bluuebunny/crossref_metadata_2025 huggingface dataset:
Detection of DDR2 mutations in malignant melanoma: A potentially targetable feature of advanced stage disease.
Authors: Wang Yongbao , Billouin-Frazier Shere S , Windham Justin P , Jones Daniel
Published: March 2020

9100

Background: The discoidin domain receptor tyrosine kinase 2 (DDR2) gene is mutated in a subset of non-small cell carcinoma of the lung. In lung cancer, targeting of DDR2 with the inhibitor dasatinib has been shown to inhibit DDR2-mutated cell line growth. Responses to dasatinib in DDR2-mutated lung tumors are currently being investigated in clinical trials. We investigated whether somatic DDR2 mutations also occur in melanomas using a set of different clinical subtypes bearing a variety of melanoma-associated molecular alterations. Methods: DNA was extracted from macrodissected FFPE sections of 168 melanomas and subjected to next-generation sequencing using a custom-designed 36-amplicon panel including the coding regions of DDR2 and exons 11 and 15 of BRAF. PCR products were prepared by Access Array, sequenced on the Ion Torrent PGM, and analyzed using Sequence Pilot software. All DDR2 mutations were confirmed by bidirectional Sanger sequencing. Relative expression analysis of the DDR2 gene was performed using RT-PCR on RNA extracted from FFPE sections, with levels normalized to ABL1 and GAPDH. Results: Heterozygous DDR2 point mutations were identified in 3.4% of BRAF-mutated melanoma (n=117) but not in any cases that lacked BRAF mutations (n = 51). All DDR2-mutated melanomas were advanced stage with lymph node and/or extensive soft tissue involvement and included both BRAF V600K and V600E cases. In contrast to the range of mutation sites reported in lung cancers, DDR2 mutations in melanoma (I488S, F574C, S667F and L701F) were at highly evolutionarily conserved positions in the kinase domain. The mutations are expected to be disruptive and may therefore modulate kinase activity. DDR2 transcripts were expressed in tumor cells in all mutated cases. Conclusions: DDR2 mutations in advanced stage melanoma may provide a targetable genetic feature for tyrosine kinase inhibitors such as dasatinib. The invariant association of DDR2 mutation with activating BRAF mutations suggests synergy in transformation between these distinct signaling pathways.
Systematic review and indirect treatment comparison (ITC) of dabrafenib (Dab) and trametinib (Tram) versus first-line (1L) treatments for metastatic melanoma (MM).
Authors: Srivastava Kunal , Pathak Purnima , Amonkar Mayur , Stapelkamp Ceilidh , Swann R. Suzanne , Casey Michelle , Rana Cheena
Published: March 2020

e20012

Background: In PhIII randomized controlled trials (RCTs), Dab and Tram have shown significant improvement in the primary endpoint of progression-free survival (PFS) as monotherapies vs dacarbazine (DTIC) in 1L patients (pts) with BRAF V600E+ MM. Overall survival (OS) in these studies was confounded by crossover of DTIC pts to active treatment (trt) upon disease progression. This study compares PFS and OS for Dab and Tram with other 1L MM trts. Methods: Embase, MEDLINE, CCTR, and conferences were systematically searched through 10/2012 for relevant RCTs. Comparators were DTIC, vemurafenib (Vem), and ipilimumab (Ipi). Using random-effects network meta-analysis, Dab and Tram were compared directly (D) vs DTIC and indirectly (I) vs Vem and DTIC+Ipi. Results: 48 studies (147 publications) met inclusion criteria; 4studies (1,603 pts) contributed data to current network meta-analysis.Both Dab and Tram showed statistically significant reduction in the risk of progression directly vs DTIC and indirectly vs DTIC+Ipi and comparable PFS indirectly vs Vem (no statistically significant difference). Dab and Tram also demonstrated a statistically nonsignificant but numerically lower hazard of death directly vs DTIC and indirectly vs Vem and DTIC+Ipi. Conclusions: Using ITC, 1L trt of MM with Dab and Tram monotherapies was statistically significantly better than DTIC and DTIC+Ipi for PFS, with comparable efficacy to Vem for PFS and OS. Results must be interpreted cautiously given methodological assumptions and immature OS data for Dab and Tram. H2H studies remain gold standard for comparing trts. [Table: see text]
Patterns of pharmaceutical therapy in advanced melanoma.
Authors: Bilitou Aikaterini , Zhao Zhongyun , Barber Beth L. , Clapton Genevieve Sian , Saltman Deborah
Published: March 2020

e20014

Background: Since 2011, two therapies that provide novel approaches to the treatment of advanced (unresectable or metastatic) melanoma have been introduced to the market: ipilimumab for second line and vemurafenib for BRAF mutation-positive melanoma. It is not known how the new drugs influence treatment; this study investigated current treatment patterns in advanced melanoma. Methods: A clinician-validated, web-based survey was administered between August and November 2012 to clinicians who treat advanced melanoma in France, Germany, Italy, Spain, and the UK. Respondents were asked about their treatment of patients in the previous 12 months, including treatment modalities and pharmaceutical therapies used, and factors that affect treatment choice. Results: 150 oncologists and dermatologists completed the survey, 30 in each country. Pharmaceutical therapy was more commonly used than other treatment modalities and varied by stage of disease. A high proportion of patients with late stage of disease were treated with pharmaceutical therapy in Germany (85% in M1B) and France (83% in M1C). Among the countries, 51% (Italy) to 87% (France) of respondents test BRAF mutation status. In patients with wild-type BRAF tumors, dacarbazine, which has not been shown to provide any overall survival benefit, was the most commonly used drug for first-line therapy in all countries. In mutated BRAF tumors, vemurafenib was the most commonly used drug in first line therapy in 3 of 5 countries. There was no standard of care in second line for either patients with wild-type or mutated-BRAFtumors; therapies used included fotemustine, temozolomide, interferon, paclitaxel, and ipilimumab. Conclusions: Treatment options for patients with advanced melanoma are limited, particularly for patients with wild-type BRAF disease. In second line, there does not appear to be an established standard of care: a range of treatments are used, including several not indicated for melanoma.
Bortezomib and interferon alpha-2b in metastatic melanoma.
Authors: Markowitz Joseph , Luedke Eric A , Grignol Valerie P , Hade Erinn , Paul Bonnie K. , Mundy-Bosse Bethany L. , Dao Thao-Vi , Kondalasula Sri Vidya , Lesinski Gregory B. , Olencki Thomas , Kendra Kari Lynn , Carson William Edgar
Published: March 2020

e20018

Background: Preclinical studies revealed that bortezomib and interferon-α (IFN-α ) induce synergistic apoptosis in human melanoma cells. Combined treatment with bortezomib and IFN-α led to significant survival increases in a melanoma murine model. A phase I study is presented to determine the safety, tolerability and dose-limiting toxicity of bortezomib when administered in combination with interferon-alpha-2b (IFN-α) to patients with metastatic melanoma. Methods: Metastatic melanoma patients with ECOG status ≤ 2 were treated on a 5 week cycle. IFN-α (5 MU/m2) was administered subcutaneously (s.c.) on days 1, 3, and 5 of week one. During weeks 2-4 bortezomib was administered intravenously on day 1 along with IFNEα (5 MU/m2 s.c.) on days 1, 3, and 5. There was no treatment during week 5. After the first cycle, bortezomib was administered intravenously on day 1 of the weekly cycle along with IFNEα on days 1, 3, and 5. Bortezomib does levels were 1.0, 1.3, or 1.6 mg/m2 to cohorts of three patients. Results: 16 patients (8 men, 8 women, median age 58.5 (34-82) years) were treated. The most common metastatic disease sites included the lung, subcutaneous nodules, lymph nodes, and soft tissue. Other sites included: brain, skin, viscera, and bone. Grade 3 toxicities most frequently included fatigue, vomiting, and diarrhea. Syncope, depression, hypokalemia, motor neuropathy, and dyspnea were also observed. Grade 4 toxicities included fatigue and lymphopenia. There were 1 PR, 7 SD, and 8 PD. Median PFS and OS were 2.5 months (95% CI: 1.4-3.7) and 10.3 months (95% CI: 5.5-12.8), respectively. Bortezomib did not limit the ability of IFN-α to induce STAT1 phosphorylation in PBMCs. Levels of proEangiogenic cytokines (VEGF and IL-8) were higher in melanoma patients than in normal controls. Levels of VEGF, IL-8 and IL-6 all decreased during week 2 in the patient who experienced a PR. Bioplex cytokine analysis revealed decreases in IL-8 and VEGF in melanoma patients. Conclusions: Bortezomib and IFN-α represents a novel immune based treatment for melanoma. This combination reduces levels of pro-angiogenic factors in melanoma patients, is generally well tolerated, and can be safely administered to melanoma patients including those patients with treated CNS metastases. Clinical trial information: NCT01462773.
Efficacy and cost of nab-paclitaxel (nab-P) in metastatic melanoma (mM).
Authors: Agarwala Sanjiv S , Whiting Scott , Binder Gary , Hersh Evan
Published: March 2020

e20033

Background: A recent phase III trial of nab-paclitaxel (nab-P, 130 nm albumin-bound paclitaxel) vs dacarbazine (DTIC) in mM demonstrated a significant improvement in progression-free survival (PFS). An economic analysis was applied to the results of this trial. Methods: Chemotherapy naive stage IV mM patients received nab-P 150 mg/m2 on days 1, 8, and 15 every 4 weeks or DTIC 1000 mg/m2 every 3 weeks. 529 patients were randomized to nab-P (n = 264) or DTIC (n = 265). The primary endpoint was independently assessed PFS, with overall survival (OS) as a secondary endpoint. Costs of nab-P and DTIC were taken from published 2013 Medicare reimbursement rates. A literature review identified costs for expected adverse events (AE), administration, and recently approved mM treatments. Results: In the intent-to-treat population, median PFS was 4.8 and 2.5 months in the nab-P and DTIC arms, respectively (HR: 0.792; P = 0.044). Median OS at the time of an interim analysis was 12.8 months with nab-P and 10.7 months with DTIC (HR: 0.831; P = 0.094; determination of ultimate statistical significance is pending full analysis at study conclusion). The most common grade ≥3 treatment-related AEs were neuropathy (nab-P: 25% vs DTIC: 0%) and neutropenia (nab-P: 20% vs DTIC: 10%). Grade 4 neutropenia rates were similar between arms (nab-P: 3% vs DTIC: 4%). Median time to neuropathy improvement by >1 grade was 28 days. Median treatment duration was 3 months with nab-P vs 2.1 months with DTIC. Incremental costs per patient were $23,359 ($24,663 for nab-P vs $1,304 for DTIC) including drug, infusion, and AE management costs. These costs compare favorably to incremental costs of over $50,000 for newly approved therapies with similar median OS gains vsDTIC. Conclusions: nab-P is the only chemotherapy in a phase III trial to demonstrate a significant and clinically meaningful delay in disease progression over dacarbazine. Total costs are attractive in the context of other agents recently approved for mM. Further analysis is merited when final OS is available. Clinical trial information: NCT00864253.
Differential clinical associations of BRAF and NRAS mutations among histologic types of cutaneous melanomas.
Authors: Stockman David , Tetzlaff Michael T. , Al-Zaid Tariq , Torres-Cabala Carlos A. , Bucheit Amanda Dawn , Lazar Alexander J. F. , Sui Dawen , Jakob John Andrew , Bassett Roland , Prieto Victor G. , Davies Michael A. , Curry Jonathan L.
Published: March 2020

e20034

Background: Previous studies have investigated whether BRAF and NRAS mutation status in melanoma correlate with histologic parameters and overall survival (OS), but evaluation of mutation groups irrespective of specific mutation among histologic types of melanoma has led to variability in the reproducibility of results. We tested the hypothesis that different histologic types of melanoma (nodular [NM] and superficial spreading [SSM]) have distinct clinical associations with specific BRAF and NRAS mutations. Methods: Primary tumor histology, BRAF/NRAS mutation status, and clinical outcomes were collected for 195 patients (pts) with stage III or IV disease. Clinical associations with specific mutations were determined separately for patients with NM (n=105) and SSM (n=90) histologic types of primary cutaneous melanomas. Results: Mutational status in NM: 69 BRAF (66%), 19 NRAS (18%), & 17 wild-type (WT;16%). Specific BRAF mutations in NM: V600E 50 (75%), V600K 13 (19%), V600R 4 (6%). Specific NRAS mutations in NM: Q61K 6 (32%), Q61L 2 (11%), Q61R 8 (42%); other 3 (16%). Mutation status in SSM: 45 BRAF (50%), 24 NRAS (27%), 21 WT (23%). Specific BRAF mutations in SSM: V600E 32 (71%), V600K 12 (24%), V600R 0. Specific NRAS mutations in SSM: Q61K 2 (8%), Q61L 5 (21%), Q61R 12 (50%). The distribution of specific BRAF (p=0.21) and NRAS (p=0.29) mutations between NM and SSM was not significantly different. Among NM pts, pts with activating NRAS mutations had shorter OS from the diagnosis of Stage IV melanoma than WT (HR 3.42, p=0.02) and BRAF (HR 2.40, p=0.009). There was no significant difference for BRAF pts vs WT (HR 1.43, p=0.47). Among SSM patients, neither NRAS (HR 1.3, p=0.53) nor BRAF(HR 0.54, p=0.16) were significantly associated with OS compared to WT. Comparison of patients with BRAF V600E vs V600K showed significant association for OS from stage 4 in SSM pts (HR 0.24, p=0.01), but not in NM pts (HR 0.64, p=0.36). Conclusions: The prognostic significance of BRAF and NRAS mutations on OS from stage IV differed for pts with NM and SSM primaries. Further investigation of the histologic types of melanoma with specific BRAF and NRAS mutations in a larger series is necessary to validate these apparent impacts on patient outcomes.
Expression and function of CTLA4 in melanoma.
Authors: Seliger Barbara , Maio Michele , Cuaia Ornella , Calabro Luana
Published: March 2020

e20040

Background: The definition of co-inhibitory molecules negatively interfering with immune responses has provided novel targets for therapeutic intervention. These include CTLA4, which directly binds to CD80 and CD86 on T cells leading to a down-regulation of immune responses. Recently, anti-CTLA4 antibodies have been established, which were able to stimulate T cell responses and anti-tumour immunity in vitro and cause objective responses in melanoma patients even months later after clinical progression. Since CTLA4 was found to be expressed on tumour cells, which might explain the distinct anti-tumour immunity of CTLA4 in tumour patients, the aim of this study was determine the expression and function of CTLA4 in 60 human tumour cells of distinct origin. Methods: qPCR, Western blot, cytometry and/or immunohistochemistry was performed to determine the expression of CTLA4. Cell proliferation and anchorage-independent growth of CTLA4+tumor cells was determined by XTT and soft agar colony formation, while CTL-mediated lysis was determined by standard chromium release assay. Results: Expression analysis revealed n extremely heterogeneous and tumour-specific CTLA4 mRNA expression in the tumour cell lines tested with the highest frequency (85 %) and expression levels in melanoma. In contrast, only low constitutive CTLA4 surface expression levels, but high levels of intracellular CTLA4 protein were found. Immunohistochemical analyses with seven distinct anti-CTLA4 antibodies showed a heterogeneous staining pattern in selected melanoma cell lines analysed. In order to understand the molecular mechanisms of CTLA4 expression different CTLA4 expression models were established in melanoma and subjected to functional analysis. High levels of CTLA4 expression caused a down-regulation of their cell proliferation as well as a reduced anchorage independent growth. However, CTLA4 expression did not affect the immunogenicity of tumour cells as determined using co-culture assays of CTLA4+tumour cells with either HLA-matched PBMCs or melanoma antigen-specific CTL. Conclusions: In conclusion, CTLA4 is expressed in melanoma cells and reveals non-immunogenic functions by modulating the growth properties, rather than inhibiting T cell responses.
Biochemical and immunologic markers in patients with metastatic melanoma treated with chemotherapy and dendritic cell vaccine.
Authors: Samoylenko Igor , Zabotina Tatiana , Mikhaylova Irina N. , Chkadua George Z. , Korotkova Olga V. , Vikhrova Anastasia S , Nazarova Valery V , Kharkevich Galina , Demidov Lev V.
Published: March 2020

e20042

Background: The purpose of this sub study was to identify peripheral blood biomarkers associated with the therapeutic effect of immunotherapy with dendritic cell vaccine in patients with metastatic melanoma (MM). Methods: Patients (pts) with low disease burden achieved disease control after two cycles of chemo (cisplatine, vinbalstie, DTIC) were randomized dendritic cell vaccine (DC) or three cycles of chemo. Vaccination schedule consisted of 5 subcutaneous injections of dendritic cell (DC) vaccine (2×106 cells pulsed with autologous lysate) with 14 days intervals. S100B level, LDH level, and peripheral blood lymphocytes immune phenotype were assessed before treatment, after two cycles of chemo and after each vaccination cycle. Results: 104 pts were included in the study, 30 pts were randomized to DC arm, 29 pts were randomized to continue chemo. In pts with rapid disease progression baseline serum S100b level was significantly higher compared to patients with objective response or stable disease (0.874±1.15 mcg/L vs. 0.361±0.66 mcg/L, P=0.002). Similar results were found for baseline serum LDH level (559.8±469.7 U/L vs. 412.5±184.4 U/L, P=0.005) and serum S100b level after 2 cycles of chemo (0.688±0.855 mcg/L vs. 0.187±0,29 mcg/L, P<0.001). Contrary, baseline CD3+HLA-DR+ and CD4+CD25+ lymphocytes levels after 2 cycles of chemo were significantly higher in pts with disease control (11.9±8.9% vs. 8.9±5.3%, P=0.047 and 14.4±8.3% vs. 11.3±5.5%, P=0.036 respectively).In pts randomized to DC arm following markers were associated with long lasting objective response or stable disease course (>6 months): lower baseline S100b level (0.133±0.120 mcg/L vs. 0.445±0.406 mcg/L, P=0.014), lower S100b level after 2 cycles of chemo (0.105±0.095 mcg/L vs. 0.255±0.154 mcg/L, P=0.048), higher proportion of active CD8+lymphocytes prior to vaccination (74.7±3.6% vs. 51.7±14.2%, P=0.05); and more prominent increase of NK-cells CD3-CD16+CD56+ from baseline (increase in 76.5%±41.12% vs. 4.5±28.8%, P=0.01). Conclusions: Biochemical and immunological markers may be helpful when selecting patients with metastatic melanoma for immunotherapy with dendritic cell vaccine.
Socio-demographic and psychological features in Moroccan patients with cancer: A prospective multicentric large cohort study.
Authors: Errihani Hassan , Amzerin Mounia , Kharmoum Saoussane , Zidouh Ahmed , Benider Adellatif , El Kadi Abir , El Fakir Samira , Mrabti Hind , Nejjari Chakib
Published: March 2020

e20516

Background: To explore socio-demographic features and functional dimensions in patients included in a large Moroccan cohort study. Methods: This is the first Moroccan study which was designed to evaluate the quality of life in cancer patients. It is a prospective multicentric cohort study (the 10 existing centers). Patients with breast, cervical, lung or colorectal cancer were included during 2009. EORTC QLQ C30, BR23, CX24 and LC13 questionnaires were used after a transcultural validation. Results: Over 12 months, 2903 patients were included. Breast cancer was the most common (50.4%). Socio-demographic features: The average age at diagnosis was 52.7 years old. Most of them were women (75%). All of patients were Muslims. 75.1% were married. 60% were illiterate. 20% of patients were professionally active and 59.3% were housewives. 27.2% came from rural towns. The socioeconomic status was 65.8% low and 32.4% intermediate. 71.4% of patients had no social welfare. To get to the oncology centers, 77.8% of patients used public transportation while only 0.6% of total cases came in ambulances. The average distance was 150 kilometers. Psychosocial dimensions: For all types of cancer, functional dimensions were noticeably deteriorated with the stage. The lowest scores were observed in lung cancer, whereas the highest ones were for breast cancer. (Emotional function 62.54 vs. 53.05 professional function and leisure 74.14 vs. 42.22 cognitive activity 83.25 vs 26.93 social activity 86,17 vs. 77.69 p<0.001). The financial problems score was higher in lung cancer (68.34). The future perspective was the most affected dimension in QLQ BR23 questionnaire (score40.51), while in QLQ CX24, the sexual enjoyment was the most impacted dimension (score 52.1). Conclusions: In the Moroccan culture, the social relationships the social relationships offset the negative impact of cancer on other functional dimensions. Social activity scores were the less affected. Financial issues are the major concern, resulting in a negative impact on the quality of life of our patients. Finally, over a period of one year, the scores of reported dimensions were significantly improved by the cancer treatment.
The relationship between performance status and sleep quality in cancer patients.
Authors: Velinova Silviya , Kazlauskaite Rasa , Aguirre Roxana , Zarei Khosrow , Hussein Lily Parhad , Rogowski Wendy , McDunn Susan H. , Lad Thomas E.
Published: March 2020

e20544

Background: Poor sleep is common, and is linked to impaired cognitive, psychological, and physical functioning and a lower quality of life. The purpose of this study is to measure quality of sleep in cancer patients and determine the relationship between quality of sleep and performance status. Methods: Patients with cancer (n=139) were recruited at the public hospital between November 2011 and January 2012 and asked to complete the Pittsburgh Sleep Quality Index (PSQI) and the Eastern Cooperative Oncology Group (ECOG) performance status (PS) questionnaires. Twenty patients repeated the questionnaires after 3 months. For the purpose of this study PSQI global score >5 was considered insomnia. PS score 0-1 was considered good, and PS 2-4 was considered poor. Results: The mean age of participants was 55±11 years, 56% were women, 78% were ethnic minority, 77% had advanced cancer, and 71% were undergoing cancer treatment. Among all patients, 73% reported good PS. Median PSQI score was 7 (IQR 4; 11) and 62% had insomnia. Sleep medication was used by 25%. Patients with poor PS had worse PSQI score (Mann-Whitney test, p< 0.0001), and 7.34 (95%CI 2.11-25.49) higher odds of insomnia (p=0.0002) compared to patients with good PS.(Table1) No significant correlation was found between insomnia and gender, ethnicity, primary tumor type, tumor stage, or treatment status. Conclusions: The incidence of insomnia among cancer patients is high. There is a higher incidence of sleep disturbance and worse sleep quality among patients with poorer performance status. [Table: see text]
Potential use of Pain Vision as an objective method to evaluate chemotherapy-induced peripheral neuropathy.
Authors: Tanabe Yuko , Shimizu Chikako , Hirakawa Akihiro , Nara Eriko , Noguchi Emi , Kodaira Makoto , Yamamoto Harukaze , Yunokawa Mayu , Yonemori Kan , Tamura Kenji , Fujiwara Yasuhiro
Published: March 2020

e20557

Background: Chemotherapy-induced peripheral neuropathy (CIPN) is a dose-limiting adverse event, but no objective method exists to evaluate CIPN in an easy-to-use and reproducible manner. Pain Vision (PS-2100; Nipro Co., Osaka, Japan) (PV) was developed to quantitatively evaluate peripheral neuropathy using minimum threshold electric current (mTEC) by painless stimulus. PV has been reported useful in evaluating diabetic neuropathy and neuropathic pain induced by other causes. We investigated the usefulness of PV as an objective method to evaluate CIPN. Methods: Breast and ovarian cancer patients, who were intended to receive adjuvant chemotherapy including paclitaxel (PTX), were enrolled in a clinical study to explore SNPs related to CIPN (UMIN000005294). CIPN was prospectively evaluated at baseline, mid-treatment after receiving a total PTX dosage of 480mg/m2 and three weeks following treatment completion using NCI-CTC (v4), FACT-Neurotaxane (FACT-Ntx) and mTEC as measured by PV. Correlations between changes of mTEC readings and NCI-CTC or FACT-Ntx were analyzed using generalized estimating equations. Results: Ninety-four women were enrolled in this study between April 2011 and December 2012, 15 patients had not reached the post-treatment evaluation point at time of this analysis. Median age was 50 years (range, 27-78) and the incidence of CIPN was 99%. No patient had CIPN at baseline. Mid-treatment and post-treatment CIPN grades were 0/1/2/3=9/70/15/0 and 3/41/30/5 using NCI-CTC while median mTEC readings at baseline, mid-treatment and post-treatment points were 7.8 (4.9-19.9), 8.6 (5.1-17.8) and 9.7 (5.3-22.4)μA, respectively. In baseline and post-treatment comparisons, median mTEC reading changes were significantly correlated with every NCI-CTC grade (median mTEC changes for grades 1/2/3=0.39/0.36/0.64; p=0.003/0.019/0.004) and FACT-Ntx questionnaire item nine, “I have trouble feeling the shape of small objects when they are in my hand” (median mTEC change of 0.14; p=0.049). Conclusions: PV may be potentially useful as an objective method to evaluate CIPN, in particular sensory dominant CIPN, but further study is necessary. Clinical trial information: 000005294.
Bowel obstruction with stage IV cancer: The benefit of introduction of formal palliative care service.
Authors: Kukar Moshim , Groman Adrienne , Satchidanand Yashodhara K. , Alvarez-Perez Amy I. , Dunn Kelli B. , Francescutti Valerie
Published: March 2020

e20573

Background: Patients with stage IV cancer and bowel obstruction (BO) present a complicated management problem. The aim of this study was to evaluate the role of introduction of an organized palliative care service in the management of this complex disease process. Methods: We conducted a retrospective analysis of all patients admitted to the Roswell Park Cancer Institute with stage IV cancer and BO after the institution of formal palliative care service (PS) in 2009. This cohort was compared to a group prior to 2009 (No Palliative care service Group; NPS). The two groups were compared with respect to demographics, comorbid conditions, DNR status, laboratory parameters, medical, surgical management, length of stay and disposition status. Results: 28 patients were identified in PS group as compared to 40 patients in NPS group. The 2 groups were similar in terms of age, gender, race, comorbid conditions, primary site of cancer, chemotherapy, radiation therapy and weight loss. There was a statistically significant difference in the medication regimen provided, as those who had palliative care consults were more likely to receive alternative medications to standard anti-emetics (Table). The palliative care team followed 19/28 patients and 14/19 patients showed improvement in their symptoms (nausea, pain control) in initial 24 hours after the palliative care consult. 50 % ( n=14) of patients in PS group had a formal DNR order in place as compared to 15.4% in NPS group (p<0.001). In 9/14 patients the first discussion regarding DNR was held by palliative care team. A significantly higher percentage of patients were discharged to the hospice care in PS group (42.9% vs. 7.5%, p =0.006). Conclusions: BO in patients with stage IV cancer often poses a dilemma in the choice of surgery versus medical management. Palliative care consults, early in the hospitalization, may help improve symptom management, end of life discussions, better psychosocial support, discharge placements and will eventually translate to shorter length of stay. [Table: see text]
Upper limb function: Comparison of postmenopause women with and without a history of early breast cancer.
Authors: Foroughi Nasim , Lee Mi-Joung , Kilbreath Sharon
Published: March 2020

e20578

Background: Long term upper limb impairments following early breast cancer treatment are commonly reported in women years following surgery. However, the extent to which the symptoms are related to menopause and ageing, rather than cancer, has not been explored. This study aimed to compare upper limb strength, shoulder forward flexion range of motion (FF RoM), and presence of impairments in post menopausal women with and without a history of breast cancer. Methods: Community–dwelling age and body mass index (BMI)-matched post menopausal women with (n=40) and without a history of early breast cancer treatment (n=40) participated. Women with other types of cancer, metastatic cancer, and significant neurological or musculoskeletal history unrelated to breast cancer were excluded. Peak shoulder muscle strength was assessed using pneumatic resistance machines and FF RoM with a digital inclinometer. Participants completed the Disability of arm, shoulder and hand (DASH) questionnaire. Between groups comparison were made using analysis of co-variance with age and BMI as confounding variables. Results: Upper limb strength (206.22±45.0 vs. 225.36±86.9 Nm/kg, p=0.091) and FF RoM (166.75±7.9◦ vs. 170.14±6.9◦, p=0.259) were not significantly different between the study and the control group. There were no significant differences between the groups on any of the DASH sub scores (pain: 9.18±8.1 vs. 8.62±8.2, P=0.770). Conclusions: Upper limb impairments are often presumed to be a consequence of surgical procedures in women with breast cancer. However, some of the symptoms women perceive years following surgery may be related to the changes due to aging or menopause rather than cancer treatment.
Risk of fatigue with the targeted therapy for renal cell carcinoma.
Authors: Iqbal Bilal , Wu Shenhong
Published: March 2020

e20611

Background: Fatigue is one of the major side effects associated with targeted therapeutic agents in the treatment of renal cell carcinoma (RCC), and has negatively affected the optimal use of these drugs. Currently the risk of fatigue has not been well defined. We performed a systematic review and meta-analysis of published randomized controlled clinical trials (RCT) to determine the risk of fatigue in RCC patients treated with targeted therapy. Methods: Databases including PUBMED, Web of Science, and abstracts presented at the American Society of Clinical Oncology meetings up to October, 2012 were searched to identify relevant studies. Eligible studies included prospective RCTs in which a targeted therapy was compared to a control of non-targeted therapy (placebo or interferon) with data available. Incidences and relative risk (RR) were calculated using a random- or fixed-effects model depending on the heterogeneity of the included studies. Results: A total of 5,192 RCC patients (targeted therapy: 3023, control: 2092) from 11 RCTs were selected for analysis. The overall incidences of all-grade and high-grade (ie, grade 3 or above) fatigue were 45.4% (95% CI: 33.0-58.5%) and 7.6% (95% CI: 4.1-13.5%) respectively. The incidences varied significantly among different agents (P<0.001). In comparison with overall controls, the targeted therapy did not significantly increase the risk of all-grade (RR=1.07, 95% CI: 1.0-1.35, p=0.055) or high-grade fatigue (RR= 1.01, 95% CI: 0.68-1.50, P=0.95). However, the targeted therapy significantly increased the risk of all-grade fatigue (RR 1.60, 95% CI: 1.40-2.32; P<0.001), but not high-grade fatigue (RR 1.74, 95% CI: 0.91-3.32; P=0.095) when compared to placebo. There was no significant difference between the targeted therapy and interferon in the risk of all-grade (RR 1.02, 95% CI: 0.90-1.14; P=0.90) or high-grade fatigue (RR 0.86, 95% CI: 0.55-1.36; P=0.53). Conclusions: The targeted therapy may significantly increase the risk of fatigue in a magnitude comparable to interferon.
Characteristics and outcomes of advanced cancer patients referred to outpatient supportive care who missed their appointment.
Authors: Delgado-Guay Marvin Omar , Tanzi Silvia , San-Miguel Maria Teresa , Williams Janet L. , Allo Julio , Chisholm Gary B. , Bruera Eduardo
Published: March 2020

e20612

Background: Supportive Care Outpatient Clinics (SCOC) offer comprehensive care and symptom management to patients with advanced cancer (AdCa). Missed appointments (MA) are frequent but they are no studies on the clinical outcomes of patients who fail to show for consultation. Methods: We determined the frequency of MA, including clinical and demographic data, and reviewed clinic appointment records for 218 consecutive kept (KA) and 218 MA for distinct patients referred to SCOC from January to December 2011. Results: 218/1,352 (16%) AdCa who were referred to our SCOC, missed their appointment. The median age was 57 years (interquartile range 49-67). The mean (range) time between referral and appointment was 7.4 days (0-71) for KA vs. 9.1 days (0-89) for MA (p=0.0062). Age, gender, marital status, and cancer types or stages, and reasons for referral to SCOC were not significantly different between MA and KA patients. African Americans had more MA 49/218 (22%) vs. 31/217 (14%), p=0.06. The reasons for MA were: admission to the hospital 17/218 (8%), death 4/218 (2%), appointment with primary oncologist 37/218 (18%), other appointments 19/218 (9%), visits to emergency room(ER) 9/218(9%), and unknown 111/218(54%). MA patients visited more the ER at 2 weeks 16/214 (7%) vs. 5/217 (2%), p=0.01, and 4 weeks 17/205(8%) vs. 8/217(4%), p=0.06. Median survival for MA patients was 177 days (range:127-215) vs. 253 days (range:192-347) for KA patients (p=0.013). Multivariate analysis showed that MA were associated to the time between referral and scheduled appointment (OR: 1.026/day, p=0.03), referral from targeted therapy services (OR:2.177, p=0.004), living at Texas/Louisiana regions (OR;2.345, p=0.002), having advanced directives (OR:0.154, P<0.0001), and being referred for symptom control (OR:0.024, p=0.0003). Conclusions: AdCa with MA have worse survival and increased ER utilization. We identified AdCa at higher risk for MA who should undergo more aggressive follow up. More research on MA prevention is needed.
Psychosocial impact of parental cancer on Moroccan children: Result of an exploratory study.
Authors: Kharmoum Saoussane , Sbitti Yassir , Amzerin Mounia , Mesmoudi Mohamed , Kharmoum Jinane , Mrabti Hind , Errihani Hassan
Published: March 2020

e20624

Background: Cancer diagnosis and treatment of a parent has considerable impact on the lives of their children. The aim is to identify whether the diagnosis of parental cancer is associated with an increased risk of psychosocial difficulties amongst children and adolescents in Moroccan population. Methods: At the National Institute of Oncology in Rabat, from September to December 2009, 194 Children and adolescents whose parents were diagnosed with a cancer were interviewed. We used a questionnaire covering socio-epidemiological characteristics exploring the disease repercussions to their psychic. Results: There were 52% son and 48% daughters, aged between 10-15 years old (yo) in 26%, 15 - 20 yo in 44% and 20-22 yo in 30% of cases respectively. 67% were studying. Communication difficulties between parents with cancer and their children were observed in 100%. 20% of children were not aware of their parents' cancer. Only the children who were informed about their parents’ cancer were interviewed. All of them had traumatism, initial denial and anguish of loss of the parent. Guilt feelings were present in 90% of cases. 87% of them felt abandoned. The fear of having a stepfather or stepmother was observed in 41.2% of daughters and 12.8% of son, especially when the parent who had the cancer was the mother. Fear of inheriting cancer was seen in 80% of daughters whose mothers were suffering from breast cancer. The process of parentification was benign in 54% and destructive in 23% of cases. Enuresis was present in 30% of cases (20.6% in daughters 9.4% in son). Introversion was seen in 70% of cases. 30% of children noted a regression in their school abilities. Toxic habits appeared in 15% of cases. Conclusions: The result of this transversal study suggests that Moroccan children who have parents suffering from cancer, experiment an important distress. Unfortunately, the Moroccan parents do not use the services of psychological assistance. Thus, we should be vigilant to detect any potential psycho-pathologic disorders and to enable the family to live as normal as possible.
Patients’ perceptions of early palliative oncology care: A qualitative analysis.
Authors: Hannon Breffni , Swami Nadia , Krzyzanowska Monika , Leighl Natasha B. , Oza Amit M. , Moore Malcolm J. , Rodin Gary , Tannock Ian , Zimmermann Camilla
Published: March 2020

e20639

Background: Early palliative care referral is encouraged for patients with advanced cancer. However, little is known about patients’ perceptions of the impact and relevance of early referral. We conducted a qualitative study in which patients with advanced cancer were interviewed following completion of a randomized controlled trial comparing early palliative care with standard oncology care. Our aim was to delineate what, in the opinion of patients, were the respective roles of the oncology and palliative care teams in an outpatient setting. Methods: We conducted qualitative interviews with patients following completion of a cluster randomised controlled trial of early versus routine palliative care referral. Participants were recruited from 24 medical oncology clinics at a comprehensive cancer center. Selective sampling was employed to ensure equivalent numbers of participants from intervention vs. control arms, male vs. female, age ≥60 vs. <60 years, with high vs. low self-reported quality of life, and with high vs. low satisfaction with care. Forty-eight patients (26 intervention and 22 control) with advanced lung, breast, gynecological, gastrointestinal and genitourinary cancers completed interviews lasting 25 to 90 minutes. Control patients were asked about the role of oncology; intervention patients were asked about both teams. Interviews were recorded, transcribed and analysed using NVivo. A grounded theory approach was used to explore emerging themes. Results: Several themes emerged in relation to the contrast between oncology (OC) and palliative care (PC) including (1) the focus of the consultation, with OC tending to focus on cancer or treatment options while PC was regarded as being more holistic, including physical, psychological and family domains; (2) the model of care delivery, with OC described as being clinician-led and time-limited, in contrast with PC where time was more flexible and the patient set the agenda; and (3) the complementary nature of early palliative care alongside standard oncology care in terms of overall well-being. Conclusions: From a patient perspective, palliative care and medical oncology have distinct and complementary roles, supporting the relevance of early referral.
Developing a culturally and linguistically responsive survivorship care plan for breast cancer.
Authors: Ashing Kimlin Tan , Rosales Monica , Serrano Mayra , Fulcher Gingi , Paz Isaac Benjamin , Weitzel Jeffrey N. , Lai Lily L. ,   African American Cancer Coalition, Latina Breast Cancer Taskforce
Published: March 2020

e20651

Background: African and Latina-American breast cancers patients (BCA) experience the greatest morbidity and mortality, suggesting a critical need for improved surveillance and quality care. The Institute of Medicine (IOM) and the Commission on Cancer (CoC) recommend that survivors receive personalized Treatment Summaries and Survivorship Care Plans (TSSCP) in order to facilitate best practice in clinical surveillance and follow-up care. This TSSCP template development study joined advocacy, scientific and medical communities to comprise a diverse advisory council (AC, N=38) to inform the development of the TSSCP-AA (African American) and TSSCP-S (Latino) templates targeting BCA. This abstract reports on the development, and presents the TSSCP-AA and TSSCP-S. Methods: The overall study was guided by the Shared Care and Psychooncology Models, and Contextual Model of Health Related Quality of Life. The AC provided input into the culturally relevant modifications of the American Society of Cancer Oncology (ASCO) TSSCP template to create the TSSCP-AA and TSSCP-S. Health care professionals enlisted from cancer centers and community hospitals (n=51) evaluated the TSSCP-AA and TSSCP-S templates on the following domains: content, clarity, utility, and cultural and socioecological responsiveness. Results: AC input revealed that the clinical (i.e., comorbidities) and cultural contexts (i.e., language, spirituality) must inform TS and SCP, respectively. Preliminary evaluation analyses documented that health professionals rated our TSSCP-AA and TSSCP-S templates as excellent to outstanding on content, clarity, utility, cultural responsiveness, and socioecological responsiveness (p<0.01). Conclusions: The evaluation results imply that the TSSCP-AA and TSSCP-S templates achieved cultural responsiveness with high acceptability and utility among professionals and survivors. We created both paper and electronic versions of theTSSCP-AA andTSSCP-S (English and bilingual English-Spanish formats) for providers to create individualized TSSCPs. Further, our TSSCP development approach can be adopted for TSSCP template development targeting ethnic/linguistic minority cancer survivors.
Purified dry extract of Paullinia cupana (guaraná) (PC-18) for chemotherapy-related fatigue in patients with solid tumors: An early discontinuation study.
Authors: del Giglio Adriana Braz , Lerner Tatiana Goberstein , Paiva Henrique Soares , Azevedo Renata Guise Soares , tuma Guariento Ricardo , Goldman Cecilia , Carelli Bruno , Schindler Fernanda , Pianowski Luiz , Cruz Felipe Melo , Del Giglio Auro
Published: March 2020

e20680

Background: Paullinia cupana (guaraná) is an Amazonian plant that has been previously shown to be effective in treating chemotherapy-related fatigue (CRF) in patients with breast cancer. We aimed to evaluate the efficacy of a purified dry extract of P. cupana (PC-18) in patients with various solid tumors treated with chemotherapy. Methods: We included 40 patients with solid tumors who showed increases in their Brief Fatigue Inventory (BFI) questionnaire scores after one week of systemic chemotherapy. PC-18 was administered at 37.5 mg by mouth two times per day (PO bid), starting after one week of chemotherapy, for three weeks (induction phase). Patients who had an improvement in or stabilization of their BFI scores were randomized to receive either PC-18 at the same dose or placebo for the following three weeks (maintenance phase). Results: After PC-18 treatment, the BFI fatigue scores improved or stabilized in 36 out of the 40 patients (mean BFI score difference = 2.503; 95% CI: 1.716 – 3.375, P = 0.0002). Three weeks after randomization (16 patients on PC-18 and 17 on placebo), we observed no significant differences in the BFI, FACIT, HADS, and PSQI scores between patients randomized to PC-18 versus placebo. Conclusions: We conclude that the PC-18 extract is effective for the treatment of CRF in patients with a variety of solid tumors. A conditioning effect, which was observed in patients with early positive effects of PC-18 on CRF, may explain the better than expected fatigue scores of the placebo-treated patients.
More positive attitude and less symptom burden for male smokers with lung cancer.
Authors: Niu Zhimin , Wang Yongsheng
Published: March 2020

e20692

Background: Cigarette smoking causes many kinds of cancer, and it is more closely related with lung cancer, rather than other cancers. Smoking is the leading cause of lung cancer and ninety percent of the smokers are male in China, but there is little published data concerning the psychological responses in the male smokers with lung cancer and its influence on the symptom burden. The aim of the study is to verify the hypothesis that male smokers with lung cancer have more positive attitude and less symptom burden, comparing to male non-smokers. Methods: 194 men with cancer in West China Hospital, Sichuan, China, were assessed by self-administered questionnaire. Psychological response was measured by the Chinese version of Mini-Mental Adjustment to Cancer scale (Mini-MAC), and symptom burden was measured by the physical symptom distress scale from the Rotterdam Symptom Checklist (RSCL). Results: We found that smokers with lung cancer got higher scores in Positive Attitude and less symptom burden than non-smokers. Patients with degrees lower than high school got higher scores of positive attitude comparing to college graduate patients (p=0.038). Smokers with lung cancer who knew the potential carcinogenicity of cigarette showed less negative emotion (p=0.011). The psychological response was not affected by age, clinical stage, cell type, smoking duration and amount. Conclusions: Our study suggests that smokers with lung cancer have more positive attitude and less symptom burden, and prone to accept subsequent treatment.
Advanced gynecologic cancer patients and healthy parents: Emotional distress and information given to their children.
Authors: Rodriguez-Morera Anna , Limonero Joaquin T. , Barretina Pilar
Published: March 2020

e20704

Background: Describe relationship between advanced gynaecologic cancer (AGC) patients and healthy parents emotional distress (ED) and information amount related to the disease they give to their children. Methods: We studied 28 children, aged between 5 and 18 years, whose mothers had AGC, 13 breast (72.2%), 2 cervix (11.1%) & 3 ovarian (16.7%). Interview with numerical scale from 1 to 10 points was used to assess the amount of children's information described by parents. Hospitality Ansiety Depression Scale (HADS) was used to assess parents ED. Parents and children older than 12 years gave Informed Consent. Results: 18 mothers diagnosed of AGC were included. They added up to a total of 31minor children (M=1.7;SD=0.7) 3 of them, younger than 5 years old were excluded. Emotional distress of parents did not significantly correlate with the number of minor children they had. In the other hand, depression symptoms increased with the duration of disease, for patients and healthy parents (rho=0.5,p<.01;rho=0.6,p<.01) also when patient's functional capacity decreased (rho=-0.4,p<.05;rho=-0.5,p<.05). Mothers gave the information in 60.7% of the cases, 35.7% both parents shared this task. Anxiety among patients (M=10.21;SD=5.4) and healthy parents (n=13,M=8.8;SD=4.8) had not significant correlation with the amount of information given (n=28,rho=-0.01,p>0.05;n=19,rho=-0.2,p>.05). Patients (M=7.3;SD=4.2) and healthy parents (n=13,M=5.2;SD=3.1) depression grade did not correlate with the amount of information children had (n=28,rho=0.2,p>.05;n=18,rho=-0.1,p>.05). Information given by mothers was slightly higher (M=6.8; SD=2.3), it was the same for sons and daughters (U=93.5,p>.05). Yet, fathers tended to give more information to daughters (M=6.2; SD=1.8;U=22.5,p=0.06). Information given by patients and healthy parents was concordant (rho=0.5;p<.05). Conclusions: AGC patients and healthy parents ED is not related with the information amount parents give to their children. We must be aware of the need to provide support to fathers during mothers’ disease in order to ease communication with the children, taking into account that mothers are who mainly give information to their children.