bluuebunny/crossref_metadata_2025 huggingface dataset:
Efficacy of regional nodal ultrasound surveillance for metastatic detection in sentinel- and complete lymph node dissection-eligible melanoma patients.
Authors: Swetter Susan M. , Liu Lucy Y. , Gyurdzhyan Samvel , Zaba Lisa C.
Published: June 2021

e21568

Background: Nodal ultrasound (US) is the preferred method for regional surveillance of clinically node-negative (cN0) primary cutaneous melanoma (CM) when sentinel lymph node biopsy (SLNB) is not performed or unsuccessful, and for pathologically node-positive (pN+) disease without completion lymph node dissection (CLND). Methods: Retrospective review was performed of nodal US surveillance from 2011-2021 in SLNB-eligible cN0 CM patients when SLNB was deferred or technically not feasible ( i.e., from failure of lymphoscintigraphic dye migration) or those with pN+ disease on SLNB, without subsequent CLND. Patients were followed for at least 2 years or until recurrence. The primary endpoints were US detection of regional nodal recurrence and comparison to clinical exam or cross-sectional imaging (PET-CT and/or CT). Results: In total, 67 patients met inclusion criteria and underwent a median of 4 nodal US exams (interquartile range, IQR 3-5) over 2-3 years of follow-up. Thirty-two (47.8%) patients declined or had unsuccessful SLNB, and 35 (52.2%) deferred CLND in favor of nodal US surveillance. Sixteen (23.9%) patients had clinical stage IA/IB (cIA/IB) CM, 15 (22.3%) had clinical stage II (cII) disease, and 36 (53.7%) had pathologic stage III (pIII) disease. Three (4.5%) patients developed satellite/in-transit metastasis, 6 (8.9%) had regional nodal recurrence, 4 (6.0%) had both local and regional recurrence, and 7 (10.4%) developed distant metastasis. Eighteen (26.9%) patients underwent tissue sampling, with 10 positive for melanoma. Nodal recurrence was observed in patients with initial cIB (1), cIIA (1), cIIB (1), cIIC (2), pIIIA (1), and pIIIC (4) disease. Three patients (cIIA, cIIB, and pIIIC due to microsatellites) had abnormal clinical exams with concurrent palpable regional adenopathy and in-transit metastasis. One patient (pIIIC) developed local satellite metastasis followed by palpable regional adenopathy. The most common surveillance method for metastatic detection was US (6/10), followed by clinical exam (3/10) and PET-CT (1/10). All metastatic nodes on US were metabolically active on subsequent PET-CT. One patient in whom PET-CT was the initial method of detection had no confirmatory US. Conclusions: Nodal US for CM requires specific radiologic expertise and is gaining traction as a cost-effective imaging modality in the United States. Our findings support the effectiveness of nodal US surveillance in cN0 or pN+ CM patients in whom SLNB or CLND is not performed.[Table: see text]
Genetic and clinical characterization of multigene hereditary breast and ovarian cancer (HBOC) panels in Málaga (Spain).
Authors: Pajares Bella , Iglesias Campos Marcos , Díaz Tamara , Peralta Rafael Jesus , Alba Emilio , Marquez Antonia
Published: June 2021

e22530

Background: Next Generation Sequencing (NGS) technologies have transformed hereditary breast and ovarian cancer (HBOC) testing process. Several multigene panels (MP) include from 10 to 100 candidate cancer susceptibility genes, but there is a debate about what genes should and should not be tested because of lack of actionability. Few studies have been reported about MP in Europe or Spanish cancer families and no studies in Andalusian population (southern Spain). Methods: We investigated a panel of 17 known genes of high/moderate-risk for HBOC in 938 clinically suspicious HBOC Andalusian families (SEOM 2015 criteria), tested from 2017 to 2019. Multigene panel including BRCA,1 BRCA2, CHEK2, PALB2, BRIP1, ATM, MLH1, MSH2, MSH6, PMS2, CDH1, NF1, PTEN, p53, STK11, RAD51C and RAD51D was performed. Results: We identified 130 patients who carried a high- or moderate-risk pathogenic variants: 61 in BRCA2 (47%), 30 in BRCA 1 (23%), 10 in CHEK2 (8%), 7 in ATM (5%), 7 in PALB2 (5%), 4 in RAD51 (3%), 4 in BRIP1 (3%), 4 in MSH6 (3%), 2 in MLH1 (1,5%) and 1 in MSH2. We detected 220 patients carry variants of uncertain significance (VUS), with a total of 248 VUS (some patients carried more than one VUS): 46 (19%) in ATM, 38 (15%) in BRCA 2, 28 (11%) in MSH6, 19 (8%) in PMS2, 17 (7%) in BRIP1, 16 (6%) in NF1, 14 (6%) in MSH2 and 12 (5%) in CDH1 and PALB2. The most frequent criteria in the entire cohort was “High-grade epithelial non-mucinous ovarian cancer”, reported in 243 cases (26%)”, whereas “Breast cancer (BC) diagnostic under 35” was the most frequent criteria between positives (48 cases (40%)). One case carried two pathogenic variants: BRCA2 and MUTYH. Conclusions: This is the first study reporting the mutational profile of MP gene testing in Andalusia. 70% of mutations were due to BRCA1 and 2 followed by far by CHEK2, ATM and PALB2. We also identified a large amount of VUS in BRCA2, ATM and MSH6. MP improve the diagnostic in andalusian HBOC patients.
Evaluation of dystrophin expression by immunohistochemistry as a prognostic factor in leiomyosarcomas (LMS).
Authors: Terés Raul , Cerdà Paula , Sebio Ana , Gallardo Pablo , Bujosa Aida , Borrell Maria , Martin Berta , Lopez-Pousa Antonio , Gallardo Alberto , Bague Silvia , Orellana Ruth
Published: June 2021

e23525

Background: Leiomyosarcomas (LMS) are soft tissue sarcomas that derive from smooth muscle cells and can arise anywhere in the body (most frequently in extremities, uterus or retroperitoneum). The clinical prognostic factors are well established but molecular factors influencing prognostic are unknown. The DMD gene, which codifies for the dystrophin protein, has been proposed as tumour suppressor gene in LMS. The aim of our study is to evaluate dystrophin expression in LMS and its relation with the patient prognosis. Methods: A total of 103 patients (pts) with LMS were analysed. Clinical and pathological data were collected retrospectively from patients’ electronic board system. Dystrophin expression was analysed by immunohistochemistry (IHC) in paraffin embedded tissue LMS samples using the Novocastra NCL-DYS2 (Leica Biosystems). Semiquantitative assessment of the staining was classified from score 0 to 3 (0 = no dystrophin expression, 1 = low expression, 2 = moderate expression, 3 = high expression). Results: Of all 103 pts, 70 (68%) had localized disease and the majority of tumours were larger than 5 cm (75%). The most frequent locations of primary LMS were extremities (n = 31; 30.1%), uterus (n = 23; 23.2%) and retroperitoneum (n = 21; 20.4%). Most LMS were high grade (G): 7 pts G1 (6.8%), 35 pts G2 (34%) 2 and 53 pts G3 (51.5%). 50 of all grade LMS (48.6%) had loss of dystrophin expression (score 0), 17 (16.5%) had score 1, 23 (22.3%) score 2 and 10 (9.7%) score 3. Loss/low dystrophin expression measured as score 0 or 1, was more frequent in grade 3 LMS compared to grade 2 or grade 1 (77.4% vs. 57.1% vs. 16.7%; p = 0.005). There were no differences in dystrophin loss between localized or metastatic disease at diagnosis (64.2% vs. 72.2%; p > 0.05). In our series, loss or reduced dystrophin expression did not correlate with the risk of relapse in localized patients or overall survival in metastatic patients. Conclusions: Loss of dystrophin expression is a common event in LMS. Loss/low dystrophin expression is more frequent in grade 3 LMS compared to grade 2 and grade 1 LMS. Loss of dystrophin expression did not correlate with risk of relapse or overall survival in our series. Additional genetic evaluations to study DMD in LMS are underway.
Abdominal desmoid- course, unique genetic background, and severe outcomes in a large local series.
Authors: Gilad Ophir , Gilad Ophir , Strul Hana , Rosner Guy , Gluck Nathan , Fliss-Isacov Naomi , Klausner Joseph , Wolf Ido , Merimsky Ofer , Goldberg Yael , Levi Zohar , Zer Alona , Kariv Revital
Published: June 2021

e23544

Background: Abdominal desmoid tumors are locally aggressive, non-metastatic tumors that develop mainly in Familial adenomatous polyposis (FAP) patients, within the mesentery or abdominal wall. Understanding and implications of treatment regimens are evolving. We aimed to assess course, treatment and outcomes of FAP and non-FAP abdominal desmoids and their related genetic alterations. Methods: Retrospective cohort study. Demographics, tumor characteristics, oncological and surgical history, complications, genetic-testing and mortality data were retrieved from two tertiary referral centers. Results: Sixty-two patients were identified (46 FAP, 16 non-FAP) with a median follow up of 72.4 months. Thirty-eight patients (61.3%) underwent surgical procedures: twelve urgent and 26 elective. Out of 33 tumor resections, 39.4% recurred. Hormonal therapy, COX-inhibitors, chemotherapy, imatinib and sorafenib were used in 35(56.4%), 30(48.4%), 18(29.1%), 7(11.3%) and 8(12.9%) of patients, respectively, with 2 years progression-free survival of 67.8%, 57.7%, 38.4%, 28.5%, respectively. Only 1/9 patients treated with sorafenib had disease progression after a median follow up of 6.8 months. Forty-one patients (66.1%) suffered complications: bowel obstruction (30.6%), hyperalimentation (14.5%), ureteral obstruction (12.9%), perforation (11.3%), abscess formation (3.2%) and spinal cord compression (3.2%). Two patients died. Non-FAP patients presented with three renal-cell carcinomas and one germ-cell tumor and carried pathogenic mutations in CHEK2, BLM, ERCC5, MSH6 and PALB2. Conclusions: Abdominal desmoids are mostly FAP-related and are associated with severe outcomes. We report a group of non-FAP abdominal desmoids that includes patients with additional cancer-related gene alterations. This interesting group should undergo genetic consultation and be further explored.
Efficacy of temozolomide in pretreated patients with metastatic sarcoma.
Authors: Paksoy Nail , Dogan Izzet , Ekenel Meltem , Basaran Mert
Published: June 2021

e23550

Background: Sarcoma is a rare heterogeneous group malignancy and most commonly arises from soft tissue. The primary treatment modality is surgery. However, in metastatic disease, treatment options are limited. Cytotoxic chemotherapy is preferred for palliative treatment. This study aimed to assess the efficacy of temozolomide in heavily pretreated soft tissue sarcoma. Methods: We evaluated the patients with a metastatic various types of soft tissue sarcoma retrospectively. The patients with gastrointestinal stromal tumors and bone sarcomas were excluded from the study. We recorded the clinical, pathological, and treatment data of the patients. SPSS 25v was used for statistical analysis. Survival analysis was performed with the Kaplan-Meier method. Results: Sixteen patients were included in this study. The median age was 48 (range, 21-73) years. Six (37.5%) patients were de-novo metastatic. Tumor localizations were intra-abdominal (43.8%), extremity (31.2%), intrathoracic (12.5%), and head-and-neck (12.5%). The most common metastatic sites were lung (75%), bone (31.8%), liver (18.8%), respectively. For metastatic disease, the patients received at least two different chemotherapy regimens (75%), pazopanib (50%) and palliative radiotherapy (31.3%). Metastasectomy was also performed on five (31.3%) patients. Median progression-free survival was 3.5 (95% CI, 2.6-4.3) months. Partial response was observed in one (6.3%) patients, stable disease in four (25 %) patients. Eleven (68.8%) patients had progressive disease. Grade 1-2 adverse events were observed in nine (56.3%) patients, grade 3-4 in one (6.3%) patients. Conclusions: We showed that temozolomide was well-tolerated but had a limited efficacy for the treatment of patients with metastatic sarcoma. Treatment options for metastatic sarcomas are limited. Temozolomide may be considered a treatment option in patients with heavily pretreated soft tissue sarcoma.
Outcomes of metastatic synovial sarcoma with doxorubicin, pazopanib, and ifosfamide therapy.
Authors: Barreto Coelho Priscila , Costa Philippos Apolinario , Espejo Freire Andrea P. , Kwon Deukwoo , Jonczak Emily , D'Amato Gina Z. , Trent Jonathan C.
Published: June 2021

e23552

Background: Synovial sarcoma (SS) accounts for 5-10% of all soft tissue sarcoma. SS are aggressive tumors with a median 5-year survival of 60-70% when localized disease but also a propensity for metastatic spread with 40-45% of patients developing metastasis within 5 years. It is considered a chemotherapy-sensitive sarcoma and treatment options are increasing. Herein, we present the outcomes of SS patients by systemic regimen and multimodality approach. Methods: This is a single institution, retrospective cohort of 79 patients with histopathologically confirmed SS treated at from 2004 to 2019. Clinical characteristics, treatment, response and survival were analyzed. We estimated medians of progression-free survival (PFS) and overall survival (OS) using the method of Kaplan-Meier along with the Log-Rank test. All tests were two-sided and statistical significance was considered when p<0.05. Results: Median follow-up was 3.7 years (range 3.13 to 4.33), 59.5% were women and median age at diagnosis was 41 (range 5-77). At presentation, 60 patients (75.9%) had localized disease and 19 (24.1%) presented with metastatic disease. Among the entire cohort the three-year OS rate was 78.9% (95%CI = 66.3-87.3) and five-year OS rate 68.7% (95%CI = 53.5-79.9). OS between localized disease (N = 45) and metastatic (N = 12) was not statistically significant (log-rank p = 0.098). When comparing different regimens, doxorubicin-based regimens (DBR) showed longest median PFS of 10.1 months (95%CI = 3.97-21.16), while pazopanib had a median PFS of 7.45 (95%CI = 2.63-12.3), high dose ifosfamide (HDI) 6.4 months (95%CI = 2.79-15.5) and trabectedin 3.12 months (95%CI = 0.99-6.97). Conversely, patients with metastatic disease treated with pazopanib experienced a median PFS of 11.47 months (95%CI = 2.63-32.9) while those treated with a DBR 8.15 months (95%CI = 1.08-35.8). Conclusions: SS is highly aggressive and, in our cohort, patients with local presentation had non-significant difference in OS to the metastatic disease, this could be due to a small sample size or the high probability for relapse this tumor has. Chemotherapy with DBRs showed superiority to other regimens and pazopanib showed to be slightly superior when evaluating only metastatic disease. Addition of pazopanib maintenance therapy may improve PFS and OS. Continuous evaluation of these patients with further inclusion of SS on immunotherapy is warranted.
Predictors of home death and the quality of end-of-life care at a cancer center in Brazil.
Authors: Gomes Sarah , Silva Danielle , Sá Júlia , Passarini Thais , Viana Matheus , de Paula Marcela , Silva Bruna , Vieira Clarissa , Jácome Alexandre A. , Ferrari Bruno Lemos
Published: June 2021

e24004

Background: Early palliative care has shown an improvement in the quality of life of cancer patients by reducing overtreatment at the end of life and improving symptomatic control. Little is known about the quality of death in developing countries. End-of-life cancer care varies widely, and very few centers evaluate it systematically. The aim of the present study is to analyze the impact of follow-up of cancer patients by an outpatient palliative care team (OPCT) on the end-of-life outcomes at a Cancer Center in Brazil. Methods: We retrospectively retrieved data from electronic medical records of cancer patients who were treated at a Cancer Center in Brazil and who died from cancer or associated complications during the year of 2020. They were divided into two groups: OPCT and No-OPCT. OPCT group was followed-up by a multidisciplinary team composed of physician, nurse, physiotherapist, psychologist, nutritionist, social worker, speech-language therapist, and pharmacist, who regularly evaluated cancer patients during their treatments at outpatient setting. During COVID-19 pandemic, some patients were evaluated by telemedicine appointments. No-OPCT group was followed-up by cancer physicians exclusively. We performed univariate comparisons and multivariate analysis by Cox proportional hazards model. p < 0.05 was deemed as statistically significant. Results: A total of 315 patients were included in the study: OPCT (N=122) and No-OPCT (N=193). The groups were well balanced in relation to median age (61yo vs 63yo), gender (women: 51% vs 54%), and TNM stage (stage IV: 69% vs 65%). Gastrointestinal and breast cancers were the most prevalent. The rate of home death was 44% in the OPCT group, compared to 16% in the No-OPCT group (p<0.001). The rate of admission in intensive care unit in the last 30 days of life (ICU30) was 13% vs 10%, respectively (p=0.413). Likewise, the rate of patients treated with chemotherapy in the last 30 days of life (CT30) was 42% vs 51% (p=0.146). In multivariate analysis, follow-up by the OPCT was the strongest independent predictor of home death (Table). In contrast, ICU30 and CT30 were inversely correlated with this outcome. Age, gender, and TNM stage did not have influence on the place of death. Conclusions: Follow-up by an OPCT had a strong positive impact on end-of-life care of cancer patients in a country which does not have Hospice culture. The OPCT was able to offer home death to a greater number of patients, with proximity to caregivers, and respect to their beliefs and values. Our data highlight the importance of early conversations about goals of care, prognostic awareness, and end-of-life preferences, while also reinforcing the need of early referral to a palliative care team.[Table: see text]
Disparity between the use of postoperative psychosocial and physical services among older adults with head and neck cancer.
Authors: Raab Gabriel T. , Restifo Daniel , Tin Amy L. , Zakeri Kaveh , Shahrokni Armin
Published: June 2021

e24016

Background: It is unclear whether older adults undergoing head and neck cancer (HNC) surgery have significant functional and mental health impairments perioperatively. We examined postoperative physical, nutritional and psychosocial service use among a cohort of older adults with HNC co-managed by geriatricians and surgeons. Methods: Our sample consisted of older adults who were referred to the Geriatrics Service at MSKCC between 2015-2019 and took a geriatric assessment (GA) prior to undergoing HNC surgery. Physical, nutritional and psychosocial service utilization during the patient’s stay was assessed. Physical services included a physical, occupational or rehabilitation consult. Nutritional services consisted of speech and swallow or nutritional consult. Psychosocial services consisted of a psychiatry, psychology, or social work consult. All patients were comanaged by geriatricians and surgeons. Relationships between each service use, all 12 geriatric deficits, demographic, and surgical characteristics were assessed using chi-squared analysis and t-test for continuous variables. Results: 159 patients (median age 81) were included. The median time in the OR was 342 min and the median length of stay (LOS) was 6 days. The most common GA impairments were major distress (61%), depression (59%), Social Activity Limitation (SAL) (53%) and deficits in Activities of Daily Living (ADL) (44%). Nutritional and physical services were used much more frequently than psychosocial services (79% and 85% vs 31%; p=.01 and p=.003, respectively). Lower ADL, increasing OR time and LOS were statistically associated with utilization of the three services and SAL was associated with a greater proportion of physical and psychosocial consults (Table). No demographic characteristics were associated with any of the services. Only 38% of patients with major distress and 40% of patients with depression had a mental health consult. In comparison, 93% of patients with an abnormal TUG had a physical consult and 92% of patients with weight loss greater than 10 pounds prior to surgery got a nutritional consult. Conclusions: Many older adults with head and neck cancer experience aging-related impairments. Physical impairments are more commonly addressed than psychosocial impairments. Future studies should aim to identify and overcome barriers to addressing psychosocial issues in HNC patients. [Table: see text]
Survivors Overcoming and Achieving Resilience (SOAR): An 8-week breast cancer survivorship and nutrition program.
Authors: Desai Poorvi Kirit , Riccardi Diane , Gray Heewon L. , Pflanzer Sonya , Thompson Zachary , Pabbathi Smitha
Published: June 2021

e24025

Background: The American Cancer Society (ACS) published Diet and Physical Activity Guidelines in 2020. Emerging evidence suggests that healthy dietary patterns are associated with reduced cancer risk, especially colon and breast. ACS estimates there are 3.5 million breast cancer survivors in the US. The transition from active treatment into survivorship is a critical period where they are uniquely positioned to adapt healthy behaviors, yet there is a lack of empirical research to best guide the transition. Methods: We developed an 8-week breast cancer survivorship program to educate and develop healthy habits. 40 participants were recruited through Moffitt breast and survivorship clinics, social media, and website. Weekly topics were: cancer survivorship, nutrition, emotional health and well-being, exercise, medical management after treatment, grocery store tour, meditation and mindful eating, and moving forward. To assess health-related quality of life (QoL), we used FACT-G Version 4, a validated patient-reported survey with 27 questions and 4 domains of wellbeing (physical, social/family, emotional, and functional) on a 5-point Likert scale (not at all to very much). Similarly, a nutrition questionnaire evaluated the understanding of healthy choices, confidence in making healthy changes, knowing how to purchase healthy foods and read nutrition labels, confidence in preparing healthy foods, and understanding of a plant-based diet. Surveys were administered pre- and post-intervention. Data analysis included those who completed both (n = 30). Pt characteristics and data trends were summarized using descriptive statistics. Paired Wilcoxon rank sum tests were used to assess the significance of the change in scores between surveys. Results: Participant ages ranged from 41 to 77. The majority (34.5%) completed treatment 13-24 months prior. Compared to baseline, greater proportions of participants had positive responses after intervention in all nutrition questions. The nutrition sum was significantly increased by 3.07 (p = 0.0001). There was no significant change in overall QoL (-1.77; p = 0.1178) or sub-domain wellbeing scores. Conclusions: Our 8-week intervention for breast cancer survivors showed significant improvement in nutrition domain. While a small sample size is limiting, it is evident that survivors can improve their confidence in making healthy changes and develop better understanding of a plant-based diet.[Table: see text]
Clinical and demographical factors associated with fertility counseling in colorectal cancer.
Authors: Peng Chengwei , Masri Lena , Roman Stefanie , Sherman Scott , Becker Daniel Jacob
Published: June 2021

e24047

Background: The incidence of colorectal cancer in patients younger than 50 has been increasing over the past 2 decades. This demographic shift has important implications for survivorship care, in particular regarding issues of future fertility especially in light of USPSTF’s recommendation for colorectal cancer screening to begin at 45. Although ASCO has longstanding recommendations for fertility counseling in patients with cancer, the rates of fertility counseling in younger patients with colorectal cancer are unknown. Methods: Records for new patient visits for colorectal cancer in patients younger than age 55 in a large academic cancer center between 2012 and 2019 were queried for patient demographics, disease characteristics, and documentation of fertility counseling. Associations between demographic/clinical characteristics and fertility counseling were explored. Univariate and multivariable logistical regression analyses were performed using SAS v9.4. Results: Among 194 patients who met inclusion criteria, 39.2% of patients were female, 10.4% were African American, 31.4% had rectal cancer, and 69.6% were treated with curative intent. Approximately 14.5% of patients had Medicaid insurance. Age ranged from 22-55. The overall rate of fertility counseling among all patients was 15.5%. Of these patients, 43.3% were male. In univariate analysis, age less than or equal to 40 (p < 0.01), female gender (p = 0.03) and curative intent therapy (p = 0.03) were associated with fertility counseling. These factors were again statistically significant in multivariate analysis: age < 40, female, and curative intent therapy (Table). Race, stage of cancer, insurance status, prior exposure to chemotherapy, year of diagnosis and colon vs rectal cancer were not associated with counseling. Conclusions: The rate of fertility counseling was very low among patients with colorectal cancer, and exceptionally low among men. Despite changes in the demographics of colorectal cancer, it does not appear that appropriate changes have been made in fertility counseling. Increases in fertility counseling were not seen in more recent years despite recognition of increasing incidence in younger patients. Additional studies to identify barriers to counseling and strategies to improve survivorship care are urgently needed.[Table: see text]
The experience of pain among cancer patients at the University of the Philippines: Philippine General Hospital Cancer Institute—A cross-sectional study.
Authors: Tan Harold Nathan C. , Velasco Rogelio Nona , Catedral Lance Isidore Garcenila , San Juan Michael Ducusin , Ngelangel Corazon , Calvo Emiliano
Published: June 2021

e24078

Background: Pain is one of the most common and dreaded sequelae of cancer, occurring in approximately 55% of patients. The experience of pain takes a toll on the patients’ quality of life. However, many patients do not receive adequate pain management. This study aimed to determine the prevalence of pain, its severity, and the adequacy of pain management among cancer patients in the Philippines. Methods: A cross-sectional study was conducted at a representative cancer center in the Philippines, enrolling 351 cancer patients. Pain severity was assessed using the Brief Pain Inventory-Short Form (BPI-SF) Filipino. The BPI evaluates pain severity and its impact on daily functioning (pain interference). To ascertain the adequacy of pain control, the pain management index (PMI) was calculated by subtracting the subtracting the severity of pain reported by the patient from the type of analgesic treatment received. Logistic regression analysis was conducted to evaluate the factors associated with worst pain and adequacy of pain management. Data were analyzed using Stata version 16.0, with statistical significance set at p < 0.05. Results: Three hundred three cancer patients (86.3%) experienced pain. Approximately 3 out of 5 patients (n = 208) did not receive adequate pain control, and one-third of patients experienced severe pain (n = 121). Patients who reported severe pain interference (n = 110) had three times greater odds to experience severe pain (OR 3.2, 95% CI 1.82-5.61, p < 0.001). Those patients who had regular follow up were 65% less likely to experience severe pain (OR 0.35, 95% CI 0.16 – 0.78, p = 0.01). Patients who used pain medications (n = 196) were 14 times more likely to experience adequate pain management (OR 14.19, 95% CI 6.53 – 30.83, p < 0.001). Patients who were referred to pain service (n = 25) were seven times more likely to report adequate pain control (OR 6.62, 95% CI 2.50 – 17.56, p < 0.001). Conversely, those patients who reported a severe rating on total pain interference were 75% less likely to experience adequate pain management (OR 0.25, 95% CI 0.17 – 0.35, p < 0.001). Conclusions: Unexpectedly, there was a high prevalence of pain among cancer patients at a representative cancer center in the Philippines. Pain exerts a heavy toll on patients, affecting daily functioning. The undertreatment of pain discovered in this study (59% of cancer patients) is alarming. Timely pain evaluation can help identify the presence of pain and the need for appropriate use of analgesics. The assessment and management of pain is a critical component of cancer care that should not be neglected.
Survivorship care plans and adherence with surveillance schedule in patients with invasive melanoma.
Authors: Shah Hemali , Feustel Paul , Davis Lindy
Published: June 2021

e24079

Background: Melanoma accounts for 5.5% of new cancer diagnoses in the United States, and the 5-year overall survival is 93%. Overall, 7% of patients develop a recurrence, and 4-8% develop a second primary melanoma. This study aimed to assess how the standards set by the American College of Surgeons Commission on Cancer (CoC) to provide survivorship care plans (SCP) to patients may improve adherence to surveillance visits. Methods: All patients treated for invasive melanoma at our institution between 8/2018-2/2020 were included. SCP containing stage, treatment summary, and surveillance plan were delivered in-person to patients and sent to primary providers and dermatologists as outlined by CoC Standards for Optimal Care. Psychosocial distress (PSD) screening was performed using the National Comprehensive Cancer Network Distress Thermometer, with scores > 4 requiring further evaluation by oncology social worker. SCP and PSD were provided during the initiation phase of our cancer care program, and half the patients received services. Surveillance adherence was determined from chart review. The two groups were compared by t-test for continuous or chi-square test for categorical variables. Multiple regression analysis with odds ratios were performed. Mann-Whitney analysis was performed to assess the impact of SCP on PSD. Results: Of 146 patients identified for our cohort, 73 received SCP and PSD screening. Stage IA was the most common diagnosis (44%), followed by IB (13%) and IIIC (9%). Ninety-eight patients (67%) were adherent to all surveillance visits, and 55 of these received SCPs. Most patients noted low distress without the need for further support (79%), and 12 (21%) scored ≥4, benefiting from emotional and financial support and appointment and health insurance navigation. High PSD score did not correlate with advanced stage. Reception of SCP (p = 0.036) and close distance to treating facility (p = 0.016) improved adherence to surveillance visits. For patients who did not receive SCP, likelihood to follow up decreased by a factor of 0.469 (95% CI 0.231 - 0.952). Sex, age, PSD score, and stage did not affect surveillance adherence (p = NS). There were 6 recurrences, of which 4 were physician-detected during surveillance, and 8 patients developed second primary melanomas, all physician-detected. Conclusions: Delivery of SCP, a component of which includes counseling regarding signs and symptoms of recurrence or possibility of second primary melanoma, leads to significantly higher rates of surveillance adherence. This was shown for all stages. Melanoma survivors require close clinical follow-up, as demonstrated by our study finding that even with patient education, most recurrences and all new primary melanomas were physician-detected. PSD among melanoma patients is common, and all patients regardless of stage should undergo screening, as even early-stage patients exhibited distress.
Pan-cancer analysis of fear of cancer recurrence in cancer survivors.
Authors: Adashek Jacob J. , Thompson Zachary , Martinez Tyson Dina , Pabbathi Smitha
Published: June 2021

e24104

Background: Fear of cancer recurrence (FCR) in cancer survivors is an understudied phenomenon estimated to one-third to over half of all cancer survivors. FCR has been shown to contribute to treatment noncompliance and portend a decrease in overall survival (OS). The purpose of this study was to examine factors associated with needs related to FCR among patients seen at a solid tumor survivorship clinic at a National Cancer Institute designated center. Methods: Data collected as part of a patients’ needs assessment that is administered to patients (n = 657) with solid tumors such as breast, genitourinary, gastrointestinal malignancies at their initial clinic visit were analyzed. Correlations between responses were calculated and univariable and multivariable logistic regression was used to identify predictors of met or unmet needs related to FCR. Results: There were a total of 657 patients included 442 (67.3%) female and 215 (32.7%) male. The majority of patients (84.5%) were white (n = 555), followed by 9.74% black (n = 64), the remaining patients identified as ‘other’ or Asian. The patients median age was 67 years, median age of diagnosis 55 years, and median years since diagnosis 10 years. 613 patients had recorded distress scores ranging from 0 (n = 214), 1-4 (n = 255), 5-7 (n = 106), or 8-10 (n = 38). Of 647 patients, 241 (37.2%) reported FCR was not a need and 386 (59.7%) reported FCR was a met need. According to univariate logistic regression gender had no impact on FCR (p = 0.8427) nor did years since diagnosis (p = 0.1014). Results of multivariable regression indicate the odds ratio of reporting FCR as an unmet need (vs not a need) decreases by 6% (p = 0.0023) for every year increase in age. For each unit increase in distress score the odds ratio of reporting FCR as an unmet need is increased by 32% (p = 0.0007). Conclusions: Our data suggests that patients reporting higher distress scores are more likely to report FCR as an unmet need. Therefore, survivors with high distress scores reported in clinic visits should be evaluated for FCR. FCR reported as an unmet in our study is significantly less. Further stratification of FCR can be helpful for providers caring for survivors to identify and address FCR more effectively in clinical care. Further study is needed to learn how survivors have come to identify the need as being met.
Biomarker-oriented study of durvalumab in combination with olaparib and paclitaxel in gastric cancer: A phase 2 trial-in-progress.
Authors: Kim Tae Yong , Yoon Jee Sun , Nam Ah-Rong , Bang Ju-Hee , Oh Kyoung Seok , Seo Hye-Rim , Kim Jae-Min , Oh Do-Youn
Published: June 2021

TPS4153

Background: Olaparib (PARP inhibitor) leads to DNA damage and cell death. In phase III study (GOLD), olaparib plus paclitaxel did not improve overall survival (OS) compared with paclitaxel in second-line gastric cancer (GC) patients with statistical significance, even though there was absolute increase of OS (Lancet Oncol 2017). This highlights the importance of biomarker-based patient selection. The changes of tumor microenvironment by paclitaxel/olaparib have not been explored. Besides DNA damage, olaparib induces positive or negative immune modulation by recruiting T cells, promoting type I interferon and upregulating PD-L1, which suggests anti-PD (L1) inhibitor plus olaparib could enhance anti-tumor immunity. Combination of Anti-PD-1 agents with chemotherapy showed a good clinical efficacy in first-line of GC compared with chemotherapy alone (Checkmate 649). Based on these findings, the combination of paclitaxel/olaparib/anti-PD(L1)1 inhibitor, with different mode of actions, might enhance antitumor activity. This is phase II study of paclitaxel/olaparib/durvalumab combination in second-line GC patients, to find out immune modulation effects by paclitaxel/olaparib combination, and to see the efficacy, safety, optimal biomarkers for this combination. Methods: All patients with histologically confirmed unresectable GC have failed to prior one chemotherapy and measurable lesion. Prior exposure to anti-PD(L1)1, PARP inhibitor is excluded. At 1st cycle, paclitaxel (80 mg/m2) on D1, 8 and 15 and olaparib (150 mg bid) on D1-28 is administered. Pre-treatment biopsy and after first cycle biopsy is done. From second cycle, durvalumab 1500 mg on D1 every 4 weeks is added. At the time of disease progression, tumor biopsy is mandatory. Blood samples for biomarkers should be obtained every cycles. Response evaluation is performed after first 3 cycles and repeated every 2 cycles. Primary endpoint is the disease control rate (the percentage of patients who have achieved complete or partial remission, stable disease based on RECIST v1). Key secondary endpoints are overall response rate, progression-free survival, OS, quality of life and safety. Clinical trial information: NCT03579784.
A phase 2 study of cabozantinib in combination with atezolizumab as neoadjuvant treatment for muscle-invasive bladder cancer (HCRN GU18-343) ABATE study.
Authors: Kilari Deepak , Szabo Aniko , Bylow Kathryn A. , Alter Robert S. , Nelson Ariel Ann , Lemke Emily , Hall William Adrian , Johnson Scott , Langenstroer Peter , Jacobsohn Kenneth , Davis Nancy B. , Fung Chunkit , Milowsky Matthew I.
Published: June 2021

TPS4591

Background: ABACUS and PURE-01 trials demonstrated the activity of single agent atezolizumab and pembrolizumab respectively as neoadjuvant therapy for muscle invasive urothelial carcinoma (MIUC). However, downstaging to non-muscle invasive disease was noted in only 50 percent of patients. Resistance to programmed death (PD)- 1/L-1 antibodies is likely to include factors such as impaired dendritic cell maturation/function, infiltration of T-Regs and myeloid derived suppressor cells, impaired T-cell priming and T-cell trafficking in tumors. Cabozantinib is a tyrosine kinase inhibitor which targets MET, AXL, MER, Tyro3 and VEGFR2. Cabozantinib has a unique immunomodulatory profile and has demonstrated clinical activity as monotherapy and in combination with PD-1/L1 antibodies in various solid tumors including UC, renal cell cancer, castrate- resistant prostate cancer, and non-small cell lung cancer. We hypothesize that the combination of cabozantinib and atezolizumab as neoadjuvant therapy for MIUC would improve rates of pathologic downstaging compared to single-agent checkpoint inhibitors. Methods: ABATE(NCT04289779) is an open-label, single arm, multi-center study to assess the efficacy and safety of cabozantinib with atezolizumab as neoadjuvant therapy for cT2-T4aN0/xM0 MIUC. An estimated 38 patients will be enrolled and receive cabozantinib 40 mg PO daily with atezolizumab 1200mg every 3 weeks for a total duration of 9 weeks followed by radical cystectomy. Adults (≥18 years) with resectable UC who are either cisplatin-ineligible or decline cisplatin are eligible. Patients are required to have an ECOG PS of 0-2 and provide tumor tissue for PD-L1 analysis. UC should be predominant component (≥ 50%). Previous systemic anticancer therapies for MIUC are not permitted. CT/MRI will be performed before investigational therapy and cystectomy. Primary endpoint is pathologic response rate defined as the absence of residual muscle-invasive cancer in the surgical specimen ( < pT2). Secondary endpoints are safety and toxicity, pathologic complete response rate and event-free survival. Exploratory end points include patient-reported outcomes and outcome associations with biomarkers. Accrual began May 2020. Clinical trial information: NCT04289779.
CYCLONE 1: A phase 2 study of abemaciclib in patients with metastatic castration-resistant prostate cancer (mCRPC) previously treated with a novel hormonal agent and taxane-based chemotherapy.
Authors: Agarwal Neeraj , Oudard Stephane , Piulats Josep M. , Schweizer Michael Thomas , Flechon Aude , Alonso Gordoa Teresa , Nacerddine Karim , Lithio Andrew , Johnston Erica L. , Smith Matthew Raymond
Published: June 2021

TPS5086

Background: In cancer cells, the cyclin-dependent kinases 4 and 6 (CDK4 & 6)/retinoblastoma protein (Rb) pathway is commonly altered, resulting in uncontrolled cell cycle entry and proliferation. CDK4 & 6 inhibitors represent a major advance in the management of hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2-) advanced or metastatic breast cancer (ABC or MBC, respectively). Abemaciclib is an oral selective inhibitor of CDK4 & 6 administered on a continuous dosing schedule, approved in combination with endocrine therapy for HR+, HER2- ABC or MBC. In addition, abemaciclib is also approved by the FDA as monotherapy for HR+, HER2- ABC or MBC following endocrine therapy and prior chemotherapy in the metastatic setting. Similar to the estrogen receptor signaling pathway in breast cancer cells, there is evidence that the androgen receptor axis activates CDK4 & 6 to sustain prostate cancer cell proliferation and survival. Preclinical studies in prostate cancer cell lines and xenograft models showed that abemaciclib exhibits single agent activity by inducing cell cycle arrest and tumor growth inhibition. Clinical activity of abemaciclib in combination with abiraterone and prednisone is investigated in a randomized phase 2 study in the first-line mCRPC setting (CYCLONE 2, NCT03706365). Despite recent advances, management of heavily pretreated mCRPC remains a major clinical challenge. Herein, we hypothesize that mCRPC patients whose disease progressed after novel hormonal agents (NHA) and taxane therapies may derive therapeutic benefit from single agent abemaciclib. Methods: CYCLONE 1 is a phase 2, single-arm, multicenter study to assess the safety and efficacy of abemaciclib monotherapy in 40 patients with mCRPC progressing after ≥1 NHA and 2 taxane regimens. Patients will be enrolled at time of prostate specific antigen (PSA) or radiographic progression per PCWG3 criteria and have at least 1 measurable lesion per RECIST 1.1. Metastatic tumor tissue (fresh biopsy or archival material <12 weeks) is required at baseline for biomarker analysis. Patients will receive abemaciclib 200 mg twice daily until unacceptable adverse events or disease progression. The primary objective is investigator-assessed objective response rate (ORR). Key secondary objectives include safety, radiographic progression-free survival, overall survival, PSA response rate, time to PSA progression, time to symptomatic progression, Ki-67 expression, patient-reported outcomes, and pharmacokinetics. Assuming an ORR of 15%, the study has over 73% power to observe a response rate of at least 12.5%. Accrual began in January 2021. Clinical trial information: NCT04408924.
Trial in progress: A phase I/II trial of novel MDM2 inhibitor alrizomadlin (APG-115), with or without platinum chemotherapy, in patients with p53 wild-type salivary gland carcinoma.
Authors: Swiecicki Paul , Tang Yuefen , Pearson Alexander T. , Muzaffar Jameel , Fidler Mary J. , Winkler Robert , Fu Tommy , Li Mingyu , Ahmad Mohammad , Yang Dajun , Zhai Yifan
Published: June 2021

TPS6094

Background: Salivary gland carcinoma is a rare tumor that accounts for 6% of all head and neck cancers. This histologically and anatomically heterogeneous malignant tumor type is largely resistant to platinum and other chemotherapies but commonly has wild-type TP53 based on next-generation sequencing analysis. Alrizomadlin is a novel, orally active, small molecular agent that binds to MDM2, restoring p53 tumor suppressor function and inducing apoptosis in tumor cells retaining wild-type p53. Preliminary clinical evidence suggests promising antitumor activity and a favorable safety profile for alrizomadlin in the treatment of solid tumors (Rasco 2019). Methods: This US multicenter open-label trial is evaluating alrizomadlin with or without platinum chemotherapy in adults with histologically documented wild-type TP53 salivary gland carcinoma, including primary or metastatic lesions, an ECOG performance status 0-1, and a life expectancy of at least 12 weeks. In addition, subjects need to have measurable disease by computed tomography according to RECIST v1.1, with radiographic disease progression within the prior 12 months, high-grade status with or without metastases, and/or not amenable to curative treatment. An initial randomized phase (Part 1) will be followed by a single-arm phase (Part 2). Treatment arms include a cycle length of 21 days, and the study is using a time-to-event continual reassessment method. In Part 1 (42 patient target), patients are randomly allocated (in a 1:2 ratio) to one of two arms: single-agent alrizomadlin at a starting dose of 150 mg (Arm A) or at a starting dose of 150 mg with concomitant IV carboplatin administered at starting AUC = 4.5 (Arm B). Based on overall response rate (ORR; complete or partial response after Cycle 2) and safety profile, the most promising treatment arm will be advanced to Part 2, which has a target enrollment of 20 patients. Study endpoints are (1) dose-limiting toxicity (DLT), which is defined by the rate of drug-related grade ≥ 3 adverse events (by NCI CTCAE v5.0) over the first 2 cycles (6 weeks) of study treatment; (2) maximum tolerated dose based on these DLTs; and (3) ORR by RECIST v1.1 observed at up to 12 months. As of January 27, 2021, 11 of 42 patients had been enrolled in Part 1. Internal study identifier APG-115SG101. Clinical trial registration: NCT03781986. Clinical trial information: NCT03781986.
The PLATON pilot-study “Platform for analyzing targetable tumor mutations”: A PLATON network study.
Authors: Vogel Arndt , Zäpf Bianca , Goetze Thorsten Oliver , Westphalen Benedikt , Müller Lothar , Broeckling Sebastian , Moulin Jean-Charles , Potenberg Jochem , Sohm Michael , Gabrysiak Thomas , Heuer Vera , Klump Bodo , Chater Jack , Zeth Matthias , Saborowski Anna , Quader Facher , Michael Felicia , Pauligk Claudia , Amstein Leonie , Al-Batran Salah-Eddin
Published: June 2021

TPS6598

Background: PLATON Network is designed as a platform to improve personalized therapy based on genomic profiles in gastrointestinal cancer patients. PLATON’s study-design focuses on patient’s molecular profiling and will provide a network web application for interlinking PLATON investigators which integrates information of the participating centers, their patients, the molecular profiles and available clinical trials at PLATON`s study-sites. Methods: The PLATON Network is designed as a permanent open, multicenter, prospective, cohort study with biobanking, with a shared platform infrastructure for associated sub-studies. In a first approach the PLATON Network enrolls within its pilot-study 200 patients in Germany of both sexes and ages over 18 at 40 study sites (NCT04484636) with signed informed consent. All patients of the pilot-study are diagnosed with hepatocellular cancer (HCC), intra- and extrahepatic cholangiocellular carcinoma (CCA), gallbladder carcinoma (GBCA), pancreatic cancer (PDCA) or esophagogastric cancer (EC/GC). At the time of enrolment, patients are within their first-line therapy and no local curative therapy is available. Molecular profiling will be performed with the Foundation Medicine Assays FoundationOne CDx and FoundationOne Liquid CDx. Investigators may use the platform for searching clinical trials matching the individual molecular profile of their patients or may identify a patient, who may be eligible for a study or other treatment options available at the corresponding centers of the PLATON network. The interactive network web application will comprise a dashboard and a moderated chat room to interact for example in a virtual Molecular Tumor Board. The first patient was included on the 25th of November 2020. Up to 12th of February 2021, a total of 36 patients HCC (N = 1), CCA (N = 6), PDCA (N = 12), GBCA (N = 0) and EC/GC (N = 16) were enrolled at 11 study-sites and the results of 29 genetic analyses were completed. All cohorts of the pilot-study are open for recruitments up to a maximum of 40 individuals per diagnostic group. Clinical trial information: NCT04484636.