Gr3 infections were pneumonia/respiratory (n=5). One event of disseminated herpes zoster occurred. Second malignancies during MNT included: basal cell CA (n=1), squamous cell carcinoma (n=5), and colon cancer (n=1). No unexpected second malignancies were observed in pts receiving LR. Two-year PFS (defined from day 1 of MNT therapy) is 90% (95% confidence interval [CI] 0.78-1), and the median follow-up for 24 patient who started maintenance therapy is 1.79 years (95% CI 1.53-2.7). There have been no deaths. Conclusion: The combination of LR is effective in sustaining remissions after a BR induction in previously untreated CLL, but with frequent neutropenia and infections even at low doses of LEN. Most patients discontinuing MNT did so due to neutropenia and/or infections. A shorter planned interval of MNT LR (i.e., 6-12 months) may confer similar benefit to extended dosing that is more tolerable. Pts at high risk for short remissions after front-line chemotherapy (e.g., unmutated heavy chain status, 11q deletion and/or failure to achieve minimal residual disease after induction) may be the populations for which LR MNT therapy is most appropriate. Disclosures Chang: Genentech: Research Funding; Adaptive Biotechnologies: Research Funding; Celgene: Research Funding. OffLabel Disclosure: Lenalidomide administered as maintenance therapy for first treatment of CLL/SLL.

Abstract Background: In Chuvash polycythemia (CP) (Problemi Gematologii I Perelivaniya Krovi 1974, 10:30), impaired degradation of hypoxia inducible factor (HIF)-1α and HIF-2α from a homozygous germline VHLR200W mutation leads to augmented hypoxic responses during normoxia (Nat Genet 2002, 32:614). In addition to elevated hematocrit, CP is marked by leg varices, benign vertebral hemangiomas, decreased systemic blood pressure, increased systolic pulmonary artery pressure, and by the defining phenotypes of thrombosis and early mortality (Blood 2004, 103:3924; Haematologica 2012, 97:193). There is no effective therapy. While phlebotomy has been recommended for idiopathic polycythemia by the British Committee for Standards in Haematology (Br J Haematol 2005, 130:174) and is administered to some CP patients, its benefits are unknown. Phlebotomy-induced iron deficiency inhibits PHD2 enzyme, the principal negative regulator of HIFs, which further augments hypoxic responses. This affects the transcription of many genes (BCMD 2014, 52:35). Hypoxia-regulated IRAK1 is augmented in inflammation and may promote thrombosis (Circ Res. 2013, 112:103). Methods: 165 patients with CP were enrolled in a registry between 2001 and 2009 after providing written informed consent. Survival analysis was used to examine the predictors of new thrombosis and death during the follow-up period. mRNA from peripheral blood mononuclear cells (PBMCs) was profiled by Affymetrix Human Exon 1.0 ST Array in 42 of the subjects. Results: The median age at enrollment was 35 years and 90 participants were females, 25 had a history of one thrombosis, 5 of two thromboses and 3 of three thromboses. In the year prior to study entry, 72 had received phlebotomy therapy (Table 1). In July 2015 the median follow-up was 9.0 years (range 1-14.5). During this follow-up period, 30 (18.2%) participants had one new thrombosis, 6 (3.6%) had two new thromboses and 17 (10.3%) died. The median age of death was 55 years (range 16-76) and deaths were related to thrombotic cerebrovascular accident (n = 4), myocardial infarction (n = 4), mesenteric or portal vein thrombosis (n = 3), other major thromboembolic events (n = 2) and trauma or unknown cause (n = 2). Baseline characteristics of older age, prior thrombosis, pentoxifylline treatment, smoking and splenomegaly were independently associated with greater thrombosis risk during follow-up (P < 0.003). After adjustment for these variables, the estimated probability of new thrombosis at 10 years was 26% in those receiving phlebotomies compared to 12% in those not phlebotomized (log rank P = 0.014) (Figure 1). There was also a trend for increased risk of death with phlebotomy: estimated probability 8.7% versus 3.7% (P = 0.15). Examination of gene transcripts affecting thrombosis by logistic regression identified 12 protective and 16 risk genes at 5% false discovery rate. Upregulation of two mRNAs was of singular significance: 1) IL1RAP, a proximal signaling adaptor of IRAK1 (Immunity 1997, 7: 837) and 2) THBS1, encoding thrombospondin1 (Blood 2015, 125: 399). Both genes have known roles in thrombosis promotion and we previously reported that THBS1 is upregulated in CP (BCMD 2014, 52:35). Further analysis revealed a further upregulation of THBS1 in patients with baseline history of phlebotomy (β=0.41, P=0.046). Conclusion: These findings underscore a high rate of thrombosis and death in patients with CP and reveal a potential role of increased IRAK1/IL1RAP signaling in these complications. They raise the possibility that phlebotomy therapy has a detrimental rather than beneficial effect, possibly contributed to by increased THBS1 expression. Table 1. Baseline characteristics by phlebotomy in the year prior to enrollment. Results in median (interquartile range) or n (%); four without phlebotomy data. No phlebotomy N=89 Received phlebotomy N=72 Age (years) 32 (18-48) 37 (26-49) 0.08 Female gender, n (%) 52 (58%) 34 (47%) 0.16 Smoking, n (%) 18 (20%) 24 (33%) 0.060 History of thrombosis, n (%) 20 (23%) 12 (17%) 0.4 Splenomegaly, n (%) 2 (2.3%) 2 (2.8%) 0.8 ASA treatment, n (%) 27 (30%) 36 (50%) 0.011 Pentoxifylline, n (%) 7 (7.9%) 17 (23.6%) 0.005 BMI (kg/m2) 20.4 (18.3-22.9) 21.6 (19.9-24.6) 0.010 Systolic BP (mm Hg) 109 (100-123) 118 (105-124) 0.6 Diastolic BP (mm Hg) 76 (68-84) 78 (71-83) 0.8 Hemoglobin (g/dL) 18.1 (16.4-21.0) 17.9 (16.0-19.8) 0.5 WBC (per uL) 5.7 (4.6-7.0) 5.5 (4.6-6.7) 0.9 Figure 1. Figure 1. Disclosures No relevant conflicts of interest to declare.

Abstract Background: There is evidence of a leukemogenic effect of purine analogues, mainly when combined with DNA-damaging agents. Various series report an approximately 5% rate of t-MDS/AML in patients treated with a fludarabine-based regimen. Patients are generally old, and old age is associated with worse outcomes. To date, there is no established standard therapy recommendation for this group of patients, and results of prospective treatment evaluations are scarce. Aim: To determine the characteristics and treatment outcomes of patients with CLL and t-MDS/AML. Methods: We analyzed a group of 6 patients with newly diagnosed t-MDS/AML who were treated in our institution from September 2011 to July 2014. Patients were enrolled in a phase II trial of azacitidine (75 mg/m2 IV daily x 5 days) in combination with vorinostat (200 mg orally three times daily x 5 days) (Arm A) or azacitidine alone (Arm B), with courses repeated every 3-8 weeks. This trial was designed to uniformly treat patients not eligible for other leukemia protocols due to comorbidities. Results: At baseline, all patients had an underlying diagnosis of CLL that was in remission or minimally active. The median percentage of CLL bone marrow involvement was 10% (range 0-60%), and ALC was 0.9 K/uL (range 0.2-9.79). The median number of prior CLL treatments was 2 (range 0-3). All patients had previously received fludarabine-based regimens. The median time from chemotherapy to t-MDS/AML diagnosis was 10 years (range 4-10). All patients were male, and the median age was 72 years (range 52-72). All patients had 3-line cytopenia, with median WBC 2.3 K/uL (range 0.8-8.9), ANC 0.55 K/uL (range 0-1.22), hemoglobin 9.6 G/DL (range 8.3-10.4), platelets 39 K/uL (range 6-80), and bone marrow blast percentage of 5% (range 1-18%). The karyotype was complex in all patients. Molecular studies showed that 3 patients had TP53 gene mutations. Five patients received treatment in Arm A, and only 1 patient was randomized to Arm B. Patients received a median of 4 cycles (range 2-7) and remained in the study for a median time of 216 days (range 86-329) before progression. None of the patients achieved remission, but stable disease was observed in 5 out of 6 patients. At the time of this analysis, 4 patients are dead and 2 are still alive: one discontinued treatment because of prolonged myelosuppression and is receiving best supportive care, and the other is recovering from cycle number 4 of treatment. The median survival in the group from the time of treatment initiation was 10.1 months and from the time of study discontinuation was 3.1 months. Further therapy was attempted in 3 patients without response. Conclusion: This is a group of patients with poor prognostic features. Azacytidine and vorinostat have been previously reported to be a safe combination (Garcia-Manero et al. ASH 2010, abstract 604) and may constitute a reasonable treatment alternative. Further prospective studies involving larger numbers of patients are required. Abstract 5627. Table 1: Baseline Patient Characteristics. Patient Age WBC K/uL Hb G/DL Plt K/uL BM Blast % CLL BM % Cytogenetic Molecular Prior CLL Treatments Treatment Arm Best Response 1 52 11 9.6 6 18 60 -3,-4,-5q,-6,-7, -7p,-12, +16 TP53 mutation 1.FCR x 62. Rituximab + Lenalidomide A NR 2 74 1 10 41 3 10 -3p,-5q,-7,-15,-17,-19 TP53 mutation 1. FCR x 42. FCR x 53. BR x 2 A SD 3 68 2.2 9.4 27 6 30 +7,-7p,t(7,21) Negative 1. FCR x 62. FCR x 4 B SD 4 73 2.3 9.7 39 6 0 +2,-5q,+8,-17,-18,+19,+20,-Y Negative 1. FCR x 6 A SD 5 71 0.8 8.3 39 4 0 +2,+4,t(5;17),+6,-7,-9, +13, +15,-16,-17,+18,+19,-20,+21 Negative 1. FR x 12. BR x43. MEDI-551 A SD 6 74 2.4 10.4 80 1 10 t(1;3),inv3,-5q,-18 TP53 mutation 1. R-CHOP x 62. BR x 13. FCR x 4 A SD WBC: White blood cells, Hb: hemoglobin, Plt: Platelets, BM: Bone Marrow, CLL: Chronic Lymphocytic Leukemia, F: Fludarabine, C: Cyclophosphamide, R: Rituximab, B: Bendamustine, MEDI-551: anti-CD19 antibody, NR: no response, SD: stable disease. Disclosures O'Brien: Amgen, Celgene, GSK: Consultancy; CLL Global Research Foundation: Membership on an entity's Board of Directors or advisory committees; Emergent, Genentech, Gilead, Infinity, Pharmacyclics, Spectrum: Consultancy, Research Funding; MorphoSys, Acerta, TG Therapeutics: Research Funding. Kantarjian:ARIAD, Pfizer, Amgen: Research Funding.

<p>ABSTRAK<br />Penggunaan varietas jahe yang responsif terhadap pemupukan dosis<br />rendah, diharapkan mampu meningkatkan efisiensi pemupukan dan<br />menekan pencemaran lingkungan. Penelitian dengan tujuan untuk<br />mengetahui respon lima aksesi jahe putih kecil terhadap pemupukan dosis<br />rendah telah dilaksanakan di Kebun Percobaan Cimanggu pada bulan<br />Agustus 2009 sampai Mei 2010. Lima aksesi jahe putih kecil dari daerah<br />marginal ditanam dalam polibag dan disusun menggunakan rancangan<br />acak kelompok yang diulang 3 kali. Setiap perlakuan terdiri atas 20<br />tanaman. Dua perlakuan yang diuji secara faktorial adalah, faktor I adalah<br />5 aksesi jahe putih kecil, yaitu (1) Ziof 0004, (2) Ziof 0007, (3) Ziof 0008,<br />(4) Ziof 0013, dan (5) Ziof 0014, dan faktor II adalah dosis pupuk, yaitu<br />(a) 50% dosis anjuran (200 kg/ha urea + 150 kg/ha SP-36 + 150 kg/ha<br />KCl), (b) 75% dosis anjuran (300 kg/ha urea + 225 kg/ha SP-36 + 225<br />kg/ha KCl), dan (c) dosis anjuran (400 kg/ha urea + 300 kg/ha SP-36 +<br />300 kg/ha KCl). Masing-masing perlakuan diberi pupuk kandang sebagai<br />pupuk dasar dengan dosis 20 t/ha. Pengamatan dilakukan terhadap<br />parameter pertumbuhan (tinggi tanaman, jumlah anakan, diameter batang,<br />dan jumlah daun), hasil dan serapan unsur hara N, P, dan K pada umur 4<br />BST dan 9 BST. Hasil penelitian menunjukkan bahwa masing-masing<br />aksesi memberikan respon yang berbeda terhadap penurunan dosis pupuk,<br />baik pada fase pertumbuhan maupun produksi tanaman jahe. Pengurangan<br />dosis pupuk sampai 25% tidak mengurangi produksi jahe, tetapi penurunan<br />dosis pupuk sampai 50% dari dosis rekomendasi menyebabkan penurunan<br />produksi jahe secara nyata. Komposisi unsur hara N, P, dan K yang<br />diserap berbeda pada setiap fase pertumbuhan tanaman.<br />Kata kunci : Aksesi, Zingiber officinale, pemupukan, pertumbuhan,<br />produksi</p><p>ABSTRACT<br />Response of five accessions of small white ginger to<br />fertilizers<br />The use of ginger varieties responsive to low fertilization dosages,<br />is expected to increase fertilizer use efficiency and reduce environmental<br />pollution. Research aimed at observing response of five small white ginger<br />accessions of low-dosage fertilization has been conducted in the Cimanggu<br />Experimental Station in from August 2009 through May 2010. Five small<br />white ginger accessions from marginal areas were planted in polybags.<br />The experiment was and arranged using a randomized block design was<br />repeated with 3 times replications. Each treatment consisted of 20 plants.<br />Two treatments were tested factorially, where factor I : 5 small white<br />ginger accessions, namely (1) Ziof 0004, (2) Ziof 0007, (3) Ziof 0008, (4)<br />Ziof 0013, and (5) Ziof 0014, and factor II : 3 fertilization dosages is<br />dosage of fertilizer, namely (a) 50% recommendation dosage (200 kg urea<br />+ 150 kg SP-36 + 150 kg KCl per hectare), (b) 75% recommendation<br />dosage (300 kg urea + 225 kg SP-36 + 225 kg KCl per hectare), and (c)<br />recommendation dosage (400 kg Urea + 300 kg SP-36 + 300 kg KCl per<br />hectare). Each treatment was given 20 t/ha of manure as basal fertilizer.<br />The parameters observed were growth parameters (plant height, number of<br />tillers, stem diameter, and number of leaves), yield and nutrient uptake of<br />N, P, and K at 4 and 9 months after planting (MAP). The results showed<br />that each of the accessions responded differently to the reduction of<br />fertilizer dosages, either in vegetative or generative growth phase of ginger<br />plants. Reduction of fertilizer dosages to 25% did not significantly reduce<br />the yield of ginger, however, fertilizer dosages reduction up to 50% of the<br />recommended dosages led to significant decrease of ginger yield.<br />Compositions of N, P, and K nutrients absorbed by plants were different in<br />every phase of plant growth.<br />Keywords : Accessions, Zingiber officinale, fertilizer, growth, yield</p>

Abstract. Volatile inorganic and size-resolved particulate Cl- and Br-species were measured in near-surface air over a broad range of conditions within four distinct regimes (European – EURO, North African – N-AFR, the Intertropical Convergence Zone – ITCZ, and South Atlantic – S-ATL) along a latitudinal gradient from 51° N to 18° S through the eastern Atlantic Ocean. Median dry-deposition fluxes of sea salt, oxidized N, and oxidized non-sea-salt S varied by factors of 25, 17, and 9, respectively, among the regimes. Sea-salt production was the primary source for inorganic Cl and Br. Acidification and dechlorination of sea salt primarily by HNO3 sustained HCl mixing ratios ranging from medians of 82 (ITCZ) to 682 (EURO) pmol mol−1. Median aerosol pHs inferred from HCl phase partitioning with super-μm size fractions ranged from ~3.0 for EURO to ~4.5 for ITCZ. Because SO2 solubility over this pH range was low, S(IV) oxidation by hypohalous acids was unimportant under most conditions. Simulations with a detailed multiphase box model indicated that BrCl photolysis and ClO + NO were the major sources for atomic Cl in all regimes. Simulated midday concentrations of Cl atoms ranged from 2.1×104 to 7.8×104 cm−3 in the ITCZ and N-AFR regimes, respectively. Measured particulate Br− (median enrichment factor = 0.25) was greater and volatile inorganic Br less than simulated values, suggesting that the halogen activation mechanism in the model overestimated Br-radical production and processing. Reaction with atomic Br was an important sink for modeled O3 (5% in EURO to 46% in N-AFR). Formation of halogen nitrates accelerated the oxidation of NOx (NO + NO2) primarily via hydrolysis reactions involving S aerosol. Relative to simulations with no halogens, lower NOx coupled with direct reactions involving halogens yielded lower steady state mixing ratios of OH (20% to 54%) and O3 (22% to 62%) and lower midday ratios of OH:HO2 (3% to 32%) in all regimes.

<p>O objetivo deste trabalho foi avaliar a dinâmica nouso e cobertura da terra em área de abrangência de Viçosa, <br />Minas Gerais. Para tanto, utilizou-se o algoritmo SEBAL (Surface Energy Balance Algorithm for Land) e o <br />método de classificação não supervisionada por meio do algoritmo ISODATA. Foi utilizada uma série <br />históricade temperatura do ar (ºC), da Estação Meteorológica Convencional (EMC) do Instituto Nacional de <br />Meteorologia (INMET) e imagens do sensor TM Landsat 5 do Instituto Nacional de Pesquisas Espaciais <br />(INPE), noperíodo que compreendeu 16 anos (1994-2010). Os resultados mostraram que nos anosde 1999, <br />2000, 2003, 2006, 2009 e 2010 mais de 20 mil hectares foram antropizadas, porém, a partir de 1999 inicia-se <br />um acentuado crescimento das áreas classificadas como mata. Os valores demonstraram avanço das áreas <br />antropizadas (58,92% em 1994 para 71,90% em 2010) e uma redução das áreas de pastagens (27,04% em <br />1994 para 5,90% em 2010). A temperatura da superfície estimada pelo algoritmo SEBAL para os anos de <br />1994 e 2010, apresentaram valores máximos de 38ºC em áreas antropizadas e valores mínimos de 18ºC em <br />áreas de vegetação. Com base no cálculo do viés médio (VM), o presente estudo mostrou que os dados <br />estimados da temperatura da superfície apresentaram boa correlação de 0,67 com os dados do INMET, já que <br />as temperaturas foram subestimadas e superestimadas com valores mínimos e máximos de -3,83ºC e 2,65ºC <br />em 1994 e 2003. Os resultados obtidos, ainda que em caráter preliminar, indicam a eficiência do <br />Sensoriamento Remoto (SR) por meio da análise das bandas refletivas e termal do satélite Landsat 5 como <br />ferramenta de análise na identificação da dinâmica do uso do solo, mostrando-se eficaz quanto à <br />espacialização dessas anomalias no espaço e no tempo.</p>

Abstract. Volatile inorganic and size-resolved particulate Cl- and Br-species were measured in near-surface air over a broad range of conditions within four distinct regimes (European – EURO, North African – N-AFR, the Intertropical Convergence Zone – ITCZ, and South Atlantic – S-ATL) along a latitudinal gradient from 51° N to 18° S through the eastern Atlantic Ocean. Processes within each regime were interpreted in conjunction with box-model calculations. Median dry-deposition fluxes of sea salt, oxidized N, and oxidized non-sea-salt S varied by factors of 25, 17, and 9, respectively, among the regimes. Sea-salt production was the primary source for inorganic Cl and Br. Acidification and dechlorination of sea salt primarily by HNO3 sustained HCl mixing ratios ranging from medians of 82 (ITCZ) to 682 (EURO) pmol mol−1. Aerosol pHs inferred from HCl phase partitioning with super-μm size fractions (~3 for EURO to the low 4 s for ITCZ) were similar to modeled values. Within all regimes, the dominant sources for atomic Cl were BrCl photolysis and ClO+NO. Maxima in atomic Cl ranged from 2.1 to 7.8×104 cm−3 in the ITCZ and N-AFR regimes, respectively. Because SO2 solubility over the aerosol pH range was low, S(IV) oxidation by hypohalous acids was unimportant under most conditions. Measured particulate Br− (median enrichment factor=0.25) was greater and volatile inorganic Br less than simulated values. Reaction with atomic Br was an important sink for O3 (5% in EURO to 46% in N-AFR). Formation of halogen nitrates accelerated the oxidation of NOx (NO+NO2) primarily via hydrolysis reactions involving S aerosol. Relative to simulations with no halogens, lower NOx coupled with direct reactions involving halogens yielded lower OH (by 20% to 54%) in all regimes. Halogen chemistry resulted in net O3 destruction and steady-state mixing ratios that were lower by 22% (EURO) to 62% (N-AFR) relative to "no-halogen" runs.

Abstract The feasibility and efficacy of hypofractionated salvage radiotherapy (HS-RT) for prostate cancer (PC) with biochemical recurrence (BR) after prostatectomy, and the usefulness of prostate-specific antigen (PSA) kinetics as a predictor of BR, were evaluated in 38 patients who received HS-RT without androgen deprivation therapy between May 2009 and January 2017. Their median age, PSA level and PSA doubling time (PSA-DT) at the start of HS-RT were 68 (53–74) years, 0.28 (0.20–0.79) ng/ml and 7.7 (2.3–38.5) months, respectively. A total dose of 60 Gy in 20 fractions (three times a week) was three-dimensionally delivered to the prostate bed. After a median follow-up of 62 (30–100) months, 19 (50%) patients developed a second BR after HS-RT, but only 1 patient died before the last follow-up. The 5-year overall survival and BR-free survival rates were 97.1 and 47.4%, respectively. Late grade 2 gastrointestinal and genitourinary morbidities were observed in 0 and 5 (13%) patients, respectively. The PSA level as well as pathological T-stage and surgical margin status were regarded as significant predictive factors for a second BR by multivariate analysis. BR developed within 6 months after HS-RT in 11 (85%) of 13 patients with a PSA-DT &lt; 10 months compared with 1 (17%) of 6 with a PSA-DT ≥ 10 months (median time to BR: 3 vs 14 months, P &lt; 0.05). Despite the small number of patients, our HS-RT protocol seems feasible, and PSA kinetics may be useful for predicting the risk of BR and determining the appropriate follow-up schedule.

<p>ABSTRAK<br />Langkah antisipatif pemenuhan kebutuhan massal benih temulawak<br />dilakukan dengan perbanyakan secara in vitro menggunakan medium<br />tumbuh yang murah mengandung air kelapa. Penelitian bertujuan untuk<br />menganalisis kandungan kimia air kelapa dan peranannya dalam multi-<br />plikasi tunas temulawak in vitro, serta pengaruhnya terhadap produksi<br />rimpang dan kandungan xanthorrizol. Penelitian dilakukan mulai Mei<br />2009 sampai Agustus 2010 di Laboratorium dan Kebun Percobaan Balai<br />Penelitian Tanaman Rempah dan Obat; serta Balai Besar Penelitian dan<br />Pengembangan Pascapanen Pertanian. Air kelapa yang digunakan berasal<br />dari kelapa muda (7-8 bulan) dan kelapa tua berumur (10-12 bulan).<br />Penelitian dilakukan secara bertahap, terdiri atas 4 kegiatan. Pertama,<br />analisis zat pengatur tumbuh, vitamin dan mineral dalam air kelapa<br />menggunakan metode HPLC. Kedua, pengaruh konsentrasi air kelapa (0,<br />5, 10, 15, 20, dan 25%) terhadap multiplikasi tunas temulawak in vitro.<br />Kegiatan dirancang secara acak kelompok, 3 ulangan. Pengamatan<br />meliputi parameter pertumbuhan. Ketiga, aklimatisasi dan kandungan<br />klorofil tanaman hasil in vitro. Keempat, pertumbuhan dan produksi<br />rimpang benih temulawak in vitro dalam pot berisi media tanah + pasir dan<br />analisis kandungan xanthorrizolnya. Rancangan penelitian acak kelompok,<br />3 ulangan, dan parameter pengamatan karakter pertumbuhan, produksi<br />rimpang, dan kandungan xanthorrizol. Hasil penelitian menunjukkan<br />bahwa air kelapa mengandung kinetin, zeatin, auksin, vitamin, mineral dan<br />sumber karbon yang berguna untuk multiplikasi tunas in vitro. Kandungan<br />kimia air kelapa muda lebih tinggi dibanding air kelapa tua. Medium<br />tumbuh mengandung air kelapa 15% terbaik dalam merangsang pertum-<br />buhan tunas in vitro (rata-rata 4,6 jumlah tunas per botol selama periode<br />awal pertumbuhan (8 minggu) sehingga dijadikan sebagai standar perba-<br />nyakan. Bibit temulawak hasil perbanyakan in vitro tumbuh baik (72%)<br />pada masa aklimatisasi, walaupun sebagian kecil ada yang menguning.<br />Kandungan klorofil a, b, dan total klorofil temulawak asal kultur in vitro<br />lebih tinggi dibandingkan dengan yang konvensional, dan bentuk<br />rimpangnya normal. Poduksi rimpang generasi awal (Vo) mencapai rata-<br />rata 320,2g, lebih rendah dibandingkan dengan rimpang konvensional<br />(800,5g). Kandungan xanthorrhizol temulawak hasil kultur in vitro lebih<br />rendah dibandingkan rimpang konvensional. Hasil penelitian mengindi-<br />kasikan potensi air kelapa sebagai zat pengatur tumbuh alami pada<br />temulawak in vitro.<br />Kata kunci: air kelapa, Curcuma xanthorrhiza, in vitro, xanthorrhizol,<br />hasil</p><p>ABSTRACT<br />Anticipated step for Java turmeric seed massal fulfillment was<br />conducted by in vitro using cheap growth medium enriched with coconut<br />water. The aim of the research was to analyse the chemical content of<br />coconut water and its role on java turmeric micropropagation in vitro and<br />their effect on yield and xanthorrhizol content. The experiement was<br />conducted from May 2009 to August 2009 at Indonesian Spices and<br />Medicinal Research Institute and Indonsian Center for Agricultural Post<br />Harvest Research and Development. The coconut water used comes from<br />young coconut (7-8 months) and old coconut (10-12 months). The research<br />consisted of four steps. First, analysis of growth regulator, vitamin and<br />sucrose from coconut water using HPLC method. Second, the effect of<br />several concentration od water coconut: 0, 5, 10, 15, 20, and 25% on in<br />vitro multiplication. The experiment was arranged in completely block<br />design with three replicates. The parameters observed were growth of<br />culture during in vitro. Third, acclimatization and chlorophyll content of<br />plant derived from in vitro and fourth, growth, and yield of java turmeric<br />seed on pot containing soil + sand as growth medium and xanthorrhizol<br />analysis. The experiment was arranged in completely block design with<br />three replicates. The parameters observed were growth characters, yield<br />and xnthorrhizol content. Result showed that coconut water contain<br />kinetin, zeatin, auksin, vitamin, mineral and carbon source which used for<br />in vitro shoots multiplication. The chemical of young coconut water was<br />higher than old coconut. The growth medium enriched with 15 % coconut<br />water gave the best result on inducing shoots in vitro (average 4.6<br />shoots/bottle during 8 weeks culture), so it’s used as multiplication<br />standard. Java turmeric seed from in vitro culture grew well (72%) on<br />acclimatization. Although, some of them were greenish.The content of a,<br />b, and total chlorophyll of java ginger from in vitro culture was higher than<br />conventional rhizome and have a normal rhizome. The production on Vo<br />(plantlet generation) around 320.2 g/plant, is lower than conventional<br />rhyzome (800.5 g). Xanthorhizol and essential oil content of Java turmeric<br />from in vitro seed were lower than conventional rhyzome. Result research<br />indicated potency of the coconut water as a nature growth regulator in<br />vitro.<br />Key words: coconut water, Curcuma xanthorrhiza, in vitro, growth,<br />xanthorrhizol, yield</p>

Background: Most high cost anticancer drugs (HCAD) are indicated in noncurative advanced (stage IV) cancer patients (NCP) for palliative reasons with variable impacts on quality of life and survival. HCAD challenge health care systems because of their high prices specially in nonhigh income countries. Aim: To evaluate the proportional impact (HDCA indications/overall survival) in NCP throughout years. To analyze causes of HDCA discontinuation. To calculate time elapsed from end of HCDA treatment to end of life (ETEL index). Methods: We reviewed charts of 268 NCP treated in a Patagonian cancer institution between 2009 to 2017 with an HCDA (either alone or in combinations) according to standard of care. Mean age was 58 y (26-84), sex (m/f) 126/142, primary tumor: GI 106 (40%), GU 27 (10%), GYN 20 (7%), BR 58 (22%), LG 43 (16%), others 14 (5%). 29 different HCAD were indicated in 402 treatments (small targets therapies 35%, Moabs 60%, others 5%): 1st line 268 (100%), 2nd line 89 (33%), 3rd line 34 (13%), thereafter 11 (4%). Results: Median OS for the entire population was 26 m (1-120), while it was: GI 20 m, GU 28 m, GYN 27 m, BR 47 m, LG 18 m, Others 21 m. Proportion of OS with HCAD indications: 50% (1-100) in the whole population, while it was: GI 49% (25-100), GU 62% (5-100), GYN 39% (6-93), BR 50% (3-100), LU 45% (6-93), others 61% (25-100). HDAC indications increased over time: 26% (2009-11), 33% (2012-14), 40% (2015-17), with a more than 2% of new NCP increment per year. Additionally proportion (HCAD/OS) was: 43% (2009-11), 47% (2012-14), 52% (2015-17). Median time of HCAD according to line of therapy was: 1st line 6 m, 2nd line 4 m, 3rd line 6 m, 4th+ lines 4.5 m. Causes of discontinuation of HCAD were: disease progression in 87% of cases and 13% for toxicity/others. Median ETEL index (days) was 80 d (1-340). Conclusion: 1) HCAD are indicated during a significant proportion of life (50%) in stage IV NCP with many solid tumors. 2) Its use is increasing over years with a rate of 2% of NCP per year and for more proportion of time. 3) A great number of HCAD treatments are discontinued due to failure reasons, while it is expected more than 10% of adverse events causes. 4) ETEL index is proposed as a measurement indicator of GCP. 5) Impact of HCAD treatments is a major issue in health care policies.