bluuebunny/crossref_metadata_2025 huggingface dataset:
ABCB1/P-glycoprotein (Pgp) expression as stratification factor for treatment of patients with non-metastaticextremity high-grade osteosarcoma: A merged analysis of an Italian (ISG) and a Spanish (GEIS) sarcoma groups' multicentric prospective trials.
Authors: Palmerini Emanuela , Marquez Catalina , Meazza Cristina , Tamburini Angela , Bisogno Gianni , Sirvent Francisco José Bautista , Ferraresi Virginia , Asaftei Sebastian Dorin , Milano Giuseppe Maria , Luksch Roberto , Canete Adela , Echebarria Aizpea , Quintero Víctor , Mata Cristina , Bertulli Rossella , Longhi Alessandra , Picci Piero , Fagioli Franca , Hindi Nadia , Ferrari Stefano
Published: June 2021

11527

Background: Overexpression of ABCB1/P-glycoprotein (Pgp) predicts poor outcome in retrospective osteosarcoma series.Two prospective trials with Pgp expression and post-induction histologic response as stratification factors were activated in Italy (ISG/OS-2) and Spain (GEIS-33). Methods: Patients ≤ 40 years with extremity non-metastatic high-grade osteosarcoma were eligible. Analysisi of Pgp expression from diagnostic biopsy was centralized. Preoperatively, all patients received methotrexate, adriamycin, cisplatinum (MAP). Surgery was performed at week 8. All patients received a dose of adriamycin following surgery. In case of Pgp overexpression (Pgp+), mifamurtide (2 mg/m2 twice/week for 3 months then weekly for 6 months) was added after surgery, with 4 consecutive cycles of ifosfamide 3 gr/m2/day, day 1-5 (HDIFO) in case of poor histologic response (necrosis < 90%) to MAP. Patients without overexpression of Pgp (Pgp-) received MAP postoperatively, regardless the pathological response. From March 2013, an amendment increased high dose methotrexate cumulative dose from 60 g/m2 (5 cycles) to 120 mg/m2 (10 cycles). The post-amendment regimen was adopted in the observational prospective study by GEIS. Here we present the merged analysis of ISG/OS-2 patients treated post-amendment and GEIS-33. Results: From March 2013 to April 2018, 274 patients were included. Median age was 14 years (range 4-38), male/female: 163/111; 90 were Pgp-, 164 were Pgp+, 20 not evaluable. With a median follow-up of 48 months (1.3-78.5 months), the 3-year EFS and OS were 71.9% (95%CI 66-76.9) and 88% (95%CI: 83.2-91.5) respectively, with no inferior survival for Pgp positive patients and improved survival for good responders (Table). Conclusions: In this prospective uncontrolled study with a risk-adapted strategy for non-metastatic osteosarcoma, survival is superior to that of all ISG/GEIS previous series. The 3-year EFS of 71.9% compares favorably with other reports. Pgp+ patients performed well in this study, in which mifamurtide and HDIFO were added after a poor response to MAP. Clinical trial information: NCT01459484; NCT04383288. [Table: see text]
Accumulation of genome-wide somatic loss of heterozygosity (LOH) as a prominent feature of advanced malignant soft tissue tumors and association with the BRCAness status, suppression of immune responses, and lower survival rates.
Authors: Takahashi Katsuhito , Miyaji Yasutomo , Ohkuma Ryotaro , Higuchi Hajime , Komohara Yoshihiro , Aida Shinsuke , Yashima Jun , Yamamoto Hiromasa , Suzawa Ken , Takahashi Yuko , Toyooka Shinichi , Ashimine Hiroya , Oyama Yu , Narahara Hiroyuki , Yotsumoto Junko , Ishida Hiroo , Tsunoda Takuya , Sasaki Yasutsuna , Ono Yasuo , Teraoka Satoshi
Published: June 2021

11533

Background: Malignant soft tissue tumor is a rare cancer with few therapeutic options. Recent genomic analysis revealed widespread CNA and the cumulative burden of cancer-related pathogenic germline mutations/variants, their clinical and therapeutic significance were unknown. Methods: We recruited 155 patients with advanced malignant soft tissue tumors (135 female and 20 male, mean age 51 at analysis, 100 LMS, 19 LPS, 4 ESS, 3 UPS, 3 AS, 3 MPT, 3 GIST and others) with confirmed metastasis/recurrence and information on familial cancer burden. Whole exome sequencing was performed in both blood and tumor samples as described in 2018ASCO. The copy number of BRCA2 gene was determined by the MLPA method. Tumor immune microenvironment was assessed by immunohistochemistry. The MSI status was analysed by PCR. Results: We analyzed the LOH status in 595 COSMIC genes and found that genome-wide accumulation of somatic LOH of polygenic germline mutations/variants. Patients with more than 33% LOH genes (n=102) in the total of somatic and LOH mutations showed significantly lower OS rates compared with those (n=53) with less LOH genes (5-year survival rates; 49 vs 75%, p=0.010), which constitute 78% of LMS (n=78/100) and 26% of LPS (n=5/19). Total of 41 patients (26%, n=41/155) including 33 LMS (33%, n=33/100) showed LOH in the BRCA2 locus with hemizygous VUS. Those patients with BRCA2 LOH (n=41) showed significantly lower OS rates compared with those without BRCA2 LOH (n=114) (5-year survival rates; 43 vs. 64%, p=0.019). Neither TMB nor the MSI status was associated with LOH. In contrast, accumulation of somatic LOH (mean LOH values of 71.7 vs. 15.7%) was clearly and negatively associated with CD8+T-cell immune infiltrates (T-cells; 44±23 vs 555±180/mm2, n=7, p=0.016), CD20+B-cell accumulation in tertiary lymphoid structures (TLS) (TLS; 0.57±0.43 vs. 20.1±6.1/tumor, n=7, p=0.008) and low levels of neutrophil-to-lymphocyte ratio (NLR) (NLR; 3.63±0.45 vs. 1.71±0.17, n=7, p=0.002), hallmarks of the immunological response to tumors. Conclusions: This study suggests that in advanced malignant soft tissue tumors, accumulation of genome-wide LOH of germline mutations/variants is associated with the BRCAness status and suppression of the immune responses to tumors, and thus influences therapeutic response and survival of the patients.
Durvalumab and pazopanib in patients with advanced soft tissue sarcoma: A single-center, single-arm, phase 2 trial.
Authors: Kim Hyo Song , Cho Hee Jin , Yun Kum-Hee , Lee Young Han , Kim Sung Hyun , Baek Wooyeol , Jeon Min Kyung
Published: June 2021

11551

Background: Based on the central role played by the vascular endothelial growth factor receptor (VEGFR) in immunosuppression, we assessed the activity and safety of VEGFR inhibitor pazopanib plus anti-PD-L1 blockade durvalumab in soft tissue sarcoma (STS). Methods: We did a single-arm, single-center, phase 2 study that enrolled patients with metastatic or locally advanced STS aged 19 years or older, ECOG PS 0-1, with at least one measurable lesion, and received at least one previous line of systemic therapy. Patient were given pazopanib 800 mg orally daily and durvalumab 1500 mg intravenously for 60 min every 3 weeks. The primary endpoint was investigator-assessed objective response. Results: Between September 2019 and October 2020, 47 participants were enrolled, of whom 46 (97.9%) were evaluable for the efficacy analyses. With a median follow up of 12.3 months, complete and partial response (PR) was achieved in 1 (2.2%) and 12 (26.1%) patients, resulting in 28.3 % of objective response rate. Median time to achieve PR was 1.4 months and median duration of response was 11.0 months. The most common treatment-related adverse events of any grade include fatigue (20 [42.6%]), anorexia (17 [36.2%]), diarrhea (17 [36.2%]), and AST elevation (16, [34.0%]). Thirty-one patients (67.3%) had progressive disease, and the median progression free survival was 8.6 months (95% CI 3.6-13.6). Conclusions: Durvalumab and pazopanib showed encouraging activity in patients with advanced STS. Molecular predictors with whole exome and RNA sequencing will be presented. Clinical trial information: NCT03798106.
Retrospective world-wide registry on the efficacy of immune checkpoint inhibitors in alveolar soft part sarcoma: Updated results from sixty patients.
Authors: Hindi Nadia , Rosenbaum Evan , Jonczak Emily , Hamacher Rainer , Rutkowski Piotr , Skryd Anthony , Connolly Elizabeth , Blay Jean-Yves , Gutierrez Antonio , Bogefors Carolina , Gelderblom Hans , Boye Kjetil , Henon Clemence , Martinez-Trufero Javier , Lopez-Martin Jose A. , Redondo Andrés , Valverde Claudia , Vincenzi Bruno , Tap William D. , Martin Broto Javier
Published: June 2021

11564

Background: Alveolar soft-part sarcoma (ASPS) is a highly metastasizing ultra-rare sarcoma subtype, frequently affecting young adults. Conventional cytotoxic drugs are not effective in ASPS, but antiangiogenics demonstrated significant improvement in tumor burden reduction and PFS in the only ever conducted comparative trial. Immune check-point (PD-1/PD-L1) inhibitors (ICI) are emerging promising drugs in the therapy of ASPS, from small reported retrospective and prospective series. A world-wide registry has been set up with the aim of exploring the efficacy of ICI in ASPS. Methods: Data from adult patients (pts) diagnosed with ASPS and treated with PD- 1/PD-L1 inhibitors for advanced disease in expert sarcoma centers from Europe, Australia and US was retrospectively collected. IRB approval was obtained. Demographics, data related to treatments and outcome were considered. Radiologic assessment was based on RECIST 1.1. Progression-free (PFS) and overall survival (OS) were calculated with Kaplan-Meier method. An updated analysis of this series is presented here. Results: Sixty ASPS pts (27 female/33 male) with a median age at diagnosis of 25y (range 3-61) were registered. Primary tumor arose in limbs in 47 pts (78%) and 41 pts (68%) were metastatic at diagnosis. 52/60 pts (87%) had received previous systemic therapy (including chemotherapy in 19 pts and antiangiogenics in 47pts), with a median of one previous line (0-6). All pts received ICI for metastatic disease. Immunotherapy regimens consisted of monotherapy in 31 pts (52%) and combination in 29 pts (48%) (23 with an antiangiogenic agent). 29/60 pts (48%) received ICI within a clinical trial. Among the 52 evaluable pts, there was 1 complete response (CR) and 20 partial responses (PR) (ORR 40.4%). After a median follow-up of 21 months -mos- (range 4-59), 37/60 pts have progressed to ICI, with a median PFS of 13.4 mos (95% CI 10.1-16.7). Eleven pts received a subsequent line of ICI with a median PFS of 26 mos (95%CI 0-57). 16 pts have died, being the median OS from ICI initiation 38 mos (95% CI 33-43). The 12-mos and 24-mos OS rates were 94% and 70% respectively. Conclusions: This registry constitutes the largest available series of ASPS treated with immune check-point inhibitors. Our results suggest that treatment with ICI provide long-lasting disease control and prolonged OS in pts with advanced ASPS, an ultra-rare entity with limited active therapeutic options. The results on subsequent ICI lines suggest a lack of cross-resistance among different ICI therapies.
Assessing the risk of severe post-treatment (tx) cancer-related fatigue (CRF) among breast cancer survivors (BCS) in the CANcer TOxicity (CANTO) cohort.
Authors: Di Meglio Antonio , Havas Julie , Martin Elise , Pistilli Barbara , Menvielle Gwenn , Dumas Agnes , Charles Cecile , Everhard Sibille , Martin Anne-Laure , Coutant Charles , Tarpin Carole , Vanlemmens Laurence , Levy Christelle , Rigal Olivier , Delaloge Suzette , Ganz Patricia A. , Partridge Ann H. , Andre Fabrice , Michiels Stefan , Luis Ines Maria Vaz Duarte
Published: June 2021

12022

Background: CRF is among the most common and troublesome symptoms experienced by BCS. While preventing severe post-tx CRF is a major survivorship need, limited tools exist to predict this risk. We aimed to describe the long-term prevalence rates and to identify BCS that are more likely to develop severe CRF. Methods: CANTO is a multicenter, prospective clinical study of stage I-III BCS (NCT01993498). Longitudinal data were collected at diagnosis (dx), 0.5 (T1), 1 (T2) and 3 (T3) years post-tx. The primary outcome of interest was severe post-tx global CRF (score ≥ 40/100, EORTC QLQ-C30). Secondary outcomes were physical, emotional and cognitive dimensions of CRF (QLQ-FA12). Multivariable logistic regression models retained associations with severe CRF by bootstrapped Augmented Backwards Elimination, validated using 10-fold internal cross-validation and overoptimism-corrected AUC. Results: Among 6619 BCS, mean age at dx was 56.5 years (SD 11.5), mean BMI was 25.9 Kg/m2 (SD 5.4), 53.3% and 80.8% received chemotherapy (CT) and hormonotherapy (HT), respectively. Prevalence rates of severe global CRF were 25.0% (dx), 35.6% (T1), 34.0% (T2) and 31.6% (T3). Severe post-tx global CRF was consistently associated with higher BMI, worse insomnia and pain, and severe pre-tx CRF. Receipt of CT increased odds of severe CRF at T1, whereas associations of HT with CRF emerged at T2 and T3 (Table). The estimated risk of severe CRF at T3 was 14% for a BCS with BMI 23.0 Kg/m2 and no concomitant symptoms at dx, whereas it was 82% for a BCS with BMI 32.0 Kg/m2, severe insomnia, pain and pre-tx CRF, receiving HT. Anxiety and depression at dx were consistently retained in models of severe post-tx emotional and cognitive CRF (all p <.05). Conclusions: Over 1/3 BCS endured persistent, severe global CRF, particularly those that were medically more fragile and reported heavier pre-tx symptom burden. A transient impact of CT on CRF was evident on the short aftermath of tx, whereas exposure to HT seemed to affect CRF on the longer run. Consistent factors flag BCS whose risk of severe CRF is high and who should be upfront targeted and aggressively helped. Dimension-specific risk factors can guide prevention of distinct CRF symptoms. Clinical trial information: NCT01993498. [Table: see text]
Change in the comprehensive geriatric assessment scores at day 30 post-cancer treatment in geriatric oncology patients.
Authors: Tannous Toufic , Debs Dany , Ceyhan Erkan , Somasundar Ponnandai Sadasivan
Published: June 2021

12048

Background: The comprehensive geriatric assessment (CGA) is a multidimensional tool for assessing the functional, cognitive, nutritional and frailty status of patients above 65 years of age with cancer. It includes several components: patient health questionnaire (PHQ-9), timed up and go (TUG), mini mental status exam (MMSE), mini nutritional assessment (MNA), Poly Pharmacy (PP), activities of daily living (ADL), instrumental activities of daily living (IADL) and comorbidities. Previous studies showed that some baseline CGA scores (pre-treatment) are predictors of mortality. However, to our knowledge, there has been no study evaluating the change of those scores in response to treatment at different time periods. We sought to evaluate the evolution of the CGA scores after 30 days post-treatment. Methods: We conducted a single institution, prospective cohort registry of patients with solid cancers aged 65 or older in Rhode Island from 2013-2018. All patients underwent a CGA before starting treatment (day 0) and post-treatment (day 30). Treatment included surgery, chemotherapy, radiation, or any combination. Baseline demographic characteristics as well as CGA components were abstracted. TUG, MMSE, PHQ-9, IADL, PP, BMI, MNA and ADL performed at day 0 and 30 were collected. The mean for each score was obtained at both days. Student T test was used to test for significance for nominal data and Chi square test for ordinal data. A P value of less than 0.05 was deemed statistically significant. Results: 283 patients were enrolled. The mean age was 76 (+-6.86) of which 54% were females. 92% of patients were white and 8% were black. Colorectal and lung cancer were among the most common. The mean Charleston comorbidity index was 12.3 (+-3.2). The mean BMI decreased from 26.92 (+-5.84) at day 0 to 26.1 (+-5.45) at day 30 (p < 0.01). The mean IADL decreased from 5.93 (+-2.03) to 5.2 (+-2.12) (p < 0.01). At day 0, one patient had impaired ADLs compared to 7 patients at day 30 (p = 0.03). PHQ-9, MMSE, MNA, TUG and PP scores did not significantly differ at day 30 post treatment (Table). Conclusions: The ADL, IADL and BMI scores showed a statistically significant change at Day 30, indicating deteriorating scores in those patients. Our study showed that ADL, IADL and BMI were the only variables that worsened at day 30 post-treatment compared to PHQ-9, MMSE, MNA, TUG and PP. This suggests that they may be used as early markers of clinical deterioration in geri-onc patients undergoing treatment. More studies are needed to assess their prognostic significance.[Table: see text]
Impact of using volumetric dosimetry to screen childhood cancer survivors for radiation-related late effects.
Authors: Cohen-Cutler Sally , Kaplan Cameron , Olch Arthur , Wong Kenneth , Malvar Jemily , Constine Louis S. , Freyer David R.
Published: June 2021

12066

Background: Late effects screening guidelines for survivors of childhood cancer treated with radiation therapy currently use irradiated regions (IR) rather than volumetric dosimetry (VD), which more precisely identifies organs-at-risk (OAR). We recently showed that VD reduced mean number of recommended screening diagnostic imaging studies and procedures by 37.0% per patient (p<0.001).1 Here we have incorporated chemotherapy and refined volumetric dosimetry dose thresholds. Methods: This was a cross-sectional cohort study of patients (n=132) treated for cancer using computerized tomography-planned irradiation at Children’s Hospital Los Angeles from 2000-2016. For each patient, both VD and IR methods were used to determine radiation exposure to the cochlea, heart, lung, breast, and colon. Dose thresholds for VD were based on those supplied in the Children’s Oncology Group (COG) Long-Term Follow-Up Guidelines. Relevant chemotherapy exposures were recorded. Under each method, COG Long-Term Follow-Up Guidelines were applied to determine potential chemotherapy- and radiation-related late effects and their correlative screening practices (complete audiologic evaluation, pure tone audiometry, mammogram, breast MRI, echocardiogram, pulmonary functions test, and/or colonoscopy). Identified OAR were compared using Exact McNemar’s test. Total numbers of screening practices were computed using VD and IR and compared. Results: Median age at end of treatment was 10.6 years (range 1.4-20.4). The most frequent cancer type was brain tumor (45%), followed by bone and soft tissue tumor (39%) and leukemia/lymphoma (16%). Head/brain was the most commonly irradiated region (61%), followed by abdomen (22%). Anthracyclines were received by 25% of patients at < 250 mg/m2 and by 16% at ≥ 250 mg/m2. With use of VD, fewer patients were flagged for screening for each organ of interest: cochlea (-21.3%, p<0.001), heart (-22.5%, p<0.001), lung (-13.8%, p=0.219), breast (-25%, p=0.625), colon (-51.9%, p<0.001). Over the lifetime of this cohort, use of VD resulted in recommendations for 1,333 fewer pure tone audiometric tests (-21.5%), 9 fewer complete audiologic evaluations (-16.1%), 4 fewer pulmonary function tests (-13.8%), 112 fewer mammograms (-25.0%) and breast MRIs (-25.0%), 349 fewer echocardiograms (-16.1%), and 275 fewer colonoscopies (-51.9%). Conclusions: Use of VD rather than IR significantly reduces guideline-based screening for radiation-related late effects in long-term childhood cancer survivors. This work forms the basis for a comparative cost-effectiveness analysis of these two approaches. (1) Cohen-Cutler et al, Cancer Medicine, 2020.
Associations between preexisting nociplastic pain and early discontinuation of aromatase inhibitor therapy in breast cancer.
Authors: Joyce Elizabeth , Wang Sidi , Motamed Mehrdad , Kidwell Kelley M. , Henry Norah Lynn
Published: June 2021

12068

Background: Aromatase inhibitors (AI) are recommended for at least five years to reduce risk of breast cancer recurrence in postmenopausal women with hormone receptor-positive disease. Despite the potential benefit, up to 50% of patients discontinue AI early, primarily because of musculoskeletal side effects. Some patients, including those with fibromyalgia and other chronic pain conditions, have preexisting pain that arises from altered nociception without clear evidence of tissue or peripheral nerve damage, called nociplastic or centralized pain. We hypothesized that preexisting nociplastic pain is associated with early discontinuation of AI therapy due to toxicity. Methods: Patients diagnosed with breast cancer between 2012-19 and who enrolled in the Michigan Genomics Initiative (MGI) were identified. Patients who were female, had hormone receptor-positive breast cancer, had not received neoadjuvant therapy, and who initiated adjuvant AI therapy were included in the analysis. Prior to breast cancer surgery patients completed surveys about pain in the affected breast and overall worst pain (Brief Pain Inventory [BPI]), nociplastic pain (2011 Fibromyalgia Survey [FS], which assesses widespread pain plus somatic symptom severity), and anxiety (PROMIS Anxiety 4a v.1). Demographics, cancer characteristics, and treatment history, including date and reason for discontinuation of AI therapy, were abstracted from the medical record. Patients were censored at date of last oncology follow-up. Univariate and multivariable analyses were conducted to assess relationship between age, BMI, surgical site pain, overall worst pain, FS score, anxiety, and time to discontinuation of initial AI medication. Results: Of 207 analyzed patients, the average age was 61 years, average BMI was 30.3 kg/m2, 181 (87%) were postmenopausal at the time of breast cancer diagnosis, and 31% received chemotherapy. The majority were prescribed anastrozole (n=196); 6 took letrozole and 5 took exemestane. Average scores prior to surgery were 1.5/10 for worst pain, 0.2/10 for surgical site pain, 4.2/31 for FS score, and 54.1/100 for anxiety. On univariate analysis, only use of exemestane (HR 5.55, p<.001) and use of letrozole (HR 3.11, p<.001) were associated with shorter time to ET discontinuation; age, BMI, surgical site pain, worst pain, FS score, and anxiety were not statistically significantly associated with time to AI discontinuation. On multivariable analysis, only higher FS score was statistically significantly associated with time to AI discontinuation (HR 1.11, p=.021). Conclusions: Greater pre-existing nociplastic pain was associated with early discontinuation of AI therapy. For these patients, early interventions that target centralized pain, or treatment with tamoxifen instead of AI therapy, may be appropriate in order to reduce risk of nonpersistence with AI therapy.
Marijuana use among US adults with cancer: Findings from the 2018-2019 Behavioral Risk Factor Surveillance System.
Authors: Lee Min Jee , Salloum Ramzi , Sharma Arun
Published: June 2021

12088

Background: Cancer survivors experiencing adverse effects from their cancer and treatment report decreased symptom burden with marijuana use. An increasing number of U.S. states have legalized marijuana use for both medical and recreational purposes. This study aimed to assess the prevalence of current marijuana use and to identify the factors associated with its use among US adults with cancer living in 17 U.S. states and territories. Methods: Data from the 2018-2019 Behavioral Risk Factor Surveillance System Marijuana Use module were analyzed. In 2018, 13 states (California, Florida, Idaho, Maryland, Minnesota, Montana, New Hampshire, North Dakota, Ohio, South Carolina, Tennessee, West Virginia, and Wyoming) and 2 territories (Guam and Puerto Rico) participated in the optional marijuana use module. In 2019, 12 states (California, Idaho, Illinois, Maryland, Minnesota, New Hampshire, North Dakota, South Carolina, Tennessee, Utah, West Virginia, and Wyoming) and 1 territory (Guam) participated in the optional marijuana use module. The analytic sample included 13,174 adults with cancer. The analysis was weighted to account for BRFSS’s complex survey design. The primary outcome was current marijuana use (in the past 30-days). Multivariable logistic regression was used to identify demographic, socioeconomic, clinical, and behavioral factors associated with marijuana use among US adults with cancer. Results: Overall, 9.2% of adult cancer survivors (n = 13,174; weighted 5.7 million; 37.9% men) reported marijuana recently current use, 51.3% of whom used it for medical reasons only, with 65.2% reporting smoking as the main method of administration. Adult cancer survivors were significantly more like to use marijuana if they were younger (odds ratio [OR] for 55-64 versus 18-44 years old: 0.60; 95% CI: 0.38-0.93; P < 0.01); male (OR for female versus male: 0.65; 95% CI: 0.48-0.87; P < 0.01); non-Hispanic Black race/ethnicity (OR: 2.00; 95% CI: 1.21-3.33; P < 0.01); having depression (OR: 1.58; 95% CI: 1.17-2.14; P < 0.01) and current (OR: 3.23; 95% CI: 2.20-4.74; P < 0.01) or former tobacco smoker (OR: 2.40; 95% CI: 1.70-3.38; P < 0.01) and binge drinker (OR: 2.25; 95% CI: 1.53-3.29; P < 0.01). Conclusions: Among a large cohort of US adults with cancer, marijuana use was commonly reported and certain subgroups were at higher risk for marijuana use. Health professionals should identify the risk factors for elevated marijuana use, especially as more states legalize medical and recreational marijuana use despite uncertain health risks.
A 10-hour time-restricted eating intervention to address cancer-related fatigue among cancer survivors.
Authors: Kleckner Amber , Reschke Jennifer E , Altman Brian James , Belcher Elizabeth , Dunne Richard Francis , Fleming Fergal J. , Gilmore Nikesha , Jensen-Battaglia Marielle , Kleckner Ian , Lin Po-Ju , Mustian Karen Michelle , Peppone Luke Joseph
Published: June 2021

12109

Background: Cancer-related fatigue is a common, debilitating condition that can persist for months or years after cancer treatment. Time-restricted eating has been shown to improve circadian rhythm and strengthen rest and activity patterns, and therefore could help reduce persistent fatigue. Herein, we evaluated the feasibility of recruiting cancer survivors to a two-week, single-arm, time-restricted eating intervention with a 10-h eating window, assessed safety of the intervention, monitored adherence, and obtained initial estimates of within-group change in patient-reported fatigue. Methods: We recruited adults 4-60 months post-cancer treatment who had a fatigue level ≥3 on a scale from 0-10 and who did not already consume food within a 10-h window. Participants were asked to consume all food and beverages within a self-selected 10-h eating window for 14 days; water was allowed at all times. Participants completed a daily diary indicating when they began and stopped eating each day. To assess fatigue, participants completed the Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) and the Brief Fatigue Inventory (BFI) at pre- and post-intervention. We report mean±standard deviation and used a t-test to assess differences in pre- vs. post-intervention scores. Results: A total of 21 participants consented (20 breast cancer, 1 prostate cancer; 20 female; age 57.7±11.4 years; 1.6±1.1 years post-primary treatment). The study was feasible: 19/21 (90.5%) completed pre- and post-intervention assessments and daily diaries. It was also safe: there were two mild adverse events—one unlikely (insomnia) and one possibly related to the intervention (acute headache) and no severe adverse events. Most of the participants adhered to the intervention; 14/19 (73.7%) ate all of their food within a 10-h window at least 80% of the days, and 16/19 (84.2%) reported an average eating window ≤10 h. Fatigue scores improved a clinically meaningful degree for FACIT-F total score, FACIT-F fatigue subscale, and the BFI total score from pre- to post-intervention per established cutoffs (Table). Conclusions: Cancer survivors were willing and able to adhere to a two-week time-restricted eating intervention, and the intervention was safe. Also, fatigue was reduced with moderate to large effect sizes after two weeks of time-restricted eating. Based on our results, a follow-up randomized controlled trial to investigate time-restricted eating to alleviate cancer-related fatigue among cancer survivors is indicated. Funding: NIH/NCI UG1CA189961, T32CA102618. Clinical trial information: NCT04243512. [Table: see text]
Improving cancer pain management in the emergency department: An EMR-based solution.
Authors: Coyne Christopher John , Kettler Ellen , Dong Kelly , Killeen James
Published: June 2021

12110

Background: Pain is common reason for patients with cancer to seek care in the emergency department (ED). Unfortunately, these patients frequently receive inadequate doses of pain medication, partially due to opioid reduction efforts in the ED, as well as opioid tolerance among those with chronic cancer pain. The purpose of this study was to investigate the effectiveness of an electronic medical record (EMR) based best practice advisory (BPA) at improving analgesic dosing for cancer patients in the ED. Methods: We performed a retrospective cohort study on cancer pain at two academic medical centers from 05/18/20 to 10/27/20. The BPA algorithm identified ED patients with cancer that were taking prescription opioids with a morphine equivalent daily dose (MEDD) of at least 100, as calculated by the EMR. If the ED provider ordered opioids for these patients, a BPA alert appeared with a recommended opioid dose based on the patient’s individual MEDD. This alert also included pre-set safety orders for O2 and end tidal CO2 monitoring as well as naloxone. We compared outcomes based on whether an ED provider accepted or cancelled the BPA recommendation. These outcomes included the change in opioid dose and ED disposition. Continuous variables were compared using the students t-test, while categorical variables were compared with the chi-squared test with an alpha of 0.05. Results: Our BPA identified 92 patients that met our criteria, representing 143 BPA alerts. The mean age was 52, 43.5% were female, 54.3% had metastatic disease, and 56.5% presented with a painful chief complaint. Of the ED providers that accepted the BPA, 57.5% increased their dose of opioid medication. BPA usage led to a 33.3% mean increase in medication dosage (p <.001). Patients that presented with a painful chief complaint, whose providers utilized the BPA were admitted at a rate of 60.5%, verses a 77.8% admission rate among those whose providers did not utilize the BPA (p <.01). No patients required an opioid reversal agent. Conclusions: Among cancer patients on chronic opioids presenting to the ED, use of an EMR-based BPA led to more appropriate opioid dosing without the need for opioid reversal agents, and was associated with an overall decrease in hospital admissions.
CORONET; COVID-19 in Oncology evaluatiON Tool: Use of machine learning to inform management of COVID-19 in patients with cancer.
Authors: Lee Rebecca , Wysocki Oskar , Zhou Cong , Calles Antonio , Eastlake Leonie , Ganatra Sarju , Harrison Michelle , Horsley Laura , Huddar Prerana , Khan Khurum , Mckenzie Hayley , Palmieri Carlo , Rogado Revuelta Jacobo , Thomas Anne , Wilson Caroline , Cooksley Tim , Dive Caroline , Freitas Andre , Armstrong Anne Caroline ,   CORONET Consortium
Published: June 2021

1505

Background: Patients (pts) with cancer are at increased risk of severe COVID-19 infection and death. Due to COVID-19 outcome heterogeneity, accurate assessment of pts is crucial. Early identification of pts who are likely to deteriorate allows timely discussions regarding escalation of care. Likewise, safe home management will reduce risk of nosocomial infection. To aid clinical decision-making, we developed a model to help determine which pts should be admitted vs. managed as an outpatient and which pts are likely to have severe COVID-19. Methods: Pts with active solid or haematological cancer presenting with symptoms/asymptomatic and testing positive for SARS-CoV-2 in Europe and USA were identified following institutional board approval. Clinical and laboratory data were extracted from pt records. Clinical outcome measures were discharge within 24 hours, requirement for oxygen at any stage during admission and death. Random Forest (RF) algorithm was used for model derivation as it compared favourably vs. lasso regression. Relevant clinical features were identified using recursive feature elimination based on SHAP. Internal validation (bootstrapping) with multiple imputations for missing data (maximum ≤2) were used for performance evaluation. Cost function determined cut-offs were defined for admission/death. The final CORONET model was trained on the entire cohort. Results: Model derivation set comprised 672 pts (393 male, 279 female, median age 71). 83% had solid cancers, 17% haematological. Predictive features were selected based on clinical relevance and data availability, supported by recursive feature elimination based on SHAP. RF model using haematological cancer, solid cancer stage, no of comorbidities, National Early Warning Score 2 (NEWS2), neutrophil:lymphocyte ratio, platelets, CRP and albumin achieved AUROC for admission 0.79 (+/-0.03) and death 0.75 (+/-0.02). RF explanation using SHAP revealed NEWS2 and C-reactive protein as the most important features predicting COVID-19 severity. In the entire cohort, CORONET recommended admission of 96% of patients requiring oxygen and 99% of patients who died. We then built a decision support tool using the model, which aids clinical decisions by presenting model predictions and explaining key contributing features. Conclusions: We have developed a model and tool available at https://coronet.manchester.ac.uk/ to predict which pts with cancer and COVID-19 require hospital admission and are likely to have a severe disease course. CORONET is being continuously refined and validated over time.
Association of the COVID-19 pandemic with patterns of cancer services.
Authors: Yabroff Robin Robin , Wu Xiao-Cheng , Negoita Serban , Stevens Jennifer , Coyle Linda , Zhao Jingxuan , Mumphrey Brent , Jemal Ahmedin , Ward Kevin C.
Published: June 2021

1514

Background: The COVID-19 pandemic led to delays in medical care in the United States. We examined changes in patterns of cancer diagnosis and surgical treatment in 2020 using real-time electronic pathology report data from population-based SEER cancer registries in Georgia and Louisiana. Methods: Bi-weekly numbers, distributions, and patterns of pathology reports were compared between January 1st and December 31st in 2020 and the same period in 2019 by age group and cancer site. Results: During 2020, there were 29,905 fewer pathology reports than in 2019, representing a 10.2% decline. Absolute declines were greatest among adults aged ≥50 years (N=23,065); percentage declines were greatest among children and young adults ≤18 years (38.3%). By cancer site, percentage declines were greatest for lung cancer (17.4%), followed by colorectal (12.0%), breast (9.0%) and prostate (5.8%) cancers. Biweekly reports were statistically significantly lower in 2020 than in 2019 from late March through the end of December in most biweekly periods. The nadir was the month of April 2020 – the number of reports was at least 40% lower than in April 2019. The number of reports in 2020 compared with 2019 also declined sharply in early November (26.8%) and late December (32.0%). Numbers of reports in 2020 never consistently exceeded those in 2019 after the first decline. Patterns were similar by cancer site, with variation in magnitude and duration of declines. Conclusions: Significant declines in cancer pathology reports from population-based registries during 2020 suggest substantial delays in screening, evaluation of signs and symptoms, diagnosis, and treatment services for cancers with effective screening tests as well as in cancer sites and age groups without effective screening tests as an indirect result of the COVID-19 pandemic. Ongoing evaluation will be critical for informing public health efforts to minimize any lasting adverse effects of the pandemic on cancer screening, diagnosis, treatment, and survival.[Table: see text]
The influence of race on financial toxicity among cancer patients.
Authors: Panzone John , Welch Christopher , Pinkhasov Ruben , Jacob Joseph M , Shapiro Oleg , Basnet Alina , Bratslavsky Gennady , Goldberg Hanan
Published: June 2021

1525

Background: Studies show that cancer patients and survivors are likely to endure financial toxicity long after being diagnosed. Methods: To examine the influence of race on financial toxicity among individuals with a history of cancer, a US based cross sectional study was conducted using data on 1,328 cancer patients collected from the Health Information National Trends Survey. Multivariable logistic regression analyses were used to analyze the relationship between race and financial toxicity, adjusting for known confounders. Results: Blacks, Hispanics and other races were shown to have a lower rate of insurance compared to Whites. Whites were also more likely to receive cancer treatment than other races (6.1% received no treatment vs 15.0% of Blacks, 17.8% of Hispanics, and 9.7% of other races, p<0.001). Considerably more Whites underwent surgical treatment of their cancer (77%) vs. 60% of Blacks, 55% of Hispanics and 74.2% of other races, p<0.001. Blacks were found to be over 5 times more likely to be denied insurance (OR 5.003, 95% CI 2.451-10.213, p<0.001) and more than twice as likely to be hurt financially than Whites (OR 2.448, 95% CI 1.520-3.941, p<0.001). Other racial minorities were also more than twice as likely to be hurt financially than Whites (OR 2.421, 95% CI 1.248-4.698, p=0.009) (Table). Conclusions: These data suggest that race is significantly associated with increased rates of being hurt financially and being denied insurance due to cancer. Awareness of race inequality should be raised so that equal cancer treatment can be provided, irrespective of race, gender or socioeconomic status.[Table: see text]
Impact of a deep learning model to reduce variation and costs of federally mandated breast density legislation.
Authors: Cavallo Hom Katherine , Dontchos Brian Nicholas , Mercaldo Sarah , Dang Pragya , Lamb Leslie , Lehman Constance Dobbins
Published: June 2021

1550

Background: Dense breast tissue is an independent risk factor for malignancy and can mask cancers on mammography. Yet, radiologist-assessed mammographic breast density is subjective and varies widely between and within radiologists. Our deep learning (DL) model was implemented into routine clinical practice at an academic breast imaging center and was externally validated at a separate community practice, with both sites demonstrating high clinical acceptance of the model’s density predictions. The aim of this study is to demonstrate the influence our DL model has on prospective radiologist density assessments in routine clinical practice. Methods: This IRB-approved, HIPAA-compliant retrospective study identified consecutive screening mammograms without exclusion performed across three clinical sites, over two time periods: pre-DL model implementation (January 1, 2017 through September 30, 2017) and post-DL model implementation (January 1, 2019 through September 30, 2019). Clinical sites were as follows: Site A (the academic practice where the DL model was developed and was implemented in late 2017); Site B (an affiliated community practice which implemented the DL model in late 2017 and was used for external validation); and Site C (an affiliated community practice which was never exposed to the DL model). Patient demographics and radiologist-assessed mammographic breast densities were compared over time and across sites. Patient characteristics were evaluated using Wilcoxon test and Pearson’s chi-squared test. Multivariable logistic regression models evaluated the odds of a dense breast classification as a function of time period (pre-DL vs post-DL), race (White vs non-White) and site. Results: A total of 85,865 consecutive screening mammograms across the three clinical sites were identified. After controlling for age and race, adjusted odds ratios (aOR) of a mammogram being classified as dense at Site C compared to Site B before the DL model was implemented was 2.01 (95% CI 1.873, 2.157, p<0.001). This increased to 2.827 (95% CI 2.636, 3.032, p< 0.001) after DL implementation. The aOR of a mammogram being classified as dense at Site A after implementation compared to before implementation was 0.924 (95% CI 0.885, 0.964, p<0.001). Conclusions: Our findings suggest implementation of the DL model influences radiologist’s prospective density assessments in routine clinical practice by reducing the odds of a screening exam being categorized as dense. As a result, clinical use of our model could reduce downstream costs of supplemental screening tests and limit unnecessary high-risk clinic evaluations.[Table: see text]
Disparities in government and nonprofit organization funding may hinder clinical trial development for underfunded cancers.
Authors: Kamath Suneel Deepak
Published: June 2021

1573

Background: National Cancer Institute (NCI) and nonprofit organization (NPO) funding is critical for research and advocacy, but may not be equitable across cancers. This could negatively impact clinical trial development for underfunded cancers. Methods: This study evaluated funding from the NCI and NPOs with > $5 million in annual revenue supporting leukemia, lymphoma, melanoma, lung, breast, colorectal, pancreatic, hepatobiliary, prostate, ovarian, cervical and endometrial cancers from 2015-2018 based on publically available reports and tax records. The primary objectives were to assess for disparities in NCI and NPO funding across different cancers compared to their median incidence and mortality from 2015-2018, and to determine if underfunding correlates with fewer clinical trials found in clinicaltrials.gov. Correlations between combined NCI and NPO funding for each cancer and its incidence, mortality and number of clinical trials were evaluated using descriptive statistics and Pearson correlation coefficients. Results: Diseases with the largest combined NCI+NPO funding were breast ($3.75 billion), leukemia ($1.99 billion) and lung cancer ($1.56 billion). Those with the least funding were endometrial ($94 million), cervical ($292 million), and hepatobiliary cancers ($348 million). These data are summarized in the Table. Disease-specific NCI+NPO funding correlated well with incidence, but less so with mortality (Pearson correlation coefficients: 0.74 and 0.63, respectively). Disease-specific NPO funding correlated moderately well with incidence, but was poorly correlated with mortality (Pearson correlation coefficients: 0.54 and 0.39, respectively). Breast cancer, leukemia and lymphoma were consistently well-funded compared to their incidence and mortality, while colorectal, lung, hepatobiliary and uterine cancers were consistently underfunded. The amount of NCI funding, NPO funding and combined NCI+NPO funding for a particular cancer each correlated strongly with the number of clinical trials for that disease (Pearson correlation coefficients: 0.88, 0.87 and 0.91, respectively). Conclusions: Many cancers with high incidence and mortality are underfunded. Cancers with higher mortality rates receive less funding, particularly from NPOs. Underfunding strongly correlates with fewer clinical trials, which could impede future advances in underfunded cancers.[Table: see text]
Time intervals between U.S. Food and Drug Administration (FDA) and European Medicines Agency (EMA) new cancer therapy approvals.
Authors: Lythgoe Mark , Krell Jonathan , Warner Jeremy Lyle , Desai Aakash , Khaki Ali Raza
Published: June 2021

1575

Background: Novel therapies are transforming cancer care. Regulatory review and approval are essential to deliver safe and efficacious innovations to patients. Studies prior to 2010 describe quicker approval decisions for new oncology drug registrations with the FDA compared to the EMA (median delay 238 days). Both regulatory agencies have subsequently improved procedures to expedite approval times. We compared regulatory market authorisation dates at the FDA and EMA for new oncology therapies from 2010-2020. Methods: New oncology therapeutic approvals between 2010-2020 were identified from the FDA and EMA regulatory databases. We analysed only initial approvals (not supplementary licenses) for active anti-cancer therapies (excluding biosimilars and supportive drugs). The delay in regulatory approval between the FDA and EMA was calculated in calendar days. We further analysed therapies by therapeutic class, evaluating for significant differences. Results: We identified 108 new therapy registrations during the study period. 104 (96.3%) therapies were approved by the FDA and 90 (83.3%) had EMA market authorisation. 4 (3.7%) drugs were not FDA registered, including 3 unsuccessful applications and 1 which sought licensing in a different indication. 18 (16.5%) drugs were not EMA registered, including 9 (8.8%) which did not pursue EMA licensing, 3 (2.9%) withdrawn licensing applications, 3 (2.9%) sought licensing in different tumour group/indication, 1 (0.9%) rejected application and 2 (1.9%) with applications under review at submission date. Of the 86 drugs approved by both agencies, 80 were approved first by the FDA and 6 by the EMA. The median delay in approval between the FDA and EMA was 227 days (IQR:124-354 days). Table shows approvals by therapeutic class. The shortest median time difference for approval was for monoclonal antibodies (171 days) with the longest for kinase inhibitors (281 days). Conclusions: This study shows more new oncology therapies are approved by the FDA than the EMA. Patients in the US typically have access to approved therapies earlier than in Europe. From 2010 to 2020 the median delay between FDA and EMA approval was 227 days, falling by 11 days compared to 2003-10, [non-statistically significant]. Such lengthy delays could exceed the life expectancy of many patients with advanced cancer. Innovations for accelerated approval at both the FDA (e.g. Project Orbis) and EMA (e.g., PRIME) have potential to lead to faster approval.[Table: see text]