bluuebunny/crossref_metadata_2025 huggingface dataset:
C-kit, B-raf, and N-ras mutations in melanoma subtypes.
Authors: Pracht Marc , Mogha Ariane , Fautrel Alain , Lespagnol Alexandra , Mouchet Nicolas , Le Gall Francois , Oger Emmanuel , Galibert Marie-Dominique , Lesimple Thierry
Published: March 2020

e19037

Background: The recent understanding of melanomas’ molecular pathways improved their classification and clinical strategies. Initial studies showed that B-Raf/N-Ras mutations (respectively V600E and Q61) are the most frequent alterations being present in 70 to 80% of melanomas, characterizing non Chronic Sun-induced Damage skins (CSD). These include Superficial Spreading Melanomas (SSM) and Nodular Melanomas (NM). Other studies showed that c-Kit mutations are present at low rate (20-40%) in Acro-Lentiginous Melanomas (ALM), Mucous Melanomas (MM) and in melanomas arising on CSD skins. C-kit mutation pattern is complex with four exons being affected leading to numerous mutations. Because c-Kit targeted therapy is a critical clinical issue, we aimed to identify the most frequent mutations to propose appropriate screening test and adapted therapy. Methods: 186 melanoma samples corresponding to an homogeneous white-caucasian population (Brittany, France) were screened. c-Kit exons 11, 13,17 and 18 were sequenced, c-Kit copy number was quantified by q-PCR and level of c-Kit determined by immunohistochemistry (CD117). Samples were also analyzed for B-Raf mutations (codon 464, 466, 469, 600) and for N-Ras mutations (codon 12, 13, 61) by pyrosequencing. Results: Detectedmutations are shown in the table. Uveal melanomas (n=13) were never mutated. These mutations were never overlaped and comparable profiles were obtained between the primary tumour, nodes or metastatic lesions from a same patient. Conclusions: C-Kit mutations are much less common than in other previously described populations especially for MM or ALM. B-Raf/N-Ras mutations appeared also less frequent than waited in non-CSD , reaching 46% in SSM. Interestingly our population presents a high incidence of N-Ras mutations, especially in SSM and NM. Screening of B-Raf/N-Ras mutations is fundamental not only for SSM but also for NM, CSD and ALM for prescribing targeted therapies such as MEK-inhibitors. [Table: see text]
Clinical behavior and prognosis of lymph-nodal Merkel cell carcinoma (MCC) in the absence of a primary tumor.
Authors: Albertelli Manuela , Faggiano Antongiulio , Grimaldi Franco , Ameri Pietro , Palmieri Giovannella , Scarpelli Giovanni , Federico Piera , Bellevicine Claudio , Troncone Giancarlo , Grillo Federica , Minuto Francesco , Crino Lucio , Colao Annamaria , Ferone Diego , Ferolla Piero
Published: March 2020

e19038

Background: MCC is a rare cutaneous neuroendocrine neoplasm characterized by an aggressive behavior and a high recurrence rate, generally associated with poor prognosis. Nodal and distant metastases are frequent. Aim of this study was to report histological, clinical and prognostic features of a series of 12 patients with nodal MCC in the lack of evidence of a primary. Methods: The cases were collected from a multicentric database: mean age at diagnosis was 67 years; F:M ratio was 1:1.4; mean follow up was 54 months (8-108). Involved nodal sites were: inguinal (9) and axillar (3). All cases had typical MCC immunoprofile: neuroendocrine (CgA, NSE, Syn) and epithelial (CK 20 dot-like) marker positivity. Complete and extensive clinical, dermatologic, radiologic and endoscopic work-up was performed. All patients underwent surgical excision; in one case chemotherapy, in another case biotherapy and in one further case radiotherapy was administered. Results: All cases were in stage III of disease, according to AJCC. All patients were alive without recurrence at the time of the study. The overall mean survival was 52 months. The 4-yr survival was 100%. Conclusions: In patients with nodal metastases of MCC in the absence of a primary lesion, survival seems to be more similar to stage I rather than stage III, since 4-yr survival is reported about 60% for stage III disease in MCC. This finding must still be completely explained. Regression of a small skin primary with nodal metastases or alternatively a primary nodal MCC might be hypothesized. In conclusion, the unknown primary nodal metastatic skin MCC seems to be associated with a more favorable prognosis.
Preferential enrichment of myeloid-derived suppressor cell subsets in patients with metastatic melanoma.
Authors: Meyer Christiane , Cagnon Laurene , Montandon Nicole , Berthod Grégoire , Leyvraz Loredana , Michielin Olivier , Romano Emanuela , Speiser Daniel E
Published: March 2020

e19050

Background: Myeloid derived suppressor cells (MDSC) are key immunosuppressive cells enriched in peripheral blood during chronic inflammation. While these cells have been extensively studied in mice, their human counterparts are less well characterized. Several MDSC populations have been identified in cancer patients, depending on tumor type and experimental settings. MDSC include immature macrophages, granulocytes and dendritic cells, at different degree of maturation, from immature CD33+, to mature CD14+ and CD15+HLA-DR- cells. The goal of this study was to characterize myeloid cells in melanoma patients compared with healthy donors (HD) to identify inflammation-mediated alterations involved in melanoma progression. Methods: PBMC were isolated by Lymphoprep gradient centrifugation from fresh blood samples of patients with malignant melanoma. We performed 9-color FACS staining of the freshly isolated cells. Results: CD15+ granulocytic MDSC are enriched in the mononuclear cell layer after gradient centrifugation, together with the CD14+ monocytic MDSCs. They display significantly different sedimentation abilities compared with neutrophils. Furthermore, CD14 and CD15 were partially co-expressed by the monocytic and granulocytic MDSC subsets, respectively. Our data show that CD14+HLA-DR- monocytic and CD15+HLA-DR- granulocytic MDSC were significantly enriched in peripheral blood of metastatic melanoma patients, regardless of whether or not they received any prior therapy for metastatic melanoma. The more immature CD33+CD11b- subset was found at significantly lower frequencies in melanoma patients compared with HD. We found a trend for accumulation of non-classical CD14+CD16+ monocytes. However, the increased percentages did not differ significantly from HD. The frequencies of classical CD14+CD16- monocytes were unchanged. Conclusions: Melanoma is associated with increased frequencies of CD14+ monocytic and CD15+ granulocytic MDSC, and decreased frequencies of the more immature CD33+CD11b- cells. This finding demonstrates tumor-mediated changes in the composition of myeloid cells, which could influence response to treatment and clinical behavior of the disease.
Mechanism of action of ingenol mebutate gel in reconstructed human skin assessed by transcriptomics.
Authors: Zibert John Robert , Hoeyer-Hansen Maria Helena , Eriksson Andre Huss , Loevendorf Marianne Begtson , Matthews Josselyn , Litman Thomas
Published: March 2020

e19056

Background: Ingenol mebutate (IM) gel topical applied once daily for 2-3 consecutive days, has recently been approved by FDA in treating actinic keratoses (AK), as a safe, tolerable and effective treatment. IM, a highly active biological diterpene ester, has shown in vitro and in vivo to induce a dual mechanism of action characterized by, first, cell death induced at high micromolar concentrations and, second, a protein kinase C dependent immune activation in the nanomolar range. The aim of this study was to investigate the mechanism of action of IM in reconstructed human skin (RHS). Methods: IM 0.05% gel or vehicle was applied topically to RHS (EpiDermFT) and normal pigskin and IM concentrations were measured after 2 and 24 hrs. In RHS, biopsies were obtained 1, 6 and 24 hrs after treatment and global transcriptomic profiling (Affymetrix HG 1.0 ST) was assessed. The analysis included transcription factor binding site (TFBS) and gene set enrichment analysis (GSEA). Results: We compared IM’s penetration through normal skin to RHS and found a 10-fold higher permeability in RHS, which likely models the increased permeability of AK lesions. Consequently we further investigated IM’s effects on RHS. Based on GSEA, we identified the major effects of IM to comprise: cell death, inflammation and wound healing responses, indicated by differential expression of e.g. caspases, DAPK1, chemokine ligands, HAS2, MMPs, SERPINs, ILs (and their receptors). A TFBS analysis identified E2F regulated genes as overrepresented, albeit in opposite directions in dermis (up-regulated) compared to epidermis (down-regulated). IM transiently activates PKC, and via this activation causes transcriptional silencing of E2F-responsive genes. The differential effect on dermis and epidermis could be due to different levels of PKC isoforms in the different skin layers. Indeed, a specific, inflammatory response was observed and several genes, including MMP10 and IL1R2, displayed a time-dependent increase in expression, reaching a maximum at 24h. Conclusions: In conclusion, IM displays pleiotropic effects, of which many are identified on a transcriptional level. Our data suggest involvement of in particular PKC, ERK2, and E2F regulated genes.
Performance status of patients with advanced melanoma over time in routine clinical practice.
Authors: Sadetsky Natalia , Zhao Zhongyun , Barber Beth , Wagner Volker Jean
Published: March 2020

e19060

Background: Measurements of Eastern Cooperative Oncology Group Performance Status (ECOG-PS) are widely used to assess disease progression, determine appropriate treatment and prognosis; however, ECOG-PS over time in routine clinical practice is rarely published. This study examined ECOG-PS in patients with stage III and IV melanoma during 1-year from diagnosis in community oncology clinics. Methods: Electronic medical records from 47 oncology clinics across the US were used for this analysis. Patients who had melanoma diagnosis, stage information, and ECOG-PS scores were included. Patient clinical, demographic, and treatment characteristics were described. ECOG-PS at diagnosis of stage III and IV melanoma and at every three months were analyzed. Mixed model analysis was undertaken to examine changes in ECOG-PS over time. Results: A total of 266 patients (102 stage III and 164 stage IV) were included in this study. At baseline, stage IV patients had significantly worse mean ECOG-PS scores than stage III patients (0.79 versus 0.35, p=0.001). In patients with both baseline and at least one post-diagnosis assessment (84 and 110 patients with stage III and IV, respectively), mixed model estimated mean ECOG-PS scores changed from 0.69 at baseline to 1.14 at 1-year for stage IV patients and were relatively stable for stage III patients (0.47 (baseline) and 0.54 (1-year)). There were 25 stage III and 43 stage IV patients who received drug treatments for melanoma. The majority of stage III patients (84%) received Interferon only; while 44.2% of stage IV patients received carboplatin+paclitaxel, 32.6% dacarbazine, and 11.6 % cisplatin. Among drug treated patients with stage IV, worsening ECOG-PS over time (from 0.87 at baseline to 1.14 at one year) was observed. Conclusions: In patients with advanced melanoma treated in community oncology practices, worse ECOG-PS scores and faster deterioration were observed for patients diagnosed with stage IV compared to stage III. Even in patients treated with systemic therapies, worsening ECOG-PS was also observed over time.
Assessing the value of an optional radiation oncology clinical rotation during the core clerkships in medical school.
Authors: Zaorsky Nicholas George , Malatesta Theresa Maria , Den Robert Benjamin , Wuthrick Evan John , Werner-Wasik Maria , Shi Wenyin , Ahn Peter H. , Dicker Adam , Anne Pramila R. , Bar-Ad Voichita , Showalter Timothy Norman
Published: March 2020

e19507

Background: Few medical students are given proper clinical training in oncology, much less radiation oncology. We evaluate the value of adding a radiation oncology clinical rotation to the medical school curriculum. Methods: In July 2010, Jefferson Medical College offered a 3-week radiation oncology elective rotation for third-year medical students during the core surgical clerkship. During 2010-2012, 52 students chose to enroll in this rotation. The rotation included outpatient clinics, inpatient consults, didactic sessions, and case-based presentations by the students. Tests of students’ knowledge of radiation oncology were administered anonymously before and after the rotation to evaluate the educational effectiveness of the rotation. Students and radiation oncology faculty were given surveys to assess feedback about the rotation. Results: The students’ pre-rotation test scores had an average of 64% (95% confidence interval [CI]: 61%, 66%), which improved after the rotation to 82% (95% CI: 80%, 83%; 18% absolute improvement). In exam question analysis, scores improved in clinical oncology from 63% to 79%, in radiobiology from 70% to 77%, and in medical physics from 62% to 88%. Improvements in all sections but radiobiology were statistically significant. Students rated the usefulness of the rotation as 8.1 (scale 1-9, 95% CI: 7.3, 9.0), their understanding of radiation oncology as a result of the rotation as 8.8 (95% CI: 8.5, 9.1), and their recommendation of the rotation to a classmate as 8.2 (95% CI: 7.6, 9.0). Radiation oncology faculty rated their belief that this rotation would be valuable to students as 8.2 (scale 1-9), that students had appropriate responsibilities in the clinic as 7.9, and that the lectures and meetings that students attended were at an appropriate level as 8.1. Conclusions: Integrating a radiation oncology clinical rotation into the medical school curriculum improves student knowledge of radiation oncology, including aspects of clinical oncology, radiobiology, and medical physics. The rotation is appreciated by both students and faculty. We recommend including exposure to radiation oncology as part of the core clinical curriculum for all medical students.
Cancer patients in the hospital damaged by the Japan earthquake and tsunami.
Authors: Morikawa Naoto , Yanagisawa Satoru , Iwasashi Hajime , Tabata Toshiharu , ABE Tatsuya , Nakamura Ryuji , Tabayashi Koichi
Published: March 2020

e19508

Background: On March 11, the Great East Japan Earthquake hit the Sendai City. Water supplies and electric facilities were damaged seriously in many establishments, and our hospital was no exception. Because our hospital wards itself were also in the danger of collapsing, whole the oncologic patients were to be discharged. We investigated what became of the patients with cancer after the earthquake. Methods: We extracted the medical records of the patients with cancer, who were hospitalized when an earthquake occurred. Then, we retrospectively analyzed the destinations after the discharge and prognosis of each patient. Results: Among the 400 patients admitted, there stayed 75 patients with cancer, on March 11. Of these, the 75 patients were discharged to their home later, and the 48 patients were transferred to the other hospitals. The remaining four patients died in the hospital, all of which were due to their primary cancer. The earthquake did not cause any death. Although, most of the patients with cancer were relatively in good physical condition, their discharge to the home did not go on smoothly. Some patients could not make any contacts with their families, and others lost their houses because of the earthquake or resultant tsunami, all of which prevented them to return home. Public networks such as Disaster Medical Assistance Team (DMAT) did not have use for coordinating where the patients should be transferred, because they gave the first priority to the acutely-ill patients, such as trauma patients. Transfer to another hospitals largely depended on the personal networking between each physicians. Conclusions: On the face of the national disasters, the current emergency care system must prioritize the acutely-ill patients, sometimes at the sacrifice of chronically-ill patients such as oncologic patients. It seems necessary to create the medical cooperation system for the patients with cancer.
Active combination with aprepitant, palonosetron, and dexamethasone for preventing emesis of anthracycline-containing regimens in patients with breast cancer.
Authors: Nakayama Yoshie , Ito Yoshinori , Takahashi Shunji , Hatake Kiyohiko
Published: March 2020

e19512

Background: Anthracycline and cyclophoshamaide containing regimens for breast cancer are classified as highly emetogenic chemotherapy. Aprepitant (A), palonosetron (P), granisetron (G) or dexamethasone(D) are recommended as antiemetic drugs. However, it is uncertain which combination would be best effective. We have retrospectively examined the efficacy of these antiemetic drugs. Methods: We reviewed the medical records of 501 patients with breast cancer treated with anthracycline and cyclophoshamaide containing regimens between August, 2009 and September, 2010. The combination of GD were G: 3 mg on day1 (i.v.), 2 mg on days 2-6 (p.o.) and D: 16.5 mg on day1 (i.v.), 8mg on days 2-4 (p.o.). The AGD were A: 125 mg on day1 (i.v.), 80 mg on days 2-3 (p.o.), G: 3 mg on day1 (i.v.), 2 mg on days 2-6 (p.o.), and D: 13.2 mg on day1 (i.v.), 4 mg on days 2-4 (p.o.). The APD were A: 125 mg on day1 (i.v.), 80 mg on days 2-3 (p.o.), P: 0.75 mg on day1 ( i.v.), and D: 13.2 mg on day1 (i.v.), 4 mg on days 2-4 (p.o.). Results: The number of patients who were treated with GD, AGD, and APD were 170, 159, and 172, respectively. Complete response (CR) rate in acute phase (0-24h) or delayed phase (24-120h) and complete control (CC) rate in acute or delayed phase in each regimens were summarized in the table. AGD or APD was significantly superior to GD in CR rate of acute or delayed phase (P<0.01). Of note, CC rate of APD in acute phase was significantly superior to AGD (P<0.01). AGD or APD was significantly superior to GD in CC rate in delayed phase. Conclusions: The combination with APD was the most effective antiemetic therapy in patients who were treated with anthracycline and cyclophosphamide containing regimens. [Table: see text]
Health resource utilization and patient burden associated with SREs in a randomized controlled trial setting.
Authors: Body Jean-Jacques , Von Moos Roger , Saad Fred , Richardson Gary Edward , Brown Janet Elizabeth , Lipton Allan , Fizazi Karim , Ying Wendy , Goessl Carsten Dietrich , Richhariya Akshara
Published: March 2020

e19514

Background: Bone metastases (BM) are common in patients (pts) with solid tumors and may result in skeletal related events (SREs) such as spinal cord compression (SCC), pathologic fracture (PF), surgery to bone (SB), and radiation to bone (RT). SREs result in significant morbidity, debilitating pain, decreased health-related quality of life and increased health resource utilization (HRU). Data from 3 registrational phase 3 trials that showed superiority of denosumab over zoledronic acid in patients with solid tumors and BM were combined to assess HRU associated with different SRE types. Methods: Data through 41 weeks for pts with solid tumors and ≥ 1 BM enrolled in these randomized, active-controlled trials were included in this posthoc analysis. HRU were evaluated by SRE type and data were compared between pts with ≥ 1 on-study SRE and those not experiencing an on-study SRE. The index date for pts with on-study SREs was defined as the date that the first SRE was reported. The median time from randomization to incidence of first SRE for each SRE type was used to establish an index date for the control (no SRE) group. The HRU window encompassed a 3-month period (i.e.1 month before and 2 months after the index date) and was assessed by mean number of various types of medical visits during this window. Results: Data from 5,543 pts were included. PF was the most common type of first SRE (n=1,017), followed by RT (n=940), SCC (n=156), and SB (n=74). 3,618 pts did not have an on-study SRE. For all types of medical visits, HRU was higher for pts with an on-study SRE than those without (Table). Conclusions: SREs are associated with increased health resource utilization, reflecting an increased burden for patients with solid tumors and bone metastases. [Table: see text]
Perception and reaction of cancer patients to the diagnosis of cancer and their attitude towards disclosure of diagnosis: Local perspective from Saudi Arabia.
Authors: Aljubran Ali Husain , Kandasamy Ravichandran , Al-Dalee Abdelmuniem
Published: March 2020

e19524

Background: Understanding the attitudes of cancer patients towards different cancer related issues is important for care delivery. However, in Saudi, there is yet no clear knowledge about the patient’s perception of cancer diagnosis or preferences regarding the disclosure of information. This study explored that area. Methods: The subjects were adult cancer patients who attended the outpatient clinics at King Faisal cancer center in Riyadh, Saudi Arabia. They completed a validated questionnaire of six sections. In this abstract, we present the data of the first three sections: The first section is about the sociodemographic characteristics, the second explores the patient’s perception and reaction to the diagnosis, and the third enquires about the patient’s preference regarding the disclosure of diagnosis. Estimated sample size: 225. Results: 234 patients participated. Age range: 15-86, median: 40.5 y. Males: 61.5%. 12.4% from suburban areas. 41.5% had higher than high school education. 76% had annual income < $32,000. Regarding of what they thought to be the cause of their cancers, 42.4% thought that someone’s envy or eye of evil was the cause, and 11.7% thought it was environmental, while 44.2% could not attribute to any cause. About the disclosure of diagnosis, 34.5% were not the first to know about the diagnosis. However, 78% thought that no one should know about the diagnosis before the patient, but 33.5% agreed that family may know at the same time. For decision making, 40% wanted to take decision by themselves, while 52.4% wanted the family to participate in making decisions. Conclusions: In contrast to the public attitude regarding the disclosure of diagnosis, this study shows that majority of cancer patients believed that no one should know about the diagnosis before themselves. This result will help the current national debate. Also, it shows large proportion of patients believe of a metaphysical etiology for their diseases, which may affect their choices and directions. A similar study in the community is recommended to include patients who do not seek conventional treatments.
Coping with the burden of taste alteration, a toxicity of taxane-based chemotherapy.
Authors: Speck Rebecca M , DeMichele Angela , Farrar John T , Hennessy Sean , Mao Jun , Stineman Margaret G , Barg Frances K
Published: March 2020

e19531

Background: Taste alteration is a poorly recognized toxicity of chemotherapy, with limited research. This study examined the experience of taste alteration in female breast cancer patients treated with taxane chemotherapy. We explored the self-management coping strategies utilized by patients. Methods: A purposive sample of 25 patients currently receiving docetaxel or paclitaxel or within six months of having completed treatment was recruited. This exploratory, descriptive study utilized semi-structured interviews and patient-level data from the electronic medical record. Interview data were analyzed with the constant comparative method. Descriptive statistics were used for patient-level data. Results: Participants were 24-60 years of age, mean 46. Ten patients received docetaxel and 15 received paclitaxel. Of all side effects reported from taxanes, the most common was taste alteration (7 (70%) docetaxel patients, 3 (20%) paclitaxel patients). Taste alteration was described as a metallic taste, bad taste, weird taste, or lack of taste. Taste alteration affected normal or routine behaviors in that they chose not to eat as much, ate on an irregular schedule, and lost interest in preparing meals for themselves and/or their family. Women adopted new behaviors to deal with the taste alteration and its effect, including the use of plastic silverware, eating strongly flavored foods, honoring specific food cravings, eating candy before meals, cutting food with lemon, drinking sweetened drinks, drinking from a straw, brushing their teeth and tongue before meals, and using baking soda and salt or antibacterial mouthwash. The majority (59%) of patients gained weight during taxane treatment (mean = 2.7 lbs; range = 1-12.5 lbs). There was insufficient power to detect a difference in weight gain by taste alteration status. Conclusions: Taste alteration affects breast cancer patients’ normal routine, but they develop management strategies to deal with the effect. However, given the association of obesity with poor treatment outcomes, the potential for increased caloric consumption associated with some coping strategies is cause for concern, and further studies are warranted for the development of appropriate interventions.
An evaluation of the drug interaction potential of netupitant with substrates, inhibitor and inducer of CYP3A4.
Authors: Kammerer Klaus Peter , Rossi Giorgia , Calcagnile Selma , Timmer Wolfgang
Published: March 2020

e19533

Background: Neurokinin-1 receptor antagonist (NK1 RA) is commonly administered in combination with a 5-HT3 RA such as palonosetron (PALO) to prevent the stimulus of nausea and vomiting caused by emetogenic chemotherapy. Netupitant (NETU), a new NK1 RA under evaluation for its antiemetic efficacy and tolerability, is both a substrate for and a competitive inhibitor of CYP3A4. Two studies were designed to determine the potential risk for drug-drug interaction in clinical practice. In the first study, the effects of NETU on the metabolism of two representative CYP3A4 substrates, erythromycin (ERY) and midazolam (MID) were determined. In the second study, a CYP3A4 inhibitor, ketoconazole (KETO), or an inducer, rifampicin (RIF) was coadministered with a fixed dose combination of NETU/PALO to observe the potential effects on NETU and PALO metabolism. Methods: Serial blood samples were collected from healthy volunteers and pharmacokinetic (PK) parameters were determined in both studies. The first trial was a 3-period crossover performed in 20 subjects receiving NETU (300 mg), ERY (500 mg) or MID (7.5 mg). The second trial was a 2-way crossover in 36 subjects receiving a single dose of NETU/PALO (300 mg/0.5mg, Day 1) administered as a fixed dose combination and KETO (400 mg QD, from Day-2 to Day 10) or RIF (600 mg QD from Day -7 to Day 10). Results: NETU, by inhibiting the CYP3A4, increased Cmax and AUC parameters by 40% and 130%, respectively, when administered with MID and by 30% when administered with ERY. KETO increased NETU AUC by 140% and Cmax by 25%, while RIF decreased NETU AUC by 83% and Cmax by 62%. A decrease of 19% was observed in PALO AUC when administered with RIF, while KETO had no relevant effect on PALO PK. Conclusions: The results of these studies suggest that the coadministration of NETU with drugs that are substrates, inhibitors, or inducers of the CYP3A4 enzymes, may require dose adjustments. These results are in line with pharmacokinetic data of aprepitant, the only commercially available NK1 RA. The effect of RIF on PALO is not considered clinically relevant. Treatments were well tolerated in all studies.
Relationship between time to onset of relief and total pain relief of breakthrough pain in patients with cancer using fentanyl pectin nasal spray.
Authors: Conroy John D. , Torres Luis M. , Revnic Julia , Tayi Ravi , Perelman Michael Sidney , Knight Alastair D.
Published: March 2020

e19544

Background: Breakthrough pain in cancer (BTPc) is typified by a rapid onset of severe pain with a limited duration. Treatment for BTPc requires rapid onset of pain relief. The main purpose of this analysis was to assess the relationship between time to onset of pain relief and overall pain relief in patients treating BTPc with fentanyl pectin nasal spray (FPNS, Lazanda, PecFent). Methods: Data were pooled from FPNS-treated episodes of 2 randomized, double-blind, crossover studies assessing efficacy of FPNS in adults who experienced BTPc despite background pain that was adequately controlled with at least 60 mg/day morphine (or equivalent). Patients initially entered a dose-titration phase to establish dose of FPNS (100 to 800 mcg) to be used during the treatment phase of each study. Pain intensity (PI) was assessed at baseline and scheduled time points on an 11-point scale (0=no pain, 10=worst possible pain). This analysis assessed the relationship of time to onset of pain relief (≥1 point reduction in PI from baseline) to total pain relief (Summed Pain Intensity Difference [SPID] at 30 and 60 min postdose [SPID30 and SPID60]) by ANOVA. Responses are also provided for the placebo-treated episodes during the placebo-controlled trial. Results: There were 831 episodes of BTPc that were treated with FPNS. Mean SPID was highest when pain relief was earliest (p<0.001). When PI difference (PID) ≥1 was attained by 5, 10, and 15 min postdose, mean (SD) SPID30 scores were 13.1 (6.7), 7.6 (4.0), and 3.5 (1.8). In the placebo-controlled trial, a similar overall response (p<0.001) was observed during the 200 placebo-treated episodes: among those attaining PID ≥1 by 5, 10, and 15 min postdose, SPID30 was 12.2 (7.0), 5.3 (3.3), and 2.5 (1.0), respectively. Similarly, significant differences were observed for SPID60 with both treatments. Conclusions: Earlier time to onset of pain intensity reduction in BTPc treatment resulted in higher SPID at 30 and 60 minutes postdose of FPNS and placebo. Results suggest that early onset of relief may be associated with a greater overall degree of relief for episodes of BTPc, which emphasizes the need for rapid-acting agents in the management of breakthrough pain.
Correlation between low-dose cyclophosphamide-induced hyponatraemia and the use of aprepitant.
Authors: Tono Yasutaka , Mizuno Toshiro , Saito Kanako , Tamaru Satoshi , Yamashita Yoshiki , Oda Hiroyasu , Kageyama Shinichi , Katayama Naoyuki
Published: March 2020

e19546

Background: For prevention of nausea/vomiting during anthracyline/cyclophosphamide (CPA) therapy for breast cancer, use of aprepitant (AP) combined with serotonin antagonist and dexamethasone is recommended. It has been reported that AP does not influence AUC’s of 4-hydro-cyclophosphamide, an active metabolite of CPA, and DCE, a CPA-metabolite causing nephrotoxicity. Although, in the previous clinical reports for anthracyline/CPA, the toxicities were not significant in patients who were given AP, compared to those without AP, we have experienced several cases of severe hyponatremia probably caused by AP. Occurrence of hyponatremia during chemotherapy might be an issue to be cautious. Methods: We investigated serum levels of Na in 67 breast cancer patients who received CPA-combined therapy with the use of AP, or not. They all received 600mg/m2 of CPA combined with either of doxorubicine, epirubicin, or docetaxel. Their prior electrolytes were to be within normal range. In the first cycle, we evaluated serum Na levels before the CPA start and those of 24 hours after. We defined a serum Na level lower than 135 mEq/L as “hyponatremia”. Results: The background between the two groups, with AP and without AP, were comparable, in whom the prior Na levels were 140.0 ±1.97 mEq/L, and 140.1 ±1.88 mEq/L, in the AP- and in non-AP-group, respectively. The chemotherapies including CPA, the clinical stages, the uses of serotonin-receptor antagonist and dexamethasone were comparable between the two groups. Hyponatremia occurred in 11 patients out of 42 (26.2%) in AP-group, whereas 2 patients in 25 (8.0%) in non-AP-group. Since the rate in non-AP-group was comparable to the previous reports, hyponetremia seemed to occur frequently in AP-group. The average Na level at 24 hours after chemotherapy was 136.429 ±3.94 mEq/L in AP-group, and 138.68 ±3.05 mEq/L in non-AP-group, respectively. Among 11 patients who developed hyponateremia, they were resolved within 48 hours without any treatments in 10 patients, and only one needed Na replacement. The patient did not develop hyponatremia without using AP in the third cycle. Conclusions: According to our cohort study, AP might frequently cause hyponatremia in the CPA-combined chemotherapy.
Celiac plexus block in patients with nonpancreatic GI malignancies: Experience from a single institution.
Authors: Patel Shejal B , Shaw James Edward
Published: March 2020

e19551

Background: Celiac plexus block (CPB) has been well described in the treatment of pancreatic cancer pain. A recent Cochrane Library review of the subject concluded that CPB often resulted in fewer adverse effects when compared to chronic opioid use. CPB has not been well described in non-pancreatic GI malignancies. This study sought to determine the effectiveness of CPB in non-pancreatic GI malignancies. Methods: The Virginia Commonwealth University Massey Cancer Center database was queried for all patients who had undergone celiac plexus block, 2001-2010, using specific CPT billing codes. In addition, VCU Radiology Department records were also examined. Diagnosis, physician assessment of effectiveness, pre and post procedure pain scores, complications of procedure, and pain medication dosage pre and post procedure were all assessed. Results: 68 total patients were identified. 12 patients underwent a CPB for non-pancreatic GI malignancies and 56 for pancreatic cancer patients. The most common non-pancreatic GI malignancies were colorectal cancer (50%), hepatocellular carcinoma (8%), carcinoid (8%), duodenal cancer (8%), and gastric cancer (8%). By study criteria, 7 of the 12 patients had sufficient data for exploratory analysis. By physician assessment, CPB resulted in pain relief in 5 (71%) of 7 patients. Furthermore, the post procedure pain score improved but the usage of pain medications did not change. By comparison, 26 of 56 patients with pancreatic CA had sufficient data and 15(58%) has pain relief by physician assessment. Conclusions: CPB appears to provide some pain relief for patients with non-pancreatic GI malignancies. However, the retrospective design revealed missing data including: pre and post procedure pain scores, complications of procedure and patient assessments of pain. A prospective study is being considered.
Use of complementary medicines by patients treated with chemotherapy: Survey in a French day care unit.
Authors: Fort Pauline , Marsault Blandine , Hertzog Antoine , Dubost Emilie , Tourani Jean-Marc , Princet Isabelle
Published: March 2020

e19555

Background: Nowadays, communication about alternative medicines and biologic therapies is very intense. Anyone can find information, more or less scientific, on internet, television or magazines. Therefore, patients treated with chemotherapy may use many complementary medicines. The purpose of our study is to do a summary of the use of those alternative therapies by our patients in order to evaluate the potential risk of interference with their antitumor treatment. Methods: We carried out a prospective study among patients in the day care unit. During an interview, they were asking for any biological treatment or non-drug alternative medicine used concurrently with the chemotherapy. We found out: antitumor agent, complementary and alternative medicine used, aim of this use (prevention, antitumor action, wellbeing), means of access, person who advised them. Results: 100 patients were interviewed (average = 63 years old, half-and-half men and women). 38% used complementary and alternative medicines: 45% of whom used homeopathy, 39% food supplements, 37% herbal medicine, 29% non-drug alternative medicine (acupuncture, magnetic healer, meditation…). 29% of them associate more than 3 medicines. 61% of patients using herbal medicine, heard about it by word of mouth (friends and family); and 75% buy it by internet or by phone. Most of them are looking for wellbeing. 31% of patients using food supplements, looking for well being too, learnt it by word of mouth; 48% buy it in pharmacy, 40% on internet or by phone. 90% of patients using homeopathy were advised by their pharmacist or attending physician, mostly to prevent chemotherapy side effects. 95% buy it in pharmacy. Conclusions: A lot of patients are concerned by complementary and alternative medicines; and in too many case, they are advised by non-medical people. This survey shows the importance for oncologist to know exactly what kind of treatment their patients are using. Indeed, at least 16 of those patients associate medicines which reduce the antitumor agent’s activity. The survey will continue in other oncologic units.
Breaking the bad news: Experiences of contingency in advanced cancer patients.
Authors: Dalen Egbert J. van , Scherer-Rath Michael , Hermans Chris A.M. , Van Laarhoven Hanneke W.M.
Published: March 2020

e19560

Background: The diagnosis of advanced cancer implies a radical change in a patient’s future outlook. The way patients interpret this change can be understood in terms of emotion and contingency theory. Events which seem to come out of the blue and augur unforeseen consequences are difficult to interpret and attribute meaning to. They can cause so-called experiences of contingency, in which the subject is in a state of being lost and faces an uncertain future fraught with vague and threatening possibilities. The aim of this study is to understand this experience that can affect a person’s fundamental beliefs. Methods: Patients with advanced cancer, not amenable to curative treatment, with a Karnofsky performance score of ≥ 70 and good command of the Dutch language were asked for participation. Patients were interviewed once, at their homes. The tape-recorded and transcribed interviews were analyzed within the framework of grounded theory. Codes were arranged along the dimensions of probability of the event and emotional impact, which influence each other. Results: 56 patients with an average age of 62 years were included in the study. Breast cancer, colorectal cancer and renal cell cancer were the most common cancer types. The average time since the diagnosis of advanced cancer was two years. 32 % of the patients were able to interpret the bad news and react calmly. However, for 68 % of the patients the event had a high emotional impact and the limits of their interpretation framework were exceeded, as evidenced by the spontaneous and highly frequent use of metaphors pointing towards the collapse of their reality. They perceived their existence as being contingent. Receiving the bad news unexpectedly shook the very foundations of their lives for reasons related to loss of confidence in life. Conclusions: The experience of contingency can be understood in terms of shaken confidence and implies an existential confrontation with life as a power which cannot always be controlled. Confidence in life can be regained after acknowledging one’s boundaries, accepting the new future perspective and finding a new attitude towards life.
Evaluation of the knowledge of medical terminology among patients with breast cancer: A pilot study.
Authors: Rucinska Monika , Kieszkowska-Grudny Anna , Kulita Patrycja , Nawrocki Sergiusz
Published: March 2020

e19561

Background: All breast cancer patients should receive clear information about diagnosis, treatment, its side effects and prognosis. The aim of this study was to determine the breast cancer patient knowledge about their illness and treatment. Methods: 50 breast cancer patients (30-70 years, median 58 years) were included. All patients were under radiotherapy, 48 patients were after breast conserving treatment or mastectomy, 36 patients have been treated previously by chemotherapy. All patients have been informed about their cancer, treatment and side effects and get written information. Subjects filled out a questionnaires with closed questions with 5 responses, of which one was correct, three incorrect, and the answer “I do not know”. Questions were aimed at understanding the knowledge of medical terminology, such as: neoplasm, cancer, radiotherapy, chemotherapy, side effects, itching, peeling skin, sleep disturbances, swallowing difficulties, heart rhythm disturbances, and others. Statistical analysis was done based on χ2 test and descriptive statistics. The significance level was p<0.05. Results: Not all breast cancer patients understand correctly the word cancer. There were significant differences by age: women below 50 years old answered correctly, while 47% of women between 61-70 years old did not know what cancer mean (χ2=18.39; p<0.05). Women with primary education more often did not know what cancer is than women with secondary or higher education (χ2=29.60; p<0.01). Correct knowledge about radiotherapy stands at 46% patients. In case of chemotherapy more than 64% of women granted the right answer. However, up 40% of patients did not know what side effects means, the majority of patients can fairly well name the various ailments, such as itching, skin’s exfoliation, sleep disorders. Significant differences were observed between the correct answers by age and education (f.ex. for itching: χ2=22.03; p<0.01 and χ2=23,92; p<0.05, respectively). Conclusions: Knowledge about cancer and treatment-related terms are not enough among breast cancer patients. Most varies depending on age and the level of education. Better known method of treatment is chemotherapy than radiotherapy.
Assessment of the relationship between ECOG score and fentanyl pectin nasal spray acceptability scores for breakthrough pain in cancer.
Authors: Torres Luis M. , Conroy John D. , Tayi Ravi , Perelman Michael Sidney , Knight Alastair D.
Published: March 2020

e19567

Background: Breakthrough pain in cancer (BTPc) involves intermittent episodes of intense pain of limited duration. Prevalence estimates range from 19% to 95% in patients with cancer.Little information is available on how the effectiveness of treatments for BTPc may be affected by patient level of function. Methods: This is a post hoc analysis of data from an open-label, long-term safety study that used fentanyl pectin nasal spray (FPNS, Lazanda, PecFent) for BTPc in patients with ECOG score ≤2. The study included patients who experienced BTPc in spite of background pain that was adequately controlled with at least 60 mg of morphine (or equivalent). Dose of FPNS (100 to 800 mcg) was established during a titration period prior to the open-label phase of the study. The study included assessment of acceptability of FPNS through a 3-question, 4-point scale survey (not satisfied-very satisfied) for ease of use, convenience, and reliability. This analysis assessed acceptability scores grouped by ECOG score after the first 4 weeks of open-label use. Results: There were 195 patients for whom information on baseline ECOG scores and acceptability scores after 4 weeks were reported. For all patients, the ease of use, convenience, and reliability of FPNS were reported as satisfied or very satisfied: 97.4%, 96.9%, and 92.3%, respectively. When sub-grouped by ECOG 0 (n=20), 1 (n=130), and 2 (n=45), results were: ease of use, 100%, 97.7%, 95.6%; convenience, 100%, 96.9%, 95.6%; reliability, 100%, 92.3%, 88.9%, respectively. The percentage of patients who were satisfied or very satisfied with treatment was always high, but increased with level of function, ranging from 88.9% to 95.6% of patients with ECOG score of 2, to 100% of patients with ECOG score of 0. Conclusions: FPNS was well accepted for the treatment of BTPc in patients irrespective of ECOG score (0-2). Overall, more than 90% of patients reported being satisfied or very satisfied with the ease of use, convenience, and reliability of treatment. Patients with lower ECOG scores had slightly higher acceptability scores. Future BTPc studies examining subjective scores should consider differences in ECOG status.
Impact of patient characteristics on compliance to adjuvant chemotherapy in hormone receptor negative breast cancer: A single institution experience.
Authors: Ahmed Alaa Abdelhalim , Ngamphaiboon Nuttapong , Kossoff Ellen , Meagher Alison , Attwood Kristopher , Edge Stephen B. , Ademuyiwa Foluso Olabisi
Published: March 2020

e19568

Background: Adherence to adjuvant chemotherapy (ACT) has been implicated in poor outcomes in early breast cancer (BC). We investigated factors that may contribute to non-compliance (NC) in hormone receptor (HR) negative BC. Methods: 310 HR- patients (pts) who received adjuvant chemotherapy (ACT) at Roswell Park Cancer Institute (RPCI) between 2002 and 2008 were eligible for this retrospective analysis. Patients were categorized as Compliant or Non Compliant (NC). Compliance was subdivided into adequate Tx (AT) and inadequate Tx due to Toxicity (ITT). NC was discontinuation or delays in ACT for reasons other than toxicities. The 3 groups were compared based on baseline characteristics, treatment-related toxicities, and survival. Fisher’s exact, logistic regression, Cox regression, and log-rank tests were used to analyze the data. A significant p value was assigned at ≤ 0.05. Results: 192 pts were included, with a median age of 55 (range 27-86), and median follow up of 4.9 yrs. NC was observed in 19 (10%) pts, ITT in 47 (24%), and AT in 126 (66%). ITT and NC pts were more likely to have a higher Charlson co-morbidity index (CCI) (p=.019), ECOG performance status (p=.048), more hospital stays (p=<.001) and more heme/non-heme toxicities (p=<.001). Comparing NC/ITT/AT groups; 63/94/100 % completed ≥ half of planned Tx (p=<.001), 22/41/5 % had hematologic toxicity (p=<.001). The groups did not differ by trastuzumab use. There were no statistically significant differences in OS and DFS among the 3 groups. Conclusions: Predictors of non-compliance among HR- breast cancer patients receiving ACT include co-morbidities, and performance status. Clinicians should be aware that this group of pts are likely to have problems completing adjuvant chemotherapy and should be proactive about managing toxicities.