bluuebunny/crossref_metadata_2025 huggingface dataset:
Novel immunotherapy combinations for betel-nuts related HNSCC: One institutional experience in Taiwan.
Authors: Chen Jo-Pai , Lu Wei-Chen , Hong Ruey-Long , Kuo Sung-Hsin
Published: May 2020

e18502

Background: The treatment of HNSCC in Taiwan is still very challenging. Betel nut chewing might contribute to (1)strong invasion; (2)easy recurrence; (3)poor response to traditional therapies. In our retrospective analysis for 75 patients receiving front-line EPF, patients, with rapid progression within 3 months after previous CCRT, had significantly worse survival with only 2.6 months; however, the survival increased significantly to 7.5 months in the same population if under later-line immunotherapy. Methods: From 2016 to early 2020, 46 R/M HNSCC patients receiving immunotherapy-containing regimens in Yun-lin Branch of National Taiwan University Hospital were reviewed. Results: These patients consisted of 2 HPV and 44 non-HPV; 24 pembrolizumab and 22 nivolumab; 18 with afatinib(11 pembrolizumab & 7 nivolumab); 7 with bevacizumab; 9 with chemotherapy. The objective response rate was 48%(22/46) and clinical benefit was 80%(37/46). 20 patients were still under use(8 afatinib with pembrolizumab; 4 afatinib with nivolumab). 1 patient under afatinib and pembrolizumab had hyperprogression but then got pCR after bevacizumab & strong CT. 1 patient had rapid skin metastasis over previous radiation fields after pembrolizumab, bevacizumab, and CT. 5 patients under afatinib & pembrolizumab developed autoimmune cholestasis(3 also with pneumonitis). Afatinib with nivolumab had similar efficacy but less toxicity. 18 patients receiving afatinib combined with anti-PD1(11 failing EPF, 14 with pleural/pericardial/skin metastases, 13 rapid progression within 3 months after CCRT) had 67% response rate(12/18) and 89% clinical benefit(16/18). 11 patients under afatinib & anti-PD1, who had failed EPF, had the response rate in 55%(6/11). 7 patients under front-line afatinib & anti-PD1 had the response rate in 86%(6/7). Post-progression use of anti-PD1 with other treatments were seen in 12 patients(esp. 1 with nivolumab & ipilimumab; 3 with Avastin, taxane, cisplatin). 7 patients got benefits and had longer survivals. Conclusions: Novel immunotherapy-containing combinations are of clinical significance in refractory betel-nuts related HNSCC in Taiwan. Afatinib has several immuno-modulatory effects in high risk patients(pleural/pericardial/skin metastases failing EPF, rapid progression within 3 months after definite CCRT). Afatinib with anti-PD1 may be a good option to avoid hyperprogression for more immunotherapy efficacy. Adding on CTLA4 blockage to previous afatinib/anti-PD1 after progression seemed potential for further studies.
End-of-life health care utilization (EOLHCU) in patients with recurrent, metastatic head and neck squamous cell carcinoma (RMHNSCC) treated with immune checkpoint inhibitors (IO).
Authors: Chalker Cameron , Santana-Davila Rafael , Voutsinas Jenna M. , Wu Vicky , Hwang Victoria , Baik Christina S , Barber Brittany , Futran Neal D. , Houlton Jeffrey , Laramore George E , Lee Sylvia , Liao Jay Justin , Parvathaneni Upendra , Martins Renato G. , Eaton Keith D. , Rodriguez Cristina P.
Published: May 2020

e18516

Background: Demographic and EOLHCU trends are undefined in the growing population of IO-treated RMHNSCC; we sought to study these in a single institution retrospective study. Methods: We identified 228 RMHNSCC pts who received ≥1 IO dose between 01/2013 and 12/2018; of these, 74 were deceased with accessible EOLHCU data such as advanced care plan documentation (ACPD) or evidence of systemic therapy or ER/hospital/ICU admission within 30 days of death (DOD). Demographic, tumor and treatment data were obtained. Overall survival (OS) was estimated using the Kaplan Meier method; multivariable analysis was performed using a Cox proportional hazards model. In an exploratory analysis, EOLHCU was compared to a cohort of 379 deceased thoracic malignancy (TM) pts using a chi-square test. This project was approved by our institutional IRB. Results: Median pt age was 62 (25 – 90). Most were male (56, 75%), white (60, 81%), current/former smokers (46, 62%); 34 (46%) smoked ≥10 pack years. Common primary sites included the oral cavity (28, 37.8%) and oropharynx (24, 32.4%). ECOG PS at IO initiation was 0 in 15 pts (20%,) 1 in 37 (50%), 2 in 20 (27%), 3 in 1 (1%), and unknown in 1 (1%). Of the 42 (57%) treated off-trial, 18 (42%) had an ECOG ≥ 2. 71 (95%) had prior curative intent therapy. 42 (57%) had distant metastases. Compared to TM, IO-treated RMHNSCC pts were more likely to have ACPD (66% vs. 45% p < 0.01), an ED visit (42.3% vs 19.5%, p < 0.01) and/or a hospital admission (42.3% vs 17%, p < 0.01) within 30 DOD. There was no difference in ICU admissions within 30 DOD (9.9% vs. 8.2%, p = 0.81), ICU deaths (7% vs. 4%, p = 0.4), or systemic therapy within 7 (4.2% vs. 2.4%, p = 0.63), 14 (8.5% vs. 6.6%, p = 0.76) or 30 (25% vs 19%, p = 0.31) DOD. Among IO-treated RMHNSCC pts, multivariable analysis revealed inferior OS with worse PS (ECOG 2-3 vs. 0: HR = 7.76, p = 0.00002, 95% CI = 3.07 - 19.64; ECOG 1 vs. 0: HR = 2.97, p = 0.008, CI = 1.33 - 6.62). OS also decreased with smoking status (current/former vs. never: HR 2.18, p = 0.007, CI = 1.24-3.84). No association was observed between ECOG PS, age or smoking status at IO initiation and any EOLHCU metric. Conclusions: At our center, a significant proportion of deceased, IO-treated RMHNSCC pts had an ECOG PS ≥ 2 and an inferior OS compared to ECOG 0/1. Exploratory comparison with a non-RMHNSCC TM cohort suggests high rates of EOLHCU within 30 DOD despite ACPD, representing an opportunity for supportive care augmentation. Whether EOLHCU differs among IO vs non-IO treated RMHNSCC is unknown and merits further study.
Impact of failure to thrive on inpatient mortality and resource utilization in patients with head and neck cancer: A nationwide analysis.
Authors: Baral Binav , Lingamaneni Prasanth , Rosen Fred R. , Shrivastava Trilok , Moturi Krishna Rekha , Vohra Ishaan , Farooq Muhammad Zain
Published: May 2020

e18531

Background: Failure to thrive (FTT), encompassing malnutrition and cachexia, is a common comorbidity afflicting Head and Neck cancer (HNC), brought about either by progression of disease or complications of treatment. FTT can exacerbate infections or cytopenias and delay wound healing, and has shown to affect survival in HNC. This study aims to explore the effects of FTT on mortality and resource utilization among hospitalized patients with HNC. Methods: Adult patients with HNC admitted from 2012-2017 were identified from the Nationwide Inpatient Sample database. Temporal trends of resource utilization across six years were evaluated. Multivariable logistic regression was used to evaluate risk factors for malnutrition and mortality in patients with HNC. Results: A total of 448,255 patients met inclusion criteria, of which 27.2% had FTT. Mean age was 66.3 years. Patients were predominantly male (71.8%) and white (70.4%). Patients with FTT had higher mortality (6.3% vs. 3.6%, p<0.0001), longer hospital stay (9.1 vs. 5.7 days, p<0.0001) and higher hospital charges ($23k vs. $18k, p<0.0001). On multivariate analysis, risk factors for FTT included male sex, African American (AA) race and higher comorbidity burden. After adjusting for confounders, patients with FTT had higher inpatient mortality (OR 1.71, 95% CI 1.60-1.83, p<0.001). There is an increasing trend of FTT in HNC over the years, from 22.7% to 32.6% (p trend <0.001). Temporal trends in mortality, length of stay and hospital charges in those with FTT did not change significantly. Conclusions: Patients with HNC and FTT had higher inpatient mortality than those without FTT. AA patients especially were at higher risk of FTT. Inpatients with HNC and FTT had longer mean hospital stay by 3 days incurring higher healthcare costs. The study highlights an under acknowledged paradigm in HNC care and warrants further steps towards more vigilant nutritional surveillance and interventions, such as early/prophylactic enteral feeding in HNC patients. This could greatly improve quality of life and objective outcomes in HNC patients. [Table: see text]
Predictive scoring systems for distant metastases in oral cavity squamous cell carcinoma.
Authors: LU Hsueh Ju , Lai Kuan-Ming , Peng Chih-Yu , Tseng Hsien-Chun , Hsin Chung-Han , Huang Wei-Shiou , Lan Wen-San , Yang Sung-Fa
Published: May 2020

e18536

Background: At least 10% of patients with oral cavity squamous cell carcinoma (OCSCC) would progress to distant metastases (DM). Median overall survival (OS) after distant metastases is only one year and rare biomarkers are available to predict distant metastatic events. Methods: A total of 595 OCSCC patients who underwent curative surgical resection at Chung Shan Medical University Hospital were enrolled from Jan 2010 to Dec 2016. The clinical–pathological variables were compared using the χ2 test. Cox proportional-hazards analyses were performed for distant metastatic free survival (DMFS), defined from the date of initial diagnosis to the date of distant metastasis. Two scoring systems for predicting distant metastases were established for patients with pathologic regional lymph node –positive (pN+) or –negative (pN–), separately. Results: Nearly 10% (8.9%, 53/595) of patients with OCSCC would progress to DM during follow-up [20.6% (28/136) and 5.4% (25/459) for patients with pN+ and pN–, respectively]. Most of the distant metastatic lesions developed within 3 years after initial diagnosis (overall, 84.9%, 45/53; patients with pN+, 92.9%, 26/28; patients with pN–, 76.0%, 19/25). For patients with pN+, rapidly locoregional recurrence (≦6 months), lymphovascular invasion, and lymphocyte-monocyte ratio(<2.5) were the independent factors for DMFS. In addition, rapidly locoregional recurrence, elderly (age > 65), and close surgical margin(≦5mm) were independent for those with pN–. If each of the independent factors was scored one point to predict DM occurring within 3 years after the initial diagnosis, two scoring systems were established for the corresponding patients with pN+ or pN–, separately. The area under the curves of these two scoring systems for the corresponding patients with pN+ and pN– were 0.737 and 0.825, respectively (Table). Conclusions: The established scoring systems effectively predict distant metastases for OCSCC patients. [Table: see text]
Prevention of cisplatin nephrotoxicity (CN) in head and neck cancer patients receiving concurrent chemoradiation (CCRT) by adding oral rehydration solution (ORS) to short hydration regimen: A randomized open-label controlled trial.
Authors: Maisrikrod Aungsumal , Sakdejayont Siwat , Rongmuang Jakkapan , Sathitruangsak Chirawadee , Sunpaweravong Patrapim , Dechaphunkul Arunee
Published: May 2020

e18560

Background: CN remains a frequent occurrence despite receiving standard fluid hydration, particularly for head and neck cancer patients undergoing CCRT. We aimed to investigate whether adding ORS to short hydration regimen can reduce CN. Methods: We conducted a randomized open-label controlled trial in patients with head and neck cancer receiving CCRT with 3-weekly cisplatin (≥ 60 mg/m²). Eligible patients were randomly assigned to receive short hydration regimen (2000 mL of normal saline on day 1) alone or in combination with 2000 mL of ORS on days -1, 2 and 3 of each cycle. All patients were instructed to drink at least 2000 mL of fluid. The primary end point was the incidence of ≥ gr 1 creatinine (Cr) elevation on day 8. The planned sample size was 160 (80 patients each arm). Results: Thirty-five patients in ORS group and 34 patients in control group (43% of planned sample size) were enrolled. Baseline characteristics were balanced between the two groups, except more patients in ORS group underwent surgery (35.3% vs. 22.9%), and had less feeding tube prophylaxis (76.5% vs. 88.6%), although there were not statistically significant. The mean dose of cisplatin on day 1 was significantly higher in ORS group (91.2 mg/m2 vs. 85.1 mg/m2, p=0.01). There was no difference of volume of total fluid intake and toxicities between the two groups. Less percentage of patients in ORS group developed ≥ gr 1 Cr elevation as shown in the Table, although there were not statistically significant. Conclusions: Although our interim analysis showed no significant difference of CN between the groups, there was a trend that addition of ORS might prevent acute and chronic kidney injury secondary to cisplatin. The completed enrollment is warranted to confirm this early findings. Clinical trial information: TCTR20200207005 . [Table: see text]
Early mortality in children with cancer in the National Institution of Pediatrics, Mexico.
Authors: Diaz Ramirez Karla , Zapata Tarres Marta
Published: May 2020

e19004

Background: Children cancer represents the first cause of mortality by disease worldwide. Early mortality is defined as death within the first four weeks since the patient’s admission to the hospital, and it is an indicator to evaluate attention quality. It is considered that early mortality rate must be less than 5% in acute lymphoblastic leukemias, although it is not standardized in solid tumors. The aim of this study was to evaluate the early mortality rate in a third level pediatric center. Methods: We have conducted a retrospective analysis of oncology patient records dating from January 2012 to April 2017 diagnosed and treated in the National Institute of Pediatrics in Mexico. Patients who died in the first four weeks from diagnosis were included in our study. Clinical characteristics were analyzed with an univariate analyses using measures of central tendency for quantitative data and proportions for qualitative. We used SPSS-20 for all analyses. Results: A total of 1500 patients were diagnosed with neoplastic disease at the Institute within 2012 and 2017, 34 (2.26%) of them had an early death. Median age of diagnosis was 5 years. Central nervous system (CNS) tumors were the predominant group associated to early mortality (23.5%), followed by hepatocarcinoma, acute lymphoblastic leukemia (ALL), neuroblastoma, diffuse intrinsic pontine glioma (DIPG), and Wilms tumor (5.9% each). 70.6% had metastatic disease at diagnosis. Main cause of death was progression of disease (60%), followed by infectious complications (35%). Only one patient was treated by palliative care. Conclusions: In spite of children cancer care innovations, early death rates are still high, mainly because of delay in diagnosis at advanced stages of the disease. Another important factor in low-middle income countries is treatment abandonment, which is higher in patients who live in precarious conditions and live in isolated communities and must travel long distances to get medical attention. As healthcare professionals from a low-middle income country, we still have a lot to do to prevent our patients early mortality.
"Does better understanding of cancer care needs impact outcomes...?" The experiences of the Kigali City Cancer Challenge innovation.
Authors: Ntizimira Christian Ruchaho
Published: May 2020

e19016

Background: Launched in January 2017 at the World Economic Forum in Davos, Switzerland, City Cancer Challenge (C/Can) is a multisectoral initiative supporting cities to take the lead in the design, planning, and implementation of cancer treatment solutions. C/Can serves as a unique platform to increase the number of people with access to quality cancer care in cities through a truly multisectoral approach. With access to both technical and financial resources, cities are supported to strengthen their capacity, leadership, and accountability in the delivery of cancer care, and engage in the design and implementation of cancer treatment and care solutions that meet the needs of their population. In 2018 during the World Health Assembly, the City of Kigali has been selected as the first African City Cancer Challenge alongside with Porto-Alegre from Brazil. Methods: The Needs Assessment questionnaire was designed to provide in-depth information on the delivery of cancer treatment and care services in a city. The objective is to generate systematic and reliable data on the availability. Results: Conclusions: The Kigali C/Can has developed an innovative solution from adapted from Rwandan patients, by Rwandan patients and for Rwandan patients through a city process which include a multi-sectorial decision-makers that was not happened before. [Table: see text]
Medicare compared with private insurance for the treatment of cancer.
Authors: Martinez-Knouse Phillip , Hancock Christie , Nabrinsky Edward , Lestingi Timothy M. , Bitran Jacob D.
Published: May 2020

e19033

Background: Insurance status impacts access to cancer care and outcomes of cancer patients. Patients who are uninsured and those who are insured by Medicaid are less likely to receive cancer screening, more likely to present at later stages of disease, and more likely to die from cancer compared to those who are privately insured. It is unclear whether patients insured by Medicare have different outcomes than patients with private insurance. Methods: We undertook a retrospective analysis of patients treated in our practice from January 1, 2019 to March 31, 2019. Outcomes of solid tumor patients were tracked after treatment in the neoadjuvant or metastatic setting. Patients were stratified by their insurance status and we then compared treatment outcomes of patients with private insurance to those with Medicare. Results: We treated 86 patients from January 1, 2019 to March 31, 2019 including 63 women and 23 men with a median age of 62 years (range 22-88 years). Several types of malignancies were represented including 21 gynecologic cancers, 17 breast cancers, 11 lung cancers, 10 melanomas, 10 gastrointenstinal cancers, 7 lymphomas, 5 genitourinary cancers, and 5 other tumor types. Among our population, 48 patients had private insurance and 38 had Medicare. Thirty-four patients achieved either a complete response (CR) or partial response (PR), 24 with CR and 10 with PR. Of those who achieved a CR, 11 had Medicare and 14 had private insurance. Among those who achieved a PR, 5 had Medicare and 5 had private insurance. Conclusions: In this retrospective analysis, insurance type did not predict likelihood of achieving a complete or partial response to treatment. Other investigators have suggested that patients with Medicare have poorer outcomes than those with private insurance. One potential explanation for the discrepancy between their data and ours is that we have dedicated system designed to accelerate pre-certifications. Additional investigation is warranted to better understand these trends.
Multiple myeloma (MM) therapy within a Medicare insured patient population: Role of initial care setting and socioeconomic status.
Authors: Davidoff Amy J. , Long Jessica B. , Bewersdorf Jan Philipp , Shallis Rory , Zeidan Amer Methqal , Podoltsev Nikolai Alexandrovich , Wang Rong , Gore Steven , Giri Smith , Neparidze Natalia , Huntington Scott F.
Published: May 2020

e19057

Background: Approval of MM therapies including immunomodulatory agents (IMiDs), and proteasome inhibitors (PIs), coupled with increasing evidence supporting PI-IMiD combinations, maintenance (MT), and autologous stem cell transplant (ASCT) among fit patients, have expanded options, complexity and duration of active therapy. Prior research reported race disparities in initial therapy receipt and survival differences based on provider characteristics. It is unknown whether these effects extend to longer-term management. Methods: We selected adults with MM diagnosis (dx) between 07/07-12/15 from the SEER-Medicare linked database. We required continuous Medicare Parts A, B, and D enrollment and no HMO/PPO coverage from 12 months prior to dx through death or end of study (12/16) and MM therapy initiation w/in 12 months post dx. Outcomes including line of therapy (LOT) 1 PI-IMiD combination, LOT1 length, ASCT, MT, any LOT2, and any LOT4, were constructed using claims indicators for oral and IV drugs and receipt dates. Initial provider setting was assigned as academic &/or NCI cancer center, non-teaching hospital, or community (non-hospital) based on 1st oncologist E & M visit w/in 2 months pre- or post-MM dx. We also examined race (white, black, other), Hispanic ethnicity, Part D Low Income Subsidy (LIS) receipt and linked area poverty rate. Multivariable logistic and Cox proportional hazard regressions controlled for demographics, health status, and diagnosis year. Results: The cohort (n = 5678) was 51% male, 14% Black, and 51% age ≥75 years. Initial care setting was 50% academic/NCI, 32% non-teaching hospital, and 19% community; 22%, 53%, and 19% received LOT1 PI-IMiD, LOT 2, and LOT 4, respectively. Median LOT1 length was 165 days. Relative to academic/NCI, community care was associated with lower adjusted odds of all outcomes (e.g. LOT2, aOR: .56, 95% confidence interval (CI) .48 -.65, p < .001; LOT4, aOR: .74, 95% CI .58-.95, p = .02) except LOT1 PI-IMiD. Care at non-teaching hospitals was associated with reduced odds of LOT2. Part D LIS was associated with lower odds of LOT1 PI-IMiD, while increasing % poverty was associated with lower odds of LOT1 PI-IMiD combinations, LOT1 ASCT, LOT2 and LOT4. No associations were observed with race or ethnicity and any outcome. Conclusions: In Medicare insured adults treated for MM, initial care in a community setting was associated with shorter and less complex therapy. Socioeconomic status (Part D LIS, area poverty rates), but not race or ethnicity, was a consistent predictor of MM treatment.
Breast cancer receptor subtypes in East Africa: A systematic review and meta-analysis.
Authors: Popli Pallvi , Gutterman Elane M , Omene Coral Oghenerukevwe , Ganesan Shridar , Marlink Richard
Published: May 2020

e19074

Background: Estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) are determinants of both treatment and mortality for patients with breast cancer (BC). With a mortality to incidence ratio of 0.51, mortality rates for breast cancer in East Africa are among the world’s highest. Building on a meta-analysis of BC receptor subtypes in sub-Saharan Africa (2014) and including all recently available PubMed literature, our meta-analysis aims to investigate the differences among receptor subtype distribution in five East African countries. Methods: Receptor distributions for female samples >30 in all BC articles for Ethiopia, Kenya, Rwanda, Tanzania and Uganda were obtained from PubMed, January 1, 1998 - June 30, 2019. Outcomes were proportions of ER+, PR+, and HER2+ and/or molecular subtypes. Data included study characteristics and mean/median patient age (weighted by observations). Using metaprop for STATA 16, we estimated pooled proportions (ES) with 95% confidence intervals (CI) and assessed I2 statistics for heterogeneity across studies. Results: Among 35 BC studies with receptor data, 21 met criteria. Overall, the weighted mean age was 47.5 years (SD 3.2) and median, 48. For ER+ (18 studies/n=2,875), the overall ES was 0.55 (95% CI 0.47, 0.62), I2 of 94.4%, p<0.001, ranging from 0.62 in Ethiopia (95% CI 0.52, 0.72) to 0.42 in Uganda (95%0.36, 0.49). For HER2+ (18 studies/n=2,689), the overall ES was 0.23 (95% CI 0.20, 0.26), I2 of 70.2%, p<0.001, and ranged from 0.27 in Ethiopia (95% CI 0.18, 0.36) to 0.21 in both Tanzania and Uganda (95% CI 0.13/0.14, 0.28). For triple negative (TN, 15 studies/n=2,510), the overall ES was 0.28 (95% CI 0.23, 0.32), I2 of 84.0%, p<0.001, varying from 0.21 in Ethiopia (95% CI 0.15, 0.27) to 0.46 in Tanzania (95% CI 0.32, 0.60). Conclusions: We found differences between countries, e.g. lower distribution of TN in Ethiopia (21%) compared to Uganda (35%) and Tanzania (46%), and high between-study heterogeneity. Consistent with former studies, ER+, 55%, was the dominant subtype, particularly in Ethiopia, Kenya and Rwanda, indicating the need to prioritize hormonal treatment. Overall rates of HER2 subtype, 23%, approached overall rates of TN, 28%, yet HER2 testing is often not performed due to the cost and unavailability of anti-HER2 therapy, hence this subtype often goes untreated. These findings highlight the benefit of testing and reporting of receptor subtypes at the country level to promote delivery of more effective treatment to reduce the mortality disparity.
Forecasting global essential childhood cancer drug need and cost: An innovative model-based approach.
Authors: Denburg Avram , Empringham Brianna , Hughes Terence , Wagner Anita K. , Ward Zachary J. , Yeh Jennifer , Gupta Sumit , Frazier A. Lindsay
Published: May 2020

e19078

Background: Childhood cancer outcomes in low-middle income countries (LMICs) have not kept pace with advances in care and survival in high income countries (HICs). A contributing factor to this survival gap is unreliable access to essential cancer drugs. Lack of data on the aggregate need and cost of essential cancer drugs has hampered rational planning and acquisition in many LMICs. Methods: We created a pediatric-specific tool (FORxECAST) that estimates drug quantity and cost for 18 pediatric cancers, customizable to region, regimen, cancer stage distribution, and drug price. We used adapted treatment regimens developed by the International Society of Pediatric Oncology (SIOP), supplemented with input from disease experts, to model treatment approaches reflective of health-system capabilities. FORxECAST incorporates incidence data generated through microsimulation estimates of both diagnosed and undiagnosed (total) cases. Results: We created a pediatric-specific tool (FORxECAST) that estimates drug quantity and cost for 18 pediatric cancers, customizable to region, regimen, cancer stage distribution, and drug price. We used adapted treatment regimens developed by the International Society of Pediatric Oncology (SIOP), supplemented with input from disease experts, to model treatment approaches reflective of health-system capabilities. FORxECAST incorporates incidence data generated through microsimulation estimates of both diagnosed and undiagnosed (total) cases. Conclusions: Our results enable evidence-based forecasting of childhood cancer drug need and cost to inform health system planning in a wide range of countries. The model is adaptable to setting, diagnosis, and treatment approach, allowing decision-makers to generate results specific to their context and needs. Global estimates of essential childhood cancer drug need and cost demonstrate the comparatively small amount of aggregate resources required to treat all cases worldwide, and can help advance innovative procurement strategies with regional and international scale that drive global improvements in childhood cancer drug access.
Distance from a comprehensive cancer center: A poor proxy for serous endometrial cancer outcomes?
Authors: Blackburn Patrick , Gordon Jennifer , Zhang Naixin , Daily Laura Becca , Tillmanns Todd D.
Published: May 2020

e19084

Background: To compare the relationship between outcomes in serous endometrial cancer patients based on distance from a tertiary referral center in the Southern US. Methods: A retrospective cohort study among all women diagnosed with serous endometrial cancer between 2009 to 2018 was completed at a tertiary referral center in a low socioeconomic Southern US city with a predominately African American population. The primary exposure variable was the distance traveled by the patient to the treatment center. This distance was calculated using Google Maps from the patients’ home addresses to the cancer center. Abstracted data from each patient included patient demographics of home address, BMI at time of first visit, race, transportation method to the cancer center, and presence of primary care provider (PCP). Clinical variables of stage at diagnosis and pathology, treatment, and outcomes were included. Chi square analysis and log-rank analysis were completed. Data was analyzed by SPSS software. Results: In total, 202 patients were living a median distance of 31.4miles (range of 0.9mi to 194mi) from the cancer center. Of this cohort, the median age at time of diagnosis was 67 years old with a median BMI of 31.4kg/m2. The most common stage at diagnosis was stage 1A (26.7%). Using log rank analysis, there was no difference in overall survival when compared based on age, race, BMI and access to transportation. 92% (n=185) of the cohort had immediate access to a transportation method via personal car or family car, the remaining patients relied on other methods of transport. The total distance from treatment center was significant when compared with stage at diagnosis (p=0.011) portending greater stage at diagnosis with further distance. However, this did not correlate to progression free or overall survival (p = 0.83) in the cohort. Patients with a PCP were likely to be diagnosed at an earlier stage (Stage IA or Stage IB) compared to those without a PCP with a p=0.003, mean of 0.93, 95% CI (0.89 – 0.97). Conclusions: Living closer to a cancer center and having a PCP were associated with earlier stage at diagnosis in patients with serous endometrial cancer. Distance from the cancer center did not affect overall survival when adequate transportation methods were available.
Dynamic of time estimation and its relation with levels of distress.
Authors: Conev Nikolay Vladimirov , Ivanova Martina , Dimitrova Eleonora , Yanchev Asen , Donev Ivan
Published: May 2020

e19091

Background: Our previous study showed a potential relationship between perception of time and level of distress in cancer patients prior to starting chemotherapy. In this study we explored the dynamics of time estimation and the level of distress in cancer patients. Methods: Time estimation and distress were assessed in 262 chemonaïve patients with solid tumors by evaluating each subject’s prospective estimation of how fast one minute passed compared to the actual amount of time passed. The National Comprehensive Cancer Network Distress Thermometer was used at the beginning of the treatment to evaluate the levels of distress. Patients scoring 4 or above were regarded as having high levels of distress. The median value of time estimation was used to stratify the patients into two categories of fast and slow time estimation. After 3 months of treatment time estimation and levels of distress were reevaluated. Results: In total, 125 (response rate 47.7%) patients wanted to be reassessed for the distress level and time estimation. After 3 months of treatment 84 (67.2%) of the patients had not changed their levels of distress, 24 (19.2%) of the patients had low levels of distress, while 17 (13.6%) had high levels distressed. Wilcoxon test did not show a significant change of time estimation and levels of distress before and after 3 months of treatment. We observed a negative weak but significant correlation between the change of distress and change of time estimation (rho = -0.186; p = 0.038). The pattern of the change of time estimation distributions significantly changed according to the reported distress levels at 3rd month. Patients with a fast time estimation at 3rd month had significantly higher levels of distress (4.2±2.6) than patients with a slow time estimation (2.8±2.6). ROC analysis revealed that at the optimal cut-off value of time estimation at 3rd month, high levels of distress can be discriminated with an AUC = 0.64 (95% CI: 0.54-0.73, p = 0.008), a sensitivity of 63.1% and a specificity of 60.1%. Conclusions: Time estimation and its dynamic is a novel potent indicator for high distress in cancer patients.
Prognostic impact of hepatic involvement on spontaneous tumor lysis syndrome in solid tumors.
Authors: Verghese Dhiran , Myint Phyo Thazin , Ali Faisal S. , Sundararajan Nivedita , Gong Zimu , Kozma Kelley Elizabeth
Published: May 2020

e19098

Background: Tumor lysis syndrome (TLS) is a life-threatening oncological emergency. Spontaneous TLS (STLS) in solid tumors occurring prior to initiation of therapy is a rarely reported entity and has poor outcomes. Little is known about the prognostic factors influencing STLS in solid tumors. Methods: A systematic search of Medline, PubMed, and Embase was conducted to identify reports of patients ≥18 years diagnosed with STLS in solid tumors. Individual case reports and case series were summarized, and descriptive statistics were employed to report clinical outcomes. Fischer exact t test was used for statistical analysis. Results: 63 patients from 61 case reports and one patient from our institution resulted in a total of 64 patients. 53.1% were males with a median age of 56.1 years. The most common solid tumors were of pulmonary origin. 85.9% patients had stage 4 malignancy, 75.0% had hepatic involvement. The most common presenting symptom was abdominal discomfort. The mean serum potassium, phosphorus, uric acid, calcium, lactate dehydrogenase, and creatinine upon presentation were 6.1 mmol/l, 7.5 mg/dl, 16.4 mg/dl, 7.5 mg/dl, 4421.2 IU/L and 3.7 mg/dl, respectively. In addition to intravenous hydration, allopurinol and rasburicase were administered in 48.4% and 42.2% patients. Urinary alkalization and sodium bicarbonate administration were reported in 6.3% and 15.6% patients. 43.8% patients required hemodialysis and 39 patients died (mortality of 60.9%). Patients who underwent hemodialysis had a similar mortality of 60.4%. We assessed liver involvement (primary hepatocellular carcinoma and hepatic metastasis) as a potential prognostic factor. Compared to patients without liver involvement, patients with liver involvement had a higher unadjusted all-cause mortality (70.83% vs 25%; OR 7.29 [95% CI 1.71 - 30.98]; p = 0.006). Conclusions: Hepatic involvement is a potential prognostic factor for STLS in solid tumors and is associated with a grave prognosis. Future large prospective studies are needed to probe into the role of early hemodialysis and to identify other prognostic factors of STLS in solid tumors.
Timing of assessments for PRO measures in advanced RCC clinical trials.
Authors: Agrawal Sundeep , Cheng Joyce , Bhatnagar Vishal , King-Kallimanis Bellinda , Pazdur Richard , Kluetz Paul Gustav
Published: May 2020

e19101

Background: Efficient and thoughtful collection of PROs in randomized cancer trials is necessary, especially when comparing drugs with differing administration schedules. Assessment timing for PROs can dramatically influence results. We sought to better understand how different assessment schedules affect interpretation of toxicity using PRO data. Methods: We reviewed 3 randomized trials in advanced/metastatic RCC with a control arm of sunitinib administered 4 weeks on/2 weeks off. All 3 trials used FACT Kidney Symptom Index (FKSI-19 or -DRS) and one also used EORTC QLQ-C30. For each trial, we chose patient-reported diarrhea and bone pain due to their strong association with the therapeutic intervention and the disease, respectively. Results: For the first 12 weeks, all trials had PRO assessments at baseline but had differing schedules thereafter. PRO assessment in Trial 1 was every 3 weeks; Trial 2: week 6 and week 12; Trial 3: every 3 weeks on the investigational arm and at weeks 4, 6, 10 and 12 on the sunitinib arm. Notably, all assessments for Trial 2 were after 2-week sunitinib washout while Trials 1 and 3 had assessments before and after washout. The table shows the percentage of patients who experienced any worsening from baseline in diarrhea and bone pain in the first 2 assessments. In each trial, more patients had worsening following periods of treatment versus washout on the sunitinib arm, with no such fluctuation on the non-sunitinib arms. The pattern was more apparent for diarrhea (treatment-related) than for bone pain (disease-related). Conclusions: Patients’ recall of symptoms may vary depending on the timing of PRO assessments in relation to drug administration and may be more prominent with respect to treatment-related symptoms, as disease-related symptoms are less impacted by drug toxicity and washout. Clinical protocols should carefully consider PRO assessment timing in relation to drug administration to improve interpretation of toxicity. Higher fidelity PRO data can be obtained with weekly collection of symptoms during the first few months of cancer clinical trials. [Table: see text]
Temporal trends in inpatient outcomes and resource utilization in patients with tumor lysis syndrome (TLS) with solid and hematologic cancers: A nationwide analysis.
Authors: Moturi Krishna Rekha , Lingamaneni Prasanth , Baral Binav , Vohra Ishaan , Banskota Shristi Upadhyay , Gupta Shweta
Published: May 2020

e19102

Background: Tumor lysis syndrome (TLS) is a well-recognized complication in cancer patients with high tumor burden receiving chemotherapy and is associated with increased morbidity and mortality. Our study specifically looks at longitudinal trends in outcomes and healthcare utilization in TLS patients over time. Methods: Adult patients with TLS admitted between 2012-2017 were identified from the Nationwide Inpatient Sample database. Statistical tests for trends of outcomes (including mortality and Acute Kidney Injury (AKI)) and resource utilization across six years were performed. Multivariable logistic regression was used to evaluate risk factors for mortality in TLS. Results: A total of 57,760 patients met inclusion criteria, with 15.2% having Solid Tumors (ST) and rest hematological cancers (HC). Patients with ST were predominantly older (mean age 60.7 vs 56.4 years, p < 0.0001) and female (44.6% vs 35.2%, p < 0.0001). ST patients had higher mortality (32.3% vs 19.1, p < 0.0001) and AKI (68.6% vs 59.3%, p < 0.0001); but shorter hospitals stay (10.5 vs 15.8 days, p < 0.0001) and lower hospital charges ($34k vs $59k, p < 0.0001). Multivariable analysis showed increased inpatient mortality with ST compared to HC (OR 1.54, 95% CI 1.35-1.76, p < 0.001). Although mortality in ST non-significantly decreased from 36.2% to 28.9% over time, it remained constant in HC. Rate of AKI increased significantly in both cohorts. There were no significant temporal changes in hospital charges in either group, although those with HC were noted to have a decrease in length of stay, from 16.8 to 15.6 days (p = 0.02) over time. Trends of outcomes and resource utilization in TLS. Conclusions: TLS in ST has worse prognosis than HC, although mortality has improved over years. However, inpatient mortality remains largely unchanged in HC. Despite therapeutic advances, [Table: see text]
Variations in objective knowledge among decision-support persons of patients with early stage breast cancer.
Authors: Wytiaz Victoria A , Veenstra Christine M , Hawley Sarah T.
Published: May 2020

e19110

Background: Patients with breast cancer face complex decisions regarding treatment options, and frequently involve family, friends, and other decision supporters in decision-making. A high-quality decision is one that is both informed and values-concordant. While much has been done to evaluate the quality of decision-making among patients, very little is known about how decision supporters fit within that framework. Thus, we sought to understand variations in objective knowledge among decision supporters. Methods: Patients with stage 0-II breast cancer reported to Georgia and LA SEER registries in 2014-15 and their key decision support person (DSP) were surveyed separately. DSPs were asked 4 objective knowledge questions regarding breast cancer treatment with responses dichotomized into high/low knowledge. Bivariate analyses and multivariable regression models were used to assess associations between DSP knowledge and important DSP characteristics (type of DSP, age, race, education), level of DSP engagement in 3 domains of patients’ decision-making (feeling informed about decisions, extent of and satisfaction with their involvement in decisions, and being aware of patients’ values/preferences), and patient clinical factors (stage, chemotherapy receipt, radiation receipt, type of surgery). Results: 2502 patients (68% RR) and 1203 eligible DSPs (70% RR) responded. Most DSPs were husbands or daughters. 21% were Latino, 17% were black, 20% had <high school education. Overall,53% DSPs had high objective knowledge. DSPs with high knowledge were more likely to be non-Black, non-Spanish-speaking Latinos, have a higher level of education, and report high engagement in the domains of satisfaction with their involvement in patients’ decision-making and awareness of patients’ values/preferences (all p < 0.05). After adjustment, high objective knowledge among DSPs was associated a higher level of education (OR = 2.44; 95% CI = 1.67-3.57) and high awareness of patients’ values/preferences (OR = 1.40; 95% CI = 1.06-1.84). Conclusions: Objective knowledge about breast cancer treatment was varied among DSPs of patients with breast cancer. Highly engaged DSPs (aware and satisfied) were more likely to have high knowledge, suggesting that involving DSPs may be an untapped mechanism for improving patients’ understanding of treatment options. These finding suggest that DSPs can play a role in improving decision quality in patients, and that interventions focused on decision-making may benefit from modules directed to DSPs as well as patients.
Missing data in breast cancer: Relationship with survival in national databases.
Authors: Plichta Jennifer Kay , Rushing Christel N. , Lewis Holly C. , Blazer Dan G. , Hyslop Terry , Greenup Rachel Adams
Published: May 2020

e19114

Background: National cancer registries are valuable tools used to analyze patterns of care and clinical oncology outcomes; yet, patients with missing data may impact the accuracy and generalizability of these data. We sought to evaluate the association between missing data and overall survival (OS). Methods: Using the NCDB and SEER, we compared data missingness among patients diagnosed with invasive breast cancer from 2010-2014. Key variables included: demographic variables (age, race, ethnicity, insurance, education, income), tumor variables (grade, ER, PR, HER2, TNM stage), and treatment variables (surgery in both databases; chemotherapy and radiation in NCDB). OS was compared between those with and without missing data via Cox proportional hazards models. Results: Overall, 775,996 patients in the NCDB and 263,016 in SEER were identified; missingness of at least 1 key variable was 29% and 13%, respectively. Of those, the majority were missing a tumor variable (NCDB 80%; SEER 88%), while demographic and treatment variables were missing less often. When compared to patients with complete data, missingness was associated with a greater risk of death; NCDB 17% vs. 14% (HR 1.23, 99% CI 1.21-1.25) and SEER 27% vs 14% (HR 2.11, 99% CI 2.05-2.18). Rate of death was similar whether the patient was missing 1 or ≥2 variables. When stratified by the type of missing variable, differences in OS between those with and without missing data in the NCDB were small. In SEER, reductions in OS were largest for those missing tumor variables (HR 2.26, 99% CI 2.19-2.33) or surgery data (HR 3.84, 99% CI 3.32-4.45). Among the tumor variables specifically, few clinically meaningful differences in OS were noted in the NCDB, while the most significant differences in SEER were noted in T and N stage (table). Conclusions: Missingness of select variables is associated with a worse OS and is not uncommon within large national cancer registries. Therefore, researchers must use caution when choosing inclusion/exclusion criteria for outcomes studies. Future research is needed to elucidate which patients are most often missing data and why OS differences are observed. [Table: see text]
Distribution and frequency of patient-reported symptomatic adverse events at a comprehensive cancer center.
Authors: Cleveland Jessica , Hassett Michael J. , Lee Sherry , Chua Isaac S. , Dominici Laura Stewart , Schrag Deborah , McCleary Nadine Jackson
Published: May 2020

e19117

Background: Systematic review of electronic patient reported outcomes (ePRO) has been shown to improve quality of life and overall survival in clinical trial. We previously demonstrated feasibility of ePRO across Dana-Farber Cancer Institute (DFCI). We sought to examine the distribution and frequency of first symptomatic adverse events (SAEs) among ePRO responders in ambulatory oncology practice. Methods: The ePRO tool uses the validated NCI developed Patient Reported Outcomes – Common Terminology Criteria for Adverse Events (PRO-CTCAE) instrument to assess attributes of 15 core SAEs (fatigue, insomnia, general pain, decreased appetite, nausea, vomiting, constipation, diarrhea, shortness of breath, numbness and tingling, rash, concentration, fever, anxiety, sadness) selected by clinician stakeholders and deployed via any internet-enabled device once every 7 days. Responses are viewable in the EHR, scored 0 to 3 using an algorithm, with scores of 3 highlighted to indicate severe grade SAEs. Results: We examined the distribution and frequency of the first 5183 unique ePRO reports for unselected patients seen in the medical, radiation and surgical oncology outpatient clinics of four pilot multidisciplinary clinics (Breast, Genitourinary, Gastrointestinal and Head and Neck) between September 2018-December 2019. Twenty one percent of eligible patients responded to ePRO (5183 of 26,084). Most respondents were female (59%), Caucasian (89%), and age 50-69 years (56% compared to 16% age <50 years, 28% age ≥70; range 19-98 years). The frequency of grade 3 SAEs was pain (10%), fatigue (6%), insomnia (4%), constipation (3%), numbness and tingling/concentration/anxiety/decreased appetite (2%), diarrhea/shortness of breath/sadness (1%), and rash/fever/nausea/vomiting (none) (Table). Conclusions: We observed a consistent distribution of SAEs across cancer types, age and sex. The most frequently reported SAEs are those clinicians struggle to treat with medications - pain, fatigue, insomnia and anxiety. Research to develop effective strategies to address this constellation of SAEs should be prioritized. [Table: see text]