bluuebunny/crossref_metadata_2025 huggingface dataset:
Long-term (LT) disease control in patients (pts) with hormone receptor-positive (HR+), PIK3CA-altered advanced breast cancer (ABC) treated with alpelisib (ALP) + fulvestrant (FUL).
Authors: Juric Dejan , Andre Fabrice , Panwar Udaiveer , Janku Filip , Lu Yen-Shen , Burris III Howard A. , Cruz Jurado Josefina , Papai Zsuzsanna , Stemmer Salomon M. , Tabernero Josep , Ahlgren Johan , Leheurteur Marianne , Lorenzo Ines , Jankovic Dragana , Quadt Cornelia , Hu Huilin , Chen Xueying , Rugo Hope S.
Published: June 2021

1054

Background: PIK3CA mutations, present in ̃40% of HR+, HER2– ABC, are associated with therapeutic resistance and shorter survival. Alpelisib (ALP) + fulvestrant (FUL) demonstrated efficacy in this population for which achieving long-term (LT) disease control is challenging. Here, we report on pts with HR+, PIK3CA-altered ABC who achieved LT disease control with ALP + FUL. Methods: SOLAR-1 was a phase 3, randomized, double-blind study of ALP (or placebo) + FUL in HR+, HER2– ABC that progressed on/after an aromatase inhibitor. CBYL719X2101 (X2101) was a phase 1, open-label study of escalating ALP doses ± FUL in advanced solid tumors that progressed on/after anti-estrogen therapy (ET) or relapsed after adjuvant anti-ET. A cut-off ≥ median (progression-free survival [PFS] + 2 SE) was chosen based on Kaplan-Meier curves from SOLAR-1 to define LT disease control as PFS (SOLAR-1) or time on treatment (X2101) ≥18 mo. Results: In SOLAR-1, 51 of 169 pts (30.2%) randomized to ALP + FUL achieved LT disease control with a median PFS of 33.5 mo (95% CI, 27.4 mo-not reached). Baseline characteristics of pts in SOLAR-1 are in the table below. In pts with LT disease control, adverse events (AEs) of special interest (combined preferred terms) of GI toxicity were observed in 47 pts (92.2%; grade ≥3: 11.8%, n=6), of hyperglycemia in 41 pts (80.4%; grade ≥3: 39.2%, n=20), and of rash in 28 pts (54.9%; grade ≥3: 19.6%, n=10). Median ALP relative dose intensity was 79.9% and 82.1% for pts with LT disease control (n=51) and the overall population (n=168), respectively. In X2101, 7 of 52 pts (13.5%) with ABC who received ALP+FUL achieved LT disease control up to 47.8 mo. Conclusions: In this subset of pts with hard-to-treat, endocrine-resistant disease, LT disease control ≥18 mo is meaningful considering median PFS of 4.6-9.3 mo or 9.5-16.4 mo with FUL alone or with cyclin-dependent kinase 4/6 inhibitors, respectively. Here, LT disease control was observed in 2 studies of HR+, PIK3CA-altered ABC, including in pts with poor prognosis, diabetes/pre-diabetes at baseline, and heavy pre-treatment. AE profile was consistent with prior reports and did not preclude LT disease control. Further work is needed to better understand factors influencing LT disease control. Clinical trial information: NCT01219699, NCT02437318 .[Table: see text]
Red blood cell folate, high-risk human papillomavirus risk and cervical intraepithelial neoplasia development: A large Chinese community-based cohort study of cervical screening.
Authors: Wang Wei , Yang Aimin , Li Yuanxing , Luo Haixia , Yang Jing , Zhao Weihong , Wang Zhilian , Wang Zhe , Wang Chen , Zhang Lili , Su Xiaoqiang , Wang Wenhao , Wang Jintao , Lu Weiguo , Li Li , Song Jinghui , Hao Min
Published: June 2021

10547

Background: Although low folate status has been implicated in cervical carcinogenesis, large-scale population-based prospective cohort studies controlling for high-risk types of human papillomavirus (hrHPV) infection are lacking. The aim of this study is to evaluate the associations of red blood cell (RBC) folate, hrHPV infection risk and cervical intraepithelial neoplasia (CIN) development. Methods: In this prospective, population-based cohort study, we analyzed the cross-sectional data of 2304 women from a large cervical cancer screening program of 40,000 women aged 19-65 years in the Chinese rural area from 2014-2015. We conducted a nested case-control study including 35 CIN1 progression cases and 105 CIN1 regression controls. A logistic regression model was used to evaluate the associations of RBC folate and hrHPV infection risk and CIN1 development. Results: The median RBC folate concentration decreased gradually with cervical lesion severity. The risks of CIN 1 and CIN2 or worse (CIN 2+) in the 1st quartile of RBC folate concentration were significantly higher than those in the 4th quartile (Odds Ratio [OR], 2.27; 95% confidence interval [CI], 1.71-3.01 and OR, 2.33; 95% CI,1.52-3.56; respectively). We did not observe a significant relationship between hrHPV infection and CIN1 risk in the unadjusted and adjusted models, however, a statistically significant association was observed for CIN2+. Interestingly, RBC folate concentration was not associated with hrHPV infection among women with CIN1 or CIN2+. After full adjustment for potential confounders, a highly significant inverse linear relation between RBC folate concentration and CIN2+ was observed ( P-overall＜0.001, P-nonlinearity = 0.969). We further observed a positive additive interaction between RBC folate concentration and hrHPV infection on the risk of CIN2+ ( P-interaction＜0.01). Moreover, during the 21-month follow-up, CIN1 progression risk was significantly higher in the lowest RBC folate quartile (1st quartile compared with 4th quartile: OR, 3.86; 95% CI,1.01-14.76). Conclusions: Our findings indicates that RBC folate is inversely associated with the risk of higher-grade CIN and CIN1 progression in the Chinese rural population, either with or without hrHPV infection. Therefore, improving folate status has the potential to prevent higher-grade CIN and cervical cancer among women in the areas without mandatory folic acid food fortification. Clinical trial information: ChiCTR-ROC-15006479 .
Confirmed tumor response by molecular subtype in patients with metastatic breast cancer: Sub-analysis from a phase 3 clinical study comparing oral paclitaxel and encequidar to IV paclitaxel.
Authors: Umanzor Funez Gerardo Antonio , Rugo Hope S. , Umanzor Jorge , Barrios Francisco , Vasallo Rosa , Chivalan M , Bejarano Suyapa A. , Ramirez Julio Roberto , Fein Luis Enrique , Kowalyszyn Ruben Dario , Wang Hui , Cutler David
Published: June 2021

1073

Background: Paclitaxel, a foundation treatment in MBC, is hydrophobic and must be formulated for IV administration with Cremophor EL, increasing the risk of infusion reactions and necessitating pre-treatment with corticosteroids and antihistamines. Paclitaxel cannot be administered orally because it is a substrate for P-gp. The oral bioavailability of paclitaxel is improved when administered 1 hour after the highly selective, potent, and minimally absorbed P-gp inhibitor encequidar. As oral paclitaxel is Cremophor-free there is no need for pretreatment for infusion reactions. While targeted therapies have improved outcomes in patients with HER2+ tumors there is still an unmet need for therapies that prolong survival with reduced toxicity across all tumor subtypes. Methods: A phase 3, open-label, randomized, multicenter study in women with histologically- or cytologically-confirmed MBC for whom treatment with IV paclitaxel monotherapy had been recommended by their oncologist randomized 402 patients 2:1 to either oral paclitaxel and encequidar (oPac+E) or IV paclitaxel (IVPac). Oral paclitaxel 205 mg/m2 was administered once daily for 3 consecutive days, weekly. Encequidar 12.9 mg was administered 1 hour before each dose of oral paclitaxel. IV paclitaxel 175 mg/m2 was infused over 3 hours on day 1 of every 3 weeks. Results: In the ITT population oPac+E was superior to IV paclitaxel with a confirmed tumor response rate of 35.8% vs 23.4% for IVPac: a difference of 12.4% (p = 0.0107). A post-hoc subgroup efficacy analysis was conducted based on tumor subtypes, however, the study was not powered to detect statistical differences within these subgroups. Patients in the HR+/HER2- subgroup had a better tumor response to oPac+E (44.8% vs 21.4% IVPac-response rate difference of 23.4%) as did patients in the TNBC (30.5% vs 20.2%-response rate difference of 10.3%) subgroup. Responses were similar (49% vs 47.4% IVPac) in the HER2+ subgroup. Patients with unknown HER2 status receiving oPac+E had a 58.8% response rate vs 14.3% with IVPac (response rate difference of 44.5%). Conclusions: oPac+E is the first oral taxane to demonstrate superiority in radiologically confirmed tumor response rate compared to IVPac in a group of 402 women with metastatic breast cancer. Patients with HR+/HER2-, TNBC, and Unknown subtypes responded considerably better to oPac+E vs IVPac—especially the HR+/HER2- subtype which represented 63% of the patients treated with oPac+E and 55% of the patients treated with IVPac. Clinical trial information: NCT 02594371 .
Trends in female representation in clinical practice guidelines (CPGs) among major cancer organizations.
Authors: Chengappa Madhuri , Go Ronald S. , Poonacha Thejaswi K.
Published: June 2021

11006

Background: While women representation and sex disparities in National Comprehensive Cancer Network (NCCN) and European Society of Medical Oncology (ESMO) has been studied in a limited set of CPGs, the sex representation and disparity trend over time among all NCCN and ESMO CPG panelists has not been studied. Our study evaluates the current sex disparities and female representation for all NCCN and ESMO CPGs as of 2020 and compared it to the 2010 CPGs of both organizations. Methods: The 2010 and 2020 version of NCCN and ESMO CPGs were examined from their respective websites and archives. We catalogued the number of female versus male panelist for each CPG. We discerned the sex of the panelists based on google search and the panelists’ affiliated institutional websites. Results: 60 NCCN (2020), 51 NCCN (2010), 78 ESMO (2020) and 55 ESMO (2010) CPGs inclusive of all cancers by site, detection prevention and risk reduction, supportive care, and guidelines for specific population were reviewed. NCCN 2020 CPGs had 55.5% female representation. 35 (58%) NCCN CPGs had predominant female representation (>50% of the members being female) whereas 24 CPG (40%) were male predominant (>50% of the members being male). Solid tumors had 24 CPGs with male predominance and hematological malignancies had 14 CPGs with female predominance. Cancers specific to women had higher proportion of female panelist. NCCN 2010 CPGs had 27.1% female representation. Both solid tumors and hematological malignancies had male predominance (82% and 75% respectively). Breast cancer screening, palliative care and older adult oncology CPGs were female predominant. ESMO 2020 had 27.8% female representation. Both solid tumors (37 CPGs) and hematological malignancies (17 CPGs) had predominant male representation (72% and 85% respectively). Breast and ovarian cancer CPGs were female predominant. ESMO 2010 had 23.2% female representation. Male representation was predominant in both solid tumors (35 CPGs) and hematological malignancies (9 CPGs). Breast, cervical and ovarian cancer CPGs were female predominant. Conclusions: Over the last decade, proportion of female panelists in NCCN CPGs has doubled with more than 50% representation among its 60 CPGs, indicating adequate representation of women. In ESMO, although there has been a significant improvement in female representation in hematological malignancies over time, it continues to have overall female underrepresentation (<30%).[Table: see text]
Corresponding about death: Analyzing letters from patients with cancer to medical students.
Authors: Zhang Tianyi , Tilahun Mekaleya , Perlis Cynthia , Brondfield Sam
Published: June 2021

11021

Background: Clinicians frequently discuss death and dying with patients who have cancer. However, the doctor-patient hierarchy and the unfamiliar clinical environment may prevent these patients from discussing death and dying authentically. Patients may feel more comfortable expressing themselves when given the time and space to write at home. Firefly, an award-winning program at UCSF, facilitates written correspondence between patients with cancer and medical students over the course of one year. Firefly’s archive contains thousands of patient letters and constitutes a unique resource for analyzing authentic patient expression outside of the clinical context. The aim of the current study is to improve curricula pertaining to severe illness and end-of-life by providing educators with an analysis of authentic patient perspectives about death and dying expressed in these letters. Methods: We (two medical students, an expressive artist, and an oncologist) read all Firefly letters written by patients between 2014 and 2019 and identified 12 patients whose letters meaningfully discussed death or dying. We performed a thematic analysis of these letters using the Buckman three-stage model of dying as a reference. Results: Four themes emerged: turmoil; grief; making peace; and past, present and future. The first three themes aligned with the Buckman stages. The fourth theme—past, present and future—spanned the three stages and also elaborated the Buckman model by describing multiple paths that patients may take after passing through these stages. Conclusions: The authentic ways in which patients with cancer discussed death and dying in their letters provided deep insight into their coping process. The Buckman model appears useful for framing death and dying from the patient perspective but may not fully reflect modern oncologic care in which many patients live for years beyond a severe or terminal diagnosis. Educators can use the identified themes to shape medical school curricula pertaining to severe illness and end-of-life care.
Improving feedback for hematologists and oncologists in training.
Authors: Schlam Ilana , Sewaralthahab Sarah , Peravali Monica , Chou Calvin , Gilligan Timothy D. , Veytsman Irina , Shenoy Aarthi G.
Published: June 2021

11025

Background: Feedback is an integral part of the learning process, allowing learners to remain on course in reaching competence in clinical, research, and interpersonal skills. However, the impact of teaching feedback during hematology-oncology training has not been studied. We aimed to identify barriers in delivering and receiving high-quality feedback in our fellowship program and to create a curriculum aimed at teaching fellows and faculty how to engage in more effective feedback conversations. Methods: This pilot study aimed at determining and addressing perceived barriers to high-quality feedback in the hematology-oncology fellowship program. A pre-intervention questionnaire, consisting of Likert scale and open-ended questions, was administered to identify barriers to giving feedback and to assess satisfaction with the quality of feedback received in our fellowship program. The results of the baseline questionnaire were utilized to build a virtual interactive three-session workshop provided by the ASCO Quality Training Program in which the importance of feedback and methods of providing effective feedback were taught. Topics included feedback set-up, low-inference observation, and a structured approach to reinforcing and modifying feedback. One month after the intervention the participants completed a follow up questionnaire. This project was developed through the ASH Medical Educators Institute. Results: Each questionnaire was completed by 11 participants. The two main barriers to high-quality feedback identified were the discomfort with both giving and receiving feedback, and the lack of protected time. At baseline only 54% of the participants reported they were comfortable giving feedback, increasing to 81% post- intervention. Pre-intervention, 81% of participants reported they did not have protected time for feedback, decreasing to 64% after the intervention and institution of weekly protected time for feedback. Half of the participants reported that the feedback was not actionable in the initial questionnaire, decreasing to 10% post-intervention. Overall, fellows reported that their feedback was mostly focused on notes, followed by presentations and interpersonal skills. Faculty reported that most of the feedback they received was about time management and patient care. Conclusions: This pilot study helped address a major barrier to improvement and growth within our training program and confirmed that feedback skills must be taught and practiced. A 6-hour virtual workshop showed tangible results in the satisfaction with and quality of feedback given to both fellows and faculty. Our findings are salient as we completed the intervention during the COVID pandemic. Limitations of the study include its single-institutional design and sample size. A major challenge anticipated is sustainability, which will be addressed by maintaining periodic lectures and assigning protected time for feedback.
Genomic alterations and associated pathway abnormalities in Ewing sarcoma.
Authors: Rock Adam , Chow Warren Allen , Uche An , Millis Sherri Z.
Published: June 2021

11532

Background: Ewing Sarcoma (ES) is an aggressive, translocation-associated, bone cancer associated with a poor prognosis in the recurrent or metastatic setting. ES is identified by the canonical balanced reciprocal chromosomal translocation involving EWSR1 and ETS transcription factors. Secondary somatic alterations in ES are rarely described and genomic alterations (GA) affecting various molecular pathways may work synergistically with ETS-FL1 translocations to promote oncogenesis. Alterations in fibroblast growth factor receptor 4 (FGFR4), a receptor tyrosine kinase protein that functions in cellular processes, have been observed to affect carcinogenesis. Moreover, the FGFR4-Gly388Arg (G388R) single nucleotide polymorphism (SNP) is found to increase the risk of cancer with mouse embryonic fibroblasts derived from knock-in strain of homologous Fgfr4 G385R mice exhibiting a transformed phenotype. We sought to further evaluate the frequency of FGFR4 G388R SNP in relation to other identifiable pathway alterations observed with Comprehensive Genomic Profiling (CGP). Methods: Next generation sequencing (NGS) analysis was obtained in the context of clinical care with clinical status, outcomes, and source acquisition (primary tumor, metastasis, or recurrence) unknown to Foundation Medicine. CGP, FoundationOne Heme, evaluated GAs including base substitutions, indels, amplifications, copy number alterations, gene fusions and rearrangements. 189 samples were assayed by hybrid-capture based CGP, including 406 DNA-sequenced genes in addition to 265 RNA-sequenced genes commonly reported to be rearranged in cancer, as previously described. Tumor mutational burden was assessed from a minimum 1.4 Mb sequenced DNA. Microsatellite instability (MSI) status was determined by a novel algorithm analyzing 114 specific loci. Results: The median age of evaluated patients was 20 (range 0-70) with the number of alterations averaging 7 per patient. Pathways noted to be altered in the presence of FGFR388R SNP occurred frequently with the following pathways most observed: MAPK (33%), WNT (32%), NOTCH1 (20%), HRR (19%), Histone/chromatin remodeling (18%). FGFR388R SNP was observed in more than half (51%) of evaluated samples. Most affected pathways irrespective of FGFR388R SNP status included: MAPK (n = 89), HRR (n = 75), and PIK3 (n = 64). All evaluated samples were TMB low ( < 10 mut/mb) and Microsatellite Stable. Conclusions: Secondary GAs affecting major pathways were observed in high frequency, often co-occurring with the FGFR4 G388R SNP. Secondary alteration of known oncogenic pathways may contribute to sarcoma formation in ES potentially informing further therapeutic strategies in the future.
Recurrence and disease-specific survival after 10-year disease-free interval in patients with primary retroperitoneal liposarcoma: Implications for long-term surveillance.
Authors: Eckardt Mark Archer , Graham Danielle S. , Kadera Brian E. , Klingbeil Kyle D. , Nelson Scott D. , Dry Sarah M. , Kalbasi Anusha , Singh Arun S. , Chmielowski Bartosz , Eilber Frederick R. , Crompton Joseph G. , Eilber Frederick C.
Published: June 2021

11546

Background: Surveillance imaging of patients with retroperitoneal liposarcoma (RP-LPS) following surgical resection is based on a projected risk of locoregional and distant recurrence. The duration of surveillance is not well defined as the long-term natural history of RP-LPS after treatment is poorly understood. We evaluate a cohort of RP-LPS patients—without evidence of disease 10 years following initial resection—to assess the long-term risk of recurrence and disease-specific survival (DSS). Methods: The prospectively maintained UCLA Sarcoma Database was used to identify RP-LPS patients who demonstrated 10-year progression-free survival (10yr-PFS) after initial diagnosis and treatment. Patients in the 10yr-PFS cohort were subsequently evaluated for recurrence and DSS. Time intervals start at date of initial surgical resection. Cox proportional hazards models were used to determine factors associated with recurrence and DSS. Results: From 1972-2010, 76 patients with RP-LPS had at least 10 years of follow-up. Of these, 37 (49%) demonstrated 10yr-PFS. Median follow-up was 15 years (range 10-35 years). Among the 10yr-PFS patients, 43% (16/37) developed a recurrence >10 years after the initial surgery, and 19% (7/37) died of disease. Neither long-term recurrence nor DSS were significantly associated with age, sex, tumor size, LPS subtype, surgical margin, or peri-operative treatment with radiation or chemotherapy (Table). Conclusions: Patients with primary RP-LPS treated with surgical resection +/- multimodality therapy have a long-term risk of recurrence and disease-specific death that is unacknowledged by current surveillance imaging guidelines. Among the patients with a 10yr-PFS, 43% developed a recurrence and 19% died of disease. These findings suggest a need for lifelong surveillance imaging in patients with RP-LPS.[Table: see text]
Patient reported outcomes in patients with desmoid type fibromatosis.
Authors: GARG VIKAS , Rastogi Sameer , Barwad Adarsh , Panday Rambha , Bhoriwal Sandeep Kumar , Dhamija Ekta
Published: June 2021

11574

Background: Desmoid type fibromatosis (DTF) is a rare benign neoplasm with infiltrative growth and high local recurrences. Due to long disease course, unpredictable growth pattern, and low mortality, using only survival outcomes may be inappropriate. In this study we assessed the impact of DTF on health related quality of life (HRQoL). Methods: This was a cross-sectional study done in patients with DTF. The study participants were asked to fill the EORTC QLQ-C30, GAD-7 and PHQ- 9 q uestionnaires to assess HRQoL, anxiety and depression . Outcomes were also compared with healthy controls. Results: 204 subjects (102 DTF patients and 102 healthy controls) were recruited. Study parameters have been summarized in Table. Appendicular skeleton (limbs + girdle) was most commonly involved in 59 % patients and abdominal wall or mesentery was involved in 22.5 %. Patients have received median of 2 lines of therapy. 54 % patients were currently on sorafenib and 41 % were under active surveillance. Mean global health status in DTF patient 65.58 ± 22.64, was significantly lower than healthy controls. Similarly, DTF patients scored low on all functional scales except cognitive functioning. Symptom scale showed significantly higher symptom burden of fatigue, pain, insomnia and financial difficulties. Anxiety & depression was observed in 39.22 % and 50 % of DTF patients respectively. DTF patients had higher rates of mild, moderate and severe anxiety and depression compared to healthy controls. No difference was observed based on site of disease. Conclusions: DTF patients have significant symptom burden, poor functioning, and heightened anxiety and depression. Patient reported outcomes should be routinely used to assess treatment efficacy in DTF patients.[Table: see text]
Characteristics of elderly-specific oncology trials registered in ClinicalTrials.gov.
Authors: Wu Bian , Yang Yun , Tang Yun , Zheng Yongqiang , Xie Mingxing , Yang Kunyu , Wu Gang
Published: June 2021

12040

Background: Clinical trials dedicated to the elderly cancer patients are essential to help to define optimal cancer therapy for this rapidly growing population. Our study aimed to analyze the characteristics and the evolution of elderly-specific oncology trials registered in ClinicalTrials.gov. Methods: A dataset of 61120 oncology trials registered in ClinicalTrials.gov between Jan 1th, 2000 and Dec 17th, 2019 was downloaded. Interventional trials were identified and systematically reviewed to validate classification into elderly-specific (at least using a chronological landmark to define the elderly) and age-unspecified trials. Cancer type and other registration information were extracted. Characteristics of elderly-specific trials were compared with characteristics of age-unspecified trials. Chronological shifts in elderly-specific trials between 2000 to 2009, and 2010 to 2019 were analyzed. Results: Of the 49273 trials eligible for analysis, only 791 (1.6%) were elderly-specific. The most frequently used threshold to define the old was 60 years (36%), followed by 70 years (28%) and 65 years (26%). More than half of the elderly-specific trials were phase 2 (56.8%) trials and enrolled 100 or fewer participants (59.4%). Compared with age-unspecified trials, elderly-specific trials were less likely to be funded by industry (28.3% vs 37.1%; p < 0.001), and more likely to be conducted in Europe (42.1% vs 24.5%, p < 0.001). During the two time periods between 2000 to 2009, and 2010 to 2019, the proportion of elderly-specific trials of all the oncology trials remained stable (1.57% vs 1.62%). The proportion of treatment-oriented trials decreased from 91.9% to 71.4% (p < 0.001) while supportive care-oriented trials increased from 1.9% to 13.2% (p < 0.001). Industry-funded elderly-specific trials decreased from 34.0% to 25.6% (p = 0.014). Concerningly, the use of clinically meaningful end points in elderly such as disease-specific survival, patient-reported outcomes (PROs) and functional status as a primary end point were uncommon (0.5%, 8.0%, and 6.9%, respectively). However, the use of PROs as a primary end point tended to increase in the second time period, from 2.4% to 10.5% (p < 0.001). There was no correlation between the number of trials for a given cancer type and relative incidence and mortality. 336/791 (42.5%) of the trials were conducted for patients with blood cancer, although the incidence and mortality of blood cancer were relatively low. The most common solid cancer types were breast cancer (13.9%), lung cancer (10.0%), and colorectal cancer (7.8%). Conclusions: Although the majority of all new cases of cancer occur in the elderly population, elderly-specific trials account for only a minority of all oncology trials. Our study helps us to better understand the current state of elderly-specific trials and provides insights for future development that can improve the care of elder patients with cancer.
Safety of using hormone replacement therapy in breast cancer survivors: A systematic review and metanalysis.
Authors: Poggio Francesca , Del Mastro Lucia , Bruzzone Marco , Ceppi Marcello , Razeti Maria Grazia , Fregatti Piero , Cosso Maurizio , Pronzato Paolo , Massarotti Claudia , Franzoi Maria Alice B , Lambertini Matteo , Tagliamento Marco
Published: June 2021

12067

Background: Improvements in breast cancer (BC) care have led to increased survival of patients; hence, more attention to long-term treatment-related adverse events and quality of life (QoL) is required. Symptoms of spontaneous and treatment-induced menopause significantly affect the QoL and adherence to endocrine therapy among BC survivors, with potential negative implications on outcome. Use of systemic hormone replacement therapy (HRT) to mitigate menopause-associated symptoms is not recommended to reduce the burden of these side effects being historically associated with an increased risk of disease recurrence. This systematic review and metanalysis aimed to estimate the effect of HRT on risk of disease recurrence in BC survivors. Methods: A systematic search of Pubmed and Embase libraries up to January 15, 2021, was conducted in order to identify randomized controlled trials (RCTs) investigating the risk of disease recurrence with the use of HRT in BC survivors. We used the random-effect model to calculate the overall risk of recurrence, reported as pooled hazard ratio (HR) with 95% confidence intervals (CI). Moreover, we performed a subgroup analysis to estimate the risk of recurrence according to hormone receptor status. The Higgins I2 index was computed to assess the heterogeneity between studies. The likelihood of publication bias was assessed by Egger’s test. Results: Four RCTs were found and three were included in the metanalysis (n = 3.973 patients); one study (n = 100 patients) was excluded due to the impossibility to extract the HR for disease recurrence. Overall, 1.990 patients were randomized to receive HRT (estrogen-progesteron combination or tibolone), while 1.983 patients were included in control groups (placebo or no HRT). As compared to control group, HRT significantly increased the risk of BC recurrence (HR 1.49, 95% CI 1.15-1.93, p = 0.002). The heterogeneity between the studies was low (39%, p = 0.194), and no publication bias was found ( p = 0.537). Two studies reported the HR according to hormone receptor status. At the subgroups analysis, the risk of BC recurrence with the use of HRT was significantly increased in hormone receptor-positive patients (HR 1.8, 95% CI 1.15-2.82, p = 0.010) but not in those with hormone receptor-negative tumors (HR 1.25, 95% CI 0.83-1.88, p = 0.290). Conclusions: Use of HRT significantly increases the risk of recurrence in BC survivors, particularly in those with hormone receptor-positive disease. Therefore, this approach remains contraindicated in this setting. Alternative interventions to mitigate menopause-related symptoms should be proposed to these patients.
Comparison of inpatient outcomes of pathological fractures in metastatic breast cancer and osteoporosis.
Authors: Ahuja Kriti , Lingamaneni Prasanth , Weir Catherine , Elsebaie Maha A.T. , Rodriguez Alarcon Pierre Alexander , Aguilera-Astudillo Maria , Tamkus Deimante
Published: June 2021

12115

Background: In the United States, an estimated 1 in 8 women will be diagnosed with breast cancer during her lifetime. Of those with metastasis, over half have bone metastases leading to risk for pathological fractures. Further, approximately 1 in 4 women over 65 years have osteoporosis of the femur neck or lumbar spine. We performed a retrospective analysis on outcomes in pathological fractures secondary to breast cancer metastasis in comparison to osteoporosis, including disposition at discharge. Methods: The Nationwide Inpatient Sample (NIS) database was queried to include all adult women admitted with osteoporotic fractures and pathological fractures due to metastatic breast cancer between 2016 and 2018. T-test was used to compare means of continuous variables and chi-square test to compare proportions of categorical variables. Multivariate analysis of predictors of pathological fractures in women with breast cancer metastatic to bone, as well as mortality, resource utilization and disposition in this group were performed. Results: A total of 91,494 fractures, combining osteoporosis and pathological fractures secondary to metastatic breast cancer were identified, of which the latter accounted for 4.9%. Patients with pathologic fractures secondary to metastatic breast cancer were younger (mean age 62.8 vs 79.5 years, p < 0.0001) and were more likely to be black (14.6% vs 3.1%, p < 0.0001) or Hispanic (8.3% vs 4.7%, p < 0.0001). Adjusting for demographic variables and comorbidity burden, pathological fractures secondary to metastatic breast cancer were not associated with a significant increase in inpatient mortality (aOR 1.57, 95% CI 0.84-2.95, p = 0.16), but were independently associated with increased length of hospital stay by 0.7 days per admission (p = 0.01) and higher hospitalization costs by $3,381 USD per admission (p < 0.01). Regarding disposition, patients with pathological fractures secondary to breast cancer were less likely to be discharged to a nursing facility (aOR 0.57, 95% CI 0.48-0.68, p < 0.001) and were more likely to be transitioned to home health care (aOR 1.46, 95% CI 1.20-1.78, p < 0.001). Conclusions: In adult women, pathological fractures secondary to breast cancer are less frequent than osteoporotic fractures and were not independent predictors of inpatient mortality. They do however prolong length of stay and increase healthcare costs. Further efforts should focus on risk prediction and prophylactic management of high risk bone lesions in order to enhance patient’s quality of life, decrease hospitalization admissions, stay and cost.
Documentation of goals of care (GOC) by medical oncologists is associated with improved oncology patient end-of-life (EOL) care outcomes.
Authors: Xiao Han , Riley Michael , Donopria Richard , Martin Steven , Nelson Judith Eve , Epstein Andrew S.
Published: June 2021

1507

Background: Documenting GOC is integral to patient care and quality performance but has been underutilized by oncologists due to many barriers. As oncologists play a key role in initiating GOC discussions, we implemented a clinical initiative to improve their GOC documentation and evaluated the impact of such documentation on patient care during the EOL (last 30 days of life). Methods: We launched the initiative among 270 medical oncologists in an academic cancer center in 4/2020. A newly formulated GOC note to ease documentation was embedded in oncology outpatient and inpatient notes. Oncologists completed components in the GOC note that applied to their communication about GOC with the patient: 1) cancer natural history, 2) patient goals, and 3) EOL discussion: patient resuscitation preferences and, when pertinent, receptivity to hospice referral. GOC notes were pulled to a centralized location in the electronic health record (EHR) that displays documents relevant to patients’ values, goals and preferences. A dashboard allowed continual monitoring of documentation performance. We evaluated the association between GOC notes and outcomes of patient care at EOL. We further analyzed the impact of EOL discussion on EOL care. Results: The GOC note completion rate steadily rose after implementation. GOC notes were present in EHR for 46% of 10,006 patients who were either seen in outpatient clinic or discharged from hospital during the 1st week of January 2021. Among 1790 patients who died between 7/1/20 and 12/31/20 and had either at least an outpatient visit or hospitalization during EOL, the median days from first GOC note and first EOL discussion to the patient’s death were 71 days and 24 days, respectively. Linear regression analysis demonstrated that patients who had GOC note 60 days before death spent less time as inpatient during EOL (0.4 day less/patient, from 8.1 to 7.7, P = 0.01). When EOL discussion was documented 30 days before death, patients also spent less time in the hospital (1.2 days less/patient, from 9.7 to 8.5, P < 0.001) and in the ICU (0.3 days less/patient, from 1.7 to 1.4 ICU days, P = 0.04), and were 4% less likely to receive chemotherapy (from 38% to 34%, P = 0.004) at EOL. During the same period, among 1,009 patients with hospital admission in the last 30 days of life, those with a prior documented EOL discussion had shorter inpatient stay (7.7 vs 13.1 days, P < 0.001) and were more likely to be discharged to hospice (34% vs 22%, P = 0.003). Conclusions: During the COVID-19 pandemic, we successfully implemented GOC documentation by medical oncologists that is easily visible by the full care team. Documentation of GOC including EOL discussion was associated with fewer days in the hospital and ICU, increased hospice referral, and lower likelihood of receiving chemotherapy during patients’ last 30 days of life.
Veterans on anticancer medications in rural and community environment support (VA CARES) program: A pharmacist-led telemedicine medication management program for veterans receiving oral antineoplastic therapies through the MISSION Act.
Authors: Healy Regan , Passey Deborah , Pinnell Derek , Qualls Joshua , Hamilton Clayton , Burningham Zach , Tilley Elizabeth , Hood Tanya , Sauer Brian C , Halwani Ahmad Sami
Published: June 2021

1545

Background: Cancer therapies are leveraging oral targeted treatments over traditional cytotoxic chemotherapy (CT) at an increasing rate. Compared to CT, use of oral antineoplastic treatments (OATs) shift some of the burden of medication management onto patients. To address these challenges, several health systems have developed multidisciplinary OAT management teams or ‘clinics’ whereby an Oncology Clinical Pharmacist (OCP) collaborates with oncology teams to ensure optimal use of these agents. Through the VA MISSION Act of 2018, Veterans can be prescribed treatments in the community which are dispensed by VA. These Veterans often live in rural areas and may lack access to comprehensive medication management resources. Methods: The VA CARES Program is a telemedicine medication management ‘clinic’ and care delivery model for patients receiving OATs leveraging custom designed health information technology (HIT) tools to remotely coordinate OAT related care. Veterans are automatically enrolled in the program if they have OATs prescribed by community providers which are to be dispensed by VA. An OCP provides telemedicine medication management services. The OCP performs a screening assessment, ensures appropriate indication and dosing, reviews baseline laboratory results, and performs a thorough drug-drug interaction analysis. The OCP then provides OAT education. Throughout the duration of therapy the OCP ensures necessary therapeutic monitoring, and regularly follows up with the Veterans. Subsequent encounters are to assess knowledge, adherence, toxicities, new drug-drug interactions, and need for OAT refills. The outcome measures for the VA CARES Program include safety (number and type of pharmacist interventions), economic benefits (cost savings or cost avoidance), and patient satisfaction. Results: In the initial 13 months, the VA CARES Program screened N = 78 and enrolled N = 64 (82%) Veterans from three VA medical facilities in VISN-19 from January 2020 to January 2021. The CPS performed n = 342 telemedicine visits and n = 80 interventions leading to improved safety, effectiveness, and/or an economical benefit. The most common interventions included detection and/or prevention of drug-drug interactions (n = 45) and adverse events (n = 18), drug not indicated (n = 13), alternative therapy suggested (n = 7), and limited-quantity dispensed (n = 7). The CPS interventions saved an estimated $210,864 in medication-related costs or avoidance. The Veterans surveyed were highly satisfied with the program services. Conclusions: Telemedicine delivery of oncology medication management by an OCP across systems is feasible, and provides clinical and economic benefits.
A natural language processing tool for automatic identification of new disease and disease progression: Parsing text in multi-institutional radiology reports to facilitate clinical trial eligibility screening.
Authors: Clayton Eric J. , Banerjee Imon , Ward Patrick J. , Howell Maggie D , Lohmueller Beth , Pierson Sunita , Hall Rachel , Harrison Peter B , Waterhouse David Michael
Published: June 2021

1555

Background: Screening every patient for clinical trials is time-consuming, costly and inefficient. Developing an automated method for identifying patients who have potential disease progression, at the point where the practice first receives their radiology reports, but prior to the patient’s office visit, would greatly increase the efficiency of clinical trial operations and likely result in more patients being offered trial opportunities. Methods: Using Natural Language Processing (NLP) methodology, we developed a text parsing algorithm to automatically extract information about potential new disease or disease progression from multi-institutional, free-text radiology reports (CT, PET, bone scan, MRI or x-ray). We combined semantic dictionary mapping and machine learning techniques to normalize the linguistic and formatting variations in the text, training the XGBoost model particularly to achieve a high precision and accuracy to satisfy clinical trial screening requirements. In order to be comprehensive, we enhanced the model vocabulary using a multi-institutional dataset which includes reports from two academic institutions. Results: A dataset of 732 de-identified radiology reports were curated (two MDs agreed on potential new disease/dz progression vs stable) and the model was repeatedly re-trained for each fold where the folds were randomly selected. The final model achieved consistent precision (>0.87 precision) and accuracy (>0.87 accuracy). See the table for a summary of the results, by radiology report type. We are continuing work on the model to validate accuracy and precision using a new and unique set of reports. Conclusions: NLP systems can be used to identify patients who potentially have suffered new disease or disease progression and reduce the human effort in screening or clinical trials. Efforts are ongoing to integrate the NLP process into existing EHR reporting. New imaging reports sent via interface to the EHR will be extracted daily using a database query and will be provided via secure electronic transport to the NLP system. Patients with higher likelihood of disease progression will be automatically identified, and their reports routed to the clinical trials office for clinical trial screening parallel to physician EHR mailbox reporting. The over-arching goal of the project is to increase clinical trial enrollment. 5-fold cross-validation performance of the NLP model in terms of accuracy, precision and recall averaged across all the folds.[Table: see text]
Continuous unobtrusive assessment of meaningful change in older adults with cancer: The Pacific Aging & Cancer Study Collaborative—PACS collaborative.
Authors: Wu Chao-Yi , Tibbitts Deanne , Beattie Zachary , Dodge Hiroko H. , Beer Tomasz M. , Marks Daniel , Shannon Jackilen , Kaye Jeffrey , Winters-Stone Kerri M.
Published: June 2021

1569

Background: Knowledge of changes in health that precede a cancer diagnosis is challenging because of a lack of longitudinal, objective measurement techniques. Current approaches rely on periodic assessment via self-report which may miss when and how health changes, particularly when changes may appear subtly over time. Remote-monitoring technologies provide a mechanism to continuously, passively, and unobtrusively monitor changes in health so that trajectories of change in relation to a life event (i.e., cancer diagnosis, treatment) can be detected and described. We examined the changes in digital indicators of health and life events 1 year before and after a self-reported cancer diagnosis in community-dwelling adults aged 65 and older. Methods: This is a secondary, retrospective data analysis of older adults who self-reported a new cancer diagnosis in the Oregon Center for Aging & Technology (ORCATECH) cohort. Ten older adults (age = 71.8±4.9 years, 30% women) were included with various cancer types (esophageal, prostate, uterine, pancreatic, b-cell follicular lymphoma, multiple myeloma, basal cell melanoma, basal and/or squamous cell carcinoma). Daily physical activity was measured using step counts derived from an actigraph watch. Weekly health and life events (pain severity, loneliness, hospitalization/emergency room (ER) visits, days away from home overnight) were self-reported from weekly online surveys. Results: A total of 3,624 days of actigraphy data (210 ± 88 days pre-cancer; 153 ± 81 days post-cancer) and 750 weeks of self-reported online survey data (36 ± 12 weeks pre-cancer; 39 ± 14 weeks post-cancer) were collected. Longitudinal linear mixed-effects models revealed that the trajectory of step counts was different pre- and post-cancer (β = -1.52, p <.001), with a gradual decrease in step counts before a cancer diagnosis. The trajectory of pain severity was different pre- and post-cancer (β = 0.01, p <.001), with a gradual increase in pain severity before a cancer diagnosis. There was a gradual increase in the occurrence of hospitalization/ER visits (OR = 1.07, p = 0.02) and days away from home overnight (OR = 1.04, p = 0.01) before a cancer diagnosis. Feelings of loneliness increased over time, regardless of pre- or post-cancer (OR = 1.04, p <.001). Conclusions: Changes in health and life events 1-year before a cancer diagnosis in older adults with varying cancer types and severity were unobtrusively observed. This study suggests that a remote-monitoring technology platform deployed in homes can detect meaningful intra-individual changes before and after a cancer diagnosis. Future studies can employ this technology as a pathway for improving the timeliness of detection and more effective therapeutic follow-up for older adults.
Alliance A071601: Phase II trial of BRAF/MEK inhibition in newly diagnosed papillary craniopharyngiomas.
Authors: Brastianos Priscilla Kaliopi , Twohy Erin , Geyer Susan Michelle , Gerstner Elizabeth Robins , Kaufmann Timothy J. , Ruff Michael , Bota Daniela Annenelie , Reardon David A. , Cohen Adam Louis , De La Fuente Macarena Ines , Lesser Glenn Jay , Campian Jian Li , Agarwalla Pankaj , Kumthekar Priya , Cahill Daniel P. , Shih Helen Alice , Brown Paul D. , Santagata Sandro , Barker Frederick G. , Galanis Evanthia
Published: June 2021

2000

Background: Craniopharyngiomas, a rare brain tumor along the pituitary-hypothalamic axis, can cause significant clinical sequelae. Surgery and radiation, the only effective treatments, can cause significant morbidity. Genetic analysis of craniopharyngiomas revealed that 95% of papillary craniopharyngiomas (PCP) have BRAF V600E mutations (Brastianos et al. Nature Genetics 2014). We evaluated the efficacy of BRAF/MEK inhibition in patients (pts) with previously untreated PCP. Methods: Eligible pts without prior radiation whose PCP screened positively for BRAF mutations were treated with oral vemurafenib/cobimetinib in 28-day cycles. The primary endpoint of response rate (RR) based on centrally determined volumetric data was evaluated in 16 pts, where a partial response was defined as >20% decrease in volume. This single arm, Simon two-stage phase 2 trial had 89% power to detect a true RR of at least 30% (vs. the null RR 5%; alpha=0.04). In this design, 3 or more observed volumetric responses in 16 evaluable pts would be considered promising activity. Results: In the 16 pts evaluated, 56% were female, and the median age was 49.5 years. Median follow-up was 22 months (95% CI: 16-26.5) and median number of treatment cycles was 8. Three patients progressed after therapy was discontinued and none have died. Based on volumetric response criteria, 14 of 15 pts with volumetric data available for central review had response to therapy (93%; 95% CI: 68% to 99.8%). Of 16 patients evaluable based on local review, 15 had response to therapy (93.75%; 95% CI: 70% to 99.8%). The median tumor reduction was -83% (range: -52% to -99%). The one nonresponder received 2 days of treatment before coming off therapy due to toxicity. Median progression-free survival was not reached. Grade 3 toxicities at least possibly related to treatment occurred in 12 pts (rash in 6 pts). Grade 4 toxicities were observed in two pts: hyperglycemia (n=1) and increased CPK (n=1). Three pts discontinued treatment for adverse events. Conclusions: Vemurafenib/cobimetinib resulted in an objective response in all pts who received 1 or more cycles of therapy. Our study indicates that BRAF/MEK inhibitors could be a powerful tool in the treatment of previously untreated PCP and warrants further evaluation in larger studies. A second arm of this study is enrolling pts with progressive PCP after prior radiotherapy. Support: U10CA180821, U10CA180882; U24CA196171, U10CA180868 (NRG); Genentech; https://acknowledgments.alliancefound.org. Clinical trial information: NCT03224767.