bluuebunny/crossref_metadata_2025 huggingface dataset:
Characteristics of first relapse in stage III melanoma patients with no evidence of disease (NED): Guidelines for follow-up
Authors: Romano E. , Scordo M. , Chapman P.
Published: August 2020

9069

Background: Follow up (F/U) of patients (pts) with AJCC stage III melanoma but with NED is currently empiric with respect to frequency of clinical exams, F/U duration, and diagnostic tests. Data-based F/U guidelines are needed. Methods: Clinical records of 429 pts with stage III NED pts seen at MSKCC between 1998 and 2002 and who ultimately relapsed were reviewed retrospectively to evaluate: site and date of 1st relapse, interval between the stage III NED and 1st relapse; how the 1st relapse was detected, date of death or last F/U. We also determined the overall 5 yr relapse-free survival (RFS) of all stage III pts seen at MSKCC during this period. Results: The overall 5 yr RFS for stage IIIA, B, and C patients at MSKCC was: 52%, 29%, and 15%, respectively. Among the relapsing pts, 280 had adequate F/U to be evaluable for all parameters (35 stage IIIA, 155 stage IIIB, 90 stage IIIC). The site of 1st relapse was local/in-transit (28%), regional nodal (20%), or systemic sites (52%). The most common sites of 1st systemic relapse were lung, liver, brain. There were significant differences among substages. First relapses were detected by the pt or family, MD, or by screening radiological tests in 52%, 19%, and 29% of cases, respectively. Multivariate analysis revealed better overall survival (OS) was not associated with time to relapse but was associated with younger age and if 1st relapse was: a) local/in-transit or nodal, b) asymptomatic, or c) resectable. By noting when the risk for 1st local/intransit, nodal, or systemic (lung, liver, brain) relapse became sufficiently low (<5%) for each substage, we generated tentative F/U guidelines ( Table ). Conclusions: Our data suggest that F/U strategies for stage III should be adapted by substage and indicate time ranges beyond which more prolonged F/U would be unlikely to benefit pts. Whether frequent F/U within these time ranges can increase the chances of complete surgical resection or improve OS is not known.

[Table: see text]

No significant financial relationships to disclose.
Prognostic factors for survival in patients with stage (stg) IV malignant melanoma (MM)
Authors: Seetharamu N. , Hamilton H. , Tu T. , Christos P. , Osman I. , Pavlick A. C.
Published: August 2020

9072

Background: Prognosis for survival in MM is not uniform with some pts being long-term survivors. Identifying this subset of pts may have implications on surveillance and treatment (tx). Unfortunately, prognostic data available for MM and the utility of AJCC staging in predicting survival is limited. We analyzed prospectively collected data from the NYUCI Interdisciplinary Melanoma Cooperative Group program (IMCG) to identify clinicopathological variables predictive of MM survival. Methods: We identified 185 pts enrolled in the IMCG with MM diagnosed and treated at NYUCI. Demographic, clinical, and tx-related factors were included in the analysis. Kaplan-Meier (KM) survival analysis was used to identify univariate predictors of post-stage IV survival and their independent effect was assessed in a multivariate Cox proportional hazards regression model. Results: Median age at diagnosis (dx) of metastatic MM was 64 years (22–92). Median overall survival: 13.8 months(m) (128 deaths and a median follow up of 18.6 m (4–141) for survivors). Factors identified on univariate analysis at p<0.20 were evaluated in the multivariate model ( table ). Co-morbidities, site and histology of primary melanoma, initial staging, prior loco-regional recurrences, and adjuvant tx of primary melanoma were not associated with MM survival. Univariate analysis also showed significant survival advantage (p value 0.0011) for patients with AJCC stages M1a and M1b (21.6 m and 17.2 m respectively) over those with AJCC stage M1c (9 m). Conclusions: This cohort study of MM identified female gender, nl serum LDH, nl albumin, and solitary organ involvement as independent survival predictors. Patients who received systemic therapy± local measures had survival benefit over those that had surgery and/or radiation alone suggesting a role for systemic treatment in MM. Patients with personal history of another malignancy (n=37) showed a trend towards improved survival. This novel observation needs to be validated and studied further.

[Table: see text]

No significant financial relationships to disclose.
Effect of mebendazole on melanoma xenograft growth through targeting of bcl-2
Authors: Doudican N. A. , Pennell R. , Tu T. , Liebes L. , Pavlick A. , Berman R. , Shapiro R. , Goldberg J. D. , Osman I. , Orlow S.
Published: August 2020

9075

Background: Defects in apoptosis are thought to contribute to melanoma chemoresistance, making the anti-apoptotic protein Bcl-2 an attractive therapeutic target. We identified mebendazole (MBZ), a microtubule binding agent, as an inducer of melanoma cytotoxicity via a Bcl-2 dependent mechanism in vitro (Mol Cancer Res, Aug 2008). In the present study, we assessed the effect of MBZ on human melanoma tumor growth and progression in a mouse xenograft model and compared the ability of MBZ to inhibit growth of cultured melanoma cells to that of oblimersen (OBL), an antisense drug targeting Bcl-2. Methods: Growth of human M-14 melanoma xenografts in mice administered MBZ orally at doses from 0.1 to 2 mg were compared to tumor growth in mice receiving 100mg/kg intraperitoneal temozolomide (TMZ) or vehicle alone. Tumor diameter, volume, histopathology, and immunohistochemical staining of caspase 3 and Ki67 were assessed. Bcl-2 phosphorylation was determined by immunoblotting. MBZ and OBL-induced melanoma growth inhibition was analyzed by MTT assay. Results: Anti-melanoma effects of MBZ were dose- dependent up to 1 mg which displayed a 72% reduction in tumor volume compared to vehicle treated mice. This reduction in volume was accompanied by a 46% decrease in proliferating cells and an 81% increase in apoptotic cells. Moreover, 1 mg MBZ inhibited tumor growth as effectively as high dose TMZ, the current melanoma standard of care. Orally administered MBZ treatment resulted in Bcl-2 phosphorylation in vivo, further confirming its mechanism of action. MBZ inhibited growth of melanoma cells in culture more effectively than OBL with GI50 values of 0.32 uM and 7.45 uM, respectively. Conclusions: MBZ safely and effectively inhibits melanoma growth and progression in a xenograft model. A phase II clinical trial investigating MBZ's utility as adjuvant therapy in patients with stage IV, resected melanoma is planned.

No significant financial relationships to disclose.
Effect of celastrol on temozolomide cytotoxicity in melanoma cells and inhibition of NF-kB signaling
Authors: Chen M. , Osman I. , Orlow S. J.
Published: August 2020

9076

Background: Temozolomide (TMZ) exhibits clinical activity in the treatment of melanoma and glioblastoma, but response rates are low. Identification of agents that improve TMZ's efficacy and overcome resistance is of great interest. In this study, we have identified celastrol as a natural product that significantly enhances TMZ-induced cytotoxicity by testing a library of drugs and natural products for cytotoxic activity against glioma and melanoma cell lines and have examined its mechanism of action in melanoma cells. Methods: A preliminary screening of a library of 2000 drugs and natural products was performed and a short list of drugs was identified as able to enhance TMZ-induced cell killing in TMZ-resistant cancer cell lines. The effects of these compounds were further confirmed in five melanoma cell lines. A cell proliferation assay was used to compare growth inhibitory effects of single agent TMZ versus combination treatments. Synergy in inhibiting cell proliferation was assessed using combination-index methods. The expression of NF-kB, IkB, MAPK, and PARP were examined using Western blot analysis. The effect of treatments on the cell cycle was examined by flow cytometry. The localization of NF-kB in melanoma cells was evaluated through immunofluorescence microscopy. Results: Combining celastrol and TMZ synergistically inhibited cell proliferation, enhanced cell cycle arrest, and increased apoptosis in a series of melanoma cell lines, compared to treatment with TMZ alone. We further found that celastrol inhibited proteasome activity, TNF-α induced IkB phosphorylation and NF-kB translocation to the nucleus. Inhibition of NF-kB with siRNA mimicked the ability of celastrol to sensitize melanoma cells to TMZ-induced cell killing, suggesting inhibition of NF-kB was indeed involved in TMZ/celastrol-induced cytotoxicity. Furthermore, combination treatment induced phosphorylation of JNK. Conclusions: Our data suggest that combined use of TMZ with celastrol, a natural product derived from a vine extract that has been used orally in Chinese medicine for over a thousand years, may enhance the chemotherapeutic efficacy of TMZ in melanoma.

No significant financial relationships to disclose.
Divergent cancer pathways for early-onset and late-onset cutaneous malignant melanoma
Authors: Anderson W. F. , Pfeiffer R. M. , Tucker M. A. , Rosenberg P. S.
Published: August 2020

9079

Background: Emerging data suggest that cutaneous malignant melanomas (CMM) may arise through divergent cancer pathways, linked to intermittent versus accumulated sun exposure. However, numerous questions remain regarding the timing and/or age of exposure. Methods: We, therefore, systematically examined the effect of aging upon CMM incidence in the Surveillance, Epidemiology, and End Results program of the National Cancer Institute. Standard descriptive epidemiology was supplemented with mathematical models. The impact of advancing age upon CMM incidence was assessed by gender, histopathological subtype (superficial spreading melanoma (SSM) or lentigo maligna melanoma [LMM]), and anatomic site (face, head, and neck [FHN] or lower extremity [LE]). Results: Gender, histopathological and anatomic site were age-specific effect modifiers for CMM, showing divergent (or bimodal) early- and late-onset cancer pathways. Early-onset melanomas were predominantly associated with female gender, SSM, and LE. Late- onset melanomas were correlated with male gender, LMM, and FHN. Early- and late-onset melanoma populations were confirmed with age-period-cohort models (adjusted for period and cohort effects) and two-component mixture models. Conclusions: These results are consistent with a divergent and age-dependent solar hypothesis for CMM. Early-onset melanomas may represent gene-sun exposure interactions occurring early (and/or intermittently) in life among susceptible individuals. Late-onset melanomas possibly reflect accumulated lifelong sun exposure in comparatively less susceptible individuals. Future analytical studies should be adequately powered to account for this age-dependent effect modification for acknowledged (gender, histopathology, and anatomic site) as well as suspected melanoma risk factors such as constituent genetic variants.

No significant financial relationships to disclose.
Identification of targetable cellular subsets within melanoma tumors
Authors: Sekulic A. , Miller A. , Barrett M. , Ejadi S. , Mengos A. , Pockaj B. , Markovic S.
Published: August 2020

9082

Background: Human tumors, including melanoma, are complex mixtures of individual, molecularly distinct subpopulations, or clones of cancer cells. Effective cancer therapy will likely require targeting of all tumor subsets within a given cancer. Understanding the tumor complexity and the ability to identify points of therapeutic vulnerability within the individual tumor subsets will be essential for development of effective personalized cancer therapies. Methods: We have developed an approach that combines identification of individual tumor subsets using a multiparameter nuclear flow cytometry coupled with a high-resolution genomic analysis using the array-based comparative genomic hybridization (aCGH). Melanoma nuclei were isolated from tumor tissues and subjected to flow cytomery using melanocyte-specific antibodies (to separate melanoma cells from stroma) and DNA content, to separate individual tumor subpopulations. DNA extracted from isolated nuclear subpopulations was extracted and analyzed by aCGH. This approach was adopted for both fresh-frozen and paraffin-embedded clinical specimens. Results: We initially demonstrate the feasibility of the outlined approach by successful separation of melanoma from stromal nuclei and separation of individual melanoma nuclear subpopulations by DNA content. aCGH analysis of the DNA derived from isolated tumor subpopulations allowed successful identification of potentially targetable molecular aberrations in individual subsets of tumor cells. Notably, such aberrations were often not detected in unsorted, bulk tumors analyzed by the same high-resolution aCGH approach. Conclusions: We demonstrate a feasible approach to in-depth molecular analysis of tumor subpopulations within a clinical cancer tissue. This approach allows identification of potentially targetable molecular aberrations within individual tumor subsets, thus opening a possibility for a broad tumor targeting through design of individually-tailored therapeutic approaches.

No significant financial relationships to disclose.
Clinical trial participants’ strategies for coping with prescription drug costs: A companion study to CALGB 80405
Authors: Schrag D. , Naughton M. , Kesselheim A. , Archer L. , Niedzwiedcki D. , Romanus D. , Goldberg R. , Venook A.
Published: August 2020

9503

Background: The strategies used by clinical trial participants to cope with the high costs of prescription drugs are poorly characterized. Methods: We identified a cohort of newly metastatic CRC patients participating in CALGB 80405, a phase III trial comparing first-line systemic chemotherapy with Bevacizumab, Cetuximab or both agents. We surveyed trial participants about their prescription drug insurance status and strategies they used to cope with out-of-pocket prescription drug costs. We surveyed patients before trial initiation and again 3 months later to assess the extent to which embarking on chemotherapy imposes additional financial burden requiring use of coping strategies. Results: Out of 1422 trial participants, 806 (57%) completed the baseline survey. The 515 enrolled before 09/01/2007 were asked to repeat the survey by phone at 3 months; 409/505 alive at 3 months (81%) did so. The 409 patients in the analytic cohort had similar clinical and demographic features to those not surveyed. 60/409 (15%) lacked prescription drug coverage and only 48/409 (12%) discussed prescription drug costs with their physicians. Conclusions: In the context of a trial in which costs of chemotherapy are covered and most participants had prescription drug insurance, patients rarely discuss prescription drug costs with their physicians. Although a considerable minority report having used coping strategies to lessen the cost burden, only a very small minority newly adopt such strategies after starting chemotherapy on trial.

[Table: see text]

[Table: see text]
An exploratory analysis of comprehensive geriatric assessment results and overall survival in 233 consecutive elderly cancer patients
Authors: Poon D. , Lee H. H. , Chan L. L. , Yap R. , Koo W. H.
Published: August 2020

9504

Background: Performance status (PS) is the main clinical parameter used by most oncologists to assess the ability of elderly cancer patients to tolerate chemotherapy and estimate prognosis. The results of comprehensive geriatric assessment (CGA) for elderly cancer patients were analyzed to investigate the impact of each CGA functional, physical, cognitive, and affective domain on overall survival in relation to performance status. Methods: CGA was used for 233 consecutive elderly cancer patients aged 70 and above. CGA tools included the Katz index of daily activities independence (ADL), instrumental activities of daily living (IADL), mini-mental state examination (MMSE), geriatric depression scale (GDS), Charlson comorbidity risk index, get up and go test, and mini-nutritional assessment. Geriatric syndrome is defined as any high risk of falls, depression, dementia, increased functional dependence, or malnutrition. Eastern Cooperative Oncology Group (ECOG) scale was used to grade PS. Cancer type and stage were also analyzed. Log rank test was used to compare overall survival and hazard ratio (HR) derived using Cox regression method. Univariate and multivariate analyses were done to assess impact of ECOG status, presence of geriatric syndrome, stage of disease and cancer type on overall survival. Results: All 233 patients were included in the analysis, median age 77 (70 - 93), all had solid tumors and predominant tumors comprising 79% of diagnoses were colorectal, lung and breast, 50% had advanced metastatic disease. ECOG grades 2,3,4 (HR 0.28, 95% CI 0.14 - 0.55), dependent IADL status (HR 0.30, 95% CI 0.11 - 0.83), presence of geriatric syndrome (HR 0.42 95% CI 0.26 - 0.69), poor cognition (HR 0.53 95% CI 0.36 - 0.77), or advanced disease (HR 0.30 95% CI 0.14 - 0.65) was associated with inferior overall survival in univariate analysis. Only poor ECOG status, presence of a geriatric syndrome and advanced disease predicted adversely for overall survival in multivariate analysis. Poor cognition (MMSE score <24) in those with borderline ECOG 2 status was associated with poorer survival (HR 0.38 95% CI 0.33 - 0.90). Conclusions: Utility of CGA will improve the assessment of the elderly cancer patient.

No significant financial relationships to disclose.
Illness understanding in patients with advanced lung cancer
Authors: Temel J. S. , Greer J. A. , Admane S. , Jackson V. A. , Billings J. A. , Dahlin C. M. , Jacobsen J. C. , Blinderman C. D. , Lynch T. J. , Pirl W. F.
Published: August 2020

9515

Background: Accurate understanding of prognosis among terminally-ill patients impacts decision-making at the end of life. The goal of this study was to explore illness understanding in patients with advanced non-small cell lung cancer (NSCLC). Methods: As part of a larger randomized study of integrated versus standard palliative care in an ambulatory thoracic oncology clinic, we recruited 120 patients within eight weeks of diagnosis of incurable NSCLC with a performance status of 0–2. Prior to randomization, patients completed questionnaires on quality of life (FACT-L) and mood (HADS), as well as the following items regarding illness understanding: 1) “My cancer is curable” (yes/no); “The goals of my therapy are: to help me live longer” (yes/no), “try to make me feel better” (yes/no), “to get rid of all my cancer” (yes/no); and 3) “My current health status is: relatively healthy, seriously but not terminally ill, or seriously and terminally ill”). Results: Approximately one third of patients (n=39/116, 33.6%) believed their cancer to be curable. While most patients felt that the goals of therapy were to help them live longer (n=110/113, 97.3%) and feel better (n=102/102, 100%), 66.0% (n=64/97) also believed that getting rid of all of the cancer was a treatment goal. Only 13.9% (n=16/115) of patients believed that their current health status was seriously and terminally ill. Patients who reported greater depression and anxiety symptoms on the HADS were more likely than those without such distress to believe that their cancer was curable (OR=2.47, p=.03) and that one of the goals of treatment was to get rid of all of their cancer (OR=3.83, p=.02). Conclusions: Despite having an incurable illness, the majority of patients with advanced NSCLC do not view themselves as terminally ill or have an accurate understanding of the goals of anti-cancer therapy. Given that patients often make treatment decisions based on their prognostic awareness, many of these individuals, particularly those with comorbid mood symptoms, may be at risk of pursuing unsuitable choices for their care. Interventions are needed to promote greater understanding of prognosis and goals of therapy in this population.

No significant financial relationships to disclose.
Cognitive function (CF) and prognostic information understanding in advanced cancer patients (ACP)
Authors: Hlubocky F. J. , Larson E. , Ratain M. J. , Sachs G. , Daugherty C. K.
Published: August 2020

9516

Background: The role of advanced cancer patients' (ACP) cognitive function (CF) and its relationship to understanding of a terminal prognosis has never been formally evaluated. Methods: ACP CF was evaluated among a population of terminally-ill patients enrolling in phase I trials at our institution using a neuropsychological battery designed to assess several domains of decisional capacity: Memory (Hopkins Verbal Learning HVLT); Executive Functioning (Verbal Fluency and Trail-making A/B); Language (Boston Naming-short); Attention (Digit Span); Comprehension (Auditory Comprehension & WAIS comprehension). Semi-structured interviews of ACPs also evaluated md-pt communication regarding prognosis, and included the Hospital Anxiety and Depression Scale (HADS), BDI-II, and the FACT-COG. Results: To date, 110 ACP enrolling in phase I trials have been interviewed: median age 60 (23–83); 66% male; 88% Ca; 62% married; 71% >high school education; 52% GI dx. 59% of ACPs reported having a discussion regarding life expectancy, and 55% stated that the physician gave them a prognostic timeframe regarding the amount of time left to live. ACP who stated the physician did not provide them a timeframe had measurable deficits in CF as indicated by Z scores for HVLT immediate recall (-1.3 ± .84 v -.74 ± 1.1, p=.03); total recall (-1.9 ± 1.2 v -1.2 ±1.5, p=.02); delayed recall (-1.7 ± 1.6 v -1.1 ±1.6, p=.04); language (.26 ± 1.3 v .78 ± .68, p=.03); Trails B (-1.6 ± 2.5 v -.61 ± 2.2, p=.04) and WAIS comprehension ss scores (14 ± 2.9 v 16 ± 3.0, p=.06). These ACP tended to exhibit more depressive symptoms (12 ± 10 v 6 ± 3, p=.04) and had lower scores for perceived cognitive impairment (96 ± 25 v 105 ±16, p=.04); impact on quality of life (26 ± 7 v 28 ± 5, p=.03); and FACT-COG total (152 ± 31 v 164 ± 22, p=.05). Conclusions: ACP enrolling in phase I trials who could not recall specific prognostic information had measurable cognitive impairment as compared to those ACP who could recall such information. Our data indicate that CF may play a role in ACP communication and/or understanding of prognostic information.

[Table: see text]
Efficacy of electroacupuncture for bone metastatic cancer patients with neuropathic pain: A randomized controlled trial
Authors: Sima L. , Yin C.
Published: August 2020

9534

Background: Bone metastatic lung cancer or breast cancer pts often have neuropathic pain which has poor reaction to opioids. A clinical trial is to investigate efficacy of electroacupuncture (EA) in cancer pts with neuropathic pain. Methods: Inclusion criteria were: bone metastatic lung cancer or breast cancer pts at least one of the symptoms as burning pain, shooting pain, dysesthesias, or allodynia; numerical rating scale (NRS) of pain intensity >=4.0; stable dose of opioids for at least 72 hours. Exclusion criteria were: chemotherapy or radiotherapy from 15 days before or during the study. Hormone or adjuvant therapy could be started before the study, but the dose could not be changed afterwards. Opioids could be increased step by step according to the pain. EA was manipulated with low-frequency (2 Hz) and high-frequency (100 Hz) dense-disperse waves alternatively, 30 minutes per day, 5-day therapy with 2-day interval, 3 weeks continuously. Acupoints were selected as ST36, SJ3, SJ5, LI3, LI4 bilateral. Controlled group accepted non-acupoint treatment close the right acupoint. Results: Ninety pts with neuropathic pain participated in a randomized, controlled design trial from 2006 to 2008. Overall, 45 pts accepted EA treatment and 34 completed the study. 45 pts accepted controlled and 32 completed. There was no difference of initial NRS which was 6.3±2.1 in EA group and 7.2±1.8 in controlled, p = 0.0669. Analysis showed a significant difference of NRS between EA group (3.2±1.7) and controlled (5.4±2.2) at the end of survey, p < 0.0001. The decrease in NRS was significantly higher in the EA group compared to the controlled (3.2±1.7 vs. baseline, p < 0.0001; 5.4±2.2 vs. baseline, p = 0.0007). Mean analgesics consumption variety in EA group was as follows: transdermal fentanyl increased by 51.2% (16 pts) and 77.3% (21 pts) in EA and controlled, p = 0.0005. Oxycodone increased by 85.5% (18 pts) and 115.6% (11 pts) in EA and controlled, p = 0.0183. Functional Assessment of Cancer Therapy-General (FACT-G) scale had no difference at the beginning, while it were 102±18 and 85±12 in EA group and controlled at the end of survey, p < 0.0001. Conclusions: EA can alleviate neuropathic pain of bone metastatic cancer pts, decrease the analgesics consumption, and promoting quality of life.

No significant financial relationships to disclose.
Palliative care training and burnout in oncology fellows
Authors: Schellhorn S. , Lessen D. S. , Levine R. L. , Panagopoulos G. , Arnold R. M. , Block S. D. , Buss M. K.
Published: August 2020

9540

Background: Burnout among physicians is associated with fatigue, exhaustion, and depression, and can result in increased medical errors and sub-standard patient care. We sought to determine rates and predictors of burnout in oncology fellows. Methods: As part of a larger study on fellows' attitudes, education, and experiences in palliative care, we administered the 22 item Maslach Burnout Inventory (MBI) to second year U.S. oncology fellows. The 104 item instrument, modified from a survey of medical students, was revised after field testing and a pilot survey. The MBI measures three domains: emotional exhaustion (EE), depersonalization (DP), and personal accomplishment (PA); higher EE and DP scores and lower PA scores indicate burnout. Bivariate and multivariate analyses were used to find associations between burnout and fellow demographics, attitudes, and educational experiences. To accommodate for multiple testing, p<0.01 was considered statistically significant. Results: The response rate was 63.2% (254 of 402 eligible fellows). Gender, race, and location of medical school (U.S. vs. other) did not differ between respondents and non-respondents. Among respondents, 28.1% reported high EE, 30.0% reported high DP, and 26.8% reported low PA. Over half reported burnout in at least one domain (32.9% in one, 16.5% in two, and 5.5% in all three domains). The following associations were found on multivariate analyses. Fellows who identified as white had higher rates of EE (p=0.0006) while EE was lower in those who: 1) rated their program's overall teaching ‘very good‘ or ‘excellent‘ (p=0.005), 2) felt prepared to address spiritual issues around end-of-life care (p=0.002), and 3) felt prepared to manage their own feelings about illness and dying (p=0.008). Fellows who identified as white (p=0.008) or reported dreading encounters with emotionally distressed family members (p=0.0002) had higher DP. The only factor associated with higher PA scores was agreement that doctors have a responsibility to help patients prepare for death (p<0.0001). Conclusions: Over half of oncology fellows experience at least one domain of burnout. Higher quality teaching within their fellowship program and higher levels of self-assessed preparation to care for patients at the end of life are associated with lower levels of burnout.

No significant financial relationships to disclose.
Outcomes of stereotactic body radiotherapy (SBRT) in 175 patients with stage I NSCLC aged 75 years and older
Authors: Senan S. , Haasbeek C. J. , Antonisse M. E. , Slotman B. J. , Lagerwaard F. J.
Published: August 2020

9545

Background: Patients aged 75 years or older comprise more than 40% of all new cases of lung cancer. SEER data show lower compliance rates with guideline-recommended therapy in such patients. The elderly have increased post-surgical mortality and morbidity, and frequently require convalescence at extended-care facilities. SBRT is an image-guided technique used to deliver high biological doses of radiation in 3–8 fractions, in an outpatient setting. We report on clinical outcomes of SBRT in patients aged 75 years or older. Methods: Since 2003, 175 consecutive patients (67% male; 32% female) were treated with SBRT at a single center. The median age was 79 years, with 47% of patients aged 80 years or older. 56% of patients had T1 lesions and 44% T2 tumors. 79% of patients were considered medically inoperable and 21% declined to undergo surgery. Eligible tumors measured 6cm or less in maximal diameter, and all underwent an 18FDG-PET scan that revealed no metastases. The median age-adjusted Charlson co-morbidity score was 7 (range 2–12), and 25% had GOLD Class III or higher chronic obstructive pulmonary disease. Risk-adapted SBRT schemes were used with the same total dose of 60 Gy in 3 (31%), 5 (53%) or 8 fractions (16%) depending upon risk for toxicity. Quality of life was scored prospectively using validated EORTC instruments. Results: All patients completed planned SBRT and survival rates at 1 and 3 years were 85% and 46%. Survival rates correlated with performance score (p<0.01) and pre-SBRT lung function (p<0.01). Actuarial local-, regional- and distant failure rates at 3 years were 11%, 8% and 21%, respectively. 60% of patients reported no early side effects, and fatigue (31%), cough (6%), dyspnea (5%), local chest wall pain (3%) and chest wall erythema (2%) were observed in others. Severe late toxicity was uncommon, with RTOG Grade 3 or higher radiation pneumonitis observed in 2%, radiation-induced rib fractures in 2%, chronic chest wall pain in 3%, and non-malignant pleural effusion in 2% of cases. Conclusions: In a population consisting of frail elderly patients with stage I NSCLC, SBRT achieved high local control rates with minimal toxicity. This indicates that active diagnostic and therapeutic approaches are justified in elderly patients who may be unfit for surgery.

[Table: see text]
Influence of age on receipt of chemotherapy for adult Medicaid beneficiaries with metastatic colorectal cancer
Authors: Klepin H. D. , Song E. Y. , Geiger A. M. , Tooze J. A. , Foley K. L.
Published: August 2020

9548

Background: Although advances in systemic treatment for metastatic colorectal cancer (CRC) have improved survival, it is unclear if this treatment is administered routinely among vulnerable individuals. Our objective was to describe treatment patterns for low income individuals with metastatic CRC and evaluate the influence of age on delivery of treatment in the context of patient, community, and health care setting characteristics. Methods: Matched North Carolina Cancer Registry and Medicaid claims data were used to identify a cohort of 390 patients with metastatic CRC diagnosed between 1999 and 2002. We assessed the relationship between treatment delivered within one year of diagnosis and characteristics of the patient (age, gender, race/ethnicity, comorbidity), community (percent poverty, percent rural), and health care setting (academic medical center, surgery volume). Treatment delivery was categorized into: 1) receipt of any chemotherapy, 2) local therapy only, and 3) no treatment. We fit a logistic regression model comparing receipt of any chemotherapy to local treatment only and another comparing receipt of any chemotherapy to no treatment. Results: Patients' mean age was 65.1±14.6 years; 56.0% were female and 45.5% were non-white. Only 27.7% received chemotherapy, while 50.3% received local therapy only and 22.0% received no treatment. After adjusting for comorbidity and all other covariates, patients aged <75 years were more likely to receive chemotherapy than patients ≥75 (versus local treatment only, OR=3.2, 95% CI=1.7–6.1; versus no treatment, OR=3.9, 95% CI=1.9–8.3). Absence of significant comorbidity was associated with use of chemotherapy only when compared to those who received no treatment (OR=3.1, 95% CI=1.6–5.9). Race/ethnicity, community, and health care setting characteristics were not associated with treatment. Conclusions: Use of chemotherapy in this low income cohort was low compared to published reports in other populations. Younger age was the only characteristic in this analysis which was consistently associated with receipt of chemotherapy. These results suggest that older low income patients may represent a particularly vulnerable population with regard to treatment disparity.

No significant financial relationships to disclose.
Use of the Comprehensive Geriatric Assessment (CGA) in elderly patients (pts) with solid tumors to predict mortality
Authors: Honecker F. U. , Wedding U. , Rettig K. , Huschens S. , Bokemeyer C.
Published: August 2020

9549

Background: The internet based IN-GHO-Registry, a project of the Initiative for Geriatric Hematology and Oncology, supported by ORTHO BIOTECH, Division of Janssen-Cilag GmbH, Germany, prospectively collects data of elderly cancer pts. We report data from 1130 pts with solid tumors. Results of a CGA, physicians' and pts' judgement of fitness were studied in relation to mortality within 5–7 months. Methods: Demographic data, data on activities of daily living (ADL), instrumental activities of daily living (IADL), Karnofsky-Performance-Statuts (KPS), comorbidity (Charlson score), number of co-medication, mobility (Timed-Up&Go), cognition (MMSE), and depression (SCID screening) were collected. Age, results of CGA, physicians' rating (fit vs compromised vs frail) and pts' self rated fitness for treatment (Likert scale 1= very fit to 6 = very unfit) were analysed for association with death. Follow-up (FU) was scheduled 5–7 months after inclusion. Results: 1130 pts, mean age 76.3 years (SD 4.7; range 69–95), 44% male, were included. Main diagnoses were gastrointestinal tumors (38%), breast cancer (12%), and lung cancer (11%). Physicians rated 58% of pts fit, 37% compromised, and 5% frail. Pts' self rating of fitness: 1 = 19%, 2 = 30%, 3 = 28%, 4 = 17%, 5 = 5%, 6 = 1%. During FU (median 177 days), 272 pts (24%) died. Mean age (76.5 vs. 76.3; p=0.75) was not associated with death. However, sex (male vs female, p<0.001), BMI (24.4 vs 25.9; p<0.001), Charlson-score (6.3 vs 5.5; p<0.001), number of co-medication (4.5 vs 3.7; p<0.001), ADL score (87.9 vs 93.9; p<0.001), IADL score (6.2 vs 7.0; p<0.001), KPS score (75% vs 83%; p<0.001), MMSE (25.6 vs. 26.2; p=0.045), categorical Timed-Up&Go (less than 10s, 10–20s, more than 20s; p<0.001), categorical SCID (0, 1, 2; p=0.012), physicians' rating of fitness (fit, compromised, frail; p<0.001) and mean pts' rating of fitness (3.1 vs. 2.4; p<0.001) were significantly associated with death during FU. Conclusions: Pts characteristics as assessed by CGA and not age are associated with death in elderly pts with solid tumors.

[Table: see text]
Cancer in the oldest old population in the United States: Current statistics and projections
Authors: Gundrum J. D. , Go R. , Kwong R.
Published: August 2020

9553

Background: The oldest old, defined as people age ≥ 85 years, in the U.S. is projected to double from 4.3 million in 2000 to 9.6 million in 2030. Since cancer is the number one cause of death, it is critical to assess the current and projected cancer burden in this population. Methods: We obtained data from the Surveillance, Epidemiology and End Results (SEER) program. We included patients who had a previous cancer before age 85, but excluded benign tumors, myeloproliferative, and myelodysplastic neoplasms. Incidence was reported per 100,000 person years and age-adjusted to the 2000 U.S. standard population. For current statistics, we included years 2001–2005. Trend analyses were based on 1973–2005 data. Results: The oldest old represents 7.2% of annual new cancers cases diagnosed and 10.5% of cancer deaths in the U.S. The 10 leading cancers by incidence (both sexes and decreasing order) are colorectal (388.9), lung (287.7), breast (250), prostate (211.5), urinary bladder (162.5), non-Hodgkin lymphoma (110.9), leukemia (85.1), melanoma (65), renal (46.4), and uterine (40.2). The incidences of melanoma, non-Hodgkin lymphoma, renal, and lung cancers are increasing, while those of leukemia, prostate, breast, and colorectal cancers are decreasing. The top 5 causes of cancer deaths are lung and bronchus (21%), colorectal (15%), pancreatic (7.1%), prostate (5.9%), and breast cancers (5.3%). Cancer specific survival (CSS) has been increasing continuously since 1973 for melanoma, non-Hodgkin lymphoma, breast, colorectal, prostate, and urinary bladder cancers but decreasing in recent years for colorectal, breast, prostate, and uterine cancers. CSS for leukemia, lung, renal, and uterine cancers showed no change over time. If the current incidence trends for each cancer continue in a linear fashion, it is projected, using 1973–2005 data, that in 2030, the oldest old will represent 8.8% of annual new cancers cases diagnosed and 13.6% of cancer deaths. Conclusions: Cancer incidence and mortality trends in the oldest old differ from the general population. Because the oldest old are likely to have multiple co-morbid conditions, there is a need to find better ways to diagnose and treat cancers in this unique segment of the population.

No significant financial relationships to disclose.
Hospitalization rates among survivors of childhood and adolescent cancer: A report from the Childhood Cancer Survivor Study (CCSS)
Authors: Kurt B. A. , Nolan V. G. , Ness K. K. , Neglia J. P. , Tersak J. M. , Hudson M. M. , Armstrong G. T. , Leisenring W. M. , Robison L. L. , Arora M.
Published: August 2020

9556

Background: Survivors of childhood cancer have a high burden of chronic health conditions following cancer therapy, but the risk for subsequent hospitalization has not been reported. Methods: Hospitalizations during 1996–2000 among a cohort of 10,367 5-yr survivors of childhood cancer (diagnosed 1970–1986) and 2,540 siblings were ascertained. Age-and gender-stratified standardized incidence ratios (SIRs) for hospitalization were calculated using the sibling cohort and U.S. population from the National Hospital Discharge Survey (NHDS). Associations between demographic, cancer/treatment-related risk factors and non-obstetrical hospitalization among survivors were evaluated in multiple variable logistic regression models. Results: At follow-up, survivors were a mean of 20.9 yrs. from diagnosis (SD: 4.6, range: 13.3–32.2) and mean age of 28.6 yrs. (SD: 7.7, range: 13–51). Overall hospitalization rates among survivors were 1.5 times (95% CI 1.44–1.52) that of siblings and 1.2 times (95% CI 1.16–1.22) that of the U.S. general population. Increased risk of hospitalization was noted irrespective of gender, age at follow-up, or cancer diagnosis, with highest SIRs noted for male (SIR=12.7, 95% CI 9.5–15.8) and female (SIR=72.1, 95% CI 58.8–85.5) survivors aged 45–54. Females (OR=1.2, 95% CI 1.04–1.3) and survivors with a chronic health condition (OR=1.6, 95% CI 1.5–1.8) were more likely to have been hospitalized for non-obstetrical causes after adjusting for age at diagnosis, age at follow-up, cancer diagnosis, household income, insurance, and history of relapse/second malignancy. Among survivors, those with Hodgkin's lymphoma had the highest hospitalization rates for neoplastic, infectious, endocrine, pulmonary and cardiovascular causes. CNS malignancy survivors had the highest hospitalization rates for neurologic, psychological and external (e.g. traumatic) causes. Conclusions: Therapy for childhood and adolescent cancer is associated with a significant increase in subsequent hospitalization rates. Regular medical follow-up and early intervention for chronic health conditions may help to limit severe toxicity that would require hospitalization.

No significant financial relationships to disclose.
Hospitalization of hyperglycemic lung cancer patients during treatment
Authors: Martin B. E. , Mott F. , Song J.
Published: August 2020

9560

Background: Approximately 20 million Americans have type 2 diabetes mellitus. This same group is at significant risk of developing malignancy. Evidence suggest that diabetics with colon and breast cancer experience inferior treatment outcomes. There are few direct comparisons of treatment outcome and/or treatment tolerability in those with and without hyperglycemia. There are no such comparisons in lung cancer patients. We anticipate those with hyperglycemia will tolerate treatment less well than those with euglycemia. With this premise, we assessed hospitalization risk between lung cancer patients with normal or elevated baseline serum glucose (BSG) prior to initial chemotherapy cycle. Methods: After obtaining institutional IRB approval, tumor registry analysis identified 364 consecutive individuals diagnosed with lung cancer between 2005 and 2007 at our institution. One hundred and fifteen were excluded: 71 not treated, 17 duplicate entries, 16 stage 1A lung cancer, 8 missing data, 2 glucose under 60 mg/dl, 1 admitted for chemotherapy. Demographic and cancer specific data were obtained from the registry. Chart review yielded: BSG, date of first chemotherapy cycle, date of hospitalization, neutrophil count at admission, radiation therapy 30 days before/after treatment. Data presented was analyzed using multivariate logistic regression. We utilized WHO strata for fasting whole blood glucose measurements. Those presenting with grade 3 (or greater) neutropenia were excluded. Results: See Table . Conclusions: Lung cancer patients with hyperglycemia are more likely to be hospitalized in the 30 days following their first cycle of cytotoxic chemotherapy. We used the WHO glucose strata to analyze our data. Compared to those with normal BSG, those with BSG between 110 and 126 mg/dl were twice as likely to be hospitalized, and those with BSG over 126 mg/dl had four times the risk. We feel this simple metric will improve clinician's treatment decisions. Prospective analysis of diabetic cancer outcomes is needed.

[Table: see text]

No significant financial relationships to disclose.
Risk of mortality in patients with cancer experiencing febrile neutropenia
Authors: Barron R. , Michels S. L. , Reynolds M. W. , Tomic K. , Yu J. , Lyman G.
Published: August 2020

9561

Background: Febrile neutropenia (FN) is a serious and potentially life-threatening condition that may develop in patients with cancer treated with chemotherapy. The risk of mortality from FN is not well characterized in clinical practice. Methods: Patients with cancer receiving chemotherapy in clinical practice were identified from the HealthCore Integrated Research Database, a geographically diverse spectrum of fully adjudicated longitudinal claims data from 13 health plans with over 20 million US lives. Patient enrollment data, full medical care, prescription drug use and mortality (confirmed using the National Death Index) were examined for each eligible patient. Patients experiencing FN were compared to propensity score-matched patients not experiencing FN within tumor types of Non-Hodgkin lymphoma (NHL), breast, lung, colorectal and ovarian cancer. Study endpoints included overall mortality (anytime during follow-up) and early mortality (during a chemotherapy course). Logistic regression was used to calculate odds ratios (OR), adjusted for demographics, comorbidities, and other covariates. Results: Matched FN and control groups each contained 5,176 patients. Crude incidence rates of overall and early mortality were significantly higher for patients in FN group compared to controls for all tumor types [7.9/1000 person-months (PM) (95% confidence interval [CI] = 7.3, 8.5) vs. 5.6/1000 PM (CI = 5.1, 6.1), P < 0.0001; and 3.4/1000 PM (CI = 3.1, 3.9) vs. 2.4/1000 PM (CI = 2.1, 2.8), P = 0.0001, respectively]. Within tumor strata, lung cancer had the highest mortality rates and breast cancer had the lowest; NHL had the largest magnitude of difference between FN and controls (overall mortality: 7.2/1000 PM [CI = 5.3, 9.7] and 3.3/1000 PM [CI = 2.1, 5.1], P = 0.0035; early mortality: 3.0/1000 PM [CI = 1.8, 4.8] and 1.5/1000 PM [CI = 0.8, 3.0], P = 0.1103). Logistic regression demonstrated a significant increase in risk of overall and early mortality in patients with FN compared to controls (OR = 1.77 [1.53, 2.05] and OR = 1.73 [1.41, 2.11]) respectively. Conclusions: The crude and adjusted risk of mortality in patients experiencing FN is almost two-fold higher than comparably matched patients without FN. Prevention of FN is of high importance and should be carefully considered in clinical practice.

[Table: see text]
The epidemiology of herpes zoster in patients with invasive cancer
Authors: Habel L. A. , Ray G. T. , Horberg M. , Yawn B. , Castillo A. , Li Y. , Silverberg M. , Quesenberry C. , Tran T.
Published: August 2020

9562

Background: Given the limited available data, the aim of this study was to estimate the incidence of Herpes Zoster (HZ) in cancer patients. Methods: In this retrospective cohort study, we used the Kaiser Permanente Northern California cancer registry to identify adult health plan members diagnosed with an invasive hematologic malignancy (HM) or solid tumor malignancy (STM) during 2001–2005. Potential episodes of HZ were ascertained from time of cancer diagnosis through 2006 from electronic databases using inpatient and outpatient diagnoses, laboratory tests, and prescriptions for antivirals. HZ diagnoses were confirmed by abstraction and clinical review of information from patients' inpatient and outpatient medical records. Incidence rates were calculated as the number of new occurrences of HZ per person-time of follow-up. Age-standardized incidence ratios (SIRs) were computed to compare HZ rates in cancer patients to reported rates in the general population (Yawn et al, 2007). Results: Among the 4,728 STM patients (mean age 66 years, range 18–102), the rate of HZ was 12/1000 person years (py) of follow-up (total 9170 py). Among the 1504 HM patients (mean age 67 years, range 18–97), the rate of HZ was 33/1000 py (total 2355 py). The SIRs and 95% confidence intervals for STM and HM were 1.7 (1.4–2.1) and 4.5 (3.5–5.6), respectively. Among patients with HM, incidence rates were highest in the first year after cancer diagnosis (40/1000 py); rates did not appear to vary markedly over time among patients with STM. For either cancer type, HZ rates were similar for males and females and did not increase consistently with increasing age. Conclusions: Compared to the general population, the incidence of HZ was nearly 2 times higher in patients with STM and over 4 times higher in patients with HM. HZ rates did not differ markedly by age or gender.

[Table: see text]