bluuebunny/crossref_metadata_2025 huggingface dataset:
What is the behavior of Breslow’s thickness?
Authors: Mendes Gelcio L. Q. , Koifman Sergio
Published: March 2020

9097

Background: Localized cutaneous melanomas (CM) have their clinical course predicted by microscopic findings in the tumor specimen, mostly Breslow’s thickness (BTL), ulceration and mitoses. It is not certain whether BTL has a linear relationship with overall survival (OS) or relapse-free survival (RFS). The aim of this study was to evaluate BTL´s linear (LC) and its non-linear component (NLC) with relation to survival. Methods: All consecutive cases of CM treated from 1997 to 2006 at a single institution were identified, individuals with stage I or II tumors, minimum follow up of one month and known BTL were selected, socio-demographic data, clinical and pathological findings, treatment and outcomes were abstracted. Information about ulceration was missing in more that 30% of cases and it was not evaluated, there was no information about mitotic rate. Survival was estimated by the Kaplan-Meier method. Multivariate analyses were performed by the Cox model. BTL was evaluated as a continuous variable, and the LC and NLC by the technique of smoothing, using p-splines. Results: There were 1465 cases of CM, 51 with no follow up, 137 had no information about BTL and 202 had advanced stages. This analysis is based on 1075 cases. In the Cox model, the variables associated OS were age [hazard ratio (HR) 1.02, 95% CI 1.01 to 1.03], sex (HR 1.56, 95% CI 1.2 to 2.04) and BTL (HR=1.079, 95% CI 1.065 to 1.094). The variables associated with RFS were age (HR 1.017, 95% CI 1.009 to 1.024), sex (HR 1.372, 95% CI 1.104 to 1.704) and BTL (1.068, 95% CI 1.057 to 1.080). In the analysis of LC and NLC of BTL, it was found that both LC and NLC were statistically significant for OS and RFS. There was an increase in the HR as BTL increased in those lesions thinner than 4mm, then such increase was not as evident and lesions with more than 10mm had a similar OS and RFS (plateau). Conclusions: BTL is one of the most powerful prognostic criteria of patients with stage I and II CM. The risk of death increases linearly for thin lesions up to 4mm, lesions thicker than 10mm behave as a uniform group with no further decrease in OS or RFS as the lesion becomes larger. In conclusion, BTL may not behave as a linear function, it has a LC for thinner lesions, but for thicker lesions, above 10mm, further increase in BTL may add no more risk.
Forecasting the efficiency of chemoradiotherapy in patients having disseminated melanoma of skin.
Authors: Komarova Yekaterina , Frantsiyants Yelena , Dzhabarov Farhad , Rozenko Ludmila , Pozdnyakova Victoria
Published: March 2020

e20005

Background: Result of scientific research testify that particularities of endocrinal status might play a role in etiology and pathogenesis of illness. In connection to this, studying of particularities of hormonal homeostasis in patients having skin melanoma becomes relevant, as on the background of the former, the tumor develops this or that reaction to remedial measures. Methods: Content of triiodothyronine (T3) in peripheral blood was studied in 40 patients of both sexes having disseminated melanoma of skin (pT2-3N1-2M0) before and after chemoradiation. Chemotherapy consisted of dacarbazine in course dose of 1000 mg/m2, radiotherapy – total boost dose was 55+5,4 Gy. Results: Assessment of direct clinical result of the complex of antitumor measures has demonstrated that in the group of patients under control the treatment proved inefficient in 15 people and was not accompanied by decrease of tumor formation sizes, while in 25 people the curative effect was manifested in 25-50% (15 cases) regress of tumor lesions and in over 50% (10 cases) regress. Conclusions: The results of chemoradiation were analyzed depending on the initial content of general T3 in the blood of the patients. It has been discovered that absence of effect from treatment was featured in patients having low content of the hormone – from 0,52 to 1,10 nmole/l, normal oscillations of its level in healthy people being 1,2 to 2,8 nmole/l. Contrary to that, in patients having regress of tumor, the initial concentration of the hormone ranged from 1,35 to 1,70 nmole/l, i.e. within the physiological norm.
Different prevalence of BRAF and NRAS somatic mutations in melanomas according to the patients’ origin.
Authors: Palmieri Giuseppe , Lissia Amelia , Cossu Antonio , Ascierto Paolo Antonio , Botti Gerardo , Caraco Corrado , Mozzillo Nicola , Ayala Fabrizio , Anniciello Annamaria , De Giorgi Vincenzo , Massi Daniela , Stanganelli Ignazio , Rubino Corrado , Palomba Grazia , Sini MariaCristina , Manca Antonella , Colombino Maria
Published: March 2020

e20013

Background: Genetic factors predisposing to melanoma at germline level have been demonstrated to be geographically heterogeneous. We here evaluated the spectrum of NRAS and BRAF mutations at somatic level, in a large subset of melanoma tissues from patients originating from different Italian geographical areas: Sardinia, whose population is genetically homogeneous, and Middle-South Italy, with a genetically heterogeneous population. Methods: Patients were enrolled consecutively between June 2008 and December 2012. Genomic DNA was isolated from tumor tissues [primary melanomas (N=439) and melanoma metastases (N=269)] or melanoma cell lines (N=32). Paired samples of primary melanomas (n=140) and synchronous or asynchronous metastases from the same patients (n=203) were included. The full coding sequences and splice junctions of NRAS (exons 2-3) and BRAF (exon 15) genes were screened for mutations through automated sequencing. Results: BRAF/NRAS mutations were identified in 63% of primary melanomas (48% BRAF; 15% NRAS), 67% melanoma metastases (51% BRAF; 16% NRAS), and 68% melanoma cell lines (56% BRAF; 12% NRAS). A non-significant increase in mutation frequency after progression from primary melanoma was observed. However, distribution of BRAF/NRAS mutations varied between in vivo tumors and melanoma cell lines, suggesting a preponderant role for BRAF activation in highly proliferating cultured melanoma cells. Among paired samples, consistency of BRAF/NRAS mutation patterns between metastatic and primary melanomas ranged from 71% (skin metastases) to about 90% (lymph node and visceral metastases). A significant inverse distribution of BRAF/NRAS mutation rates was observed in our series on the basis of the geographical origin of patients: for BRAF, 58% Sardinian vs. 42% non-Sardinian cases (p=0.045); for NRAS, 2% Sardinian vs. 21% non-Sardinian cases (p<0.001). Conclusions: Our findings provide additional insights into the spectrum and distribution of BRAF/NRAS mutations in melanoma; moreover, they support the hypothesis that differences in patients’ origins and related genetic backgrounds may contribute to even determine the incidence rate of somatic mutations in such cancer genes.
Do nonmelanoma skin cancer survivors use tanning beds more often than the general public?
Authors: Wiznia Lauren , Ferrucci Leah M , Mayne Susan T , Chagpar Anees B.
Published: March 2020

e20017

Background: Tanning bed use increases the incidence of nonmelanoma skin cancer (NMSC), however utilization of indoor tanning after diagnosis in this population is not well-studied. We sought to determine if tanning bed use among NMSC survivors differed from the general population. Methods: The National Health Interview Survey is an annual population-based survey that is representative of the civilian US population. We utilized the 2010 cancer supplement to evaluate self-reported tanning bed use in the previous 12 months in self-reported NMSC survivors compared to individuals without a history of skin cancer. Results: In 2010, 24,941 people were surveyed, 1.85% of whom had a self-reported history of NMSC. On univariate analysis, NMSC survivors were significantly less likely to use tanning beds in the previous 12 months (2.16 vs. 5.61%, p < 0.001). On multivariate analysis, however, NMSC survivors were equally likely to use tanning beds as those who had never had skin cancer (see Table). Conclusions: When controlling for other sociodemographic factors, NMSC survivors were no less likely to use tanning beds than the general population. These findings suggest a need to better educate NMSC survivors about the increased risk of future skin cancers with ongoing tanning bed use. [Table: see text]
Prognosis of melanoma in Peru: An analysis of 410 cases.
Authors: Coras Natalia , Morales Domingo , Yabar Alejandro , Beltran Brady Ernesto
Published: March 2020

e20023

Background: Little is known of the status of melanoma in developing countries. Our retrospective study was performed to determine the clinical characteristics and outcome of patients with melanoma in Peru. Methods: All cases with a pathological diagnosis of malignant melanoma from our institution between January 2002 and December 2011 were identified. Clinical data were extracted through retrospective chart review. Patients’ characteristics are presented using descriptive statistics. Survival curves were estimated using the Kaplan-Meier method. Univariate and multivariate analyses were evaluated using log-rank and Cox proportional-hazard regression tests, respectively. Results: A total of 410 cases were evaluated. The median age at presentation was 66 years (range 4-97 years) with a male-to-female ratio was 1.1:1. There were 146 cases (35.6%) of acral lentiginous melanoma, 67 (16.3%) of nodular melanoma, 54 (16.3%) of mucosal melanoma, 39 (9.5%) of superficial spreading melanoma, 55 (13.4%) were lentigo maligno and 49 (12.0%) were unclassifiable. Melanoma of unknown primary occurred in 34 (8.3%) of cases. The proportion of patients with stage I, II, III and IV disease were 24.2%, 24.8%, 21.9% and 7.8%, respectively. Ulceration status of 320 cases of cutaneous melanoma was recorded and 138 (45.1%) had ulceration. The 5-year survival rate of 409 patients was 58.4% with a median survival time of 7.6 years. The 5-year survival rates of patients with stage I, II, III and IV disease were 88.2%, 67.8%, 39.3% and 17.8% respectively (p<0.001). Univariate analysis showed age >65 years (p=0.003), male sex (p=0.0001), stage (p<0.001), nodular histology type (p<0.001), ulceration (p<0.001), Breslow thickness (p<0.001), Clark level (p<0.001) and localization (mucosal vs. cutaneous) (p<0.001) were associated with survival. In the multivariate analysis, stage was associated with worst prognosis (p=0.01), while other factors had no statistical correlation with survival. Conclusions: Based on our report, acral lentiginous melanoma is the most common type of malignant melanoma in Peruvian patients, and clinical stage was the only independent prognostic factor associated with survival.
Melanoma survivor treatment severity and correlates of psychosocial and physical health.
Authors: Bugos Kelly , Gerry Arianna Aldridge , Palesh Oxana , Swetter Susan M. , McGurk Katherine L. , Greco Ralph Steven
Published: March 2020

e20026

Background: Melanoma survivors’ psychosocial needs and physical symptoms are not well understood, despite nearly 1 million melanoma survivors in the US. In addition, there is a paucity of support available as it is generally believed that cutaneous melanoma survivors don’t suffer long term health consequences. Methods: As part of the new Stanford Cancer Survivorship Program, melanoma survivors previously treated at Stanford Cancer Center were asked to complete a quality improvement survey to explore the value of a melanoma survivorship clinic. 21% of 893 invited survivors responded to the electronic survey. We compared survivors based on treatments received: surgical excision only (SX) vs. surgical excision plus (SX+) one or more of the following: sentinel lymph node biopsy, lymph node dissection, skin graft, interferon, chemotherapy, or radiation therapy. Results: 161 melanoma survivors (SX+: 32% vs. SX: 68%) completed the survey. Those who received surgery plus additional treatment were predominantly male (SX+: 68% vs. SX: 32%, p = 0.003) and slightly older (SX+: 67 years vs. SX: 60 years, p = 0.004). Survivors who received SX+ reported greater fatigue (p < 0.001), weight loss (p < 0.001), arm or leg swelling (p < 0.001), weakness (p = 0.001), numbness/tingling (p = 0.009), pain (p = 0.015), and nausea and/or vomiting (p = 0.039) than SX survivors. Similarly, SX+ survivors reported reduced vitality (24% vs. 6%, p = 0.004), worse social functioning (12% vs. 5%, p = 0.032), and worse sexual functioning (20% vs. 6%, p = 0.017) following treatment. Related to patient care, health care providers were less likely to address these symptoms in SX survivors relative to SX+ survivors (75% vs. 57%, p = 0.019). More SX than SX+ survivors wanted education on how to protect their skin from further damage (24% vs. 8%, p= 0.016). Conclusions: Melanoma survivors receiving SX+ for more advanced disease experienced greater psychosocial and physical symptoms following treatment. However, survivors treated with excision alone for cutaneous melanoma wanted provider attention for their treatment-related symptoms and improved education on skin protection.
A phase II randomized study of adjuvant imatinib versus high-dose interferon alpha-2b for resected high-risk c-kit mutated melanoma.
Authors: Si Lu , Wang Xuan , Kong Yan , Lian Bin , Chi Zhi Hong , Cui Chuan Liang , Sheng Xi Nan , Mao Li Li , Tang Bi Xia , Li Si Ming , Yan Qiao Xie , Guo Jun
Published: March 2020

e20027

Background: Imatinib, a selective inhibitor targeting Abl as well as C-Kit and the platelet-derived growth factor receptor, has been tested for the efficacy and toxicities in metastatic melanoma patients harboring mutations in C-Kit gene. High-dose interferon for one year (HDI) is the FDA approved adjuvant therapy for patients (pts) with high-risk melanoma. This study (NCT01782508) aims to see whether imatinib is more effective than interferon alfa-2b in adjuvant therapy for patients with C-Kit mutated melanomas. Methods: This study enrolled C-Kit mutated(exon 9,11 or 13)pts who were high risk (stage IIB to stage IIIC) and randomized them to receive either imatinib (400mg daily for a year) or HDI (interferon a-2b 15X106 U/m2 d1–5/wX4w + 9X106U tiwX48w) in the absence of disease progression or unacceptable toxicity. 40 pts of each group were planned to enroll. Routine tests including blood tests, medical history updates, physical exams and Brain/Chest/Abdomen/Pelvic CT were performed every 2 months. The endpoints were recurrence-free survival (RFS) and overall survival. Results: Through Jan 2013,7 pts were recruited F3 in imatinib arm and 4 in HDI arm. The three pts received imatinib haven’t had recurrence or metastasis. The RFS were 6m+ (Exon 11: W577S), 5m+ (Exon 11: L576P), 5m+ (Exon 11: L576P) respectively. Two pts have already had lung or regional lymphnode at 4 months (Exon 13: K642E) and 5 months (Exon 11: V560D) in the HDI arm. The other two pts (both Exon 11: 579 insert) in the HDI arm were still disease free for 6 months. The toxicities were consistent with the usual reported studies. Conclusions: In the C-Kit mutated melanoma pts, it’s promising that imatinib may provide more beneficial effect than HDI for high-risk melanomas. (Supported by the National Natural Science Foundation of China (30973483, 81172196, 81102068.) Clinical trial information: NCT01782508.
Intermittent intensified high-dose intravenous interferon alpha 2b (IFNa2b) for adjuvant treatment of stage III malignant melanoma: Pooled analysis of two randomized phase III trials (NCT00226408 and ISRCTN75125874) with 980 patients.
Authors: Weichenthal Michael , Chiarion-Sileni Vanna , Hauschild Axel , Del Bianco Paola , Trefzer Uwe , Guida Michele , Enk Alexander , Romanini Antonella , Loquai Carmen , Ridolfi Ruggero , Schadendorf Dirk , Mandala Mario , Koller Josef , Silvestri Barbara , Gogas Helen , Medici Michele , Dummer Reinhard , De Salvo Gian Luca , Mohr Peter
Published: March 2020

e20028

Background: Adjuvant high-dose interferon (HDI) treatment of patients (pts) with malignant melanoma (MM) consists of 4 weeks intravenous (IV) induction with 20 MU/m² interferon (IFN) alpha 2b followed by 11 months of 10 Mio IU/m² IFN subcutaneously (sc). It is unclear whether both parts of the regimen are mandatory for the efficacy of HDI treatment. The adjuvant phase III trials DeCOG MM-ADJ-5 and the Italian Melanoma Intergroup (IMI) trial evaluated intermittent IV HDI (iHDI) regimens as compared to standard HDI. In both trials, the experimental arm consisted of iHDI for 3 or 4 cycles, respectively. To gain more insight into the role of iHDI in the adjuvant setting we performed a pooled analysis of both trials. Methods: Based on the intent-to-treat populations, the German DeCOG trial contributed data on 627 MM pts. with stage III (AJCC 2002) resected intransit or lymph node metastasis. From the Italian IMI trial 330 pts. with stage III regional lymph node metastasis excluding intransit metastasis were evaluable. We performed a combined analysis with respect to relapse free survival (RFS) and overall survival (OS), and toxicity using Cox regression models. Results: Median follow-up was 4.6 years in the DeCOG trial and 7.2 years in the IMI trial. There were 320 relapses in the DeCOG trial (51%) and 179 relapses in the IMI trial (54%) resulting in a combined hazard ratio (HR) for RFS of 1.11 (95% CI 0.93; 1.33) comparing iHDI vs.conventional HDI. OS was similar for iHDI vs. conventional HDI (HR 1.04; 95% CI 0.84; 1.29). There was no significant heterogeneity comparing different substages (IIIA vs. IIIB vs. IIIC) or ulcerated versus non-ulcerated primary tumors. In both studies more patients discontinued treatment due to toxicity or impairment of quality of life with conventional HDI as compared to iHDI (DeCOG: 31.0% vs. 16.7%; IMI: 31.2% vs. 23.8%). Conclusions: The pooled analysis of the two pulsed adjuvant HDI treatments showed no significant differences for RFS or OS as compared to conventional HDI. There is a favorable safety profile and less overall toxicity in the pulsed regimens.
Risk of skin cancer in multiple myeloma patients: A retrospective cohort study.
Authors: Robinson Austin A , Kitto Alex , Cheema Simrin K , Madden Erik K , Norberg Adam S , Fors Darron H , Diehl Joseph W , Waterman Gabriel N. , Hilger James D. , Swift Regina A. , Berenson James R.
Published: March 2020

e20044

Background: Multiple myeloma (MM) patients (pts) have shown a higher risk of developing other cancers, although the type, time course, and relationship to MM treatment of these cancers are less clear. In this study, we determined the risk of specific skin cancer (CA) types among MM patients and its relationship to onset of MM and treatment. Methods: MM pts and unrelated age, sex, and race-matched companions (controls) seen at a MM clinic were enrolled in a retrospective cohort study. Information regarding baseline characteristics of MM and history of skin CA was obtained from medical records. Overall skin CA prevalence and types were compared between groups; among MM patients, the occurrence of skin CA was analyzed relative to date of diagnosis and treatment regimens, with stratification according to treatment duration. Results: We enrolled 205 MM pts and 201 controls with 27.3% and 14.9% demonstrating skin CA, respectively (p < 0.001). Specific types of skin CA included 60 and 37 basal cell carcinomas (BCC), 50 and 17 squamous cell carcinomas (SCC), and 9 and 5 melanomas in the MM pts and controls, respectively. The standardized incidence ratios (SIR) were SCC: 2.88 (p< 0.001), BCC: 1.59 (p<0.001), and melanoma: 1.76 (p = 0.074). SCC SIR was elevated (p<0.001) across each yearly time point from 10 years prior to MM diagnosis through 10 years subsequent to MM diagnosis. BCC SIR was elevated (p <0.002) from 7 through 10 years following MM diagnosis. The SIR markedly increased over time following the diagnosis of MM for both SCC and BCC. Relative risk (RR) was determined for pts treated with bortezomib, immunomodulatory agents, alkylating agents, glucocorticoids, and anthracyclines. There was no significant increase in RR overall or for any specific type of skin CA in relationship to the type or duration of MM treatment. Conclusions: MM pts show an increased risk of skin CA (there was no increase in melanoma incidence), including SCC and BCC. SCC occurred before and following the diagnosis of MM whereas BCC followed the diagnosis of MM. The post-MM diagnosis increase in skin CA was not related to specific drugs used to treat MM.
Consequential administration of intralesional (intratumoral) GM-CSF and IL-2 in the management of metastatic and primary invasive cutaneous melanoma.
Authors: Elias E. George , Sharma Bhuvnesh K
Published: March 2020

e20052

Background: Patients with dermal and subdermal metatases as well as invasive primary melanoma allow a great opportunity to evaluate the local and systemic response to intralesional therapy. Methods: Ten patients were studied and completed 2½ years of of follow-up. Four had multiple small intransit metastases each measured 3mm-1cm with 3 to >100 lesions per patient, three had large coalesced sclerotic lesions, and two had distant metastases with palpable subcutaneous nodules. Each received intralesional GM-CSF 500 μg weekly, and in case of failure, IL-2 was substituted at 18 million IU weekly. One patient with invasive primary melanoma and a satellite lesion received both cytokines at the skin lesions one week preoperatively. All the patients had flow cytometric analysis of the peripheral blood before and during therapy. All resected tissues were examined histopathologically and by immunohistochemistry. Results: This was safe and nontoxic program. Three of the four patints with small lesions had complete response (CR) to GM-CSF and one failed but had CR to IL-2. All four patients are alive free of disease for 31-45 months. The three patients with sclerotic lesions failed to respond to either agents. One of the two patients with distant metastases had CR for 6 months. The resected tissues from the patient with primary and satellite lesions revealed complete tumor necrosis with massive histiocytosis and overexpression of CD8+, CD83+ and CD25+ cells at the injection sites and regional lymph nodes and is alive free of disease for over 32 months. The flow cytometric analysis showed no significant changes in white cell differentiation and no dendritic cells were identified before or during therapy. Conclusions: Consequential intralesional administration of GM-CSF and IL-2 seems to have a role in the management of some high-risk patients. While GM-CSF can stimulate autologous dendritic cells, IL-2 activates T cells in the presence of patient own tumor. Such combination can activate a strong antitumor response specific to the patient, which is taken-up by the lymphatics.
An evaluation of lifestyle changes in Turkish cancer patients after diagnosis.
Authors: Yumuk Perran Fulden , Kahraman Benan , Yilmaz Merve , Koyyeri Melike , Binici Merve , Turhal Nazim S.
Published: March 2020

e20503

Background: To determine lifestyle changes in cancer patients after the diagnosis of malignancy. Methods: Between March 16th and September 30th, 2011, a questionnaire consisting of 20 questions was administered via a face-to-face interview to 150 patients at the Marmara University Hospital Oncology Unit. Each patient was queried during the administration of their chemotherapy. Six of the questions were independent choices, and 14 were dependent (multiple choice). A local ethical committee approval is obtained. Results: Of the 150 patients, 70 (46%) were male and 80 were female, and their median age was 55 (range 22-82) years old. An unusually large percentage (28%) of the patients reported that they did not know their diagnosis, and in another question 25% reported that they did not want to talk about their illness. Following their diagnosis, 71% of males and 50% of females reported that they were complying with guidelines for a healthy lifestyle, and 19% of the patients said that they were eating healthier food. At the time they filled out the questionnaire, 61% said that they were hopeful; however, close to 10% said that they felt hopeless. Approximately 53% of the participants said that following their diagnosis, they had a more sympathetic view of the underserved and underprivileged. Conclusions: It was surprising that an unexpectedly high percentage of the respondents reported that they did not make any changes in their lifestyles after their diagnosis of cancer, including eating healthier food. It appears Turkish cancer patients are coping with cancer in different means and ways than we expected of them.
Psychotherapy for adjustment disorder in oncological patients: A systematic review.
Authors: Lopez Pablo , Gercovich Daniela , Bortolato Diego , Margiolakis Patricia , Morgenfeld Mirta , Rosell Laura , Musini Silvina Laura , Gil Deza Ernesto
Published: March 2020

e20504

Background: Many previous studies argue that the Adjustment Disorder is the most prevalent mental syndrome in patients with cancer. However the research about the psychological treatment for this disorder is scarce. The aim of this study was to evaluate the efficacy of psychological treatments in Adjustment Disorder for oncological patients. We systematically reviewed the randomized controlled trials of psychological interventions for this specific population. Previous related reviews include less specific studies in terms of patients and interventions selected. Methods: Electronic searches were carried out. To identify randomized studies that were published up to 2012, we have searched in the following databases: PubMed, PsycINFO and the Cochrane Central Register of Controlled Trials. The search strategy included the following terms: cancer, adjustment disorder, oncology, psychotherapy, psychosocial interventions and stress. Additionally, we have searched in Scholar Google to find gray literature. The study designs, participants, treatments and outcome characteristics of the studies were coded and evaluated by two independent researchers, following the established selection and inclusion criteria. Results: Following the criteria, we found only one randomized study about the efficacy of psychological treatment for Adjustment Disorder in cancer patients, published in 1998. Conclusions: Considering that the Adjustment Disorder is the most prevalent mental illness in cancer patients, the lack of evidence about the efficacy of psychological treatment represents a significant public health issue. This review reveals that such lack of evidence exists, indicating a serious need of increasing studies about psychological treatments for this specific population.
Efficacy of zoledronic acid in postmenopausal Japanese women with early breast cancer receiving adjuvant letrozole: 36-month results.
Authors: Takahashi Shunji , Iwase Takuji , Kohno Norio , Ishikawa Takashi , Kim Seung Jin , Hosoda Mitsuchika , Horiguchi Jun , Yamauchi Hideko , Hozumi Yasuo , Okada Morihito , Fukunaga Masao , Noguchi Shinzaburo
Published: March 2020

e20510

Background: We reported 12-month results of upfront zoledronic acid (ZOL) therapy, which prevented bone loss in postmenopausal Japanese women who were receiving adjuvant letrozole, confirming the Z-FAST and ZO-FAST studies results. But the examination in the long term of aromatase inhibitor-associated bone loss has not been proved in the Japanese or Asia women. Methods: Postmenopausal women with hormone receptor positive early breast cancer (BC) patients receiving adjuvant letrozole were randomly assigned to receive either upfront or delayed-start ZOL (4mg intravenously every 6 months) for 5 years. The delayed group received ZOL when lumbar spine (L2-L4) BMD decreased to less than young adult mean (YAM) – 2.0 S.D or when a nontraumatic fractured occurred. The primary endpoint of this study was to compare the changes in L1-L4 BMD at month 12 between the groups. Secondary endpoints, measured at other predetermined timepoints, included comparing changes in L1-L4, L2-L4and total hip (TH) BMD and markers of bone turnover, fracture incidence, and time to disease recurrence. We report the results of 36-month interim analysis. Results: At 36 months, mean change in L1-L4 BMD was 10.7% higher in the upfront group than in the delayed group ( 95% CI, 9.2% to 12.1%; p< 0.001 ), L2-L4BMD was 10.9% higher ( 95% CI, 9.3% to 12.5%; p< 0.001 ), and TH BMD was 6.7% higher ( 95% CI, 5.3% to 8.1%; p< 0.001 ). The incidence of fracture was not significantly different between each group (upfront, 1(1.0%) vs. delayed, 4(4.1%)). Disease recurrence was reported in 3 upfront (3.1%) and 1 delayed (1.0%) patients. By month 36, 11 patients (11.3%) in the delayed group initiated ZOL therapy. There was no significant difference of adverse events other than fever with ZOL at the first treatment between the two groups. Conclusions: Upfront ZOL seems to be the preferred treatment strategy versus delayed administration, as it significantly and progressively increases BMD in postmenopausal Japanese women with early BC who were receiving adjuvant letrozole for 36 months. Clinical trial information: UMIN000001104.
Impact of skeletal-related events on pain and analgesic use in patients with solid tumors and bone metastases.
Authors: Fallowfield Lesley , Cleeland Charles S. , Von Moos Roger , Patrick Donald , Body Jean-Jacques , Egerdie Blair , Stopeck Alison , Brown Janet Elizabeth , Marx Gavin M. , Palazzo Felipe , Damyanov Danail I , Zhou Ying , Braun Ada , Balakumaran Arun , Qian Yi
Published: March 2020

e20514

Background: Skeletal-related events (SREs) including pathological fracture (PF), surgery (SB) or radiotherapy to bone (RB), or spinal cord compression (SCC) occur frequently in patients (pts) with advanced cancer and bone metastases and may cause debilitating clinical sequelae for pts. Pooled results from 3 clinical trials showed denosumab was superior to zoledronic acid (ZA) for prevention of SREs. We now evaluate the burden of SREs through pt-reported pain and analgesic use. Methods: Randomized (1:1) pts in the phase III, double-blind, placebo-controlled trials received denosumab (120 mg SC) or ZA (4 mg IV, adjusted for renal function) monthly. In this posthoc analysis, data from pts with solid tumors in the 2 treatment arms were pooled. At baseline (BL) and each monthly visit, pain was assessed via the Brief Pain Inventory (BPI; 0 no pain to 10 severe pain), and pts’ analgesic use with the Analgesic Quantification Algorithm (AQA; 0 no analgesics to 7 > 600 mg oral morphine equivalent/day). Pain and analgesic use for pts with SREs were assessed from 6 months before to 6 months after the 1st on-study SRE. A control group was comprised of all pts without SREs; the index time was defined as the median time to each SRE type. SRE impact was assessed using a stratified Cox proportional hazards model adjusting for SREs, as time-dependent covariates, and other baseline characteristics, and reported as HR and 95% CI. Results: 1,925 pts had an on-study SRE (first SRE type: 923 PF; 829 RB, 119 SCC, 54 SB), and 3,618 pts did not. A greater proportion of pts with SREs had a BPI worst pain score > 4 (moderate/severe pain) or an AQA score ≥ 3 (strong opioid use) than did pts with no SREs. The development of SRE was associated with significantly greater risk of pain progression from no/mild pain at BL to moderate/severe pain on study (PF 1.29 [1.07, 1.57], P = 0.009; RB 2.51 [2.03, 3.10], P < 0.001; SCC 3.07 [1.83, 5.13], P < 0.001; and SB 2.75 [1.19, 6.33], P = 0.018). Conclusions: Pts who experienced on-study SREs had increased pain severity requiring stronger analgesic use. Effective treatments that delay or prevent SREs can reduce pain and the need for palliation with opioids. Clinical trial information: NCT00321464, NCT00321620, and NCT00330759.
Psychosocial outcomes in cancer survivors treated at a comprehensive cancer center or a minority-serving institution.
Authors: Friedman Debra L. , Sanderson Maureen , Hull Pamela , Wujcik Debra , Ashworth Dira R , Okafor Amaka , Kennedy Jane , Hill Paula , Conner Nalini , Shen Miller David , Wolff Steven N.
Published: March 2020

e20523

Background: Cancer health disparities are well described for incidence, diagnosis and treatment. Little is known about disparities among long-term survivors. Methods: At Vanderbilt-Ingram Cancer Center (VICC), an NCI-designated comprehensive cancer center and Meharry Medical College (MMC), minority serving institutional partner, we evaluated quality of life (QOL) using the FACT-G, FACT-B, FACT-L, and FACT-P; posttraumatic stress disorder (PTSD) using the PTSD Checklist (PCL); and posttraumatic growth (PTG) using the PTG Inventory (PTGI) among breast, lung or prostate cancer survivors. We used linear regression to compare the scale mean values by institution while adjusting for confounding variables. Results: Among 111 breast, 53 lung and 68 prostate cancer survivors, mean age was 62 years, 61% were female, 33% were black, 65% were married, 22% and 67% respectively had a high school degree or some college/higher education, 36% were employed and 94% were insured. MMC survivors were younger (p = 0.0005), more likely to be black (p <0.0001), less likely to be married (p < 0.0001), less educated (p<0.0001) and more likely to be uninsured (p < 0.0001). After adjusting for race, insurance status and educational level, there were no significant differences in cancer-related QOL between VICC and MMC survivors. MMC survivors did score significantly higher than VICC survivors on the PCL (33.9 vs. 28.3; p = 0.01) and the PTGI (75.9 vs. 62.5; p = 0.002). A total of 19 (8.3%) survivors met criteria for PTSD with a score of 50 or more (18.1% MMC, 3.8% VICC, p =0.003). Scores were significantly increased for MMC survivors relative to VICC survivors on all PTG subscales, especially the appreciation for life subscale (p = 0.0005). Conclusions: Cancer health disparities extend into the survivorship period. Although overall QOL did not differ, survivors treated at an underserved institution had significantly higher PTSD than those treated at a comprehensive cancer center. Underserved survivors also exhibited higher degrees of PTG. Further evaluation will identify the most significant sources of stress and resilience in order to design interventions to improve psychosocial wellbeing and decrease disparities.
Actigraphy findings and cancer-related fatigue (CRF) in advanced cancer patients treated with methylphenidate (MP) and nursing telephone intervention (NTI).
Authors: Bruera Eduardo , Yennurajalingam Sriram , Balachandran Dave , Padhye Nikhil S , Williams Janet L. , Frisbee-Hume Susan
Published: March 2020

e20528

Background: There are limited studies about actigraphic sleep, wakefulness, activity and fatigue and treatment in advanced cancer patients. The objective of this study was to evaluate the changes in the nocturnal sleep/rest, and daytime wake/activity and subjective measures of fatigue before and after treatment with MP+/- NTI. Methods: A subset of patients from a previous reported placebo and control telephone intervention (CTI) controlled RCT of MP and/or NTI for CRF were reviewed. Subjective and objective assessments were analyzed at Day-8 and Day-15 as a result of treatment with MP and/or NTI or their control arms. Actigraphic sleep measures assessed were total sleep time (TST), sleep efficiency, and wake after sleep onset (WASO). Additionally, activity (mean day-time activity), and fatigue (FACIT-F, ESAS-Fatigue item) were included in the multivariate analysis. Results: A total of 60 (MP=30, Placebo=30; NTI=35; CTI=25) patients were evaluated. The median age was 56, 62% were female; most common cancer type was breast 13/60(22%). The baseline mean FACIT-F subscale, ESAS Fatigue item, TST, WASO, sleep efficiency and day-time activity were 22.4 (9.33), 6.5(1.74), 437(162.4), 139(121.4), 71(16.4), 202(438). Multivariate outcomes at Day-8 showed significant change from baseline (η2=0.38, p<0.001) and interaction effect between MP and NTI (η2=0.26, p=0.015). WASO had an interaction effect (β=-101.4, p=0.009), an MP effect (β=80.4, p=0.002) and reduction in time (β=-52.1, p=0.003). FACIT-F and ESAS-Fatigue item showed improvement in time (β=6.9, p=0.010; β=-2.4, p<0.001). Conclusions: WASO was significantly lower in patients receiving methylphenidate and nursing telephone intervention. Further larger studies are needed to validate these findings.
Effects of NEPA (novel combination of netupitant and palonosetron) on ECG of healthy volunteers: A randomized, controlled, thorough ECG trial.
Authors: Spinelli Tulla , Moresino Cecilia , Baumann Sybille , Timmer Wolfgang
Published: March 2020

e20538

Background: Despite advances in supportive cancer care, chemotherapy-induced nausea and vomiting (CINV) is ranked by patients among the worst side effects of chemotherapy. NEPA is a new antiemetic under development composed of a unique fixed-dose combination of netupitant (NETU, 300 mg), a new, highly selective NK1 receptor antagonist (RA), and palonosetron (PALO, 0.5 mg), a pharmacologically and clinically distinct 5-HT3RA. NEPA targets the 2 most important emetic pathways with a single oral dose. Although PALO is not associated with cardiovascular issues, this study aimed to evaluate the tolerability and cardiovascular safety of different doses of NETU + PALO. Methods: This randomized, double-blind, parallel-group, placebo- and open-label positive-controlled study in 197 volunteers (106 men) included 4 treatment groups: placebo, 200 mg NETU + 0.5 mg PALO (NEPA 200/0.5), 600 mg NETU + 1.5 mg PALO (NEPA 600/1.5), and 400 mg moxifloxacin. Assessments, based on ICH E14 Guidelines, included a 24-h baseline ECG after which volunteers received a single dose of treatment, followed by ECG measurements for 2 days. The primary objective was to determine the individual heart rate-corrected QT interval (QTcI) (n=196). Safety and tolerability of NEPA groups were also assessed (n=197). Results: Mean placebo-corrected QTcI change from baseline was +5 and +4 ms for NEPA200/0.5 and NEPA600/1.5, respectively. Mean placebo-corrected change from baseline for heart rate (HR) was -3 bpm for the 2 NEPA groups. Placebo-corrected changes in pulse rate (PR) and QRS durations were similar in both NEPA groups (0 to 1 ms) and not clinically different from placebo. These data show no signs of an effect of NEPA groups on QTcI. In comparison, the moxifloxacin showed the expected increase in QTcI vs placebo (+8/9 ms). The frequency of all treatment-related AEs (TRAEs) for NEPA200/0.5 was lower than placebo but slightly higher in volunteers treated with NEPA600/1.5. The most commonly reported TRAEs in the NEPA groups were constipation, upper abdominal pain, and headache. Conclusions: NEPA treatments produced no significant effects on QTcI, HR, PR, QRS interval, or cardiac morphology relative to placebo.
The role of oncologic health care providers in end of life discussions for women with recurrent gynecologic or breast cancer.
Authors: Stuckey Ashley , Robison Katina , Dizon Don S. , Rogers Michelle , Ott Miles , Miller Susan , Politi Mary , Clark Melissa
Published: March 2020

e20543

Background: Advance care planning (ACP) is an important topic for women with metastatic or recurrent cancer. Unfortunately, data suggest ACP is often not discussed at health care visits. Because patients with metastatic or recurrent cancer are incurable, the issue of end of life (EOL) is one faced by patients and providers. This study evaluates how often oncologic health care providers initiate EOL conversations with their patients. Methods: Eligible patients included women with metastatic or recurrent gynecologic or breast cancer of ≥3 month’s duration in an academic women’s oncology program. Interviews were conducted by research staff. Clinical characteristics and documentation of EOL decisions were obtained through chart reviews. Data were analyzed using SAS v.9.3. Multivariate logistic regression was used to model the association of EOL discussions with ACP. The study was approved by the hospital and university Institutional Review Boards. Results: 200 women were enrolled; 64% had stage III-IV cancer at diagnosis. The majority was white (91%) with a mean age of 60 (range 35-82). A total of 638 providers were identified (mean: 3.2 providers per patient; 57% female). Health care provider type and gender were not associated with EOL discussions. Only 49 women (25%) recalled an EOL conversation with at least one provider which appeared to correspond to the low proportion of people with documented ACP. Only 42 (22%) had an advanced directive (AD) and 29 (15%) a health care proxy (HCP) in the chart. Having an EOL conversation with at least one provider was not associated with a chart-documented AD (OR=1.6, 95% CI=0.7-3.6) or HCP (OR=1.8, 95% CI=0.7-4.5). The time since recurrence was shorter for those reporting EOL conversations (1.7 vs. 3.1 years, p=.0274). Conclusions: In this study, oncologic health care providers infrequently initiated EOL discussions with their patients with metastatic or recurrent cancer. More concerning, patient recollection of an EOL discussion with a provider was not associated with chart-documented ACP. Further studies evaluating the factors limiting EOL discussions as well as studies testing interventions to improve provider documentation of the ACP are warranted.
Primary metastatic breast cancer in elderly: An international comparison.
Authors: Van De Water Willemien , Bastiaannet Esther , Egan Kathleen , de Craen Anton J.M. , Van De Velde Cornelis J. H. , Liefers Gerrit-Jan , Extermann Martine
Published: March 2020

e20545

Background: In primary metastatic breast cancer in elderly, both advanced age and advanced disease limit life expectancy. It remains a challenge to balancing the benefit from therapy and risk of adverse events impeding quality of life or survival. Our aim was to compare management and outcome of primary metastatic breast cancer in elderly treated in two health care settings. Methods: The first cohort comprised a hospital based series in the United States (US, n=73 women diagnosed between 2003 and 2012); the second comprised a population based series in The Netherlands (NL, n=125 women diagnosed between 2008 and 2012). All were ≥65 years at the time of diagnosis. Country was used as an instrumental variable, as a proxy for randomization to either care setting. Multivariable survival analyses were adjusted for age, comorbidity, T stage, nodal stage and hormone receptor status. Results: Characteristics of US and NL patients were similar, except for age (median 72; 79 years, p>0.001). US patients more often received breast surgery and chemotherapy in particular, less often endocrine therapy as monotherapy (Table), and received more lines of treatment (median 4; 2, p<0.001). Adverse events rarely were a reason for a next line of therapy (6% in each cohort). Three-year survival tended to be higher in US patients (HR for US patients was 0.71 (95% CI 0.48-1.05), p=0.089). Multivariable analyses revealed no survival differences (HR for US patients was 0.86 (95% CI 0.53-1.38), p=0.523). Results were similar after stratifying by age at diagnosis (<70; ≥70 years). Conclusions: Treatment of elderly with primary metastatic breast cancer varied considerably between the NL and the US cohort. However, no differences in overall survival were observed. These results warrant further studies to evaluate the extent of treatment in this population. [Table: see text]
A retrospective study of dose-dense adjuvant paclitaxel without G-CSF support in patients with breast cancer.
Authors: Singh Anurag Kumar , Malhotra Akshiv , Lemke Sheila M.
Published: March 2020

e20547

Background: Dose dense AC (Adriamycin plus Cyclophosphamide) followed by paclitaxel (Pac) given every 2 weeks with Granulocyte-Colony Stimulating factor (G-CSF) support remains the standard of care for adjuvant chemotherapy in newly diagnosed breast cancer patients . Although, the need for growth factor support with AC is clear, its role with dose dense Pac is not so clear. The objective of this retrospective single institution study was to evaluate the need for primary prophylaxis with G-CSF with dose dense Pac. Methods: Data from 115 patients treated at Upstate Medical University from 2005-2012 was collected after IRB approval. All patients received four cycles of dose dense AC (A- 60mg/m2 with C- 600 mg/m2) with G-CSF support on day 2 followed by Pac (175 mg/m2) with no primary G-CSF support. The median age of patients was 48 years. There were 11 patients (10%) with Stage I, 68 (60%) with stage II and 36 (30%) with stage III disease. The prevalence of ER/HER2 status was as follows: ER+/Her2 + (13%), ER+/Her2-(60%), triple negative (26%) and ER-/Her2+ (1%). Results: Only 3 patients (2.6%) in this study population developed neutropenic fever. 109 patients received no G-CSF support and completed a total of 382 doses of Pac (average 3.5). Dose reduction was needed in 6 patients, related to neutropenic fever (n=3), neutropenia without fever (n=2) and severe arthralgia (n=1). A total of 88 patients completed all planned four cycles. Of the 27 patients who got less than the planned 4 cycles, most stopped because of neuropathy (n=17), arthralgia (n=4), hand foot syndrome (n=2), elevated LFTs (n=1), allergic reaction (n=1) and unknown reason (n=1). Most common Grade III/IV toxicity was neuropathy. Dose delays were seen in only 5 patients, 3 related to neutropenia and 2 because of elevated liver function tests. Conclusions: G-CSF has its own side effects, most common being bone pain. G-CSF also adds significantly to climbing costs of oncology care. Although retrospective in nature, this study shows that only a small minority of the patients develop neutropenic complications with dose-dense Pac. Avoiding primary prophylaxis with G-CSF will not only reduce costs but also reduce toxicity that can be additive to Pac toxicity.
Inappropriate prescribing in older patients with cancer.
Authors: Sui Jane Sze Yin , Kelly Ciara Marie , Barry Patrick , Jordan Emmet , Rehman Zia , Akhtar Mateen , Gallagher Loretto , Horan Anastasia , O'Keeffe Carmel , O'Connor Miriam , Calvert Paula , Power Derek Gerard , Horgan Anne M.
Published: March 2020

e20550

Background: Inappropriate medication use is common among community dwelling and hospitalized older adults but understudied in the oncology population. We measured the incidence of inappropriate prescribing among older cancer patients attending an oncology day-ward for systemic therapy. Methods: The tools used to identify inappropriate prescribing were the Beers’ criteria (both Independent [ID] of and Considering diagnosis [CD] – 2012 version) and the STOPP tool (Screening Tool of Older People’s potentially inappropriate Prescriptions). The setting was an urban based hospital oncology day-ward. Consecutive subjects ≥ 70 years were screened and all had both tools applied to their prescription drugs, cross referenced with their current active medical diagnosis. Results: Medication lists were collected from 96 patients from November 1st 2012 to January 31st2013: 52% male, mean age 75 years (range 70-88). The most common cancers were colorectal (24%), breast (23%), lung (11%) and prostate (11%). 38 patients (40%) were on 0-4, 49 (51%) on 5-9 and 9 (9%) on >9 medications. The total number of inappropriate prescriptions (Beers ID and CD “medications to avoid”) was 34, prescribed in 29 (30%) patients. The most common drug prescribed inappropriately as per these criteria was the antiemetic, metoclopramide (n=10, 29%). An additional 70 prescriptions were dispensed for Beers “medications to use with caution” in 55 (57%) patients - predominantly vasodilators. The STOPP tool identified 13 inappropriate prescriptions in 12 patients (13%). The two most commonly prescribed inappropriate medications were long acting benzodiazepines (n=4) and long term use of sedating antihistamines (n=3). Conclusions: This study identified a high rate of inappropriate prescribing among this population using both tools, with a higher rate identified by the Beers Criteria. Routine application of a validated tool to identify inappropriate prescribing has merit in the oncology setting to minimize risk to patients. However, the development of an easy to apply tool that considers the underlying cancer diagnosis, prognosis, cancer treatment and necessary supportive therapy is warranted.