bluuebunny/crossref_metadata_2025_split huggingface dataset:
Multicentric ipilimumab experience in Turkish patients with metastatic melanoma: MIPI-TURK at 30 months of follow-up.
Authors: Sevinc Alper , Turna Hande , Ozdogan Mustafa , Buyukberber Suleyman , Demir Gokhan , Gokmen Erhan , Mandel Nil Molinas , Paydas Semra , Akbulut Hakan , Celik Ismail 
Published: March 2020

e20006 Background: Ipilimumab, an anti-CTLA-4 (cytotoxic T lymphocyte-associated antigen) monoclonal antibody has been shown to enhance immune responses and improve overall survival in patients with metastatic melanoma. The authors report retrospectively on metastatic melanoma patients treated under the Expanded Access Program in Turkey among 13 centers. Methods: Patients with metastatic melanoma were treated with ipilimumab 3 mg/kg every 3 week for 4 doses. Response evaluation was done on week 12. Patients with complete response (CR), partial response (PR), and stable disease (SD) at week 12 were eligible for re-treatment. Results: A total of 97 patients enrolled with 77 evaluable. Ipilimumab treatment was given as 2nd (20.0%), 3rd (64.3%), and 4th(15.7%) line. The rate of the patients receiving ipilimumab for 1, 2, 3, and 4 doses were 5.2%, 11.7%, 16.9%, and 62.3%, respectively. Seven of 77 patients were eligible for re-treatment. G1/2, G3/4, and G5 adverse events were reported in 23.4% (18/77), 14.3% (11/77), and 2.6% (2/77) of the patients, respectively. The most common G1/2 immune related adverse events were rash (14.3%), muscle weakness (10.0%), and gastrointestinal side effects (8.6%). There were seven G3 side effects (diarrhea in 4, muscle weakness in 1, hypothyroidism in 1, and GI bleeding in 1 patient) and four G4 side effects (thrombocytopenia in 1, diarrhea in 1, sinus tachycardia in 1, and multiple organ failure in 1 patient). Two deaths (G5) were associated with hepatic AEs. Regarding the response evaluation, there was no CR within 16 months of follow-up period and the median overall progression free survival duration was 2 months (95% CI, 1.6-2.5). The disease control rate was 38.8% (PR: 16.3% and SD: 22.5%). Median time to progression was 2 months (95% CI, 1.8-3.1 months). Of the patients, 31.9%, 22.2%, and 19.2% survived within 12, 24, and 30 months of follow-up period, respectively, and the median overall survival duration was 6 months (95% CI, 3.5-8.5). Conclusions: Ipilimumab treatment resulted in favorable clinical benefit for metastatic melanoma patients. Data generated by 13 centers revealed an efficacy and safety profile consistent with the currently available ipilimumab trials.
Ugly is not only skin deep: A case of osteogenic melanoma.
Authors: Williams Joshua C.M. , Sheehan Natale Tate , DeDelva Pierre , Barr Jennifer 
Published: March 2020

e20009 Background: Although the incidence of malignant melanoma is high, the incidence of metaplastic malignant melanoma is low. Within the various subtypes of malignant metaplastic melanoma, the manifestation of osteogenic melanoma remains a rarer event. Current review of the literature reveals only 12 reported cases. Of these reported cases, scant discussion is made on treatment whereas the histopathology is discussed in great detail. Methods: We present the case of a 64 year old Caucasian man that was diagnosed with synchronous tumors of the foot and lung. Initial biopsy of the foot revealed metastatic osteogenic melanoma. As a result of the initial biopsy results and imaging, the patient underwent a right lower lobe resection and lymph node dissection followed by a left lower extremity Pirigoff’s amputation and inguinal lymph node dissection. Results: Immunohistochemical staining of the extirpated tissue from the lung revealed strong reactivity to S100, vimentin, Sox10, diffuse reactivity to low molecular weight cytokeratin and HMB-45/MART-1 and no lymph node involvement. Whereas the IHC of the extirpated tissue of the left foot remained consistent with the initial biopsy of strong reactivity to S100 and MART-1 and negative to pancytokeratins, CD34, Desmin, and SMA. Conclusions: Given the features of the patient’s pathology and resected metastatic disease, he was administered adjuvant alpha interferon therapy.
Acral melanoma in the Asian/Pacific Islander population: Analysis of +8q and 8q24 chromosomal aberrations.
Authors: Morita Shane Young , Kim Iris H. , Lum Christopher A. 
Published: March 2020

e20029 Background: Acral melanoma (AM) is a distinct subtype of melanoma that displays a higher proclivity in the minority population. AM is associated with a worse outcome in comparison to conventional cutaneous melanoma (CM). Asian/Pacific Islanders with AM in particular, exhibit the poorest survival amongst all ethnic groups. Recent studies have profiled the importance of +8q and 8q24 as markers for an adverse prognosis in CM. However, a focused chromosomal analysis of minority patients with AM at this locus has not been previously described. Methods: IRB approval was obtained for this retrospective analysis. From 2004 to 2012, 14 Asian/Pacific Islander patients histologically confirmed to have invasive AM were evaluated at a tertiary institution. Data including age, gender, tumor location, Breslow thickness, ulceration, and mitoses per mm squared were compiled. In situ hybridization was performed targeting the centromeric region of chromosome 8 (Vysis CEP 8-FITC) and the myelocytomatosis viral oncogene homolog locus (MYC; 8q24.12 q24.13, Vysis LSI-Spectrum Orange). The overall ratio of signals and individual spot counts for CEP8 and 8q24 was recorded. Results: Our findings demonstrated that +8q chromosomal aberrations were highly prevalent (8/14; 57%). The majority of our entire cohort (7/14; 50%) exhibited thick primary lesions (>4.0 mm) with a high propensity for ulceration. There were no copy number gains in 8q24. Demographics of the Asian/Pacific Islander cohort included mean age of 67.4 years old (range 43-86) and male gender 9/14 (64%). Tumor location principally involved the foot 11/14 (79%); mean Breslow thickness was 4.6 mm (range 0.9-11.0), ulceration 7/14 (50%), and mean mitoses per mm squared was 3.4 (range 0-9). Conclusions: Asian/Pacific Islanders with AM were found to have a high frequency of +8q chromosomal alterations. There appeared to be an association with a thicker Breslow and presence of ulceration. This is the first study to our knowledge that has examined chromosomal aberrations of +8q and 8q24 in a non-Caucasian population of AM patients. This is compelling data that may be applied to future prognostic classifications.
Association of increased body height with BRAF mutations in male melanoma patients.
Authors: Maubec Eve , Geay Maria , Regnier-Rosencher Elodie , Fite Charlotte , Boitier Francoise , Kramkimel Nora , Chrisment Di Lucca Julie , Carlotti Agnes , Deschamps Lydia , Marinho Eduardo , Couturaud Benoit , Albert Sebastien , Kalampokas Athanasios , Sastre Xavier , Rouleau Etienne , North Marie- Odile , Lamoril Jerome , Crickx Beatrice , Dupin Nicolas , Avril Marie-Françoise 
Published: March 2020

e20032 Background: Somatic BRAF mutations occur in approximately 40-50% of patients (pts) with unresectable cutaneous melanoma (CM) and are more common in young pts. The objective of this study was to determine if body height and body mass index (BMI) are associated with BRAF mutation status. Methods: 212 consecutive BRAF-tested patients with unresectable stage IIIC or IV CM were analysed. Tumor samples from two departments of dermatology were screened by high-resolution melt curve analysis of BRAF exon 15; abnormal results were confirmed by DNA sequencing. Associations between BRAF mutation status and height, BMI and age of pts were examined using univariate and multivariate logistic regression analyses in the whole sample and according to sex. Results: The BRAF mutation frequency was 42%. On univariate analysis in the whole sample, BRAF mutated status was not associated to BMI (p=0.9) but was associated to age and height (p≤0.027). The BRAF mutation frequency was higher in taller pts reaching 59% in pts > 180 cm (p=0.003, χ² test). According to sex, this association was significant in males (p=0.004) but not in females (p=0.39). Size did not differ significantly in the 4 quartiles groups of age (<50, 50-62, 62-72 and >72 years; p >0.07). On multivariate analysis, in the whole sample, only age was associated to mutated BRAF status (p<0.001); but in the male subgroup, age and height were independent factors predicting BRAF mutations (p<0.04). Conclusions: Tallness was significantly associated with BRAF mutations in male melanoma pts. This is in agreement with published data for colorectal carcinoma. This study might suggest a genetic susceptibility to somatic BRAF mutations, increased height and melanoma. [Table: see text]
Impact of survival on health care charges during melanoma treatment.
Authors: Brixner Diana I. , Bellows Brandon Kyle , Dahal Arati , Stenehjem David D. 
Published: March 2020

e20043 Background: Treatment charges increase during the last year of life in patients with melanoma, but it remains unknown if charges differ between patients who die during treatment and survivors. The objective of this study was to examine annualized mean charges by melanoma survival status. Methods: The University of Utah Enterprise Data Warehouse was used to analyze patients ≥18 years with a diagnosis of melanoma identified by ICD-9 code (first diagnosis defined as index date) treated at the Huntsman Cancer institute (HCI) from 2002-2010. The HCI tumor registry was used to determine stage at diagnosis and other cancer diagnoses. Cause and date of death was captured from the Utah Population Database. Cancer-related (CR) and non-CR charges were assessed by ICD-9 codes from index date until death or end of the follow-up period, were weighted by the inverse probability of survival, and annualized. Generalized linear models (GLM) with gamma distribution and log link function were used to examine charges by survival status, adjusting for baseline characteristics including demographics, disease stage, and comorbidities. Results: A total of 1205 patients were included, of which 218 (18%) died. Compared to alive patients, deceased patients were older (60 vs. 56), more female (40% vs. 28%), more were diagnosed with stage IV disease (19% vs. 3%), and less with stage I disease (26% vs. 66%) (all p≤0.001). Mean unadjusted annualized charges were not significantly different between the two groups for CR charges (deceased $15,109 vs. alive $14,519; p=0.89), but non-CR charges were higher for deceased patients ($77,390 vs. $18,719; p<0.001). GLM results indicated deceased patients, relative to survivors, had 59% higher annualized CR charges (p<0.001) overall, with higher CR charges at stages I and II (86% and 76%, respectively; both p<0.001), and lower CR charges at stage IV (-127%; p<0.001). Death was associated with 154% higher annualized non-CR charges (p<0.001) at stages I, II, III, and IV (210%, 167%, 119%, and 73%, respectively; all p<0.05). Conclusions: When adjusting for confounders, deceased melanoma patients had higher charges overall compared to melanoma survivors. The exception was for decreased CR charges in stage IV, most likely related to earlier death.
Something to sing about: A global choir of cancer survivors—Building bridges.
Authors: Donnellan Paul P. , Gill Donal , Hynes Deanna , Gallagher Olive , Leonard Seamus 
Published: March 2020

e20505 Background: 68% of cancer patients live at least 5 years after diagnosis and many are cured. Cancer survivors continue to need support. Music is energising, affirming and therapeutic. More funds are needed for cancer research so that more patients become long-term survivors. In 2012 Galway University Hospital founded 'Something To Sing About' (STSA.ie), a not-for-profit organisation to support cancer survivors and cancer research. Methods: Local publicity brings small bands of cancer survivors together rehearsing the same music at the same time every week (Wednesday 7pm) in a local hall, hospital or hotel, each with its own local musical director. The music is selected by a representative music committee and music therapist. Musical instruction is disseminated by the chief musical director via website and social media. A plenary rehearsal takes place every 3 months. All profits from events and music sales are allocated to cancer research projects through an open peer-reviewed grant-application process. Results: In 6 months STSA has grown from concept to network of 20 centres with total membership of 251 cancer-survivors. Immediate feedback has been extremely positive as assessed by personal communication and facebook activity (currently 1,025 ‘likes'). Over 100 singing-survivors participated in the first plenary rehearsal. All commercial venues have donated their meeting rooms gratis. Internationally there is one participating centre in Brisbane, Australia, with others signalling their intention to join in 2013 including: Memorial Sloan Kettering Cancer Center, New York; 14 breast cancer support centres in UK; and one centre in the Czech Republic (updated at meeting). STSA members are particularly keen on establishing links with other cancer patients abroad. Professional musicians are pledging support and suggesting fund-raising collaborations. Conclusions: Cancer survivors continue to need ongoing support and find the music therapy and group therapy provided by STSA most beneficial. Cancer survivors are very interested in supporting cancer research. STSA has the potential to become a major international cancer support network and cancer research foundation.
Denosumab for the treatment of bisphosphonate-refractory hypercalcemia of malignancy (HCM).
Authors: Hu Mimi I-Nan , Glezerman Ilya , Leboulleux Sophie , Insogna Karl L. , Gucalp Rasim A. , Misiorowski Waldemar , Yu Bennett Winston , Zorsky Paul , Tosi Diego , Bessudo Alberto , Jaccard Arnaud , Tonini Giuseppe , Wang Huei , Braun Ada , Jain Rajul K. 
Published: March 2020

e20512 Background: HCM, caused primarily by tumor-induced bone resorption, is treated with intravenous (IV) bisphosphonates (BisP), but patients (pts) can relapse or become refractory. Denosumab binds to RANK ligand (RANKL) to inhibit osteoclast-mediated bone resorption. Methods: In this single-arm, open-label, proof-of-concept study, pts with HCM (corrected serum calcium [CSC] >12.5 mg/dL [CTCAE grade ≥3]) despite IV BisP treatment ≥7 and ≤30 days before screening received subcutaneous denosumab 120 mg on days 1, 8, 15, and 28, then every 4 weeks. The primary endpoint was the proportion of pts with CSC ≤11.5 mg/dL (CTCAE grade ≤1) within 10 days of denosumab initiation. Results: The study enrolled33 pts (64% men; mean age 60 years; 76% with advanced solid tumors, 39% with bone metastases [BM]), with a median (25th, 75th percentile [Q1, Q3]) follow-up of 56 (18, 79) days. Median (Q1, Q3) baseline CSC was 13.7 (13.2, 14.2) mg/dL; 19 pts (58%) had HCM symptoms. Median (Q1, Q3) time from last BisP treatment to first dose was 17 (13, 22) days. At day 10, 21 pts (64%) reached CSC ≤11.5 mg/dL, including 54% of pts with BM and 70% without BM. Over the course of the study, 23 pts (70%) reached CSC ≤11.5 mg/dL, by a median (95% confidence interval [CI]) of 9 (5–19) days. A complete response (CSC ≤10.8 mg/dL, as defined by previous studies) occurred in 12 pts (36%) at day 10, and in 21 pts (64%) during the study, by a median (95% CI) of 23 (11–43) days. Among pts who reached CSC ≤11.5 mg/dL, the median (95% CI) duration of response was 104 (9–not estimable) days. The most frequently reported serious adverse events were worsening of HCM (5 pts, 15%) and dyspnea (3 pts, 9%). Two pts had isolated episodes of CSC levels ≤8.0 mg/dL (CTCAE grade 2); no pts had CSC <7.0 mg/dL (grade 3). No osteonecrosis of the jaw was reported. Conclusions: In this study of pts with HCM despite recent IV BisP treatment, denosumab effectively lowered serum calcium to grade ≤1 in 64% of pts within 10 days, and induced durable responses. These findings are particularly meaningful given that pts entered this study with grade ≥3 HCM within a median 17 days after receiving IV BisP. No unexpected safety findings were identified. Denosumab may offer a new treatment option for HCM in these pts. Clinical trial information: NCT00896454.
Follow-up study of a randomized clinical trial with quality of life diagnosis and therapy: Long-term quality of life of breast cancer survivors.
Authors: Klinkhammer-Schalke Monika , Lindberg Patricia , Steinger Brunhilde , Koller Michael , Wyatt Jeremy , Hofstädter Ferdinand , Lorenz Wilfried 
Published: March 2020

e20517 Background: To improve breast cancer patients` quality of life (QoL) as second relevant outcome of care, a clinical pathway with diagnosis and therapy of diseased QoL has been developed, implemented and tested in a randomized trial (RCT) as part of a complex intervention. More than 6 years after RCT, long-term QoL of survivors was assessed and separately analyzed in 2 cohorts: QoL-intervention + guideline treatment in the first postoperative year (GC+) and guideline treatment alone (GC). Methods: Both cohorts were part of a randomized trial with 2 x 100 primary breast cancer patients, surgically treated between 2004 - 2006, with QoL measurement every 3 months during the first year (EORTC QLQ-C30, BR23). In GC+ cohort, QoL was presented to coordinating physicians in a QoL-profile, including recommendations for treatment of diseased QoL (cutoff <50 points on scale 0 = bad, 100 = good) in 10 dimensions (global QoL, physical, role, emotional, cognitive, social functioning, arm symptoms, body image, pain, fatigue) and up to 5 targeted therapies to improve QoL. GC was treated according to S3 guideline. At follow-up >6 years after diagnosis (range of months since surgery: GC+ 74-94; GC 74-96), rates of diseased QoL in both cohorts were analyzed and compared with QoL 12 months postoperatively. Results: Long-term QoL was assessed in 66 patients of GC+ (mean age 64.7 (±10.9)) and 67 of GC (mean age 63.7 (±10.9)) (death GC+=13, GC=18; response rate 79%). In GC+, 48% of patients reported at least 1 QoL deficit at 12 months compared with 52% at 6-year follow-up, while in GC rate of diseased QoL increased from 53% to 62%. Regarding single dimensions, in GC+ rates of diseased QoL increased from 12 months to 6 years (except global QoL), reaching significance for arm symptoms (9% vs 29%) and body image (3% vs 16%) (p<.01, McNemar`s test). In GC no dimension changed significantly, but rates of diseased QoL for arm symptoms (26% vs 31%) and body image (9% vs 17%) were already rather high at 12 months. Conclusions: Breast cancer patients need tailored QoL therapy, exceeding the first postoperative year. Similar to traditional medical care, QoL needs to be considered continuously by anchoring it in follow-up care.
Pharmacokinetics (PK), tolerability, and efficacy of APF530 in patients receiving moderately (MEC) and highly (HEC) emetogenic chemotherapy: Phase II trial results.
Authors: Gabrail Nashat Y. , Yanagihara Ronald H. , Cooper William , O'Boyle Erin , Smith Carrie L. , Spaczynski Marek 
Published: March 2020

e20518 Background: Up to 30% of patients continue to have chemotherapy-induced nausea and vomiting (CINV) despite use of antiemetics. APF530 is a sustained-release subcutaneous (SC) formulation of granisetron for preventing CINV. APF530 PK, tolerability, and efficacy were studied in two open-label, single-dose trials (1 US, 1 EU) in patients receiving MEC or HEC. Methods: In the US study, 45 patients received 250, 500, or 750 mg APF530 SC (5, 10, or 15 mg granisetron, respectively). In the EU study, 35 patients were randomized to 250 or 500 mg APF530 SC. Injections were given 30 to 60 minutes before single-day MEC or HEC. Plasma granisetron was measured from pre-dose to 168 hours. Safety, tolerability, and efficacy were also evaluated. Results: APF530 PK was dose proportional with slow absorption and elimination of granisetron after a single SC dose. Median tmax, exposure, and t1/2were similar for 250 and 500 mg APF530 in both trials, with no differences between MEC and HEC groups. Adverse events in both trials were as expected for granisetron; injection-site reactions (eg, erythema, induration), predominantly mild, were seen in ≤ 20% of patients. Complete responses (no emesis, no rescue medication) were obtained in ≥ 80% and ≥ 75% of patients in both trials with the 250- and 500-mg doses, respectively. Conclusions: APF530 showed dose-proportional PK and sustained concentrations of granisetron over 168 hours. The 250- and 500-mg doses were carried into phase III; both were well tolerated, and maintained therapeutic granisetron levels for ≥ 5 days. Clinical trial information: 2007-005068-29. [Table: see text]
Phase II randomized, placebo-controlled trial of phytotherapeutic product Catuama for breast cancer women undergoing adjuvant radiation therapy.
Authors: Cruz Felipe Melo , Cubero Daniel de Iracema Gomes , Santi Patricia Xavier , Landeiro Luciana Garcia , Tamashiro Andressa Sayuri , Ribeiro Larisse Soares , Del Giglio Auro 
Published: March 2020

e20524 Background: Fatigue and Depression are common in patients undergoing Breast Cancer (BC) treatment. Catuama is a registered phytotherapic that contains 4 brazilian herbs per capsule: Trichilia catigua (87.5mg), Ptychopetalum olacoides (87.5mg), Paullinia cupana (125 mg) and Zingiber officinale (10mg). Objectives: Since one of its constituents is Guarana (Paulinia cupana) which we already reported to have anti-fatigue effects, we decided to test Catuama potential anti-fatigue effects in BC women undergoing adjuvant 4 weeks of Radiation Therapy (RxT). Methods: This is a double blinded, randomized, placebo-controlled, Phase II cross-over trial. Patients with histologically proven BC with the indication of adjuvant RxT, non-pregnant nor breastfeeding, older than 18 years of age, with ECOG PS 0 or 1, without a history of cardiac, renal, hepatic or psychiatric decompensation, received Catuama 1 capsule twice daily versus a matching placebo for the first 2 weeks of RxT treatment, followed by a week of wash out, followed by an additional two weeks of treatment with crossover of experimental arms. Patients were evaluated on days 1, 15 and 36 with the Brief Fatigue Inventory (BFI), Hospital Anxiety and Depression Scale (HADS), Quality of Life FACIT-F, FACIT-ES questionnaires, and Chalder Fatigue scale. Results: We enrolled 90 patients with a median age of 53 years (26 – 80). We saw no statistically significant differences of FACIT ES, FACIT F, HADS, Chalder or BFI scores treated with Catuama or Placebo when we considered all included patients. When we selected only patients with a BFI score above 30, Catuama significantly decreased BFI scores as compared to baseline (p<0.0001). We observed one instance of grade 3 hypermagnesemia in the Catuama arm and one patient had hyperglicemia grade 3 both in the Catuama and in the placebo arm. No grade 4 toxicities were seen. Conclusions: Catuama may help selected patients who already start RxT with evidence of fatigue.