bluuebunny/crossref_metadata_2025_split huggingface dataset:
Development of brain metastases in patients with metastatic melanoma treated with ipilimumab plus temozolomide.
Authors: Wang Jennifer , Patel Sapna Pradyuman , Hwu Wen-Jen , Kim Kevin B. , Papadopoulos Nicholas E. , Hwu Patrick , Radvanyi Laszlo George , Mahoney Sandy , Deburr Tawania L , Bassett Roland , Bedikian Agop Y. 
Published: March 2020

e19014 Background: Melanoma has a high predilection for brain metastasis (BM), and despite treatment, survival is often 3 to 6 months. There have been a number of reports of disease regression in BM with each Ipilimumab (Ipi), an anti-CTLA 4 antibody, and temozolomide (Tem), an alkylating drug capable of crossing the blood-brain barrier, in patients with metastatic melanoma (MM). Previous Ipi trials excluded patients with BM. Previous Tem trials have BM incidence ranging from 20 to 36%. Here we describe our experience with the combination of Ipi+Tem and BM. Methods: Patients (pts) are from a 64-patient cohort with unresectable Stage III or Stage IV metastatic melanoma enrolled in a single-center Phase II trial of Ipi+Tem. Induction phase consisted of Ipi 10mg/kg intravenous (IV) on Day 1 and oral Tem 200mg/m2 Days 1-4 every 3 weeks for 4 courses. Maintenance phase was Ipi 10mg/kg IV every 12 weeks and oral Tem 200mg/m2 on Days 1-5 every 4 weeks. Brain MRI was obtained every 2 cycles as part of the protocol. We evaluated development of BM in these pts. Results: At a median follow-up of 41 weeks, 11 pts (17%) developed new BM. Two pts with a history of prior BM were enrolled; one developed new BM while the other achieved a complete response of disease in the lungs and remains on study. All pts who developed BM had Stage IV disease at baseline, five (45%) had elevated baseline LDH, and nodular melanoma was the most common histology (55%). The median time to development of BM with Ipi+Tem was 12 weeks. Mutation status, stage, and primary tumor location and depth were not significantly associated with the development of BM. Elevated baseline LDH was a significant predictor for development of BM (p=0.001, log-rank test). The median overall survival for both the BM and non-BM groups has not been reached. Conclusions: There is little known about the development of BM with various treatments for MM. To our knowledge, this is the first study to evaluate the development of BM in pts receiving Ipi-based treatment. Our data suggest that Ipi+Tem and Ipi monotherapy warrant further research in the prevention and treatment of BM in MM.
Genotype characterization and prognosis of unknown primary melanoma patients with nodal metastases.
Authors: Gos Aleksandra , Robert Caroline , Jurkowska Monika , Kamsu-Kom Nyam , Michej Wanda , Jeziorski Arkadiusz , Voit Christiane A. , Roewert-Huber Joachim , Siedlecki Janusz A , Van Akkooi Alexander Christopher Jonathan , Eggermont Alexander M. , Rutkowski Piotr 
Published: March 2020

e19022 Background: Melanoma of unknown primary site (MUP) is unique, not completely understood entity with nodal metastases as the most common clinical manifestation. The aim of this multicentric study was to assess genetic alterations in MUP with clinically detected nodal metastases in terms of clinicopathological features and prognosis. Methods: We analyzed contemporary series of 37 MUP patients (median age 51 years) after therapeutic lymphadenectomy - LND (period: 1996-2010, 20 – axillary, 16 - inguinal, 1 – other basin) not treated with BRAF inhibitors and performed molecular characterization of BRAF/NRAS mutational status in nodal metastases using direct sequencing of respective coding sequences. Median follow-up time was 37 months. Results: BRAF mutations were detected in 23 (63%) cases (21 V600E - 91%, 2 others - 9%), and mutually exclusive NRAS mutations in 3 (8%) cases (Q61K, Q61R, Q13R). Presence of BRAF mutation correlated with younger age of patients (median 47 vs 60 years for BRAF+ vs. BRAF-, p<0.05). 3-year overall survival (OS) was 45%, median – 23 months (from date of lymph node dissection). We have not found any difference in terms of OS between BRAF mutated- and wild-type melanomas (p=0.99). Conclusions: This unique, comprehensive study on molecular characterization of MUP with nodal involvement stage showed that MUPs have similar molecular features as sporadic non-chronic-sun-damaged melanomas. BRAF mutational status has no prognostic value in this group of patients, what may have potential implications for adjuvant therapy.
Vulvar melanoma: A monocentric retrospective study on 29 cases.
Authors: Tosti Giulio , Botteri Edoardo , Spadola Giuseppe , Baldini Federica , Mosconi Massimo , Ferrucci Pier Francesco , Gandini Sara , Pennacchioli Elisabetta , Zampino M. Giulia , Cocorocchio Emilia , Verrecchia Francesco , Cataldo Francesco , Buffon Rosana , Sideri Mario , Maggioni Angelo , Testori Alessandro 
Published: March 2020

e19036 Background: Vulvar melanoma (VM) represents 3-7% of melanoma in women. The 5-year survival rate ranges from 8 to 55%. Surgical excision represents the best definitive therapy but surgical radicality does not impact on recurrence or survival. Methods: Thirty women with histologically confirmed VM diagnosed between 1993 and 2009 were selected for this monocentric retrospective study. One patient with metastases at time of diagnosis was excluded from the statistical analysis. Clinical, pathological and follow-up data were collected. Cumulative incidences of events were calculated and compared across subgroups by means of the Gray test. Results: Average age at diagnosis was 62 years. Average Breslow thickness was 4.91 mm. Ulceration was present in 11 cases and was unknown in 5. One case of VM was multifocal at presentation. Eleven patients underwent a wide local excision, 11 a hemivulvectomy and 7 a radical vulvectomy Sentinel node biopsy was performed in 23 patients and at least one positive sentinel node was found in 8 cases. Eight patients received adjuvant therapy. Ten patients had a second tumor (other than melanoma); of these, a breast cancer was recorded in 5 cases. Four patients had a second primary melanoma: of the vulva (n=2), vagina (n=1), and urethra (n=1). Median follow-up among ongoing survivors was 79 months and median overall survival was 69 months. The 5-year overall survival was 55.4%. Median event free survival 34 months. Positive lymph nodal status was associated with an increased risk of loco-regional recurrences (P=0.04). Positive lymph nodal status (P=0.06), Breslow thickness > 2mm (P=0.05) and number of mitoses > 10/mm2 (P=0.04) increased the risk of distant metastases. Age, ulceration and type of surgery were not significantly associated with any type of event. Conclusions: Lymph node involvement, elevated depth of invasion and a high number of mitoses were the most important prognostic factors for locoregional recurrence and distant metastases. The same trends were observed for the overall survival, but results were not statistically significant. Conservative surgery in the form of wide local excision with adequate margins may replace vulvectomy. Sentinel node biopsy is feasible and its role in VM should be further investigated.
Ipilimumab in metastatic malignant melanoma: The Irish experience.
Authors: Donnellan Paul P. , Bambury Richard , Battley Jodie E , Power Derek Gerard , O'Byrne Kenneth John , Crown John , Breathnach Oscar S. , Teo MinYuen , Jamaluddin Muhammad Faisal , Boychak Oleksandr Volodymyrovych , Lyons Tomas , Greene John , Jayaram Anuradha ,   ICORG Melanoma Group
Published: March 2020

e19059 Background: Ipilimumab (Ipi) is a potent anti CLA-4 immunotherapy recently shown to improve overall survival (OS) in a phase III study in patients (pts) with previously-treated, unresectable or metastatic malignant melanoma. Ipilimumab (3 mg/kg) has been available on compassionate grounds to pts in Ireland since June 2010. Methods: In this retrospective observational study we examine the Irish experience with ipilimumab specifically regarding patient-factors, treatment toxicity, and outcomes including response rate and survival. Results: Between June 2010 and December 2011, a total of 93 patients received ipilimumab. Data available for analyses was conducted in 46patients. Median age of patients was 56 yrs (ranging 28 – 84). M1c disease was identified in 40 patients (83.3%). Median number of prior lines of chemotherapy is 1 (ranging from 1-4). 22 (47.8%) patients received all four planned induction doses of ipilimumab. All patients received full doses of treatment and on schedule. There are no grade 4 toxicities reported and 13% (n= 6) had grade 3 adverse events. This included renal autoimmune toxicity (n=3), diarrhoea (n=1) elevated AST/ALT (n=1), ocular toxicity (n=1) and skin (n=1). Grade 3 adverse events occurred in 3 patients who received all 4 cycles of Ipilimumab. No intestinal perforations or hypophysitis were noted. There were no drug-related deaths. From available survival follow-up data there are 22 reported deaths. Due to paucity of the data, surrogate marker for response of treatment was expressed as absence of disease progression at the time of assessment. Among the 11 (23.9%) patients who responded to treatment, 45.5% of these patients received 4 cycles of ipilimumab. Conclusions: Ipilimumab was well tolerated with a manageable side effect profile. Response rates to ipilimumab in metastatic melanoma in an Irish population are in keeping with internationally reported figures. Comprehensive survival data will be reported as well as correlation of response with hematologic and biochemical blood tests.
A psychosocial and pshycoeducational intervention for cancer patients integrated into routine care: A study from India.
Authors: Chandra Anita 
Published: March 2020

e19518 Background: Patients with cancer experience significant distress and access to effective psychosocial care is limited by lack of systematic approach. This paper presents results of a study to evaluate the effectiveness of a brief tailored psychosocial intervention delivered by health professionals in cancer care in developing countries. Methods: Health professionals deliver the multicomponent, psychoeducational and psychosocial intervention focusing on core concepts of quality of life, supportive-expressive, cognitive, social functioning, symptom scale and dignity-conserving care. A total of 100 patients recruited across all tumour sites, from July 2011 to December 2011, in a University Hospital in India. Eligible patients received 2 sessions, each for 30 minutes in length, delivered face-to-face at baseline and 12 week follow-up. Results: Quality of life was measured by using the European Organisation for Research and Treatment of Cancer (EORTC) QLQ-C30 questionnaire .In this study the functional scales were high, whereas in the symptom scales fatigue (48.9%) and financial difficulties (45.53%) were noted. Percentages of families who evaluated by the palliative care team voted as useful or very useful were: 80% (symptom control), 85% (emotional support), 86% (family support), and 87% (care coordination). Compared with participants receiving usual oncology care, those receiving a palliative care-focused intervention addressing psychosocial care provided concurrently with oncology care had higher scores for quality of life and mood. Conclusions: This study will provide important information about the effectiveness of a brief tailored psychological intervention for patients with cancer in a developing country. This model of care should be a systematic implementation in routine clinical practice cancer settings in resource restraints countries. [Table: see text]
Phase II study of caphosol oral rinse for prevention of oral mucositis (OM) in sarcoma patients (pts) receiving multicycle doxorubicin-based chemotherapy (CT): Randomized study with cross-over to palifermin for severe OM.
Authors: Vadhan-Raj Saroj , Araujo Dejka M. , Trent Jonathan C. , Zhou Xiao , Ludwig Joseph A. , Ravi Vinod , Chambers Mark Steven , Patel Shreyaskumar , Benjamin Robert S. 
Published: March 2020

e19520 Background: Mucositis is a common complication in cancer pts receiving CT. We have shown that palifermin (recombinant Keratinocyte Growth Factor), administered as single dose prior to CT, alleviated severe mucositis in pts receiving doxorubicin-based CT (Ann Int Med 2010). Caphosol is a supersaturated electrolyte solution of calcium phosphate that has been indicated as oral rinse for xerostomia and as an adjunct to treat OM induced by radiation or high-dose CT. Purpose of the study was to evaluate the preliminary efficacy of Caphosol in pts receiving CT. Methods: Pts were randomized 1:1 to Caphosol vs. baking soda (control) as an oral rinse five times daily from initiation of CT. All pts received doxorubicin (75 or 90 mg/m2 by continuous infusion over 3 days) with ifosfamide (10 gm/m2) or cisplatin (120 mg/m2). Pts that experienced Grade (Gr) > 3 mucositis received palifermin (180 mcg/kg) iv 3 days before CT in subsequent cycles. Results: 28 of 30 pts received treatment and were evaluble; 15 men and 13 women, with median age 51 (range, 20-65 yrs). Incidence of Gr > 2 OM was 57% (8 of 14 pts) for Caphosol vs. 86% (12 of 14) for control (P=0.21). Incidence of Gr > 3 OM was 29% (4/14) for Caphosol vs. 43% (6/14) for control (P=0.43). However, the benefit was limited to oral but not other GI mucosal sites. Of 10 pts (Caphosol: 4, BS: 6,) with Gr > 3 OM, 6 crossed over to palifermin (Caphosol: 3, BS: 3); the other 4 pts (Caphosol: 1, BS: 3) came off the study. All 6 pts, that received palifermin, avoided severe OM in the next cycle. The median duration of Gr > 2 OM in the cycle before cross-over was 8 days (range: 5-12) vs. 0 days (0-3) in palifermin cycle (p=0.0032) and Gr > 3 OM was 5 days (2-7) vs. 0 days (p=0.0015). Oral assessment and the pts-reported outcome were in substantial agreement for the OM grading (weighted kappa, 0.78, 95% CI: 0.44-0.87, p<0.0001). No serious adverse event related to the study drug was observed. Conclusions: There was a trend for less severe OM with Caphosol vs. control. Secondary prophylaxis with palifermin alleviated severe mucositis in all pts who previously experienced severe mucositis during multi-cycle CT.
An evaluation of the drug interaction potential of netupitant with palonosetron, dexamethasone, and oral contraceptives.
Authors: Vouis Jan , Henriksson Anders , Timmer Wolfgang , Calcagnile Selma , Rossi Giorgia 
Published: March 2020

e19532 Background: Netupitant (NETU) is a highly selective neurokinin 1 receptor antagonist (NK1 RA) developed to provide protection from nausea and vomiting in patients undergoing emetogenic chemotherapy. Three individual studies were aimed at determining NETU effect on the metabolism of the new generation 5-HT3 RA palonosetron (PALO), dexamethasone (DEX) and oral contraceptives which may be coadministered in clinical practice. Methods: Two 3-way crossover studies to determine the interaction between NETU (450 mg, day 1) and PALO (0.75 mg PO, day 1), and between NETU (100 mg, 300 mg or 450 mg PO, day 1) and DEX (20 mg PO, day 1; 8 mg BID PO, days 2-4), were performed in 18 and 25 healthy subjects, respectively. The study investigating the effect of NETU/PALO (300 mg/0.5 mg PO) as a fixed dose combination on the PK of oral contraceptives ethinylestradiol and levonorgestrel (60 μg/300 μg) was a 2-way crossover trial of 24 healthy women. Serial blood samples were collected over the course of the three studies and pharmacokinetic parameters were determined for all analytes. Results: There were no significant pharmacokinetic interactions between NETU and PALO. DEX mean AUC and Cmax increased respectively, by 1.7 and 1.1 fold on day 1 and by 2.4 and 1.7 fold on day 4 when coadministered with NETU. NETU was shown to increase exposure to DEX in a dose-dependent manner. The combination of NETU/PALO did not significantly affect exposure to ethinylestradiol; systemic exposure to levonorgestrel increased by 40%, a level that is not considered clinically relevant. Conclusions: A relevant drug interaction was seen between NETU and DEX and therefore dose reductions are recommended for DEX when administered with NETU. This drug interaction is likely due to inhibition of CYP3A4 by NETU. No interaction was clinically relevant between NETU and PALO, or between NETU/PALO and ethinylestradiol and levonorgestrel. Treatments were well-tolerated in all studies.
Efficacy of palonosetron-based antiemetic prophylaxis in breast cancer patients receiving anthracycline-containing adjuvant chemotherapy: A survey in 41 German gyneco-oncology practices.
Authors: Schilling Joerg Peter , Klare Peter , Wetzel Antje , Kittel Kornelia , Hindenburg Hans-Joachim , Gazawi Nidal , Jungberg Peter , Guth Dagmar , Busch Steffi , Geberth Matthias , Konias Marina , Ortner Petra Angelika , Feyer Petra C. 
Published: March 2020

e19540 Background: The emesis risk in young breast cancer (BC) patients (pts) receiving adjuvant anthracyclines (A) plus cyclophosphamide (C), taxanes or other cytotoxics is higher than anticipated earlier. Furthermore, antiemetic control seems to decline in subsequent cycles of chemotherapy (CT). The ASCO has classified AC to be highly emetogenic (HEC) in their antiemetic guidelines 2011. Palonosetron (P) is a 5-HT3-receptor-antagonist (5-HT3-RA) with higher receptor affinity and longer biological half-life than older compounds. Data suggest that Palonosetron is clinically more effective in the acute phase and that in contrast to the older 5-HT3-RA it is also effective in the delayed phase. P also showed to maintain its efficacy in subsequent cycles. Current antiemetic guidelines list palonosetron as preferred 5-HT3-RA in moderate emetogenic chemotherapy (MEC). Methods: To evaluate the efficacy of palonosetron after 4 cycles of A containing chemotherapy in BC patients, we have conducted a survey in 41 practices of the BNGO in Germany. Between Nov 2007 and Jan 2012 1299 patients have been documented. Median age was 55 years. Severity, frequency, duration and onset of N/V were recorded in a patient diary. Efficacy criteria were complete control CC (no V, no rescue, mild N); complete response (CR: no V, no rescue) and rescue medication. Results: At the beginning P was used as single agent (56%). Following the MASCC 2010 guidelines P was used in combination with dexamethasone (PDex, 15%) or plus dex and NK1-RA (PNDex, 23%), 16% of pts received additional medication. Efficacy after 4 cycles of CT: Overall (5 days): Complete control CC: (no V, no rescue, mild N) 63,3% of pts, complete response (CR: no V, no rescue) 73,7%; Rescue Medication was needed in 15,6% of pts. PDex CC 48,7%, CR 69,8 %, PNDex: CC 76,3%, CR % 83,33. N was also very well controlled: Overall (5 days) 56% of pts no nausea, 15% moderate N 3% severe N. Conclusions: Palonosetron in combination with dex and NK1-RA is very effective to control nausea and vomiting in A-based adjuvant chemotherapy in young breast cancer patients after 4 cycles of chemotherapy.
Factors predicting local recurrence in phyllodes tumor of the breast.
Authors: Ramakant Pooja , Cherian Anish Jacob , Abraham Deepak T , Paul MJ 
Published: March 2020

e19562 Background: Phyllodes tumor of the breast (PT) has local recurrences resulting in higher morbidity and disfiguring reoperations. Aim to find factors predicting local recurrences in PT. Methods: Retrospective data analyzed with SPSS v.17 (Pearson Chi square test, Logistic regression test for multivariate analysis) done on patients with PT managed during 2000-2010. Results: In total 141 patients with PT, mean age was 40.44 years (+0.98) and mean tumor size 11.07 cm (+0.57). Preoperatively cytology done in 96 % and was suggestive of PT in 59%; core biopsy done in 58 % and was suggestive of PT in 93% Imaging done in 65%. The mean duration of lump- 2.2 years (+0.23). Thirty two patients (23%) presented with recurrence post lumpectomy done elsewhere. Adjuvant radiotherapy was given in 28% patients. In multivariate analysis, high stromal cellularity ( p 0.002), surgery type (p= 0.000) and recurrent status (p=0.05) at first time presentation showed statistically significant p values for odd’s ratios. Conclusions: Tumor size, margins, surgery type, histological features of high stromal hypercellularity, necrosis with high mitotic rates predicted recurrence in PT. Core biopsy is more accurate than fine needle biopsy in diagnosis and recommended in suspected cases to permit the correct initial surgery. [Table: see text]
Risk factors for oral mucositis (OM) in multiple myeloma (MM) patients receiving high-dose melphalan (Mel) prior to autologous stem cell transplantation (SCT).
Authors: Bhatnagar Bhavana , Goloubeva Olga G. , Gilmore Steven , Hoffman Arnold , Ruehle Kathleen , Akpek Gorgun , Rapoport Aaron , Yanovich Saul , Badros Ashraf Z. 
Published: March 2020

e19565 Background: OM is a common complication of high-dose melphalan in MM patients (pts). Proposed risk factors for OM in SCT include: low albumin and high serum creatinine (Cr) levels, both were evaluated in MM patients undergoing Mel/ASCT. (Grazziutti, ML, Bone Marrow Transplant 2006). Methods: This is a single center retrospective chart review of 214 sequentially treated MM pts who received Mel 200mg/m2 conditioning prior to SCT between January 2005-September 2011. Data collected included: demographics, Hgb, Cr, C-reactive protein and albumin on the day of SCT, length of hospital stay. OM assessment was graded as follows: Grade 1, no OM; Grade 2, mild OM; the pts maintained adequate oral intake; Grade 3, decreased oral intake and/or use of oral narcotics; Grade 4, severe OM needing intravenous narcotics. Results: The table below describes pt characteristics grouped by OM grade. Overall, 56 pts (27%) had grade 3/4 OM. Multivariate analysis of variance revealed no statistically significant correlation between OM grade and Hgb, Cr, albumin, CRP; the overall test’s p value = 0.55. There were no racial or gender differences with regard to grade of mucositis, the p-values range are 0.75 and 0.31, respectively (likelihood ratio chi-square test). Most interestingly, OM did not impact length of hospital stay. Conclusions: We did not establish any predictive risk factors for OM as previously described. Analysis of the impact of OM on MM response and event and overall survival will be presented. Studies of Mel pharmacogenetics may provide insight to patients' predisposition to OM. [Table: see text]
Iron-deficiency anemia and cardio-renal toxicity of doxorubicin in hypertensive rats.
Authors: Toblli Jorge E , Rivas Carlos , Cao Gabriel , Giani Jorge , Dominici Fernando 
Published: March 2020

e19569 Background: Hypertension and anemia are common in patients with neoplasm and may increase the toxicity of anti-cancer drugs. This study evaluated cardio-renaltoxicity of doxorubicin (DOX) in combination with iron deficiency anemia (IDA) in Spontaneously Hypertensive Stroke Prone (SHRSP) rats. Methods: SHRSP rats were randomized into six groups (A-F; n=8 each). IDA was induced in groups A-D by 12 weeks low iron diet; groups E and F had normal diet. After 6 weekly DOX or control treatments (0.9% saline), echocardiography was performed and blood analyzed for hemoglobin (Hb) and transferrin saturation (% TSAT). Tissue sections and homogenates from heart and kidney samples were analyzed for markers of oxidative-nitrosative stress and inflammation. Results: IDA plus DOX was associated with significantly lower cardiac performance (% FS) and kidney function (CrCl) and a higher degree of cardio-renal oxidative-nitrosative stress and inflammation (Table). Conclusions: The results show that IDA can aggravate dose dependent DOX-induced cardio-renal toxicity in hypertensive rats and confirm that IDA significantly induces oxidative-nitrosative stress and inflammation. [Table: see text]