bluuebunny/crossref_metadata_2025 huggingface dataset:
Shave biopsy of pediatric melanocytic tumors compromises staging and therapy planning.
Authors: Daley Jessica , Kirkwood John M. , Seynnaeve Brittani
Published: June 2021

e21576

Background: Melanoma is the dominant skin cancer of pediatric patients, and accounts for 1-3% of pediatric malignancies. The prognosis for both adults and children with melanoma correlates with stage at diagnosis, and initial Breslow depth is a critical determinant. Kaplan-Meier melanoma-specific survival curves show survival rates ranging from 98% (T1a) to 75% (T4b) at 10 years for adult patients with stage I and II disease at diagnosis. Pediatric patients are known to present with thicker primary melanomas as compared to their adult counterparts. The preferred biopsy method of the American Academy is Dermatology for melanoma is excisional, however partial shave biopsy is most frequently performed in children, given its simplicity, efficiency, and often low clinical suspicion for cutaneous malignancy. Despite the ease of this biopsy technique, shave biopsy has a high rate of base transection, reducing accuracy of microstaging, which is crucial for therapy planning. Methods: Retrospective chart review evaluation of the potential effects of biopsy method on staging, surgical recommendations, and treatment approach for pediatric patients with melanocytic tumors. Results: Data was available for 91 pediatric patients with a spectrum of melanocytic tumors ranging from atypical with unknown malignant potential, to melanoma. Patient characteristics including gender, age at biopsy, biopsy method, status of biopsy margins, recommendations for re-excision, sentinel lymph node biopsy, and treatment plan were collected and analyzed. There were 48 females and 43 males with age range 1—22 years (mean 10 years). Sixty-eight of 91 (75%) tumors had a positive margin (deep, peripheral, or both) on diagnostic biopsy, 52/68 (76.5%) were obtained using shave method. Evaluating the deep margin specifically, 50/91 (55%) tumors had a positive deep margin, 46/50 (92%) of which were obtained using shave method. No tumor evaluated by punch had a positive deep margin (0/18). Of all shave biopsies, 77% had positive deep margin as opposed to only 13% using alternative biopsy methods. In 10/91 (11%) patients, surgical recommendations were changed based on inaccurate microstaging and positive deep biopsy margins, 9/10 (90%) of these patients had undergone shave biopsy. Most (8/10) patients had melanoma, the remaining 2/10 had highly atypical spitzoid tumors in which melanoma could not be ruled out. Conclusions: Pediatric patients with melanocytic tumors most commonly underwent shave biopsy as the initial diagnostic biopsy method. This method of biopsy was associated with higher incidence of positive margins at diagnosis and more aggressive definitive surgical management. These findings suggest that more routine use of excisional biopsy in pediatric patients with lesions being evaluated for malignancy could decrease the incidence of inaccurate microstaging and reduce the need for more aggressive definitive surgical management.
Combination therapy with anti-PD-1 or PD-1 antibody alone in pediatric patients with relapsed or refractory cancer.
Authors: Que Yi , Wang Juan , Zhu Jia , Li Na , Huang Junting , Lu Suying , Sun Feifei , Zhang Lian , Zhen Zijun , Zhang Li , Cai Ruiqing , Guo Haixia , Sun Xiaofei , Zhang Yizhuo
Published: June 2021

e22004

Background: There is limited experience of PD-1 combined with other therapies in children. We aimed to explore the antitumor activity and safety of PD-1 antibody monotherapy or combination with other regimens in relapsed or refractory pediatric cancer. Methods: This was an observational retrospective study performed at two academic medical centers (Sun Yat-sen University Cancer Center and Nanfang Hospital, Southern Medical University) The primary objective of this study was to describe the overall response rate (ORR) and disease control rate (DCR). Secondary objectives included characterizing toxicities according to the Common Terminology Criteria for Adverse Events (CTCAE) version 4.03 as well as describing progression free survival (PFS) and overall survival (OS). Results: Of the 22 pediatric cancer patients who received PD-1 inhibitors, the median follow-up for all patients after the commencement of PD-1 therapy with or without other regimens was 12.3 months (0-43 months). The objective response rate (ORR) and disease control rate (DCR) of the 6 patients with HL were 83.3% (3CR and 2PR) and 100%, respectively. No objective response was observed in patients with melanoma or Burkitt lymphoma evaluated in this study. For patients treated with PD-1 inhibitor combination therapy, PD-1 antibody combined with decitabine showed potential efficacy in advanced pediatric cancer patients. One of the Three of patients who received PD-1 combined with decitabine achieved CR and another two other patients achieved PR. At the data cutoff, 10 of the 13 (76.9%) patients achieved disease control as the best objective response. The median PFS and OS were 90 days (95%CI: 10.733-169.267) and 158 days (95%CI: 131.514-184.486) respectively. There were no severe treatment-related adverse events (TRAEs) directly attributed to PD-1 monotherapy. The severe TRAEs are due to chemotherapy in the combination regimen. Conclusions: PD-1 monotherapy demonstrated antitumor activity in a population of pediatric patients with HL. The regimen of PD-1 inhibitor combined with decitabine showed potential in treating with pediatric cancer patients.
Early cancer detection using low-coverage whole-genome sequencing of cell-free DNA fragments.
Authors: Yang Shunli , Zhihua Pei , Yu Jianing , Zhao Xiuyu , Liu Yiqian , Zhang Yaxi , Chen Geng , Chen Weizhi , He Ji
Published: June 2021

e22510

Background: Recent advances in circulating cell-free DNA (cfDNA) of plasma have shown that tumor diagnosis based on tumor-specific genetic and epigenetic changes (e.g., somatic mutations, copy number variations, and DNA methylation) is a promising non-invasive method. However, the number of tumor-specific genomic variants identified by whole-genome sequencing (WGS) in early cancer patients is very limited. Moreover, the mutations generated by clonal hematopoiesis in cfDNA can further confound the detection of cancer-specific mutations. It has been shown that ctDNA and cfDNA fragments have differences in length distribution. Compared with a limited number of genomic mutations, cfDNA fragment size index (FSI) is more abundant and easier to be detected. Methods: We designed a novel method for fragment detection of plasma cfDNA based on low-coverage WGS. The fragment length differences between healthy individuals and tumor patients were systematically analyzed. The training dataset includes 50 healthy individuals and 354 patients from eight different cancers. After the data preprocessing, we calculated the weight of fragmental bins and built a model for distinguishing healthy individuals from cancer patients. An independent dataset involving 22 healthy controls and 340 cancer patients was used to validate the model. The performance of our method was measured by the area under the curve (AUC) using the one-versus-all approach. Results: In our analysis, a total of 504 markers were selected from the dataset for model construction. Our model performed well for all cancer types on both training (AUC = 0.804) and validation (AUC = 0.837) datasets. Conclusions: The good performance of our model in large-scale plasma samples demonstrates the potential clinical application of cfDNA fragment analysis in early cancer detection based on low-coverage WGS.
A unique molecular identifier-based and clonal hematopoiesis-aware approach for accurate mutation calling in cell-free DNA assays.
Authors: Xie Hongyu , Zhang Yaxi , Zhihua Pei , Yu Jianing , Liu Yiqian , Zheng Shiqi , Chen Geng , Chen Weizhi , He Ji
Published: June 2021

e22515

Background: Given peripheral blood cells (PBCs) matched cell-free DNA (cfDNA), accurate mutation calling in next generation sequencing (NGS)-based assays relies on discriminating artifacts and clonal hematopoiesis mutations from tissue originated somatic mutations. Although clonal hematopoiesis has been considered in previous overall error modeling, it has not been adapted to PBCs without using unique molecular identifiers (UMIs). Moreover, previous studies on background error profiling were mainly based on healthy controls without matched PBC gDNA, which may lead to potential overestimation of the error rates on those sites with clonal hematopoiesis mutations. Additionally, the fraction of tissue cells is also an important influencing factor but is usually ignored. Methods: We performed UMI-assisted capture-based DNA assays on cfDNA samples, matched PBCs, and oral epithelium cells from 150 healthy donors. A site-specific and subtype-specific background error model was first built for PBCs using the SNVs called from PBCs with matched oral epithelium cells to exclude potential clonal hematopoiesis mutations. Then a similar background model was established for cfDNA with the SNVs inferred from cfDNA to exclude clonal hematopoiesis. The SNVs identified in cfDNA and matched PBCs were separately filtered with the cfDNA and PBC background error models. In this study, we used the ultrasensitive liquid biopsy approach to evaluate paired with tissue and blood samples from 56 early-stage NSCLC patients. All samples are sequenced using NGS target-capture panels covering 29 genes. Results: The mutations were detected in 91.1% of tissue and 67.9% were discovered in plasma. The coincidence rate between tissue and plasma of the 56 early-stage NSCLC patients was 66.1%. Conclusions: We have developed a novel method tailored for UMI-assisted capture-based targeted DNA assays, which outperforms currently available methods in terms of modeling background errors and filtering clonal hematopoietic mutations.
Performance characteristics of brief family history questionnaire to screen for Lynch syndrome in women with newly diagnosed ovarian cancers.
Authors: Kim Rachel Soyoun , Tone Alicia , Kim Raymond , Cesari Matthew , Clarke Blaise , Eiriksson Lua Ruhiyyih , Tae Hart , Lytwyn Alice , Maganti Manjula , Gallinger Steven , Bernardini Marcus , Oza Amit M. , Djordjevic Bojana , Lerner-Ellis Jordan , Van de Laar Emily , Vicus Danielle , Pugh Trevor J. , Pollett Aaron , Ferguson Sarah E.
Published: June 2021

e22525

Background: Ovarian cancer (OC) is the third most common Lynch syndrome (LS)-associated cancer in women but there is no established screening strategy to identify LS in this population. An adequate family history may identify patients suspected of LS, prompting a referral to genetic assessment. We have previously validated the 4-item brief Family History Questionnaire (bFHQ) in endometrial cancers. The objective of this study was to assess whether bFHQ can be used as a screening tool to identify women with OC at risk of LS. Methods: Prospective cohort study recruited women with newly diagnosed non-serous/non-mucinous OC from three cancer centers in Ontario, Canada. Participants completed bHFQ, extended Family History Questionnaire (eFHQ; encompassing Amsterdam II criteria, Society of Gynecologic Oncology 20-25% criteria and Ontario Ministry of Health criteria), immunohistochemistry (IHC) for mismatch repair (MMR) proteins and universal germline testing for LS. The performance characteristics were compared between bFHQ, eFHQ, and IHC. Results: Of 215 participants, 169 (79%) were evaluable with both bFHQ and germline mutation status; 12 of these 169 were confirmed to have LS (7%). Nine of 12 patients (75%) with LS were correctly identified by bFHQ, compared to 6 of 11 (55%) by eFHQ and 11 of 13 (85%) by IHC. The sensitivity, specificity, positive predictive values and negative predictive values of bFHQ were 75%, 66%, 15% and 98%, compared to 55%, 92%, 35% and 96% for eFHQ and 85%, 90%, 39% and 99% for IHC respectively. IHC was the most sensitive and specific approach. The 4-item bFHQ was more sensitive than eFHQ and took less than 10 minutes for each patient to complete. Conclusions: Patient-administered bFHQ may serve as an adequate screening tool to triage women with OC for further genetic assessment for LS, especially in centers without access to universal tumor testing for IHC for MMR.[Table: see text]
The MGMT (O6-methylguanine–DNA methyltransferase) promotes methylation and clinical outcomes of salvage temozolomide and irinotecan chemotherapy in progressive Ewing sarcoma: A preliminary report.
Authors: Salah Samer , Naser Walid , Jaber Omar , saleh yacob , Mustafa Rawan Mohammed Mahmoud , Abuhijlih Ramiz , Abuhijla Fawzi , Yaser Sameer , Sultan Iyad Yasin , Mustafa Nour , Tbakhi Abdelghani
Published: June 2021

e23507

Background: There remains an unmet need to identify prognostic and predictive molecular biomarkers in advance Ewing sarcoma (ES). We sought to assess the influence of MGMT promoter methylation status on response rate, time to progression (TTP), and overall survival (OS) following salvage irinotecan and temozolomide (IT) chemotherapy. Methods: Data of advanced ES patients, treated with IT chemotherapy from Jan, 2014 to Jan, 2020 were retrospectively collected. Patients were required to have previously received and progressed after vincristine, doxorubicin, and cyclophosphamide alternating with ifosfamide and etoposide (VDC-IE). MGMT promoter methylation status was assessed by Methylation Sensitive Restriction Enzyme quantitative-PCR (MSRE-qPCR) on non-decalcified Formalin-fixed paraffin embedded (FFPE) tissue using internally developed primers and the OneStep qMethyl Kit (ZYMO RESEARCH CORP). Responses were assessed by response evaluation criteria in solid tumors (RECIST v. 1.1). TTP and OS were assessed by the Kaplan-Meier method. Survival comparisons were performed by the Log-rank test. Results: Herein, we present data of the preliminary analysis of the first 18 patients who underwent MGMT promoter methylation testing. Patients had a median age of 18 years (range: 5-34 years), and were predominantly male ( n=11; 61%). The primary tumor was located in the pelvis in 9 patients (50%), femur in 3 (17%), tibia in 2 (11%), kidney in 2 (11%), chest wall in one (6%), and scapula in one patient (6%). IT was given in a second ( n=15) or third-line setting ( n=3). At the time of initiation of IT, 13 patients (72%) had distant metastasis, and 5 (28%) had unresectable local progression in the pelvis ( n=4) or chest wall ( n=1). The mean percentage of MGMT promoter methylation was 29% (range: 3-98%). Five patients (28%) had methylated MGMT promoter, whereas the remaining had partially methylated ( n=6; 33%) or unmethylated ( n=7;39%) promoter. Five patients (28%) had objective response, with no observed difference according to MGMT promoter methylation ( p=0.58 for comparison between methylated and unmethylated/ partially methylated). Median TTP was 4.9 and 2.2 months for patients with methylated and partially methylated/ unmethylated MGMT respectively; p=0.76. The corresponding median OS was 69.4 and 14.3 months in favor of the methylated group; p=0.3. Conclusions: This preliminary data suggests a possible prognostic role for MGMT promoter methylation, with a markedly extended median OS for the methylated group. Nevertheless, the median OS difference did not reach statistical significance in this preliminary analysis. We plan to report data of the final analysis after finalizing MGMT testing for the rest of our study patients.
Epidemiology, clinical features, and histopathology of sarcomas managed in a Haitian cancer clinic.
Authors: Bernard Joseph , Alcindor Thierry , Alexis Lynn Gabrielle , Gilbert Doukens Patrick , DeGennaro Vincent
Published: June 2021

e23515

Background: Sarcomas are among the least described cancers diagnosed in Haiti. Suboptimal surgery and the unavailability of radiation therapy make their management challenging. The main objective of this study was to present the epidemiology, clinical features and histopathology of sarcomas in the Haitian setting. Methods: A seven-year retrospective study was conducted in the cancer program of Innovating Health International (IHI). We included all patients with clinical or histological diagnosis of sarcoma enrolled from January 1, 2014 to December 31, 2020. Date of first visit, age, gender, stage, anatomical site, histology, outcome as of December 31, 2020 and date of death were the main variables selected for this chart review. Mortality rate and overall survival were also evaluated. Results: One hundred and twenty-two (122) patients with sarcomas were diagnosed and treated during the study period. Their mean age was 43.3 years [range: 15-88] and the sample was 62.3% women and 37.7% men. 49.2% of the patients were less than 40 years of age. Among the cases of sarcomas, 86.9% were soft tissue sarcomas and 13.1% bone sarcomas. The lower limbs (36.9%), abdomen (14.8%), head and neck (13.1%), upper limbs (12.3%) and breasts (7.4%) were the most common locations of the sarcomas. 81% of abdominal/pelvic sarcoma cases (n=21) were in women. The most common histological types (n=94) were fibrosarcoma (15.2%), liposarcoma (10.9%), dermatofibrosarcoma protuberans (8.7%), malignant histiocytofibroma (6.5%), rhabdomyosarcoma (5.4%) and gastrointestinal stromal tumor (5.4%). 19.6% of the patients had metastatic disease. The mortality rate for the study period was 53.3% and 17.2% of the patients were lost to follow-up. The median overall survival was 7.2 months for the cohort and 18.4 months for the treated patients (n=70). Conclusions: The sarcomas seen in this Haitian medical clinic mainly affect the soft tissues of limbs, abdomen and head and neck. There is a strong predominance of female patients and about half of the patients are aged less than 40. Despite a low metastatic presentation rate, the prognosis is poor, likely reflecting both the aggressiveness of this group of diseases and the disparities of outcomes between high-income and low-and-middle-income countries.
A phase II study of epirubicin combined with anlotinib followed by anlotinib in the first-line treatment of advanced unresectablesoft tissue sarcoma.
Authors: Zhou Yuhong , Wang Zhiming , Zhuang Rongyuan , Guo Xi , Zhang Chenlu , You Yang , Chen Lisha , Liu Wenshuai , Zhang Yong , Lu Weiqi
Published: June 2021

e23536

Background: Anlotinib, a multi-target TKI,showed well efficiency and tolerance for the treatment of recurrent or metastatic soft tissue sarcoma (STS). Moreover, the synergistic activity of anlotinib plus epirubicin on the sarcoma PDX modelwas confirmed in our previous preclinical study. This phase II clinical study was designed to assess the efficacy and safety of epirubicin combined with anlotinib followed by anlotinib in the first-line treatment of advanced unresectable STS. Methods: This study is an open-label, prospective, single-arm phase II clinical study. Patients (pts) with locally advanced or metastatic soft tissue sarcomas confirmed by histopathology and not suitable for surgery were recruited, and treated with 6 cycles of anlotinib and epirubicin (epirubicin 90mg/m2 CIV for 48 hours on day 1 and anlotinib 12 mg QD on day1-14, 21 days per cycle), followed by anlotinib alone unless the pts experienced progression or intolerance. Tumor imaging evaluations and echocardiography were performed every 2 cycles during combined therapy, and were performed every 3 cycles during the sequential anlotinib treatment. The primary end point was the progression-free rate at 12 weeks (PFR12w) and 6 months (PFR6m), secondary endpoints included ORR, PFS, safety, DCR and OS. Results: 33 eligible pts were enrolled from June 2019 to August 2020, and 3 pts dropped out without completing one cycle of treatment. Of 30efficacy-evaluable pts,10 were man, median age was 48 (range 18-74). The main subtypes included 10 leiomyosarcoma, 8 fibrosarcoma, 5 dedifferentiated liposarcoma, 4 synovial sarcoma, 2 undifferentiated pleomorphic sarcoma, and 1 epithelioid sarcoma. The average number of combined treatment cycle is 4.7 (range 2-6), 13 pts had entered into anlotinib maintenance treatment. The PFR12w, PFR6m, ORR, DCR were 70%,53.8%, 13.3%, and 80%,respectively. Median PFS was 11.5 months (95%CI: 5.0-NA), median OS has not been reached. As cut-off on Jan 20th 2020, 6 pts are still in treatment. The other pts discontinued trial due to disease progression (16/24), adverse events (AEs) (3/24), changes in treatment strategy because of tumor shrinkage (3/24), cytoreductive surgery (1/24), and opt-out (1/24). The main AEs were grade III-IV neutropenia (8/30, 26.7%), and 7 of them were febrile neutropenia (7/30, 23.3%). Until now, no cardiac-related AEswere observed. Conclusions: Advanced unresectable STS pts could benefit from epirubicin combined with anlotinib followed by anlotinibtreatment in first line. And it is generally well tolerated especially with no short-term cardiac toxicity. Clinical trial information: ChiCTR1900024928.
Participation of older patients with advanced gastroesophageal cancer in clinical trials: A systematic review of age-restrictive inclusion criteria over the last 25 years.
Authors: Hennessy Maeve , Hamid Munzir , Goggin Caitriona , Nay Myo Oo , Carrigan Marie , Mockler David , O'Donovan Anita G. , Horgan Anne M.
Published: June 2021

e24017

Background: Cancer is a disease of aging, however older patients are underrepresented in the clinical trials that determine the standards of care for oncological treatment. We conducted a review to identify whether there have been age-restrictive inclusion criteria in clinical trials over the last twenty five years. We focused on patients with metastatic gastroesophageal cancer. Methods: A search strategy was developed encompassing Embase, Pubmed and The Cochrane Library databases. All completed Phase III randomised controlled trials evaluating systemic anti-cancer therapies in metastatic gastroesophageal malignancies for the period 01.01.95 to 18.11.20 were identified. Reference management software (Covidence; Veritas Health Innovation Ltd) was used to screen for inclusion/exclusion. The following details were extracted from trial protocols: country of study, date of publication, patient number, age inclusion and exclusion criteria. The median age of participants and the percentage of older patients enrolled in each study was collected. A linear probability model was used to estimate the change over time in the proportion of studies using an upper age exclusion. Results: 363 phase III studies were identified. 152 studies were eligible for full text review, 86 were excluded, leaving 66 trials for final analysis. 86% (n = 56) included Gastric, 9% (n = 6) Oesophageal and 5% (n = 3) Oesophagogastric malignancies. Asian studies represented 48% (n = 32) of trials, 29% (n = 19) were worldwide and 23% (n = 15) were European. The median age of trial participants was 62, (range 18-94). No clear trend in the ages of study participants over the time period was identified. 32% (n = 21) of studies specified an upper age limit for inclusion and 57% of these were Asian studies. The median age of exclusion was 75 years (range 65-80). All studies starting before 2003 used an upper age exclusion (n = 12); whereas only 9 of the 52 that started in 2003 or later did (17%). Among these later studies, there was a very modest downward yearly-trend in the proportion of studies using an upper age exclusion (-0.02 per year; 95%CI -0.05 to 0.01; p = 0.31). 52% (n = 34) of studies specified the proportion of their study population who were over 65 years. Older patients represented only 36% of the trial populations in these studies (range 7-60%). Our search of currently enrolling trials on clinicaltrials.gov yielded 11 active studies, none of which specified an upper age limit. Conclusions: Recent years have seen improvements in clinical trial protocols, with many no longer specifying restrictive age criteria. Reasons for poor representation of older patients are complex and ongoing efforts are needed to broaden eligibility criteria and prioritise the inclusion of older adults in clinical trials.
Prevalence and risk factors for vasomotor symptoms in Hispanic female breast cancer survivors, 0-3 years post-treatment: Results of a single-center retrospective analysis.
Authors: Morin Lisellet , Zanville Noah , Guest Rosalind , Rubens Muni , Currier M. Beatriz
Published: June 2021

e24038

Background: Early detection and a growing complement of treatment options have led to improved survival among women with breast cancer in the U.S. Vasomotor symptoms (VMS) such as hot flashes and night sweats are among the most common side effects reported by breast cancer survivors (BCS) following treatment. These symptoms may affect quality of life and increase the risk of non-adherence to anti-hormonal therapies. Hispanics are one of the fastest growing ethnic populations in the U.S. However, research exploring whether Hispanic BCS report VMS at similar rates as their non-Hispanic counterparts remains an important gap in the science. The purpose of this study was to compare the prevalence and risk factors for VMS between Hispanic and non-Hispanic BCS following cancer treatment. Methods: Data for this single-center, retrospective study came from a database of self-reported symptom data collected at survivorship visits. Results: Over a 2.8-year period, 815 female BCS were evaluated for VMS (Hispanic: 63.0% (n=513) vs. Non-Hispanic: 37.0% (n = 302)). Mean age of the sample was 58.4 + 11.7 (range 24.2 - 91.8).Approximately four in ten (42.9%) BCS reported VMS at their initial survivorship visit, 0-3 years post-treatment. Results found virtually no difference in VMS prevalence between Hispanic and non-Hispanic BCS, (42.5% vs 43.7%, p = 0.735). BCS who reported VMS after treatment were 6.5 years younger, on average, than BCS who did not report VMS (54.7 ±11.0 vs. 61.2 ±11.3, p < 0.001). Multivariate logistic regression models using age, race, stage of cancer, chemotherapy, radiation and hormone therapy as predictors showed that only age was associated with reporting VMS. For every one-year increase in age, the odds of reporting VMS fell by approximately 5.3% (OR: 0.947, 95% CI: 0.933-0.963, p < 0.0001). Conclusions: Results found no difference in VMS prevalence between Hispanic and non-Hispanic BCS. VMS were reported by over 40 % of BCS in the study. In addition, symptoms were more prevalent in younger BCS. Given the potential impact of VMS on quality of life and mediation adherence, studies validating these findings as well as exploring the prevalence and risk factors for VMS in Hispanic BCS from distinct nationalities and cultures are needed.
Prevalence and risk factors for self-reported sexual dysfunction in Hispanic female breast cancer survivors 0-3 years post-cancer treatment: Results of a single-center retrospective study.
Authors: Guest Rosalind , Zanville Noah , Morin Lisellet , Rubens Muni , Currier M. Beatriz
Published: June 2021

e24039

Background: Improvements in breast cancer screening and treatment have improved survival for many women in the U.S. However, side-effects associated with cancer treatment remain a serious issue for survivors. It is estimated that up to half or more of female breast cancer survivors (BSC) report unwanted changes in sexual function following cancer treatment. Studies have also suggested that both younger BCS and Hispanic women may be at higher risk for developing sexual dysfunction following treatment. However, women of Hispanic origin remain highly underrepresented in research on sexual dysfunction, despite being one of the fastest growing racial/ethnic populations in the U.S. The purpose of this study was to compare the prevalence and risk factors for sexual dysfunction between Hispanic and non-Hispanic BCS during the first-three years post-cancer treatment. Methods: Data for this single-center, non-randomized, retrospective study came from a database of self-reported symptom data collected as part of routine clinical practice in our institution’s Survivorship Clinic. Results: Over a 2.8-year period between Apr. 2017 and Dec. 2019, a total 815 female BCS were evaluated for sexual dysfunction. Nearly two-thirds (63.0%) of BCS identified as Hispanic, and 37.0% (n = 302) of BCS identified as non-Hispanic. Mean age of the sample was 58.4 ± 11.7 (range: 24.2–91.8). Results found that approximately a quarter (25.8%) of BCS reported “vaginal dryness, discharge, or pain with intercourse” at their initial survivorship visit. Rates of sexual dysfunction were nearly identical between Hispanic and Non-Hispanic BCS (25.7% vs. 25.8%; p = 0.975). Consistent with previous studies, BCS who reported sexual dysfunction tended to be younger, on average (53.7±10.5 years vs. 60.0 ±11.6 years; p = 0.002) and more likely to have been diagnosed with Stage 2 or 3 cancer (p = 0.038) than BCS not reporting sexual dysfunction. Multivariate logistic regression models using age, race, stage of cancer, chemotherapy, radiation type, and hormone therapy as predictors confirmed this association between younger age and likelihood of sexual dysfunction, showing that for every one-year younger BCS were at their initial survivorship visit, the odds of reporting sexual dysfunction at the initial survivorship visit increased by approximately 6.5% (OR: 0.943, 95% CI: 0.927-0.96; p < .0001). Conclusions: Results suggest that signs/symptoms such as vaginal dryness, discharge, or pain with intercourse are common for both Hispanic and non-Hispanic BCS following treatment, affecting as many as one in four BCS. Results also show that symptoms are prevalent among younger BCS. Together, results underscore the need for clinicians to be prepared to assess and manage sexual dysfunction, especially in younger BCS.
An online pilot survey to assess collateral damage related to male breast cancer treatment.
Authors: Attai Deanna J. , Eshraghi Leah , Love Susan M.
Published: June 2021

e24046

Background: Fewer than 1% of all cases of breast cancer occur in men, and little is known about the late effects of the disease and its treatment in this population. We developed a pilot survey with the aim of identifying primary areas of concern among men who have been treated for breast cancer. The findings will be used to develop a more comprehensive survey assessing the late effects or collateral damage of male breast cancer treatment. Methods: An anonymous survey was developed with the assistance of patient advocates from the Male Breast Cancer Coalition (MBCC). The survey asked for the men’s current age and contained five open-ended questions. Respondents were asked to (1) describe the most significant types of collateral damage they had experienced; (2) share the effects of disease and treatment on areas of their lives (physical, emotional, psychological, financial); (3) identify resources they had found to be helpful; and (4) provide advice to other men with breast cancer. The fifth question allowed for additional free-text entry. The survey, distributed by the Dr. Susan Love Foundation for Breast Cancer Research and MBCC via social media postings and email, was open from January to February 2021. Results: Sixty-eight men responded to the survey. Mean age of respondents was 62.9 (range 34 - 87). Sexual dysfunction, peripheral neuropathy, musculoskeletal complaints, and fatigue were the most commonly reported collateral damage symptoms. In their open-ended answers, many respondents expressed anxiety about and fear of recurrence, being self-conscious regarding their appearance, and negative effects on sexual function and intimacy. Some described the social isolation of being a man with breast cancer, and several discussed job loss and financial hardship as a result of their diagnosis and treatment. Online resources, including MBCC, were popular sources of support, as were family, friends, and faith. The respondents’ advice to other men with breast cancer included many recommendations to “be your own advocate,” seek out others for support and networking, and “prepare for a pink world.” Conclusions: This pilot study provides important preliminary information regarding late effects and collateral damage of male breast cancer and its treatments, as well as insights into the male breast cancer experience not captured in prior work. This information will be used to inform a more comprehensive project that assesses collateral damage and quality of life among men who have been treated for breast cancer. The findings also will be used to develop recommendations on how to educate clinicians about the needs of male breast cancer survivors and how to better alleviate the late effects and collateral damage they experience.
Analysis of opioid and adjunctive pain medication prescriptions in lung cancer patients.
Authors: Bleiberg Benjamin Aaron , Westbrook Kyle Andrew , Ahn Chul , Khan Saad A.
Published: June 2021

e24073

Background: Between 1999-2018, the CDC reported 232,000 deaths from prescription opioids. Lung cancer patients receive many opioid and adjunctive pain medication prescriptions. The frequency, duration, and impact of these prescriptions is unknown. Methods: We used the electronic medical record to catalogue opioid and adjunctive pain medication prescriptions given to adult cancer patients at our academic and county-affiliated health systems from 2009-2016. We identified the association of opioid and adjunctive pain medication use with patient characteristics including cancer stage and radiation therapy. Results: 1510 lung cancer patients were identified, of which 1061 had opioid prescriptions (70%). Of patients with prescriptions: hydrocodone was prescribed to 90%, morphine 35%, hydromorphone 17%, fentanyl 16%, and oxycodone 13%. 330/1061 patients had adjunctive medication prescriptions, of which, gabapentin was prescribed to 90%, pregabalin 14% and carbamazepine 2%. 296/330 patients prescribed adjunctive medications also had an opioid prescription with the following frequency: hydrocodone 90%, hydromorphone 33%, fentanyl 27%, morphine 41%, and oxycodone 23% 7/1061 patients with opioids had naloxone prescribed. Opioid usage by cancer stage is shown in the table. 211/1510 patients (13%) had prescriptions for ≥3 different opioids; 97/330 (33%) patients with adjunctive prescriptions, had prescriptions for ≥3 different opioids. Of patients treated with radiation for >4 weeks, 66% received opioids, with the proportion receiving opioids increasing with each fraction of radiation up to a rate of 90% with 5 or more fractions. 87% of patients prescribed opioids alone had an active opioid prescription 3 months after their last date of radiation as did 91% of those prescribed adjunctive medications in addition to opioids. In the total dataset: 55% of patients were from the university system and 45% were from the county system and other settings. Of the lung cancer patients with opioid prescriptions: 69% were from the university system and 31% were from other settings. Conclusions: Opioids are commonly prescribed in patients with any stage of lung cancer, particularly those with stage >1 with hydrocodone being the most prescribed. In the period under study, adjunctive medications such as gabapentin were prescribed much less than and rarely without opioids. Some lung cancer patients received ≥3 distinct opioids, with higher rates seen in those with adjunctive medicine prescriptions. Further studies to evaluate system wide opioid prescribing trends and discrepancies related to demographic factors are needed.[Table: see text]
A PAncreatic cancer screening study in individuals with New-onset or DeteriOrating diabetes MEllitus (PANDOME study).
Authors: Frank Richard C. , Lo Tammy , Jin Dugho , Ferreira Cornelius , Seshadri Ramanathan , Dong Xiang Da (Eric) , Bauman James , Anand Naveen , Lee Ronald
Published: June 2021

TPS10607

Background: Pancreatic adenocarcinoma (PC) has a persistently high mortality as it presents in the advanced stages and has largely not benefited from the genomic and immunotherapeutic revolutions in oncology. Improvements in screening to detect early stage cancers are therefore urgently needed. Screening studies such as those from the International CAPS Consortium have demonstrated improved survivals in hereditary high risk individuals. In the sporadic population, individuals with new-onset diabetes (NOD) or long-standing deteriorating diabetes (DD) are at substantially increased risk of PC in the 12 months following these diagnoses and have been proposed as target populations for screening efforts. This trial will study the benefits of PC screening in the latter populations in a community setting. Methods: Individuals ≥ 50 years of age with either NOD or DD will be eligible. Criteria for NOD (within the past 12 months) include: fasting blood glucose ≥ 126 mg/dL, random blood glucose ≥ 200 mg/dL, or HbA1c ≥ 6.5%, with confirmed prior normal values. For those without prior glycemic values, a HbA1c ≥ 7.0% is required. Transition from pre-diabetes requires an increase in HgA1c of ≥ 0.5%. DD is defined by an increase in HbA1c of ≥ 2% within the past six months that is not associated with medication non-compliance or weight gain. Study participants will undergo every 6 months: evaluation by an APRN, testing for anxiety and depression and blood donation for biobanking purposes. High resolution MRI/MRCP with gadolinium will be performed at study entry and annually for 2 years. Images will be reviewed at a multi-disciplinary tumor board consisting of body-image certified radiologists, interventional gastroenterologists, hepatobiliary surgeons and medical oncologists. MRI results will be classified according to a novel PANC-RADS system. High-risk pancreatic findings will be further interrogated by endoscopic ultrasound (EUS). Study endpoints include detection rate of high-risk lesions, referrals for EUS and surgery and detection of incidental findings leading to unnecessary procedures. Adverse psychological impacts will be assessed through HADS testing. Target accrual: 500 patients within 3 years. Clinical trial information: NCT03937453 .
A multicenter, open-label, uncontrolled phase II study of ONO-4538 for cutaneous angiosarcoma (Angio Check study).
Authors: Fujisawa Yasuhiro , Yoshino Koji , Isei Taiki , Namikawa Kenjiro , Fujimura Taku , Yasuda Masahito , Yamamoto Yuki , Uchi Hiroshi , Yanagi Teruki , Kato Hiroshi , Otsuka Atsushi
Published: June 2021

TPS11579

Background: Cutaneous angiosarcoma (CAS) is a rare sarcoma and advanced cases face a complex treatment regimen and dismal prognosis. Several cytotoxic agents (anthracycline, taxane, and gemcitabine) and targeted therapies (bevacizumab and sorafenib) have been tested for advanced disease in clinical trials with poor results. Since CAS commonly develops in elderly patients, high-grade adverse events from treatment may not be ideal and thus therapies featuring durable response and low comorbidity are in great demand. Recent studies suggest that CAS has a distinct genomic profile, including higher tumor mutational burden (TMB), compared to angiosarcomas developed in other sites. Moreover, we have shown that CAS with higher PD-1/L1 in the tumor microenvironment had statistically better overall survival compared with those without, indicating CAS susceptibility to immune checkpoint blockade therapy. However, to date, reports of immune checkpoint inhibitors for CAS are nonexistent. Methods: The present study is a phase 2, multicenter, single-arm clinical trial of ONO-4538 (nivolumab, 480 mg IV every 4 weeks) for patients with unresectable or metastatic CAS refractory to first-line paclitaxel. Twenty-three patients with advanced CAS will be enrolled at 11 sites in Japan with a primary objective to assess the confirmed response rate (H0 p < 5%, H1: p > 20%) to nivolumab. Secondary endpoints include PFS, OS, time to response, and adverse events. A correlative aim includes assessing tissue biomarkers using whole-genome sequencing (1023 genes including interferon-gamma associated genes and other known factors associated with response to immune checkpoint inhibitors) for association with response to nivolumab. The study started in April 2020 and remains open with 7 patients enrolled at time of Clinical trial information: UMIN000043039.
A randomized phase II trial of cabozantinib combined with PD-1 and CTLA-4 inhibition in metastatic soft tissue sarcoma.
Authors: Eulo Vanessa Anne , Wilky Breelyn A. , Luo Jingqin , Hirbe Angela C. , Weiss Mia C. , Oppelt Peter John , Abaricia Sarah , Toeniskoetter Jacqui , Ruff Tyler , Maki Robert G , Van Tine Brian Andrew
Published: June 2021

TPS11583

Background: Soft tissue sarcomas (STS) are rare malignancies with poor prognosis in the metastatic setting. Current standard therapy includes anthracycline based chemotherapy. Cabozantinib is a multikinase inhibitor that has demonstrated efficacy in solid tumors such as renal cell carcinoma (RCC) and hepatocellular carcinoma (HCC). A phase II study of cabozantinib in advanced STS is underway. Cabozantinib in combination with immune checkpoint blockade has shown clinical benefit in several tumor types including HCC, RCC, non-small cell lung cancer, and urothelial carcinoma. Since cabozantinib may alter PD-1 expression in regulatory T-cells and promote an immune permissive environment, we hypothesize that combining cabozantinib with immune checkpoint inhibition is a therapeutic strategy that will be more effective than cabozantinib alone. Additionally, the design of the trial will allow assessment of whether pretreatment with cabozantinib will enhance the efficacy of nivolumab and ipilimumab alone. Methods: This is an open label, multicenter, randomized phase II clinical trial of cabozantinib (60mg orally daily as a single agent, 40mg in combination) with or without combination Ipilimumab (ipi, 1mg/kg IV every 3 weeks for 4 doses) and Nivolumab (nivo, 3mg/kg IV every 3 weeks for four doses, then 480mg IV every 4 weeks) in patients (pts) with unresectable or metastatic STS refractory to up to two lines of chemotherapy. 105 pts with non-translocation driven sarcomas will be enrolled at three US sites and randomized 2:1 to the combination group. Pts will be stratified by prior pazopanib use and balanced for histologies. Patients who progress on arm A will cross over to combination therapy (arm B). The primary efficacy endpoint is objective response rate (ORR) by RECIST 1.1. 35 patients in Cohort A (cabozantinib alone) and 70 patients in Cohort B (cabozantinib plus ipi/nivo) will be required to detect an increase of the ORR from 10% in cohort A to 30% in cohort B with 81% power with a one-sided alpha level of 10%. Key eligibility criteria include: at least 18 years of age, ECOG performance status of 0 or 1, ≤2 prior lines of therapy and measurable disease. Exclusion criteria include: translocation-driven sarcoma except alveolar soft part sarcoma (ASPS), prior immunotherapy, and chronic use of corticosteroids or other immunosuppression. Secondary endpoints are safety, overall and progression free survival, disease control rate, and response rate to ipilimumab and nivolumab after cabozantinib pretreatment. Mandatory tumor biopsies pre-treatment and at 6 weeks will be obtained. Peripheral blood will be collected for circulating immune phenotyping. Enrollment will occur at 3 participating institutions and is expected to be completed in 2022. Clinical trial information: NCT04551430.
Phase I/Ib study with INT-1B3, a novel LNP-formulated micro-RNA (miR-193a-3p mimic) therapeutic for patients with advanced solid cancer.
Authors: Kotecki Nuria , Opdam Frans , Robbrecht Debbie , Strijbos Michiel , Kroon Karlijn , Janicot Michel , Yahyanejad Sanaz , Telford Bryony , van den Bosch Marion , Alemdehy Farshid , de Gunst Thijs , den Boer Harm , Vos Rogier M. , van Pinxteren Laurens , Schaapveld Roel
Published: June 2021

TPS2666

Background: MicroRNAs (miR) are naturally-occurring small non-coding RNA molecules involved in the regulation of gene expression and their dysregulation plays a fundamental role in several pathological conditions including cancer. The miR-193a-3p acts as a tumor suppressor and is downregulated in many cancer types. INT-1B3 is a novel lipid-nanoparticle (LNP) formulated 1B3, a 22-nucleotide double stranded chemically-modified miR-193a-3p mimic. INT-1B3 showed significant tumor growth inhibition in a large panel of human and syngeneic tumor models. It directly targets tumor cells and the tumor microenvironment by specific modulation of multiple signaling pathway components. Furthermore, in syngeneic mice models for e.g. TNBC (4T1) and HCC (H22), INT-1B3 was able to modulate the immune tumor microenvironment by turning ‘cold’ tumors into ‘hot’ tumors via upregulation of cytokines (e.g., IL-2 and IFN-g), decreasing immunosuppressive cells/Treg (e.g., CD4+ /LAG3+ and CD3+ /FoxP3+) and triggering cytotoxic CD8+ T cell-mediated long-term memory immune protection against re-challenge with tumor cells. These preclinical results suggest potential clinical benefit in a broad range of cancer indications, and a reduced potential to develop drug resistance due to its multi-targeted mode of action. Methods: This is a 2-part, multi-center, open-label, multiple ascending dose, first-in-human, clinical study to evaluate the safety, pharmacokinetics, pharmacodynamics, and preliminary efficacy of INT-1B3 in the treatment of patients with advanced solid tumors. The phase 1 part follows a ‘hybrid’ 3+3 study design in ‘all-comer’ cancer patients enrolled and treated in cohorts to define the recommended phase 2 dose (RP2D). Upon completion of the dose escalation phase of the study, 2 expansion cohorts are planned to further confirm the safety, tolerability, and preliminary efficacy of the RP2D of INT-1B3 in patients with hepatocellular carcinoma and triple negative breast cancer. Major eligibility criteria include evaluable disease according to RECIST 1.1 and no more than one prior line of anti-PD-1/PD-L1 therapy. Patients will receive INT-1B3 via 60-min i.v. infusions twice a week in 21-day cycles. The first patient was enrolled on January the 14th 2021. Clinical trial information: NCT04675996.
Trial in progress: A phase 1b study of sotorasib, a specific and irreversible KRASG12C inhibitor, as monotherapy in non-small cell lung cancer (NSCLC) with brain metastasis and in combination with other anticancer therapies in advanced solid tumors (CodeBreaK 101).
Authors: Hong David S. , Strickler John H. , Fakih Marwan , Falchook Gerald Steven , Li Bob T. , Durm Greg Andrew , Burns Timothy F. , Ramalingam Suresh S. , Goldberg Sarah B. , Frank Richard C. , Marrone Kristen , Shu Catherine A. , Gandara David R. , Soman Neelesh , Henary Haby Adel , Govindan Ramaswamy
Published: June 2021

TPS2669

Background: Kirsten rat sarcoma viral oncogene homolog ( KRAS) p.G12C mutation is an oncogenic driver mutation in several solid tumors. Sotorasib is a specific, irreversible, small molecule inhibitor of KRASG12C that has demonstrated durable clinical benefit in NSCLC, with mild and manageable toxicities. The combination of sotorasib with other anticancer therapies may enhance antitumor efficacy. This master protocol is designed to evaluate safety, tolerability, pharmacokinetics (PK), and efficacy of multiple sotorasib combinations in patients (pts) with KRASp.G12C mutated solid tumors. Herein, we overview 1 monotherapy and 11 combination cohorts. Methods: This is a phase 1b, open-label study evaluating sotorasib alone and in combination regimens (Table) in pts with advanced KRAS p.G12C mutated solid tumors. Dose exploration will evaluate the safety and tolerability of sotorasib alone and in combination regimens; dose expansion will then verify the safety and tolerability profile of sotorasib regimens and assess antitumor efficacy. Key eligibility criteria include locally-advanced or metastatic solid tumor with KRAS p.G12C mutation identified through molecular testing in pts who have received ≥1 lines of prior systemic therapy. Primary endpoints include dose-limiting toxicities and treatment-emergent or treatment-related adverse events. Secondary endpoints include PK profile of combination regimens and efficacy (eg, objective response, disease control, duration of response, progression-free survival, and duration of stable disease assessed per RECIST 1.1). Enrollment began in December 2019 and is ongoing. Clinical trial information: NCT04185883. [Table: see text]