bluuebunny/crossref_metadata_2025 huggingface dataset:
Targeting Exportin 1 as treatment for cutaneous squamous cell carcinoma.
Authors: Rana Ricky , Hansen Laura A.
Published: June 2023

e21564

Background: Cutaneous squamous cell carcinomas (cSCC) are among the most frequent solid cancers in humans and in the U.S., cSCC cases are increasing. Molecular mechanisms transitioning premalignant lesions to cancer are not well characterized. As a result, targeted therapies need to be identified to treat these lesions. Preliminary data shows that Exportin 1 (XPO1) is one of the major proteins regulating nuclear export of proteins, helping to maintain cellular homeostasis. Previous work showed that Exportin 1 modulates the nuclear:cytoplasmic ratio of signaling proteins in skin cancer; resulting in an anti-apoptotic effect by adjusting the nuclear-cytoplasmic balance of pro-survival proteins such as CDC25A and Survivin. XPO1 expression is upregulated in many cancers, thereby affecting the nuclear:cytoplasmic ratio of many pro-survival proteins and enhancing tumorigenesis. This research project was designed to investigate the effects of XPO1 inhibition on cSCC survival. Selinexor is FDA cleared for treatment of multiple myeloma patients. Selinexor is a selective inhibitor of XPO1 regulated nuclear transport causing target molecules to remain within the cell leading to decreased cancer cell growth and decreased cancer cell survival. We hypothesize that inhibiting XPO1 with Selinexor or by CRISPRi genetic knockdown of XPO1 in cSCC cells will reduce proliferation and increase apoptosis in cSCC cells. Methods: Human cSCC cell lines SCC13 and SRB12 were seeded in 96-well plates at 8,000 cells/well density and 3,000 cells/well, respectively. Cells were treated with varying concentrations of Selinexor (0.005mM – 5mM) or DMSO as vehicle control. At 24-hour intervals, cell imaging and Neutral red staining assays were conducted to determine the IC50 concentration for Selinexor in cSCC cell lines. SCC13 cells stably expressing dCas9-KRAB and a doxycycline-inducible XPO1 guide RNA were used for CRISPRi experiments. Cells were treated with doxycycline daily and apoptosis was assayed by Caspase Glo 3/7 daily for four days. CRIPSRi enabled a doxycycline inducible XPO1 knock down on SCC13 cells allowing us to disrupt the cellular transporter protein XPO1. Results: Selinexor treatment of SRB12 cells resulted in an IC50 of 1.174 μM and 0.071 μM for SCC13. In contrast, normal human keratinocyte cell lines had higher IC50 values of 2.18 μM for HaCaT and 5.29 μM for KerCT cells. Apoptosis significantly increased after 72 and 96 hours of XPO1 knock down in SCC13 cells measured by Caspase Glo. Conclusions: These results document how XPO1 inhibition reduces proliferation and is toxic to both normal keratinocytes and cSCC cells. Additionally, cSCC cells had lower IC50 values for Selinexor, suggesting cSCC may be more sensitive to XPO1 inhibition compared to normal keratinocytes. Further, targeting XPO1 also increases apoptosis in these cells. This data supports the hypothesis that targeting XPO1 may be effective in treating cSCC.
Multicenter analysis of melanoma recurrence pattern and management after adjuvant immunotherapy.
Authors: Martínez Recio Sergio , Molina Maria Alejandra , Muñoz-Couselo Eva , Sevillano Tripero Alberto Rafael , Martin-Liberal Juan , Orrillo Mayra , Fernandez Luis Antonio , Quindós Varela Maria , Lesta Rocio , Barba Andrés , Sullivan Ivana , Majem Margarita
Published: June 2023

e21573

Background: PD-1 inhibitors improve outcomes in resected stage II-IV melanoma. However, recurrence patterns and prognostic factors are less known. Methods: We conducted a retrospective study in resected stage II-IV melanoma patients (p) treated with adjuvant PD-1 inhibitors (clinical practice or clinical trials) from 5 centers. Demographic, disease characteristics, adjuvant therapy, recurrence, treatment at relapse and outcome were recorded. Descriptive assessment for recurrence patterns and analysis for prognostic factors were performed. Results: From June 2017 to June 2022, 181 p were included. Median age was 59 years [22-81], 57% were male, 85% had cutaneous melanoma, 28% had BRAFV600E mutation. 9 p (5%) presented stage II, 147 (81%) stage III and 25 (14%) stage IV. Ulceration was present in 59% p, mitotic rate >1/mm2 in 84%, Breslow index >3 mm in 65% and elevated LDH in 51%. 81% p received PD-1 inhibitors alone and 19% in combination with other immunotherapies. 52% of p completed treatment, 12% discontinued due to toxicity and 26% due to relapse. 13% of p presented grade 3-4 adverse events and there was a grade 5 myocarditis. With a median follow-up of 18,1 months, 68 (37%) p recurred (Table). Median relapse free survival (RFS) was 48,8 months (95% CI 31,1-66,4). Recurrence was significantly associated with a higher stage, mitotic rate, LDH level and Breslow index, BRAFV600E mutation, non-cutaneous melanoma and delayed initiation of adjuvant immunotherapy in univariate analysis (p<0,05). Stage, non-cutaneous melanoma and initiation of immunotherapy >3 months (16% p) were associated with higher recurrence in multivariate analysis (<0,05). Locoregional recurrence was treated in 23 p with surgery (14p), surgery + RT (7p) or RT alone (2). Systemic recurrence was treated in 50 p: all BRAF mutant p received targeted therapy (24p, 43%) with a disease control rate (DCR) of 91% and a median progression free survival (PFS) of 56 months (95% CI 24,1-NR); BRAF wild type p (26p, 47%) were treated with anti-PD-1 alone (9p) or in combination (7p), anti-CTLA-4 (2p), chemotherapy (1p) or best supportive care (7p), with DCR of 33% and a median PFS of 8 months (95% CI 6,9-10,8). Conclusions: We observed a 37% relapse rate and systemic recurrence were more frequent than locoregional recurrence. Treatment at relapse with targeted therapy in BRAF mutant p achieved higher DCR and PFS than immunotherapy in BRAF wild type p; with better outcomes than previously reported.[Table: see text]
HLA discordance between blood and tumor: A treatment conundrum?
Authors: Seedor Rino S. , Orloff Marlana M. , Pancholy Pariseema , Terai Mizue , Sato Takami
Published: June 2023

e21577

Background: Tebentafusp is a bispecific gp100 peptide-HLA-directed CD3 T cell engager that is now FDA approved for HLA-A*02:01 patients with unresectable or metastatic uveal melanoma (UM). Tebentafusp requires the targeted gp100 peptide to be presented by the major histocompatibility complex Class I complex HLA-A*02:01 allele for optimal cell killing. HLA-A*02:01 has been reported to be carried by approximately 50% of the North American and Western European population. The clinical trials for tebentafusp all required central blood tests to determine HLA status. In March of 2021, Caris Life Sciences began the launch of HLA Genotype as a standard reporting element for patient tumors profiled by Caris. Somatic HLA mutations have been described in different tumor types and has strong implications for a possible mechanism of immune evasion. Tumor heterogeneity between tumors and within tumors may also impact HLA tumor testing. As more novel drugs that rely on HLA genotyping are developed, understanding the relationship between blood and tumor HLA testing has become crucial. Methods: A single institution retrospective analysis was performed of patients who had tumor HLA genotyping performed as part of their tumor profiling by Caris Life Sciences. HLA Genotyping by Caris was performed using Whole Exome Sequencing of the tumor. Of the patients who had tumor HLA genotyping results, patients who also had blood HLA typing were identified. The concordance rate of HLA-A status between blood testing and tumor testing was determined. The prevalence of HLA-A*02:01 in our patients was also determined (either blood or tumor). Results: Forty-seven patients with both tumor and blood HLA genotyping were identified (37 UM, 8 cutaneous melanoma, 1 mucosal melanoma, 1 renal cell carcinoma). The majority of the patients were Caucasian (n = 44), with only two Asian patients and one African patient. There were two UM patients whose tumor and blood HLA genotyping were discordant (concordance rate of 95.7%). One patient was found to be HLA-A*01:01, *026:01 by blood but tumor genotyping revealed HLA- A*01:01, A*02:01. The other patient was found to be HLA-A*02:01, A*01 by blood but tumor genotyping revealed HLA-A*03:01, A*33:03. The prevalence of HLA-A*02:01 in the entire group was 34%, while the prevalence of HLA-A*02:01 in the Caucasian patients was 36.4%. None of the non-Caucasian patients were HLA-A*02:01 by blood or tumor genotyping. Conclusions: Among our 47 patients with both tumor and blood HLA genotyping, we found two patients with discordant HLA results. Neither of the discordant UM patients had received tebentafusp yet, but it brings up a crucial question about how these patients may respond to a therapy that relies on the HLA-A*02:01 complex. Our study highlights the importance of continuing to use blood HLA genotyping as the standard test to determine eligibility for a treatment such as tebentafusp, as the concordance rate with tumor genotyping is high but not 100%.
Impact of disadvantaged socioeconomic and demographic status on survival in Kaposi sarcoma.
Authors: Swedek Michelle , Wu Xinxin , Silberstein Peter T. , Vardell Victoria
Published: June 2023

e21581

Background: Kaposi sarcoma (KS) is a soft tissue tumor that affects a wide variety of patient populations, though it is typically seen in immunocompromised patients, including those living with organ transplant or HIV/AIDS. Patients from traditionally underserved socioeconomic and demographic populations have historically had poor outcomes across malignancies, however these populations have never been studied on a large national scale in KS. To examine how socioeconomic and demographic status affects survival in KS, we examined the National Cancer Database (NCDB); a large oncology database that includes approximately 75% of newly diagnosed cancers across the United States. Methods: We conducted a retrospective analysis of the NCDB for KS patients diagnosed from 2004 to 2019. Cases missing data for variables of interest were excluded. Overall survival (OS) was examined using Kaplan-Meier and multivariate Cox regression. Results: A total of 5,233 patients with KS were identified, with a mean age of 58 years. Most patients were male (87.1%), White (70.1%), not Spanish/Hispanic (82.7%), and had government insurance (54.3%). Comorbid conditions were described using the Charlson-Deyo Comorbidity Score (CDS), and a substantial number of patients had a score above 3 (28.6%). The mean OS for all patients was 122 months. On adjusted Cox regression, decreased OS was seen in patients over 85 years old (HR 2.14, 95% CI 1.82-2.53, p<0.001) compared to patients aged 40-54 years old. Compared to White patients, Black patients had decreased OS (HR 1.24, 95% CI 1.11-1.38, p<0.001); mean survival in Black patients was 113 months compared to 124 months in White patients (p<0.001). Improved OS was seen in patients of Spanish/Hispanic origin (HR 0.80, 95% CI 0.70-0.91, p<0.001). Any CDS greater than 1 was associated with poor OS (HR 1.46 for CDS 1, 95% CI 1.26-1.70, p<0.001), and treatment at an academic facility had a protective effect (HR 0.75, 95% CI 0.69-0.82, p<0.001), as did private insurance (HR 0.65, 95% CI 0.55-0.77, p<0.001). Biological sex, education, income, and facility location did not independently impact survival. Conclusions: When adjusted for key demographic covariates, advanced age, Black race, and presence of comorbidities were each independently associated with decreased OS in KS patients. Improved OS was seen with Spanish/Hispanic ethnicity, treatment at an academic facility, and private insurance. To our knowledge, our study is the first to describe demographic and socioeconomic features impacting survival for KS patients at this scale. We revealed important disparities in survival and highlight the need for equitable care in KS, especially for patients of Black race.
Interim analysis of MelaRisk, a biomarker assay validation study in stage IB/IIA melanoma tissue.
Authors: Forchhammer Stephan , Chatziioannou Eftychia , Sinnberg Tobias , Niessner Heike , Leiter Ulrike M. , Keim Ulrike , Forschner Andrea , Garbe Claus , Flatz Lukas , Amaral Teresa Maria Santos
Published: June 2023

e21591

Background: Adjuvant therapy for melanoma patients (pts) is now available for pts from stage IIB onwards. Pts with cutaneous melanoma in early stages stage IB/IIA have low risk of relapse. However, this group still contributes to the most melanoma deaths in absolute numbers. Therefore, it is important to identify pts in stage IB/IIA that could benefit from adjuvant therapy. One promising biomarker is a proprietary 7-protein immunohistochemistry (7-P-IHC) signature (Immunoprint). Based on primary tumor tissue analysis, the 7-P-IHC has shown very high sensitivity and risk enhancement ability in previous prospective and retrospective validations.1,2 The 7-P-IHC test result indicates a risk score predicting relapse-free and melanoma-free survival (RFS, MSS), thereby allocating most relapses to the high score risk group. To further validate its key parameters, the MelaRisk trial was started in 2022, aiming to analyze up to 500 tissue samples with Immunoprint. Here we present its interim analysis and a combined analysis of all available data for Immunoprint in stage IB/IIA. Methods: All pts with available formalin-fixed paraffin-embedded blocks of the Central German Melanoma Registry diagnosed from 2005-16 and AJCC v8 stage IB/IIA were screened. Tumor tissue samples from 119 pts (83/IB; 36/IIA) were available; the 7-P-IHC was used to determine a risk group. Results: 7-P-IHC assigned 68 pts to the low-risk (57%) and 51 (43%) to the high-risk group. Median follow-up was 76 months. 15/17 relapses after 5-years were detected, resulting in a sensitivity of 88%. 5-years RFS event rate of the cohort according to AJCC v8 was 12% and 19% for stages IB and IIA, respectively. This was enhanced to a risk of recurrence of 30% (stage IB) and 29% (stage IIA) in the respective high score group. 5y-RFS rate was 97% for pts with 7-P-IHC low score risk and 71% for pts with 7-P-IHC high score risk (p=0.0001). 7-P-IHC was the only significant factor in a multivariate Cox analysis for RFS (HR 10.78 (2.38-48.74), p=0.002) and could detect 4/5 MSS events. Combined analysis including these and previous Immunoprint results in stage IB/IIA are summarized in the table. Conclusions: 7-P-IHC could concentrate 88% of stage IB/IIA RFS events in a small high score risk group. This group entails 43% of pts of the total cohort, correctly identifying pts needing adjuvant therapy. Immunoprint should be used to select pts in future studies in the adjuvant setting if these promising interim results can be confirmed in the final analysis. 1. Meyer et al. (2023) EJC; 2. Reschke et al. (2021). [Table: see text]
A national analysis of demographic trends in gynecological cases of basosquamous carcinoma.
Authors: Tuman Jaylin , Hsia Beau , Keirns Darby , Malan Augustus , Silberstein Peter T. , Wu Xinxin
Published: June 2023

e21598

Background: Basosquamous carcinoma (BSC) is an aggressive form of basal cell carcinoma. Research on BSC is minimal because of its rare nature and the lack of clinical features that distinguish BSC from other forms of basal cell carcinoma, meaning that a diagnosis is only confirmed following biopsy. BSC is distinct because it has features of squamous cell carcinoma, making it more locally invasive, more likely to metastasize and has a recurrence rate of 12 - 51% following surgical excision. While BSC most frequently presents in the head and neck, it can also occur in gynecological cases and this subset of cases has not been studied in literature. In order to more thoroughly understand the distinguishing features and epidemiological trends of this rare cancer, the National Cancer Database (NCDB) was analyzed to determine demographic factors in patients diagnosed with cases of BSC in the breast, vagina and vulva. Methods: The National Cancer Database (NCDB) was utilized to complete a retrospective cohort analysis from 2004 – 2020 that included all patients with histologically-confirmed gynecological cases of BSC (N = 211). Descriptive statistics were analyzed for demographic factors including age, sex, race, income level, insurance status, and Charlson-Deyo score. Results: Between 2004 and 2020 there were 211 identified gynecological cases of BSC. The average age of diagnosis was 71.1 years (SD = 14.6, range = 22 – 90 years) with the majority being non-Hispanic (89.1%) and White (86.3%). The primary site in the vast majority of cases was the vulva (88.6%) and remaining cases originated in other female organs including the breast, vagina and cervix (11.4%). Despite the older age of diagnosis, the majority of individuals (72.0%) had Charlson-Deyo comorbidity scores of 0. The greatest proportion of patients (38.8%) were in the top quartile of household income ( > $74,063) with 15.7% in the lowest income quartile ( < $46,277). Additionally, most patients were insured by Medicare (64.9%) which aligns with the older age of diagnosis. Conclusions: Classifying and fully understanding BSC has proved difficult due to the challenge of differentiating it from other forms of basal cell carcinoma. To further the overall understanding of this aggressive cancer and those that it impacts, this study specifically focuses on a unique subset of BSC cases that have not been well studied. To the best of our knowledge, this is the first NCDB analysis on gynecological cases of BSC. The majority of BSC patients are non-Hispanic and White with an average age of over 70 years old which is supported by the finding that most patients rely on Medicare to fund their treatment. Additional research is needed to better understand the sociodemographic factors, treatments, and overall survival of patients with BSC in aberrant locations.
Association between the primary site of disease and the stage at diagnosis for merkel cell carcinoma: A population-based analysis.
Authors: Gor Rajvi , Gwalani Pranav , Gor Dhairya , Vegivinti Charan Thej Reddy , Gwalani Twinkle , Narvel Hiba , Adhikari Anurag , Deshpande Shweta , Dongre Yutika , Musunuru Tejo Niharika
Published: June 2023

e21600

Background: Merkel cell carcinoma [MCC] is a rare, aggressive skin cancer with a high rate of recurrence, metastasis, and poor prognosis. It commonly involves the head and neck (HN) region (41% of diagnosed cases), followed by the upper and lower extremities and trunk in decreasing frequency. We used the Survival, Epidemiology, and End Results [SEER] November 2021 database to assess the incidence, cause-specific survival, and the association between the primary site of disease and the stage at diagnosis for primary MCC. Methods: Using the SEER-November 2021 (17 registry) database, a retrospective analysis was performed on the 4120 cases of pathologically confirmed MCC (ICD-O-3 code 8247), diagnosed between 2004-2015. Baseline characteristics were assessed using the Chi-squared test and the Kruskal-Wallis test. Multivariate multinomial logistic regression was performed to evaluate the association, with alpha at 0.05. Analysis was performed using SEERStat and SAS 9.4. Results: The overall age-adjusted incidence rate (IR) of MCC was 0.4 cases per 100,000 with an observed 5-year survival [OS] of 47.8% and cause-specific 5-year survival [CSS] of 68.7%. The median age at diagnosis was 79 years (interquartile range - 66,83) with a male preponderance (60.4%). At baseline, males had higher odds of being diagnosed at stages III or IV (p < 0.001). The odds of being diagnosed at stages II, III, or IV were significantly higher in patients with the trunk as the primary site compared to the HN region with an OR 3.8 (p < 0.001), 2.4 (p < 0.001), and 2.2 (p = 0.001), respectively. For patients with the upper limb as the primary site, the odds of being diagnosed at stage II were 1.4 times higher than the HN region (p = 0.0095), and stage IV was 0.4 times (p = 0.03) higher. For the lower limb and hip, the odds of being diagnosed at stages II, III, or IV were significantly higher than the HN region with an OR 2.6 (p < 0.001), 1.6 (p < 0.0005), and 1.5 (p = 0.04), respectively. Conclusions: While less prevalent than the MCC of the HN region, patients with MCC of the trunk, upper or lower extremities had a higher probability of being diagnosed with an advanced-stage malignancy compared to the former. Additional prospective studies are required to investigate this association further and explore its significance in site-specific treatment approaches and survival factors. [Table: see text]
Protective effect of the dexrazoxane against cardiotoxicity of the anthracycline in the treatment of the childhood cancers.
Authors: Tacyildiz Nurdan , Turker Nazmiye , Ucar Tayfun , Incesoy Ozdemir Sonay , Dincaslan Handan , Yaman Ortakoylu Melek , Ramoglu Mehmet Gokhan , Yavuz Gulsan , Unal Emel Cabi
Published: June 2023

e22001

Background: Cardiovascular diseases have become the most important cause of morbidity and mortality in the long-term follow-up of childhood cancer survivors. Dexrazoxane (DEX) is the only FDA-approved drug to prevent Anthracycline-induced cardiotoxicity. In this study, we aimed to evaluate the cardioprotective efficacy of DEX in patients using Anthracycline in the treatment of childhood cancer. Methods: 142 patients aged 0-18 years, who were treated with cancer diagnosis in Ankara University Faculty of Medicine, Department of Pediatrics, Department of Pediatric Oncology, and who had been treated with Anthracycline group agents, were evaluated retrospectively. The cardiac functions of 87 patients who received only Anthracycline between November 2009 and March 2019 and 55 patients who received DEX + Anthracycline between March 2019 and June 2021 were compared. An ejection fraction (EF) of less than 50% in cardiac evaluation was defined as 'cardiac dysfunction'. Results: The group that received anthracycline with DEX; While 50.9% were girls, 49.1% were boys, and the mean age was 98.42 months, 48.3% of the group that took only Anthracycline was girls and 51.7% were boys, with a mean age of 105.75 months. There was no difference between the two groups in terms of diagnosis distribution. EF values of both groups before anthracycline were normal. While none of the patients in the DEX + Anthracycline group developed cardiac dysfunction during the follow-up, 11 (12.6%) patients in the Anthracycline group with no DEX had cardiac problems. Six Of the 11 patients (54.5%) who developed cardiac dysfunction died(p=0.012). There was a significant difference between the two groups with or without DEX patients in the manner of cardiac dysfunction(p=0.006) and death(p=0.009). Cardiac dysfunction development and mortality rates were higher in patients using only Anthracycline. Conclusions: In this study, it has been shown that DEX is very effective for preventing Anthracycline-related cardiac dysfunction, which is one of the most important causes of mortality and morbidity in childhood cancer survivors.
Pediatric cancer registry in Turkey 2002-2022: 21 years of achievement (TPOG & TPHD).
Authors: Kutluk M. Tezer , Yeşilipek Akif
Published: June 2023

e22004

Background: Each year 413.000 new pediatric cancer cases are expected in children and adolescents aged 0-14 globally. The access to care is still a barrier to improve the survival rates in low and middle income countries (LMICs). Pediatric cancer registry is the essential element of pediatric cancer control. Here, we present the results of the 21 years of the pediatric cancer registry from Turkey. Methods: Turkish Pediatric Oncology Group and Turkish Pediatric Hematology Association has established the pediatric cancer registry in 2002. The childhood cancer cases registered between 2002-2022 was included in this analysis. International Childhood Cancer Classification System was used for the classification. Essential demographic findings, ICD-O-3 morphology and topography codes were recorded for each case. Results: During the 21 years from 2002 to 2022, 46067 cases were registered. For all cases, median age was 6.5 year (0-19; M/F 25079/20176, 6 hermaphrodite, 6 unknown). Age distribution was 0-4 yrs, 41.5%; 5-9 yrs, 24.7%; 10-14 yrs, 23.0%; 15-19 yrs, 10.7%) The distribution of the tumor types were [number of cases, percentage of total, median age yrs, M/F]: Leukemia (13190, 28.6%, 5.6, 7640/5550); Lymphoma & other RES tumors (8194, 17.8%, 9.1, 5435/2756, 1 hermaphrodite & 2 unknown); CNS [brain & spinal] (6606, 14.3%, 6.8, 3670/2935, 1 unkown); Symphatetic system (3411, 7.4%, 2.3, 1755/1656); Retinoblastoma (1386, 3.0%, 1.5, 726/660); Renal (2095, 4.5%, 3.1, 1032/1061, 1 hermaphrodite & 1 unknown); Liver (681, 1.5%, 2.1, 400/281); Malignant bone (2809, 6.1%, 12.5, 1569/1240); Soft tissue sarcomas (3209, 7.0%, 7.3, 1810/1399); Germ cell (2663, 5.8%, 8.6, 957/1700, 4 hermaphrodite, 2 unknown); Carcinoma & other malignant epithelial (1494, 3.2%, 13.0, 721/773); Other/non-specific malignant (329, 0.7%, 7.4, 164/165). Five year survival rate was found as 70.8% Conclusions: This is a successful example of a pediatric cancer registry from a middle income country covering the period of more than 20 years. The survival rates for children and adolescents have been improved to 70% which is comparable for middle income countries and reflects the level of the pediatric cancer care in Turkey. It became a valuable source for stakeholders in national and international level.
Impact of occupational therapy on comprehensive care in pediatric oncology.
Authors: Hsueh Hui-Yun
Published: June 2023

e22018

Background: Children with cancer can experience difficulties in performing and engaging in their usual activities and the families can also experience interruptions to their daily routines as well as family dynamics. Yet, current cancer rehabilitation tends to focus more on the aspect of bodily repair and functional restoration. This study intends to illustrate the impact of occupational therapy approaches that were identified to have positive influence on the children with cancer and their family. Methods: Three cases of children with brain tumor of age 1, 4 and 16 were reviewed and their caregivers were interviewed. Family education on disease progression, caregiver burden, unhealthy caregiving style, and activity participation facilitation, and coping strategies for the teenaged survivor were included in the regular occupational therapy sessions. Results: Of the three cases, two families of the younger clients who later deceased, reported being supported with the occupational therapy service from emotional support to facilitating activity participation. The other case was reported to have resumed activity participation both in the hospital and at home following a client-centered occupational therapy approach. Conclusions: Although it is important to facilitate functional restoration or preservation, it does not facilitate activity participation on children with cancer if psychological and/or contextual factors are not taken into consideration. It is equally important to meet children’s developmental needs and educate their caregiver/family to provide the proper care they need. Coping is required for both child survivor and their caregiver/family. Client-centered approach that is used in occupational therapy can provide comprehensive care to both children and their family in meeting the needs of the child and family and facilitating activity participation.
A multi-component educational intervention for oncologists to improve tobacco cessation treatment among patients with cancer who smoke.
Authors: Jose Thulasee , Ohde Joshua , Warner David O
Published: June 2023

e22500

Background: Oncologists are change agents to improve tobacco cessation among patients. As part of the National Cancer Institute Cancer Center Cessation Initiative, we established an electronic health record (EHR, Epic)-based "opt-out" approach to refer patients to tobacco treatment specialist without active involvement by oncologists. However, the role of oncologists in contributing to the “opt-out” approach to patients has not been explored. We tested the hypothesis that a multi-component educational program for oncologists would increase the proportion of patients who completed tobacco treatment appointments. Methods: As a quality improvement initiative, oncology providers at the Rochester Mayo Clinic Cancer Center were educated using a multimodal academic detailing approach with group and individual educational sessions. Its effectiveness was tested using a modified step-wedge implementation design. The primary outcomes were patient behaviors that could plausibly be changed by conversations with their provider: the rate at which cancer patients identified as current tobacco users scheduled an appointment in the Nicotine Dependence Center (NDC) (which required active patient involvement), and the rate at which patients scheduled for a NDC appointment completed their appointment. Comparisons were made before, during, and after the education period (from July through Dec 2019) and with a separate group of providers who did not complete education (results examined over a similar time period). Results: Education did not improve outcomes in providers who received education; indeed, the rate of appointment scheduling decreased, although this may reflect other concurrent changes in the referral process (Table). Outcomes were similar between providers who did and did not receive education. Conclusions: Tobacco cessation efforts should be routinely integrated into cancer care to improve outcomes. The “opt-out” program resulted in approximately 1 in 5 cancer patients being seen for tobacco use, but an academic detailing approach designed to equip oncology providers to encourage their patients to complete appointments was not effective. Other approaches are needed to increase the uptake of tobacco treatment in these patients. [Table: see text]
The effect of an ultraviolet photography educational exercise on sunscreen application.
Authors: Young Jade N , Poplausky Dina , Owji Shayan , Lavin Leore , Tai Hansen , Ungar Benjamin , Gulati Nicholas , Ungar Jonathan
Published: June 2023

e22506

Background: Sun exposure is a known risk factor for skin cancer development. Sun protection factor (SPF) is based on an application of 2 mg/cm2 of facial surface area (FSA). Studies demonstrate that most people do not apply a sufficient volume to achieve the intended SPF, thus overestimating their sun protection. Ultraviolet photography (UVP) is easily performed by placing an inexpensive UV filter over a digital camera lens. Chemical and physical sunscreen appear metallic black and blue, respectively, under UV light, thus helping to visualize sunscreen application. We sought to determine if visualizing application with UVP increases the volume of sunscreen applied and to investigate the effect of demographic factors and sunscreen type (physical and chemical) on the results of the intervention. Methods: Participants were recruited from June to August 2022. Subjects were randomized to either physical or chemical sunscreen for the first round of sunscreen application. Using a mirror, subjects applied sunscreen as they normally would. Subjects were then shown a UV photo that helped visualize the extent of sunscreen application. With a clean face, the process was repeated with the other sunscreen type (physical or chemical), such that each subject applied both types by the end of the study (round 2). Sunscreen bottles were weighed before and after applications to calculate the volume of sunscreen applied. Statistics were performed in RStudio version 1.4.1717, a language and environment for statistical computing. Results: 30 subjects (ages 18 to 88, Fitzpatrick skin type I-V) were enrolled. A greater percentage of participants applied > 2mg/cm2 from round 1 to round 2 (23% vs 36%). Mean application volume significantly increased from round 1 to round 2 (1.46 SD = 0.936 to 2.15 SD = 1.91, p = 0.0256). Subjects in the “chemical first” group applied a greater amount in round 2 (p< 0.001), however the same was not true in the “physical first” group. Mean sunscreen applied did not significantly differ between chemical and physical in round 1 (p = 0.187). There were no significant differences observed in sunscreen application across race, gender, skin type, and age. Conclusions: The volume of application increased during round 2, indicating that UVP may be an effective intervention to increase the volume of sunscreen application. Differences between the chemical first and physical first groups indicate the intervention may be more suited to teach the application of chemical sunscreen, which appears darker on UVP. Lack of difference between sunscreen types in round 1 suggests there was negligible pre-intervention bias in application behaviors. Overall, most subjects applied less than the recommended amount of sunscreen in both rounds, suggesting that additional counseling is paramount to ensuring proper sunscreen utilization among the public to prevent skin malignancy.
A flexible quantitative framework to assess the potential contribution of early cancer detection to improved cancer survival.
Authors: Yu Menggang , Tyson Christopher , Limburg Paul J. , Beer Tomasz M.
Published: June 2023

e22508

Background: Public health goals often articulate aspirations to improve cancer survival by some pre-specified percentage. Such survival improvements may be achieved through a combination of medical interventions and lifestyle change. Early detection of cancer can contribute to cancer survival improvements. Impact of early detection programs is realized both through innovation driving advances in screening technologies and increased access and adherence with screening tests. We develop a quantitative approach to characterize the magnitude of early detection across multiple cancer types that corresponds to a specified percent improvement in survival. Methods: A matrix equation is developed relating survival and stage shift. The percent of survival improvement is defined a priori as 20% in this case but can be set to other percentages. We populate the matrix equation with incidence and cause-specific survival for 15 cancers by stage at diagnosis from the National Cancer Institute’s Surveillance, Epidemiology, and End Results database. We then use linear programming to solve the matrix for all specified cancers simultaneously given a set of constraints formulated to steer the solution towards the least stage shift required to achieve the objective and to partially compensate for length-time bias. Results: Based on our target survival improvement of 20%, three common trends emerged across 14 of the 15 cancer types: first, we see that the bulk of survival improvement can be achieved by detecting most disease prior to stage 4; second, that the remaining survival improvement can be achieved by detecting most cancers just one stage earlier; and third, that stage 1 diagnosis is generally not necessary to achieve reasonable survival improvement goals. The solution revealed lung cancer as the one type that required more aggressive earlier detection than others, an expected result given that lung cancer has both very high incidence and very poor survival. Conclusions: The mathematical framework we develop is very flexible and can be helpful for public health officials and innovators to characterize the contribution that earlier cancer detection can make towards improved cancer survival. Our results suggest that detecting cancer prior to the development of distant metastases, even after progression beyond stage 1, has potential for significant public health benefit. This approach may also be extended to assess the impact that emerging treatment landscapes, coupled with early cancer detection, may have on improved cancer survival.
Mammography in women with sickle cell disease.
Authors: Farooqui Marwah Wafa , Hussain Faiz , Zhang Xu , Haqqani Rayyan , Sung Kaitlin , Saraf Santosh L.
Published: June 2023

e22509

Background: Sickle cell disease (SCD) is an inherited blood disorder affecting 100,000 people in the US with a median life expectancy of 54 years. As this population ages, it is important to focus on wellness screenings. Literature review has mixed results on the prevalence of malignancies in SCD. Initiation of BC screening is recommended between age 40-50. Patients with SCD have risk factors for breast cancer (BC) including radiation exposure, nulliparity/decreased parity, dense breasts, African American race, lack of physical activity, and use of allogenic Hematopoietic Stem Cell Transplant with total body irradiation and alkylating agent conditioning regimens. This study's purpose is to determine if these patients are being adequately screened and if guidelines for the general population are appropriate for SCD patients given their potential increased risk. Methods: This is a single center retrospective study of women with SCD who are >40 with an encounter between 2018-2022. Data collection included: screening age, recent mammogram date, American College of Radiology (ACR) category for breast density (BD), family history of cancer, type of SCD, menopausal status, and Body Mass Index (BMI). Ordinal logistical regression model was used for statistical analysis. Results: A total of 156 patients were identified and 71% screened for BC; however only 56% had screening in the last 2 years. With a binomial test, the difference between CDC 2019 African American women and SCD regarding screen is not significant (P=1). The average age for screening was 44. Over half of our patients (53%) have dense breasts. Younger age at screen and lower BMI are both related to a higher density score (Table). Conclusions: As per guidelines, breast awareness (age 25) and mammography (age 40) should be offered to ensure early detection in the general population. The question arises if there should be earlier screening with an alternative imaging modality in SCD patients given increased breast density, potential risk factors, and lower life expectancy. However, it is important to consider the risks versus benefits of early screening. Screening can provide better outcomes, as SCD patients might not tolerate standard treatments for advanced disease. Our findings present a new challenge regarding BD. Increased BD decreases the accuracy of mammograms and requires additional imaging. Higher BD is found in younger women with lower BMI, but here fertility may be an additional factor as it differs in patients with SCD. The limitation of our study is that it is a retrospective, single institution study during a pandemic. Future studies are needed to closely examine if SCD patients are at increased risk given density findings and if there is a need for earlier or alternative modality of screening other than mammography. [Table: see text]
Inclusive innovation: World health organization (WHO) task-shifting principles in community health workers living with disabilities through women’s cancer screening in the EMPOWER Program.
Authors: Kanari Catherine , Nyongo Dorothy Ogada , Wambua Jacqueline , Muhanji Raymond
Published: June 2023

e22512

Background: The W.H.O estimates that people with disabilities make up 15% of the world’s population. In the Horn of Africa (Djibouti, Kenya, Ethiopia & Uganda) there have been several disability inclusion programs in Education, livelihoods and empowerment through the Development Response to Displacement Impacts Project (DRDIP). In Kenya, the Government has continued to leverage on the private sector to accelerate progress towards inclusion. A strategic partnership with Safaricom enabled provision of Assistive devices and medical cover exceptional approval to a tune of USD 223,000 to Persons with Disabilities in the formal and informal economy in Kenya. Women CHVs were selected to reduce cultural barriers because many women in the communities are more comfortable being screened by a fellow woman. Objectives: To identify and deploy women living with disabilities as community health volunteers in the county EMPOWER Clinics; To build capacity of women living with disabilities and enable them to accurately screen for breast and cervical cancer. Methods: A total of 25 women living with disabilities and 7 able-bodied women from Meru and Kisumu counties were selected for the training program through county disability coordinators. The training program consisted of a basic community health volunteer (CHV) module and focused on Breast and cervical cancer awareness topics. The CHVs were equipped with mobile phones with assistive technology (AT) features such as braille keyboards, magnifiers, and text-to-speech technology. The training was delivered through Amref Health Innovations' (AHI) LEAP platform in collaboration with 5 county community health assistants. The CHVs' understanding of the material was evaluated through performance tracking on the LEAP platform. The CHVs were also given regular feedback on their progress, and any areas of difficulty were addressed through additional support and guidance. Results: The trained CHVs demonstrated an increased understanding of breast and cervical cancer screening, as well as the skills necessary to perform medical tactile breast exams. The trained CHVs were then commissioned to be integrated into the community health workforce, with a focus on breast and cervical cancer screening and awareness. Conclusions: The deployment of inclusion-centered learning for women Community Health Volunteers (CHVs) living with disabilities is a promising approach for improving access to health services for this marginalized group. This program provides a model for promoting disability inclusion in health services and underscores the need for continued investment in disability-inclusive programs. The findings of this program can inform the development of similar programs in other regions and contribute to the achievement of universal health coverage and health for all.
Cervical cancer risk factors, knowledge and attitudes towards HPV vaccine among coastal Kenyan women: A prospective cross-sectional survey.
Authors: Omar Abeid Mohamed Athman , Ahmed Zahra Mohamed , Sheikh Raiham , Mohamed Abdurahman Abud , Amoody Fatma Omar
Published: June 2023

e22515

Background: Cervical cancer is the leading cause of death among women in Sub-Saharan Africa (SSA) despite being a preventable disease. Currently, there is a global rolling out of the human papillomavirus (HPV) vaccine among young girls. However, the knowledge and attitude of Cervical Cancer and the HPV vaccine remain unknown among women in SSA. Methods: We conducted a voluntary cross-sectional survey among adult women attending the cervical and breast cancer screening during Breast Cancer Awareness month in October 2022 at the Coast General Teaching Referral Hospital Regional Cancer Center, Kenya. The demographic, cervical cancer risk factors, knowledge, and attitudes to the HPV vaccine data were collected and analyzed using descriptive analysis. Results: Two hundred and fifty women participated in the survey, of which 48% were native coastal people. Their mean age was 39.3 ±12.4, and the majority (61%) of the participants were married. The most common age onset of sexual intercourse was 21-30 years (50%), followed by 16-20 years (41%), while 7% were virgins, and a quarter (n = 67) reported having multiple sexual partners. Most (90%) of the participants knew screening and early detection of cervical cancer are associated with better survival. Nevertheless, only a third had been screened previously for cervical cancer. Concerning the cause of cervical cancer, half of the patients (n = 126) knew cervical cancer is caused by HPV, and only 45% (n = 111) were aware of the free national HPV vaccination program, with only 5 participants having been vaccinated against HPV. The most commonly sighted reason for not being vaccinated was lack of knowledge of the HPV vaccine's existence (50%), a third was afraid of the vaccine’s side effects, 10% was due to lack of access, and 3%- were due to the vaccine’s age limit. With regards to the willingness to be vaccinated if they had qualified and the HPV vaccine is available for free, only two-thirds were willing to be vaccinated. However, most (90%) would recommend it to young girls. The few who would not recommend the vaccine to young girls were due to fear and lack of knowledge about the vaccine (73%). Conclusions: There is an unmet need for awareness and understanding of the HPV vaccine, and sensitization is needed to improve its uptake. In addition, it will be worth reviewing the age limit of HPV vaccination among Kenyan women as most women are sexually active after 20 years.
Real-world data on survival outcomes and characteristics of lung cancer patients in northern serbia.
Authors: Bokan Darijo , Zaric Bojan , Kovacevic Tomi , Stojanovic Goran , Djekic Malbasa Jelena
Published: June 2023

e22528

Background: Serbia is the one of the countries with the highest incidence and mortality of lung cancer in Europe and survival rates are very low. Despite that fact, there is no recent data published on the incidence, mortality, survival time or the most significant patient characteristics for the Northern Serbian Province of Vojvodina. Methods: For the purpose of this retrospective study data for the period 2010 to 2022 were collected from Institute for Pulmonary Diseases of Vojvodina Hospital Information System and the Lung Cancer Registry. Also, we collected data from seven Public Health Institutes, one for each district to analyze incidence and mortality rates. The primary objective of the study was to determine the impact of demographic and clinical pathological characteristics of patients on overall survival. The secondary objective was to analyze the incidence and mortality of lung cancer in the region of Vojvodina. Incidence and mortality rates were directly age-standardized to the World and Europe Standard Population. Results: A total of 15072 patients were eligible for the analysis, 10413 (69.1%) males and 4659 (30.9%) females. The most of the patients were current smokers (62.9% males vs 63.3% females), stage IV (47.7% males vs 46.9% females), ECOG performance status 1 (78.5% males vs 79.0% females). One-year survival rate for the patients with stage IV squamous carcinoma was 20.5% males vs 27.2% females, adenocarcinoma 18.0% males vs 22.9% females and small-cell carcinoma 10.6% males vs 17.8% females. Three-year survival rate for all stages of squamous carcinoma was 12.7%, adenocarcinoma 11.8% and small-cell carcinoma 2.9%. Five-year survival rate for all stages of squamous carcinoma was 7.4%, adenocarcinoma 6.8% and small-cell carcinoma 1.9%. There was statistically significant difference in survival time by gender in subtypes of adenocarcinoma (p = 0.000), squamous cell carcinoma (p = 0.000) and small-cell carcinoma (p = 0.001). Analysis showed significant difference in survival by age (p = 0.000), cancer type (p = 0.000), stage of the disease (p = 0.000), ECOG performance status (p = 0.000) and smoking status (p = 0.001). Incidence (ASR-W) was 65.4/100000 for males and 21.7/100000 for females. Mortality (ASR-W) was 67.8/100000 for males and 20.9/100000 for females. Conclusions: Northern Serbian Province of Vojvodina is one of the regions with the highest incidence and mortality of lung cancer and overall survival is low. Determining the impact of the most important demographic and tumor characteristics on lung cancer patients’ survival, as well as incidence and mortality rates define the parameters necessary for adequate planning of activities and strategies for improving the prevention, diagnosis and treatment of patients in Vojvodina.