bluuebunny/crossref_metadata_2025 huggingface dataset:
Evaluation of combined BCL-2/MCL-1 inhibition as a therapeutic approach for synovial sarcoma.
Authors: Fairchild Carter Kent , Floros Konstantinos , Jacob Sheeba , Coon Colin , Puchalapalli Madhavi , Hu Bin , Dozmorov Mikhail , Koblinski Jennifer , Smith Steven , Domson Gregory , Ebi Hiromichi , Faber Anthony , Boikos Sosipatros Alexandros
Published: May 2020

e23561

Background: While Synovial Sarcoma (SS) only accounts for about 10% of soft tissue sarcomas (STS), or ~10,000 cases/year, ~4,000 of these will be fatal. Little benefit has been seen with newer combination chemotherapies and immune checkpoint inhibitors. SS is a transcription factor-driven cancer characterized by an t(X;18) chromosomal translocation resulting in the SS18-SSX fusion gene. SS is also known to overexpress the anti-apoptotic protein BCL-2, which has been used as a diagnostic marker for SS. Venetoclax, the FDA approved BH3 mimetic which specifically inhibits BCL-2, has been used to treat BCL-2-driven hematological cancers. Yet, preclinical studies of venetoclax, currently in clinical use for BCL-2 related hematologic malignancies, have failed in SS, raising the possibility of other BCL-2 family members playing a role in resistance. Methods: Publicly available gene expression databases of SS were queried for expression of BCL-2 family member expression, including the endogenous MCL-1 inhibitor, NOXA. Six SS cell lines, including ASKA, HS-SY-II, Yamato, SW982, SYO.1, and an ex vivo line from a SS patient-derived xenograft (PDX) were tested in vitro with combinations of venetoclax and the MCL-1 inhibitor S63845, using cell viability assays. In vivo testing employed both a patient-derived xenograft (PDX) model of SS and a cell line derived (SYO.1) xenograft model. Results: Queries of published gene expression data for SS demonstrated that SS expresses low levels of the endogenous MCL-1 inhibitor, NOXA, nominating a mechanism for intrinsic venetoclax resistance in these tumors, and suggesting rational combination of venetoclax and the MCL-1 inhibitor, S63845. In vitro, SS all cell lines possessing the SS18-SSX fusion gene demonstrated synergistic sensitivity to combined S63845 and venetoclax, despite generally insensitivity to either drug as monotherapy. Importantly, in an SS PDX, we demonstrated S63845 and venetoclax synergize to induce tumor regression. In the SYO.1 xenograft model, combination therapy significantly reduced tumor growth compared to no treatment or single agent groups. Conclusions: These findings provide the preclinical rationale for translation of the rational combination of BCL-2 and MCL-1 inhibitors into clinical trials for SS.
Efficacy of anlotinib in advanced soft tissue sarcoma by age, gender, and ECOG performance status.
Authors: Fang Zhiwei , Yao Yang , Cai Jianqiang , Chi Yihebali , Wang Shusen , Huang Gang , Cai Qiqing , Shang Guanning , Wang Guowen , Qu Guofan , Wu Qiong , Jiang Yu , Song Jianmin , Chen Jing , Cai Zhengdong , Zhu Xia , Bai Chunmei , Lu Yongkui , Yu Zhihua , Shen Jingnan
Published: May 2020

e23562

Background: ALTER0203 was a randomized phase IIB trial (NCT02449343) that demonstrated single-agent activity of anlotinib in advanced STS (aSTS). The primary endpoint progression-free survival (PFS) was met and presented as an oral presentation in 2018 ASCO. We evaluated the relationship between age, gender and ECOG performance status. Methods: Median PFS was analyzed in subgroups of age (≤40 y; > 40 y), gender (male; female) and ECOG performance status score (0; 1). All analyses were exploratory and required cautious interpretation. Results: A total of 158 patients received anlotinib in the ALTER0203 study. 79 patients (50.0%) were > 40 y. Median PFS was longer in patients of age > 40 y than ≤40 y (7.43 vs 5.43 months, P = 0.40). In patients receiving anlotinib, 76 patients (48.1%) were female and median PFS was longer in female than male (9.80 vs 4.43 months, P = 0.002). All enrolled patients had a Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 or 1. 107 patients (67.7%) were with poor PS (ECOG PS = 1). The median PFS was longer in PS of 1(8.43 vs 4.73, P = 0.53) than PS of 0. Conclusions: In patients receiving anlotinib, longer mPFS was observed in patients of age > 40 y, ECOG PS = 1 and female. Clinical trial information: NCT02449343 .
Retrospective analysis of intraoperative radiation therapy with low-kilovoltage x-rays (IORT-LK) in soft tissue sarcomas (STS).
Authors: David Waldec Jorge , Hanriot Rodrigo De Morais , Di Paula Filho Raphael Paulo , Amaral Silva Pedro Alexandre Ismael , Costa Marcos Andre De Sa Barreto , Yen Cheng Tzu , de Mello Evandro Sobroza
Published: May 2020

e23575

Background: STS include a heterogeneous group of malignancies that arises from or into connective tissues and limbs are the preferential primary sites. An adequate local control with multimodality therapy can be obtained in most cases. An additional approach, that is, the IORT-LK is able to deliver high dose to risky areas for recurrence, minimizing the toxicity to structures around the target. Such an importance is even greater in abdominal sarcomas, because there is some difficulty in removing the whole neoplasia with clear margins. IORT-LK has the advantage of higher Relative Biological Effectiveness (RBE), a mathematical model that measures the potential for tumour double-strand break (radiation effectiveness), that is close to Proton beam and higher than electron beam. Nevertheless, IORT-LK is not free of complications. It has been reported peripheral neuropathy and enteritis, in cases of limb and abdominal STS, respectively. Methods: In this retrospective study from a single Brazilian institution (Hospital Alemão Oswaldo Cruz), we reported 6 patients with histologically confirmed STS, that underwent IORT-LK (Intrabeam - Carl Zeiss). There are 3 male and 3 female patients, with a median age 48 years, and mean of 39 years. The histological subtypes are as follows: fibromyxoid sarcoma, high grade pleomorphic sarcoma, desmoid tumor, chondrosarcoma, dedifferentiated liposarcoma and malignant schwannoma - one subtype for each patient. The primary sites are: inferior limb (3), superior limb (1) and abdomen (2). Results: IORT-LK was administered in doses that ranged from 14 to 15 Gy to the involved area. Two patients, each one with a limb STS, received also neoadjuvant chemotherapy. With a mean follow-up of 30 months, there is no local recurrence among the 6 patients reported. The first patient received the IORT-LK in April, 2017 and the last one in July, 2019. All of them had clinical observation up-to-dated on January, 2020. No serious complications were observed, but one patient had a moderate local infection. Conclusions: The therapy was well tolerated. We must emphasize that dose previously used by Brussiers was slightly superior than ours but with electrons and not Low-Kylovoltage. In his pilot study it was used 17 Gy for treatment of abdominal sarcomas. In sum, we believe that IORT-LK has higher RBE than previous available equipment and can improve local control of STS, mainly those that arise on the extremities. Future studies must be carried out to confirm our initial impression.
Searching for the “exit ramp”: Bereaved caregivers (BCGs) describe discontinuation of transfusions at the end of life (EOL) for loved-ones (LOs) dying from acute myeloid leukemia (AML).
Authors: Cripe Larry Dean , Martin Caroline , Sargent Katie , Baker Layla , Cottingham Ann H.
Published: May 2020

e24000

Background: Transfusions may delay hospice care. This study examined how transfusions and other factors influenced care transitions, including decisions related to hospice care, for patients with AML from diagnosis to death. Methods: Nineteen BCGs participated in semi-structured interviews about their experiences. Interviews were audio recorded, transcribed and qualitatively analyzed. Results: The research team identified three stages in BCG experience: 1. Acceptance and Hope: BCG initial response to an AML diagnosis was acceptance of chemotherapy and transfusions as necessary to extend life and potentially cure the AML. Benefits of treatment were emphasized over potential harms or details. 2. Reading the Signals: BCGs learned to interpret information from a variety of sources to appreciate whether their LO was heading in the right direction or not. The signals included discussions with or decisions of the oncologist, changes or no changes in lab results, changes in the LO’s physical condition, and changes in care location in the hospital (e.g., ward bed to ICU bed). Signals were either cautionary or hard stops. Cautionary were seen as conditional, e.g., if things did not improve then LO may be at EOL. Cautionary signals were described as vague and ambiguous. Hard stops were clearer and were typically a clinician decision or recommendation to discontinue treatment and/or transfusions because there was no longer a possibility of benefit. 3. Searching for the Exit-Ramp: Hard stops precipitated awareness that death was imminent and an often-rushed search for how to care for the LO at the EOL. In retrospect the transition made sense to the BCG but they often felt unprepared at the time of transition. Conclusions: The benefits and burdens of transfusions are important signals to BCG about the EOL. Early cautionary signals and discussion may prepare BCG for transitions. Continuation of transfusions in hospice may eliminate a chance for critical conversations.
Systematic analysis of extracting data on advance directives from patient electronic health records in terminal oncology patients.
Authors: Skelton William Paul , Starr Jason Scott , Rahmanian Kiarash , Guenther Robert , Allen William L. , George Thomas J. , Moseley Ray E.
Published: May 2020

e24011

Background: Advanced care planning and living wills are critical components of caring for patients at the end of their lives. Advance directives are designed to be implemented when a patient meets the legal definition of terminal and is deemed incapacitated. By reviewing the electronic health record (EHR) in patients with terminal cancer, we sought to evaluate whether advance directives were appropriately implemented. Methods: A retrospective analysis of the EHR of 500 cancer patients from 1/1/2013 to 12/31/2016 was performed. Data points were manually collected and entered in a central database, and data analysis was completed using SAS. Results: Of the 500 patients, 160 (32%) had an advance directive (AD). The most common clinical terminology used by physicians indicating a terminal diagnosis was “progressive” (36.6%) and “palliative” (31%). The most common clinical terminology indicating incapacity was “altered mental status” (25.6%), and “not oriented” (14%). 34 patients (6.8%) met all criteria of having a terminal diagnosis, a documented AD, and deemed incapacitated. Of these patients who met all of these data points, their ADs were implemented on average 1.7 days (SD: 4.4 days) after which they should have been. This resulted in a total of 58 days of additional care provided to these patients. Conclusions: End-of-life care is a challenging albeit vital part of the practice of medicine. This study provided insight on to how ADs are managed in day to day practice in a hospital. From our analysis, it is clear that physicians are able to identify when a patient is terminal; however, it is typically later than it should have been recognized (and thereby, leading to delays in the implementation of the patient’s AD). Further studies should be performed focusing on harnessing the power of the EHR and providing physicians formative and evaluative feedback of practice patterns to ensure that ADs are honored when appropriate.
Sarcopenia and clinical evaluation in predicting treatment tolerability and outcomes in aggressive non-Hodgkin B cell lymphoma.
Authors: Drory Samuel Bernard , Forget Marie-France , Wang Han Ting , Fleury Isabelle , Ahmad Imran , Marchand Laurence
Published: May 2020

e24018

Background: Sarcopenia is associated with decreased treatment tolerance and overall survival in aggressive large B-cell lymphoma, the most common non-Hodgkin lymphoma (NHL) in the geriatric population. The impact of sarcopenia on event-free survival (EFS) in older adults with an aggressive B-cell NHL remains unclear. Our primary endpoint was to evaluate the association between sarcopenia and 6-month EFS in adults aged 65 and older diagnosed with an aggressive B-cell NHL. Methods: We performed a retrospective cohort study of adults 65 years or older diagnosed with an aggressive B-cell NHL between July 1st 2014 and June 30th 2018 who completed 1st line chemotherapy in an academic center. Sarcopenia was defined as the lowest tertile of psoas muscle index (PMI). Psoas muscle area was measured on a single axial slice at L4 using CoreSlicer software, and divided by height squared. EFS defined as no death, relapse or hospitalisation, was compared between sarcopenic and non-sarcopenic individuals using Kaplan-Meier curves and multivariable Cox regression. Results: In our cohort of 62 older adults, median age was 74 (interquartile range (IQR): 69-78) and median PMI was 7.2 cm2/m2 (IQR: 5.9-8.4). Twenty patients were sarcopenic with a median PMI of 5.5 (4.8-6.3) cm2/m2. Most patients (56%) received full dose chemotherapy. Among patients who received an attenuated dose of chemotherapy, the percentage of patients with sarcopenia was similar to the one of patients receiving full dose chemotherapy (39% vs 24%, p=0.200). After controlling for age, sex, ECOG, cardiac disease, creatinine, LDH and hemoglobin levels, sarcopenia was associated with a lower EFS (HR 3.5, 95%CI: 1.1-11, p=0.032). Although sarcopenia was not associated with the choice of an attenuated chemotherapy intensity, when stratifying for chemotherapy intensity, there was a trend in favor of decreased EFS with sarcopenia in the full dose group (p=0.095), which did not reach statistical significance. Conclusions: Sarcopenia is associated with a lower 6-month EFS in older adults who completed first line chemotherapy. These individuals may benefit from pre-chemotherapy geriatric evaluation and tighter follow-up.
The impact of frailty on the occurrence of immune-related adverse events in older patients with advanced melanoma.
Authors: Bruijnen Cheryl P. , Koldenhof Josephine J , Tonk Erwin H.J. , Verheijden Rik Jasper , van den Bos Frederiek , Emmelot- Vonk Mariëlle H. , Witteveen Petronella , Suijkerbuijk Karijn
Published: May 2020

e24028

Background: Immune checkpoint inhibitors (ICIs) have changed the melanoma treatment landscape by inducing durable responses and significantly improving survival. ICI can cause immune-related adverse events (irAES) ranging from mild to life threatening. Clinical trials have not shown major increase of irAES in older patients when compared to younger patients. However, older patients have been underrepresented and were relatively fit in these trials. In this study, we assessed the occurrence of irAEs treated with systemic corticosteroids and/or leading to treatment discontinuation (relevant irAEs) in older patients with melanoma and, if relevant irAEs occurred more often in frail patients, as assessed with the Geriatric 8 (G8). Methods: Patients ≥70 years diagnosed with advanced melanoma, about to start with ICI, and screened with a G8, were enrolled in this prospective observational study. Patients were classified according to the G8 score as “fit” (G8 score >14) or “frail” (G8 score ≤14). Toxicity was scored according to CTCAE v4.03. Primary outcome was occurrence of relevant irAEs in “fit” and “frail” patients. Secondary outcomes were the occurrence of irAEs any grade and severe irAE (grade ≥3). Results: In total, 49 patients were included for statistical analyses. Thirty-three patients were classified fit according to the G8 and, 16 patients were frail. Relevant irAEs occurred statically significantly more often in in frail patients: 12 (75%) versus 15 patients (46%) ( p=0.05). In addition, more irAEs grade ≥3 were reported in frail patients, although not significant: 7 (44%) versus 8 patients (25%) ( p= 0.11). Conclusions: Frailty, classified by the G8, is associated with the occurrence of relevant irAEs in the older patient with advanced melanoma. These data need to be confirmed in larger series.
Patient self-management and health maintenance at lung cancer diagnosis and during treatment.
Authors: Feliciano Josephine Louella , Trosman Julia Rachel , Weldon Christine B.
Published: May 2020

e24036

Background: Health maintenance is an integral part of lung cancer care starting at diagnosis and throughout cancer care continuum. Patient self-management (pSM) is a key strategy thought to contribute to promotion of health maintenance in cancer patients (McCorkle, CA Cancer J Clin. 2011, NAM 2014), but its role in lung cancer has been unexplored. We conducted this study as baseline before conducting a quality improvement (QI) to optimize health maintenance utilization and patient self-management in lung cancer. The Q will implement the 4R model (Right Info / Care / Patient / Time) for care delivery, patient self-management and teamwork (Trosman, JOP 2016). Methods: We surveyed patients with lung cancer stages I-IV undergoing cancer treatment at a tertiary cancer center 2018-2019, assessing pSM and health maintenance utilization by patients. We used simple frequencies and Fisher’s exact test in analyses. Results: Survey response rate: 81%, 149/185. We found gaps of at least 20% in all 6 assessed pSM metrics: “know stage of your cancer” (78%), “ability to explain your care to others” (73%), “clarity of care plan” (72%), “ability to manage your own care” (71%), “seldom overwhelmed, not in control of your care” (65%), and “clarity of timing and sequence of care” (35%). High level of composite pSM score ( > 2.8 on 0-4 scale) was found for 50% of patients. Patients also reported insufficient utilization of health maintenance along the 7 metrics we assessed (Table). The level of pSM impacted receipt of health maintenance: patients with high composite pSM score were significantly more likely to obtain 4 of the 7 health maintenance metrics than patients with lower composite pSM score (Table). Conclusions: While serious gaps exist in health maintenance utilization in lung cancer, it is significantly associated with the level of patient self-management. Strategies to improve patient self-management should be utilized to promote health maintenance during lung cancer treatment. Our program to implement the 4R model of cancer care delivery will evaluate if and how 4R facilitates these improvements. [Table: see text]
The prevalence and sociodemographic predictors of mobile health applications ownership among cancer survivors.
Authors: Dosunmu Gideon T , Hagan Kobina Kwantsin , Udoye Chike , Khushman Moh'd M.
Published: May 2020

e24046

Background: The transition of cancer patients from patients to survivors is challenging. Cancer survivors often experience chronic physical, social and mental health needs which remain largely unmet. Due to the growing population of cancer survivors and limited resources available to address their needs, mobile health applications (apps) have emerged to help cancer patients in assuming their new role as survivors. Here, we explored the prevalence and sociodemographic predictors of mobile health apps ownership among Cancer Survivors in the United States using a nationally representative sample. Methods: Data from cycles 1 (2017) and 2 (2018) of the 5th edition of the Health Information National Trends Survey (HINTS 5) was reviewed. Descriptive statistics was used to evaluate the sociodemographic characteristics and the prevalence of mobile health apps ownership among cancer survivors. Univariate logistic regression models were used to explore the relationship between sociodemographic predictors and mobile health apps ownership. Results: We identified 1,097 (weighted estimate of 44,666,781) individuals who self-reported having been diagnosed with cancer in the . Of these, 57.39% were females, 79% were whites, 47.18% had 2 or more medical comorbidities, 63.7% were unemployed and about 50% were aged 65 or more. Prevalence of mobile health apps ownership was 44.82%. Among all the sociodemographic variables; educational level (p = 0.015), income (p = 0.014) and employment status (p < 0.005) were predictors of mobile health apps ownership among cancer. Conclusions: Cancer survivors are digitally connected and can be approached through mobile health apps. In our study, the prevalence of mobile health apps ownership in cancer survivors was 44.8%. Educational level, income and employment status were identified as predictors of mobile health apps ownership. Due to the growing population of cancer survivors and limited resources available to address their needs, efforts to address barriers of mobile health apps adoption and utilization should be encouraged.
Khorana score as a predictive tool of venous thromboembolism in cancer patients in rural practice.
Authors: Khalil Ahmed , Ortolano Daniel , Simunich Thomas , Saad Eldin Mohamed , Hussain Munawwar , Higbee Sheetal L.
Published: May 2020

e24049

Background: The Centers for Disease Control and Prevention (CDC) estimates that 60,000 to 100,000 Americans die from venous thromboembolism (VTE) annually, costing the U.S. healthcare system $7–10 billion each year. VTE is a leading cause of mortality in cancer patients, and risk is particularly elevated in rural areas, where cancer death rates are higher than in metropolitan areas. The Khorana score has been shown to predict VTE incidence before starting treatment and as such identify those patients that would benefit most from VTE prophylaxis. We aimed to replicate the utility of the Khorana score on a rural population of cancer patients to help address VTE in advance. Methods: From our electronic health records system, we extracted data from cancer patients (age ≥ 18 years) who had begun chemotherapy from 2017-January through 2019-August. Patients who were pregnant, had undergone hormonal therapy or major surgeries within three months prior to VTE diagnosis, or had a history of coagulation disorders or VTE prior to starting chemotherapy were excluded. A Khorana score (0—6, interval = 1) was calculated for each prior to their starting chemotherapy and was used for VTE risk stratification, 0 – low; 1,2 – intermediate; ≥3 – high. We hypothesized that VTE occurrence during the first 6 months following the start of treatment would be positively associated with risk category. Results: The 144, mostly female (64%), cancer patients meeting inclusion had a mean age of 75 years (range 48—95) and VTE risk stratification: 10% (15) high, 67% (96) intermediate, and 23% (33) low. In the first 6 months of starting treatment, 6% (9/144) developed VTE, with a prevalence of 20% (3/15) amongst patients stratified as high risk, 5% (5/96) of intermediate, and 3% (1/33) of the low risk group. A linear-by-linear association of the observed Khorana scores with VTE occurrence implies a meaningful positive association between VTE risk stratification by Khorana score and VTE, chi-square (1,144) = 4.018, p = .045. Conclusions: The trend of higher VTE prevalence in intermediate and high risk patients supports the observed positive association between Khorana score VTE risk category and a greater percentage of patients experiencing VTEs with increasing risk. This trend may likely be amplified with application to a larger number of patients. The study limitations include the lack of diversity of organ affection and sample size, specifically upon risk stratification. However, initiating a discussion about the risks and benefits of VTE prophylaxis prior to starting treatment is of outmost importance.
Prevalence, screening, treatment, and complications of osteoporosis and osteopenia in Medicare patients with chronic lymphocytic leukemia (CLL).
Authors: Brander Danielle M. , Oeffinger Kevin C. , Greiner Melissa A. , Dinan Michaela Ann
Published: May 2020

e24050

Background: Despite treatment advances, patients (pts) with CLL, a common chronic cancer affecting the elderly, often experience adverse outcomes due to their comorbidities and frequent lack of routine health maintenance. We examined osteoporosis/osteopenia (OSTEO) prevalence, rates of bone mineral density (BMD, g/cm2) screening by dual-energy x-ray absorptiometry (DXA), use of bisphosphonates, and fragility fractures among Medicare pts with CLL. Methods: We identified a cohort of CLL pts >65 years with Medicare fee-for-service between 1/1/2011-12/31/2015 using the Medicare 5% national sample. Controls (5:1) were matched based on age, sex, race, and year of eligibility. Among those with OSTEO, we compared rates of bisphosphonates. Chi-square tests for categorical variables and Wilcoxon Rank-sum tests for continuous variables were used to compare CLL vs controls. Cumulative incidence of BMD screening and fragility fractures were estimated using the cumulative incidence function and compared to controls using Gray tests. For fragility fractures, we compared among subgroups with and without OSTEO. Results: Baseline characteristics are in the Table. Compared to controls, CLL pts were more likely to have OSTEO (p < .001) but less bisphosphonate use (p = .006). The 3-yr cumulative incidence of fragility fractures was higher among CLL pts (8.0%, 95% CI 7.5%-8.6%) vs controls (7.2%, 6.9%-7.4%; p = .002) as well as among those without an OSTEO diagnosis (p = .02). Cumulative 3-yr DXA use was higher among CLL pts vs controls ( < .001); however, DXA 3-yr incidence was lower in CLL pts who had chemotherapy (13.2%, 11.4%-15.4%) vs none (17.0%, 16.2%-17.9%, p = .002). Conclusions: It appears that CLL pts may have a higher risk of osteoporosis and higher rates of fragility fractures than non-CLL individuals. Fragility fractures are higher even in the subgroup of CLL pts without OSTEO, suggesting that pts may be underdiagnosed. [Table: see text]
Patterns in progression from early stage melanoma to late stage melanoma: Implications for survivorship follow up.
Authors: Switzer Benjamin , Savage David James , Song Jung Min , Stanek Carolyn , Funchain Pauline
Published: May 2020

e24055

Background: Despite an encouraging 99% five-year survival in patients diagnosed with early-stage melanoma, a higher proportion of fatal melanomas initially present with thin ( < 1mm) rather than thick ( > 4mm) melanoma.1 Therefore, early-stage melanoma survivorship remains a topic of high interest. We examined a cohort of early-stage melanomas which progressed to stage IV to inform survivorship and risk-stratification approaches in this large, understudied population. Methods: From a retrospective single-center study of 880 consecutive melanoma patients from 2016-2020, we identified new, non- de novo diagnoses of stage IV melanoma which progressed from an initial early-stage (IA-IIA) diagnosis. Descriptive data were collected via chart review on demographics, clinical features, presentation at time of progression, and follow up prior to progression. Results: A total of 50 patients met the inclusion criterion of an initial stage IA-IIA diagnosis with subsequent progression to stage IV melanoma. Primary early stage melanomas were diagnosed an average of 6.1 years prior to metastatic disease progression, with 46% (n = 23) diagnosed within 3 years, 22% (n = 11) between 4-6 years, 12% (n = 6) between 7-10 years, 8% (n = 4) between 10-12 years, and 12% (n = 6) beyond the 12 year mark from their initial early-stage diagnosis. Average age at time of diagnosis was 57.7 (median 60, range 21-68), and 62% (n = 31) were male. The two most common early-stage diagnostic sites were lower extremities (27.5%, n = 14) and back (23.5%, n = 12). The two most common sites of metastatic disease were lung (46%, n = 23) and brain (28%, n = 14). A total of 30% (n = 15) and 34% (n = 17) of this cohort maintained follow up with oncology and dermatology, respectively, prior to their stage IV diagnosis. Symptomatic disease lead to 80% (n = 40) of stage IV diagnoses, while 14% (n = 7) were diagnosed through routine oncologic or dermatologic follow up, and the final 6% were diagnosed incidentally. Conclusions: Early stage melanoma patients who develop stage IV disease exhibit wide ranges in onset of disease progression, thus survivorship plans for this group could include a combination of early provider screening and patient education for later presentations of metastatic disease. Due to relatively common metastatic involvement of the lung and brain, a high suspicion to screen for metastatic disease with symptoms involving these organs may be appropriate.
Human sperm cryopreservation prior cancer treatment: Follow up of 480 males for 23 years.
Authors: Teloken Isadora B , Petracco Alvaro , Fay Andre P. , Teloken Claudio , Badalotti Mariangela
Published: May 2020

e24061

Background: Cancer treatment represents a potential risk for spermatogenesis and may compromise male fertility. Semen freezing has become a routine process for male patients prior to cancer treatment to preserve their fertility. We sought to provide information regarding what happens to the cryopreserved material and the fertility in cancer treated patients. Using a cohort from a 23-year cryopreservation program. Methods: Patients whom cryopreserved sperm to preserve fertility due to diagnosis of cancer between 1995 and 2018 in a single private center of reproductive medicine in south of Brazil were selected. A retrospective analysis of medical records was performed and clinico-pathological characteristics were collected using standard templates. Results: A total of 480 patients were evaluated for sperm cryopreservation before cancer treatment. Testis cancer was the most prevalent (59.3%), followed by hematologic malignancies (21.4%) and prostate cancer (5.4%). The age at cryopreservation varied from 14 to 72 y/o. Among them, 61.3% were up to 30 years old, and 10.8% more than 40 y/o. 8 patients decided to not cryopreserve The mean time between the freezing and the beginning of cancer treatment was 5.5 days. Eleven patients presented azoospermia; 3 of them froze testicular tissue. A shorter time between cancer diagnosis and sperm banking was observed for hematologic malignancies ( p=0.044). Out of the 472 patients, 46.8% still keep the sperm cryopreserved, 34.3% decided to discard it, 1.9% transferred it to another clinic, 8,5% abandon the specimen and 8,5% died without using it. The main reason for discard the sample was pregnancy and/or normal sperm count after treatment. The mean age of discarding was 35.7±10.3 years old. The period of maintenance cryopreservation was 5 years (min 1 month, max 23 years). The mean time of freezing before abandoning was 7.5±4.4 years Eighty-two patients achieved pregnancy. Spontaneous pregnancies occurred in 53 cases, and 47 underwent assisted reproduction with the cryopreserved sample, with 61,7% of pregnancy (n=29).15.3% of those that have children still keep the sperm cryopreserved; 11.4% gave up on having children. Out of the 133, 66.9% authorized the use of their specimen post-mortem. Conclusions: Only one third of the patients have maintained fertility after cancer treatment and 35% of pregnancies after cancer treatment were possible due to sperm preservation. Considering the high pregnancy rate with assisted reproduction techniques in patients that lost testicular functionsemen cryopreservation is warranted.
The impact of socioeconomic factors and survivorship on radiation induced hypothyroidism in a single institution cohort study.
Authors: Milas Zvonimir , Carrizosa Daniel R. , Brickman Daniel , Frenkel Catherine , Stewart Ashley , Sumrall Ashley Love , Neelands Brittany , Trufan Sally Jeanne , Sudhakar Shwetha , Ward Matthew Christopher
Published: May 2020

e24065

Background: To determine factors associated with the development of post-treatment hypothyroidism (HY) in the head and neck (HN) population as well as evaluate the impact of socio-economic factors and survivorship program. Methods: We collected demographics, insurance coverage, disease staging, treatment characteristics, and details of thyroid function measurement as well as supplementation for all HN oncology patients (n = 608) who presented between January 2011 and January 2019 at Levine Cancer Institute, Charlotte, North Carolina. Insurance was categorized as Government (Medicaid or Medicare), Private, or Uninsured. Patient malignancies were grouped as oropharynx, oral cavity, larynx/hypopharynx, nasopharynx, nasal cavity/sinus, or primary salivary gland. Thyroid function was evaluated by use of laboratory thyroid stimulating hormone (TSH) values. Timing of thyroid supplementation was standardized to start of treatment. Details of thyroid hormone supplementation was collected. Data was analyzed with Chi-square and ANOVA methods, using SAS 9.4 (Cary, NC). Results: 483 patients (79%) had post treatment surveillance with TSH. The patients (n = 125, 21%) with no identifiable thyroid surveillance did not have any racial or socioeconomic disparities identified. Caucasian and African American thyroid surveillance rates were similar at 79% and 81%, respectively. There was no difference based on insurance: Government 81%, Uninsured 81%, and Private 76%. Of patients with thyroid surveillance, 203 (42%) developed post-treatment HY. The mean and median time frame until HY identification was 544 days and 450 days, respectively. A mean and median dose of thyroid hormone supplementation of 75 mcg of levothyroxine. Most patients had lower rates of thyroid dysfunction with TSH levels between 5-10. Fewer African Americans (24%) developed HY than Caucasians (47%). Patients with laryngeal cancer were at greatest risk to develop HY (57%), followed by oropharynx (40%) and oral cavity (40%). Staging did not demonstrate a significant difference between development of HY. Conclusions: This study is the largest cohort of HN patients to be evaluated for post HN treatment induced HY. Oncology team providers and primary care physicians should be aware of the significant rates of HY. In our institution we identified a consistency of care provided regardless of socioeconomic and racial factors.
Feasibility and acceptability of yoga to improve psychosocial and physical function among patients with lung cancer: A pilot study.
Authors: Medysky Mary E , Sullivan Donald Richard , Tyzik Anna , Thomas Charles R. , Winters-Stone Kerri M.
Published: May 2020

e24068

Background: Patients with lung cancer suffer from depression symptoms, reduced quality of life (QOL), and declines in physical function during and after cancer treatment. Since yoga is a low energy demand form of exercise, we hypothesized that yoga is a feasible, safe, and efficacious strategy to mitigate these problems in lung cancer patients. Purpose: 1) Determine the feasibility, acceptability, and safety of a yoga program in patients (pts) with lung cancer during or soon after cancer treatment; 2) Determine the preliminary efficacy of yoga to improve depressive symptoms, quality of life, and physical function among pts with lung cancer. Methods: This study was a single group 12-week (wk) pilot trial of low-moderate intensity yoga among pts with stages I-IV lung cancer (n = 20) during (n = 14) or after (n = 6) cancer treatment. Assessments conducted at baseline, 6- and 12-wks included the Patient Health Questionnaire-8, Functional Assessment of Chronic Illness Therapy-Lung (FACT-L), 6-minute walk distance (6MWD), hand grip strength, chair stand time, and flexibility (back scratch and sit-reach) tests. Results: At baseline, 20 pts, including those with metastatic disease (n = 8), enrolled and 7 pts (35%) withdrew by 6-wks due to poor/worsening health. No further withdrawals occurred at 12-wks. Among pts (n = 13) who completed the study, adherence to the intervention was 75% and 78% at 6 and 12-wks, respectively. No moderate or serious adverse events were reported. Over 12 wks, depressive symptoms (average = -1.8 ±1.23, 43.9% change) decreased, improvements in QOL improved (average = +4 ±2.9, 6.5% change),6MWD (average = +22.6m ±15.9, 6.5% change), hand grip strength (average = +1.6kg ±1.2, 5.7% change), chair stand time (average = -3sec ±2.1, 5.8% change), and upper (average = -10.8cm ±7.5, 49.4% change) and lower (average = -11.9cm ±8.4, 74.6% change) body flexibility occurred. Conclusions: In this sample of lung cancer pts, a 12-week yoga program was modestly feasible, was shown to be safe and potentially beneficial for psychosocial and physical function. Though retention was lower than expected due to early pt withdrawal for poor health, adherence to supervised practice among those pts who were able to complete the intervention exceeded the target goal. Among pts with stage I-IV lung cancer yoga may be a useful strategy to improve psychosocial outcomes and physical functioning, though alternate delivery approaches for pts with advanced disease deserves further exploration. Clinical trial information: NCT03649737 .
Pectoralis muscle wasting during chemotherapy.
Authors: Wiederin Jason , Gu Christina , Jewett Patricia , Blaes Anne Hudson
Published: May 2020

e24069

Background: Chemotherapy is often followed by muscle mass loss which has been associated with frailty. We explored factors associated with change in pectoralis muscle mass after chemotherapy. We hypothesized greater muscle loss with time would be associated with poorer overall survival. Methods: We identified individuals with breast cancer (N = 221), sarcoma (N = 115), and lymphoma (N = 216) who received chemotherapy at the University of Minnesota MHealth Fairview and had CT scans before and after chemotherapy. Right pectoralis muscle area was measured using CORESLICER and indexed to body surface (right pectoralis muscle area [cm2] / body surface [m2]). We calculated quartiles of the indexed pectoralis measure. We restricted our analyses to participants who received a follow-up CT within two years after starting chemotherapy. In a multivariate linear regression, we explored associations of sex, age, BMI, ever-smoking, time since start of chemotherapy, indexed baseline muscle area, stage, type of diagnosis, and cumulative anthracycline dose with relative (%) change in muscle area. In a Cox regression we tested the association of relative muscle change with overall mortality. We used cubic splines to test for nonlinear effects. Results: Of 477 participants (66% female; mean age 61.3 (10.1) years), 366 received anthracyclines, 61 Trastuzumab, and 60 both. The average loss in right pectoral muscle area was -10% for women and -12% for men. We detected nonlinear effects of indexed baseline muscle area, P = 0.03. In a model using quartiles of indexed baseline muscle area, significant predictors of muscle loss included sex (women vs. men, -9.0%, 95% confidence interval (CI) -14.2- -3.7%, P = 0.0008), larger indexed baseline muscle area (quartiles 2, 3, 4 compared with quartile 1, change range -7 - -24%, 95% CI range, -2 - -30%, P-range < 0.0001 – 0.006), smoking (ever vs. never, -4.1%, 95% CI -7.6 - -0.7%, P = 0.02), and diagnosis (sarcoma vs breast cancer, -5.7%, 95% CI -11.1 - -0.3%, P = 0.04). There was no significant association between muscle change and overall survival (median follow-up time 4.1). Conclusions: Being female, larger baseline muscle mass (per m2 body surface), ever-smoking, and a sarcoma diagnosis were associated with greater relative muscle loss after chemotherapy. More data is needed to understand the course of sarcopenia in terms of recovery and survivorship. [Table: see text]
Characterization of chemotherapy-induced peripheral neuropathy (CIPN) using patient-reported outcomes (PRO) and quantitative sensory testing (QST).
Authors: Bao Ting , Zhi Wanqing Iris , Chen Connie , Baser Raymond E , Li Qing Susan , Panageas Katherine , Harte Steven , Mao Jun J.
Published: May 2020

e24078

Background: CIPN is a common, potentially debilitating, and dose-limiting side effect experienced by cancer survivors. CIPN encompasses symptoms such as pain, numbness, and tingling, which can be measured subjectively by PRO, or semi-objectively by QST; however, little is known about how QST measures differ among patients with and without CIPN, or if QST outcomes correlate with symptom profiles measured by PRO. Methods: CIPN is a common, potentially debilitating, and dose-limiting side effect experienced by cancer survivors. CIPN encompasses symptoms such as pain, numbness, and tingling, which can be measured subjectively by PRO, or semi-objectively by QST; however, little is known about how QST measures differ among patients with and without CIPN, or if QST outcomes correlate with symptom profiles measured by PRO. Results: 116 patients with CIPN and 10 control patients without CIPN were analyzed. NRS and FACT/GOG-Ntx scores were significantly worse in the CIPN group compared to controls (all p< 0.001). The mean (Standard Deviation) TT for CIPN and control patients was 3.61 (0.43) and 3.38 (0.32), respectively (p = 0.059), in hands; and 3.86 (0.70) and 3.38 (0.56), respectively (p = 0.043), in feet. The mean VT was 6.06 (3.45) and 3.87 (1.01), respectively (p=0.032), in hands; and 19.14 (11.09) and 8.43 (3.22), respectively (p<0.001), in feet. There was no significant difference in THT between groups. The correlation coefficients between PRO with QST measures in all patients are listed in the table below. Conclusions: Our study suggested that patients with CIPN have significantly worse symptoms and tactile and vibratory threshold measured by QST when compared with controls. Mild to moderate correlations were observed between PROs and QST, suggesting that CIPN symptoms severity correspond to sensory sensitivity. As CIPN presents a diverse range of symptoms, improved quantification of subjective and objective measures for CIPN can help the incorporation of these tools into future clinical trials. Clinical trial information: NCT03183037 and NCT03292328 . [Table: see text]
Factors associated with frequent insomnia among breast cancer survivors.
Authors: Kwak Agnes , McDonough Allison L. , Jimenez Rachel , Lei Yvonne Y. , Haggett Dana , Johnston Katherine T. , Spring Laura , Moy Beverly , Peppercorn Jeffrey M.
Published: May 2020

e24098

Background: Insomnia is common among breast cancer (BC) survivors and often goes unrecognized and untreated. We sought to evaluate the association between frequent insomnia and potentially modifiable contributing factors to inform development of a comprehensive clinical program to address insomnia among patients with breast cancer. Methods: We adapted a 1-page survey from the National Comprehensive Cancer Network Guidelines for Survivorship, which was administered to BC survivors at oncology or primary care follow-up visits at our academic center and community based sites. The survey included 23 plain-language statements regarding symptoms, lifestyle concerns, and financial worries. Patients reported the frequency of concerns using a 5-point Likert scale (0 = never to 5 = always). We evaluated the frequency of insomnia and association between insomnia and 6 common concerns hypothesized to contribute among this population: emotional distress, fatigue, pain, hot flashes, fear of cancer recurrence, and healthcare-related financial stress. Prevalence of symptoms was dichotomized, grouping “very often” and “always” as “frequent”, and “sometimes,” “rarely”, and “never” as “infrequent”. Descriptive analysis was performed and associations between insomnia and other concerns were evaluated with Fisher’s exact test. Results: Among 192 patients (median age 59, range 34-92), 46 (24%) reported frequent insomnia (“I have problems falling or staying asleep”). Most patients (58%) reported experiencing insomnia at least “sometimes”, while 20% answered “rarely” and 23% “never”. Overall, 14% of survivors reported frequent anxiety/depression, 15% fatigue, 27% pain, 19% hot flashes, and 23% fear of recurrence. Only 6% of patients reported frequent financial worries due to healthcare costs. Emotional distress (p=0.016), fatigue (p≤0.001), pain (p≤0.001), hot flashes (p=0.017), and fear of recurrence (p≤0.01) were each associated with frequent insomnia. Conclusions: BC survivors who experience frequent insomnia are more likely to report emotional distress, fatigue, pain, hot flashes, and fear of recurrence, compared to those with infrequent insomnia. A clinical program designed for the management of insomnia may benefit from targeting these potentially contributing factors.
Diabetes mellitus in childhood and young adult cancer survivors: A meta-analysis.
Authors: Kushnir Igal , Bhatia Dominika , Srikanthan Amirrtha , Lega Iliana
Published: May 2020

e24101

Background: Diabetes mellitus (DM) has emerged as a possible late sequela after successfully treating pediatric and young adult (YA) malignancies. We conducted a systematic review and meta-analysis in order to quantify this risk and assess possible risk factors. Methods: We searched MEDLINE and EMBASE databases from inception to April 2019. We included cohort or case-control studies that reported the risk of DM (hazard ratio [HR], relative risk, or odds ratio, and 95% confidence interval [CI]) among childhood and YA cancer survivors ( < age 21 years) compared to those without a history of childhood or YA cancer. We used the Newcastle-Ottawa Score (NOS) to assess risk of bias and study quality. Study effect estimates were pooled using random-effects meta-analyses. Heterogeneity was assessed using the I2 statistic. Results: After applying our exclusion/inclusion criteria, we included 6 articles in our meta-analysis, with a median follow-up time of 11 (range 10-23) years. The median NOS score was 8 (range 7 – 8), indicating high study quality. The risk of DM was significantly higher in childhood and YA cancer survivors relative to controls (HR 1.66, 95% CI 1.54 to 1.79, I2 = 1%). Among cancer types, the highest risk for DM was reported after treatment for leukemia (HR 2.91, 95% CI 2.01 to 4.22 I2 = 75%), lymphoma (HR 1.63, 95% CI 1.37 to 1.94, I2 = 0%) and central nervous system malignancies (HR 1.77, 95% CI 1.30 to 2.39, I2 = 49%), relative to controls. Receiving total body irradiation or abdominal radiation was associated with a DM risk of 4.52 (95% CI 2.29 to 8.93, I2 = 87%), relative to controls. Conclusions: Our meta-analysis demonstrated an increased risk of developing DM among childhood and YA cancer survivors. More emphasis on screening for DM and prevention among this population should be offered.