bluuebunny/crossref_metadata_2025 huggingface dataset:
MM-005: A phase I trial of pomalidomide, bortezomib, and low-dose dexamethasone (PVD) in relapsed and/or refractory multiple myeloma (RRMM).
Authors: Richardson Paul Gerard Guy , Hofmeister Craig C. , Siegel David Samuel DiCapua , Lonial Sagar , Laubach Jacob , Efebera Yvonne Adeduni , Vesole David H. , Nooka Ajay K. , Rosenblatt Jacalyn , Raje Noopur S. , Zaki Mohamed H. , Hua Ye , Shah Sheetal , Wang Jianming , Anderson Kenneth Carl
Published: March 2020

8584

Background: Combinations of lenalidomide (LEN), bortezomib (BORT), and dexamethasone (DEX) have demonstrated preclinical and clinical activity in patients (pts) with multiple myeloma. Pomalidomide with low-dose DEX (LoDEX) has demonstrated efficacy in RRMM pts treated with prior LEN and BORT. MM-005 was designed to identify the optimal PVD dose for a phase 3 trial comparing PVD vs BORT + LoDEX (VD) in RRMM (MM-007). Methods: Eligible pts had RRMM with 1-4 prior therapies including ≥ 2 consecutive cycles of LEN and a proteasome inhibitor. Pts must have been refractory to LEN (progressive disease [PD] during or within 60 days of LEN treatment), but not refractory to BORT (at 1.3 mg/m2 twice-weekly). The maximum tolerated dose (MTD) was determined using a 3 + 3 design in 5 cohorts. Each cohort received 21-day cycles of POM 1-4mg/day on D1-14; BORT 1-1.3mg/m2on D1, 4, 8, 11; and LoDEX 20mg/day on D1-2, 4-5, 8-9, 11-12. An expansion cohort was enrolled at the MTD. Treatment was continued until PD or unacceptable toxicity. Dose-limiting toxicities (DLTs) were assessed during cycle 1. The primary endpoint was MTD; secondary endpoints were safety, overall response rate (ORR; ≥ partial response), duration of response, and time to response (TTR). Results: As of Dec 31, 2012, 21 pts were enrolled (3 pts per escalating dose cohort; 6 in the expansion cohort). Median age was 57 years (36-75). All were LEN-refractory and had prior BORT. No DLTs were observed at any dose level. The most common grade 3/4 adverse events (AEs) were neutropenia (32%) and thrombocytopenia (21%). With thromboprophylaxis, no deep vein thrombosis was observed. 17 pts remain on study and no pts have discontinued treatment due to AE. Thus far, the ORR was 72% (n = 18 evaluable) and responses were rapid (median TTR, 2 cycles). Conclusions: PVD was well-tolerated in RRMM with no DLTs and no discontinuations due to AE to date. PVD has promising activity with a current ORR of 72%. The maximum planned dose of POM 4mg/day on D1-14; BORT 1.3mg/m2 on D1, 4, 8, and 11; and DEX 20mg on D1-2, 4-5, 8-9, 11-12 of a 21-day cycle has now been incorporated into the MM-007 phase III trial comparing PVD with VD in RRMM pts (N = 782 planned). Clinical trial information: NCT01497093.
Evaluating results from the multiple myeloma subset of patients treated with denosumab or zoledronic acid (ZA) in a randomized phase III study.
Authors: Raje Noopur S. , Willenbacher Wolfgang , Hungria Vania , Spencer Andrew , Alexeeva Yulia , Facon Thierry , Stewart A. Keith , Roodman David , Terpos Evangelos , Feng Amy , Braun Ada , Balakumaran Arun
Published: March 2020

8589

Background: Denosumab (dmab) is a fully human monoclonal antibody against RANKL and is superior to ZA in preventing skeletal-related events (SREs) as shown in 3 identically designed phase 3 trials (N=5723). Overall survival (OS) was balanced between treatment groups in the overall study populations of these trials. In the trial of patients (pts) with solid tumors (excluding breast and prostate) and multiple myeloma (MM), OS was longer for dmab pts with lung cancer, shorter for pts with MM, and balanced for pts with other solid tumors. This analysis further characterizes the results from the MM subset of this trial. Methods: Pts with solid tumors or MM were randomized (1:1) to receive 120 mg of SC dmab or 4 mg of IV ZA Q4W. Daily calcium and vit D supplements were strongly recommended. The primary endpoint was the time to first on-study SRE; results from the primary endpoint and lung cancer subset were previously reported. Results: Of 1776 randomized pts, 10% had MM (93 ZA, 87 dmab). OS favored ZA (hazard ratio: 2.26; 10 subject difference in deaths). 1-year OS was 83% dmab, 97% ZA. Imbalances in baseline prognostic characteristics were observed. More pts in the dmab arm had low baseline renal function (CrCl < 40 mL/min) (ZA 2 [2%], dmab 9 [10%]) and more ZA pts underwent stem cell transplant (ZA 23 [25%], dmab 15 [17%]). Additionally, more ZA pts had stage I tumors at diagnosis (ZA 13 [14%], dmab 9 [10%]) and better performance status (ECOG = 0; ZA 30 [32%], dmab 21 [24%]). Study discontinuations due to consent withdrawal or lost to follow-up were also higher in the ZA group (ZA 17 [18%], dmab 11 [13%]) and occurred earlier in the ZA arm (ZA 59%, dmab 45% within 9 months of randomization). Conclusions: In this SRE study of dmab vs ZA, pts were stratified by baseline characteristics known to affect SRE outcomes, but not by prognostic factors or concurrent anticancer therapy that may impact survival in MM. OS results in the MM cohort are difficult to interpret due to small sample size and imbalances in baseline disease characteristics, stem cell transplant therapy, and consent withdrawal or loss of follow-up that favored ZA. A phase 3 trial is currently underway, which controls for these factors in pts with MM. Clinical trial information: NCT00330759.
A phase I/II study (NCT01541332) of pomalidomide (POM), dexamethasone (DEX), and pegylated liposomal doxorubicin (PLD) for patients with relapsed/refractory (R/R) multiple myeloma (MM).
Authors: Hilger James D. , Berenson James R. , Klein Leonard M. , Bessudo Alberto , Rosen Peter J. , Eshaghian Shahrooz , Chamras Hilda , Nassir Youram , Swift Regina A. , Vescio Robert A.
Published: March 2020

8598

Background: POM is a newer IMiD immunomodulatory compound with high in vitro potency that has shown promise in combination with DEX as an effective treatment option for R/R MM patients (pts), even those refractory to bortezomib and lenalidomide (LEN). We conducted a phase I/II trial investigating the safety and efficacy of POM in combination with IV DEX and PLD using a modified dose and longer 28-day schedule in R/R MM pts. Methods: Phase I pts had progressive MM at the time of enrollment that was R/R to at least one anti-MM regimen. Phase II pts had to be refractory to LEN (singe-agent or in combination) demonstrated by progressive disease while receiving LEN or relapse within 8 weeks of its last dose. During phase I, POM was administered orally at 2, 3, or 4 mg daily in 3 successive cohorts of 3 pts each on days 1-21 of each 28-day cycle. DEX was administered IV at 40 mg over 30 min and PLD was administered at 5 mg/m2as an IV infusion over 30-90 min on days 1, 4, 8, and 11 of each cycle. POM doses were escalated until maximum tolerated dose (MTD) was reached. Once MTD was reached, all subsequent pts were enrolled at that dose. Results: To date, 27 pts have been enrolled, with 18 evaluable for efficacy and 19 for safety. Pts received a median of 5 prior treatments (range, 1-18) with a median of 1 prior PLD regimens (range, 0-2). Pts have completed a median of 1 cycle (range: 0-8) with a median of 1.4 months of follow up (range: 0-7.1). No DLTs were seen during phase I, which established the MTD at 4 mg. Phase II has enrolled 16 pts at 4 mg so far. Clinical benefit was seen in 7 (39%) of evaluable pts (partial response = 22%; minor response = 17%) with another 44% showing stable disease. Common ≥ G3 adverse events included leukopenia (32% of pts), neutropenia (32%), lymphopenia (26%), and hyponatremia (16%). Neutropenia at ≥ G3 occurred in more than half of patients on the phase II trial (4 mg POM). Conclusions: The combination of pomalidomide with dexamethasone and PLD on a 28-day cycle shows efficacy for R/R MM pts. However, because of excessive ≥ G3 neutropenia, POM is being reduced to 3 mg for newly enrolled patients. Clinical trial information: NCT01541332.
Coexistence of multiple escape mechanisms in a BRAFV600E-mutated cutaneous melanoma treated with vemurafenib.
Authors: Michielin Olivier , Romano Emanuela , Peters Solange , Paillusson Alexandra , Weber Johann , Muehlethaler Katia , Harshman Keith , Speiser Daniel E , Pradervand Sylvain , Rimoldi Donata
Published: March 2020

9014

Background: Mechanisms of acquired resistance to vemurafenib are the subject of intense research. Here we report, for the first time, two coexisting yet mutually exclusive mechanisms of escape in a melanoma patient who presented an excellent clinical response following reintroduction of vemurafenib. Methods: To investigate the mechanisms of resistance to vemurafenib, we performed whole-exome sequencing using the Illumina technology of a pre-treatment paraffin-embedded lymph node metastasis (Pre) and of two progressing subcutaneous snap-frozen metastases of the right arm (PV1 and PV2). The tumor samples, along with germline controls, were sequenced at high coverage (mean range 268x-356x). Results: We identified 107 exonic somatic Single Nucleotide Variants (SNVs) in Pre, 139 SNVs in PV1, and 127 SNVs in PV2, generating a set of 202 different SNVs, 82 of which were common to all 3 samples. The non-synonymous to synonymous ratios were higher for PV1 (1.82) than for PV2 (1.46), and lower for Pre (1.31). C>T transitions, largely predominated in the samples, indicating light-induced damage. Two independent NRAS escape mutations (Q61K and Q61R) where observed in PV1, whereas appearance of a BRAF splice variant (lack of exon 4-10) was present in PV2. Most importantly, these 2 escape mechanisms were mutually exclusive, i.e. no BRAF splice variant was observed by PCR in PV1 and no NRAS mutation found in PV2. Conclusions: Our results clearly demonstrate that multiple molecular escape mechanisms can be both coexistent and mutually exclusive. These findings have clinical implications: firstly, local treatment of isolated progressing lesions and continuation of vemurafenib could be supported by the fact that the resistance mechanisms are not necessarily shared. This approach is currently being tested within clinical trials with preliminary results that seem to support this hypothesis. Secondly, the coexistence of divergent escapes within the same patient strongly argues that single biopsy analysis at progression might not reflect the molecular complexity of tumor progression, and therefore might not be sufficient to guide selection of second-line optimal combination therapy.
Sequential treatment with ipilimumab and BRAF inhibitors in patients with metastatic melanoma: Data from the Italian cohort of ipilimumab expanded access programme (EAP).
Authors: Ascierto Paolo Antonio , Simeone Ester , Chiarion-Sileni Vanna , Queirolo Paola , Del Vecchio Michele , Di Guardo Lorenza , Guidoboni Massimo , Marchetti Paolo , Antonini Cappellini Gian Carlo , Ferrucci Pier Francesco , Cognetti Francesco , Bernengo Maria Grazia , Guida Michele , Marconcini Riccardo , Mandala Mario , Parmiani Giorgio , Rinaldi Gaetana , Aglietta Massimo , Calabro Luana , Maio Michele
Published: March 2020

9035

Background: Ipilimumab and vemurafenib have recently been approved as single agents for the treatment of unresectable or metastatic melanoma. Currently, limited data exist on the sequential treatment with these agents in patients (pts) with the BRAF mutation; here we evaluate the efficacy outcomes of pts enrolled in the EAP in Italy who sequentially received a BRAF-inhibitor and ipilimumab, or vice versa. Methods: Ipilimumab was available upon physician request for pts aged ≥16 years with unresectable stage III/stage IV melanoma who had either failed systemic therapy or were intolerant to ≥1 systemic treatment and for whom no other therapeutic option was available. Ipilimumab 3 mg/kg was administered intravenously every 3 weeks for 4 doses. Tumour assessments were conducted at baseline and after completion of induction therapy using immune-related response criteria. Patients were considered for this analysis if they tested positive for the BRAF mutation and had received a BRAF-inhibitor before or after ipilimumab treatment. Results: In total, 855 Italian pts participated in the EAP from June 2010 to January 2012 across 55 centres. Out of 173 BRAF positive pts, 93 (53.7%) were treated sequentially with both treatments: 48 pts received a BRAF inhibitor upon disease progression with ipilimumab and 45 pts received ipilimumab upon disease progression with a BRAF inhibitor. As of December 2012, median overall survival was 14.5 months (11.1-17.9) and 9.7 months (4.6-14.9) for the two groups, respectively (p=0.01). Among the 45 BRAF inhibitors pretreated pts, 18 (40%) had rapid disease progression (median overall survival: 5.8 months) and were unable to complete all four induction doses of ipilimumab, while the remaining 27 (60%) pts had slower disease progression (median overall survival: 19.3 months) and were able to complete the therapy with ipilimumab. Conclusions: These preliminary results suggest that, in BRAF-mutated pts, to start the sequential treatment with ipilimumab can provide a better survival than the reverse sequence. These findings deserve confirmation in a prospective study.
Adjusting for treatment crossover in the METRIC metastatic melanoma (MM) trial for trametinib: Preliminary analysis.
Authors: Abrams Keith R. , Latimer Nicholas , Amonkar Mayur , Stapelkamp Ceilidh , Casey Michelle ,   test group
Published: March 2020

9040

Background: In METRIC, a randomized phase III study, trametinib significantly improved PFS (hazard ratio [HR]=0.44 [95% CI 0.31–0.64; p<0.001]) vs chemotherapy (chemo) in patients (pts) with BRAF V600E+ MM and no brain metastases. Median overall survival (OS), a secondary endpoint, has not yet been reached. OS results are likely to underestimate the effect of trametinib as pts progressing on chemo could cross over to experimental treatment (trt). This analysis attempts to adjust for confounding effects of trt crossover on OS in the overall population and first line (1L) subgroup using current METRIC results. Methods: Randomization-based crossover adjustment methods – Rank Preserving Structural Failure Time Models (RPSFTM) and the Iterative Parameter Estimation (IPE) algorithm – were used. We conducted two sets of analyses testing different assumptions regarding the durability of the trt effect. “Trt group” analyses adjusted for crossover under the assumption that the trt effect is maintained until death regardless of trt duration; “On trt – observed” analyses adjusted for crossover under the assumption that the trt effect disappears upon trt discontinuation. Results are presented as HRs. Results: 178 and 95 MM pts were randomized to trametinib and chemo, respectively; 49.5% of chemo pts crossed over to trametinib as of data cut off (Oct. 2011). Median follow-up was 4.9 months and 19.8% deaths occurred across both arms. Crossover adjustment results are presented in the Table. Conclusions: RPSFTM and IPE “trt group” analyses resulted in OS HR point estimates that represented greater trt effects in the overall population and 1L subgroup compared to the unadjusted HRs. Results are exploratory because few deaths have been observed in the current dataset. Future analyses on a mature dataset should produce more robust estimates of the OS trt effect after crossover adjustment. [Table: see text]
Impact of complete lymphadenectomy in stage I melanoma: SEER analysis, 2004-2009.
Authors: Stager Victoria , Arena Elizabeth Anne , Albright Joslyn , Faries Mark B.
Published: March 2020

9101

Background: Stage I melanoma has excellent prognosis, yet it remains a treacherous entity leading to fatal disease progression in a small and ill-defined population of patients. Role of complete lymphadenectomy in early melanoma is not determined. Methods: We used the Surveillance Epidemiology and End Results (SEER) database from 2004 to 2009 to identify patients who underwent wide local excision (WLE) with or without nodal surgery for management of AJCC Stage I primary cutaneous melanoma. Patients with complete data on age, race, sex, and primary tumor histology and anatomic site were categorized by type of surgical treatment into WLE, WLE+sentinel node biopsy (SNB), or WLE+complete lymphadenectomy (CLND) groups. Five-year disease-specific survival (DSS) was determined by treatment group and by sentinel node status. Specific risk factors were identified using multivariate analysis. Results: During the selected time period, 51,573 patients were diagnosed with AJCC Stage I cutaneous melanoma. Rate of SNB was 22%, and out of this group, 2% of patients had metastases to the regional lymph nodes. Five-year DSS was decreased in the node-positive group compared to the patients who had a negative SNB or WLE only (HR=4.95). Rate of CLND was 67%, and it did not improve survival of the patients with positive SNB (5-year DSS 83% vs. 79%, p=0.29). Performance of CLND did not correlate with age, histological type, presence of ulceration, or Breslow depth. Conclusions: SEER database suggests that a clinical equipoise regarding the utility of CLND in patients with positive SLN remains. These findings justify ongoing MSLT II.
Phase II study of selumetinib (sel) versus temozolomide (TMZ) in gnaq/Gna11 (Gq/11) mutant (mut) uveal melanoma (UM).
Authors: Carvajal Richard D. , Sosman Jeffrey Alan , Quevedo Fernando , Milhem Mohammed M. , Joshua Anthony Michael , Kudchadkar Ragini Reiney , Linette Gerald P. , Gajewski Thomas , Lutzky Jose , Lawson David H. , Lao Christopher D. , Flynn Patrick J. , Albertini Mark R. , Sato Takami , Paucar Daniel , Panageas Katherine S. , Dickson Mark Andrew , Wolchok Jedd D. , Chapman Paul B. , Schwartz Gary K.
Published: March 2020

CRA9003

The full, final text of this abstract will be available at abstract.asco.org at 7:30 AM (EDT) on Saturday, June, 1, 2013, and in the Annual Meeting Proceedings online supplement to the June 20, 2013, issue of Journal of Clinical Oncology. Onsite at the Meeting, this abstract will be printed in the Saturday edition of ASCO Daily News.
Survival of melanoma patients with brain metastases treated with ipilimumab combined with stereotactic radiosurgery.
Authors: Tazi Karim , Chiuzan Cody , Shirai Keisuke
Published: March 2020

e20019

Background: Historically, melanoma with brain metastases has a poor prognosis and is a major contributor to patient morbidity and mortality. Recently, the use of ipilimumab has improved overall survival in stage IV melanoma; however, the outcome of patients with brain metastases remains unclear. In this retrospective medical record review, we report the outcome of patients with stage IV melanoma with brain metastases treated with ipilimumab and brain stereotactic radiosurgery (SRS). Methods: All patients with metastatic melanoma treated with ipilimumab from April 2010 to March 2012 were identified and stratified by presence (A) or absence (B) of brain metastases. All patients with brain metastases received SRS. Performance status, dates of stage IV diagnosis, brain SRS and cycle 1 of ipilimumab administration were recorded. We used the Disease Specific Graded Prognostic Assessment (DS-GPA) to estimate the predicted survival. Overall survival was defined as time (months) from the date of the stage IV diagnosis and the time of ipilimumab administration to death or last follow-up. Survival curves were estimated using the Kaplan-Meier method, and compared using a two-tailed log-rank test. Results: Twelve of 30 patients treated with ipilimumab had brain metastases. Median age was 66 years. Median DS-GPA score was 3 (estimated mean survival of 8.7 months). Four patients (33%) in group A and 6 patients (33%) in group B died as of last follow-up. Median number of SRS treatment was 1 (1 to 4), and median total treated lesions were 3 (1-14). Median survivals from date of Stage IV for A and B were 29.1 and 32.9 months, respectively (p=0.67). The estimated 2 year survival rates from date of cycle 1 ipilimumab administration for A and B were 58% (95% CI: 32-100%) and 55% (95% CI: 32-93%), respectively. Ten out of 12 patients in group A maintained an ECOG PS of 0-1 as of last follow-up. Conclusions: Survival of patients with melanoma brain metastases treated with ipilimumab combined with SRS may be comparable to patients without brain metastases. Ipilimumab and SRS do not seem to adversely impact quality of life.
Role of prostaglandin pathways in radiotherapy-induced mucositis.
Authors: Grunberg Steven M. , Vithala Madhuri V. , Vizzard Margaret , Adams Nathan Bradley , Gagne Havaleh Marie , Brundage William , Ashikaga Takamaru
Published: March 2020

e20509

Background: Pathways associated with proinflammatory molecules are upregulated in oral mucositis. Lalla (Support Care Cancer 18:95, 2010) found an association between mucositis pain scores, tissue COX-1, and salivary prostaglandins in 4 patients receiving dose-dense chemotherapy. We investigated whether similar changes would be seen with radiotherapy (XRT)-induced mucositis. Methods: Patients receiving XRT including the oropharynx were evaluated at 4 time points, before XRT, midway through XRT, end of XRT, and 1 month after XRT. Subjective report of pain and objective mucositis scores were recorded. Patients also provided a 5-minute stimulated saliva specimen at each time point collected on ice with a protease inhibitor cocktail. Proteins were estimated using a Bradford assay. Prostaglandins were measured using ELISA assays. Results: 8 evaluable patients entered the study, including 7 male/1 female, median age 60 (range 48-66), primary site (oropharynx 1, unknown primary 1, base of tongue 3, tonsil 1, tongue 1, supraglottis 1), median XRT 7000 rads (range 6000-7200 rads), concomitant chemotherapy (cisplatin 7, none 1), histology (squamous 7, mucoepidermoid 1). Pain and mucositis scores increased during XRT and improved at 1 month after XRT. No increase in COX-2 levels was seen. Salivary PGD2, PGE2, and PGF2 increased from baseline with the greatest increase 1 month after XRT. There was a significant time effect for PGF2 (p=0.028) and marginal time effects for PGD2 (p=0.107) and PGE2 (p=0.069). Conclusions: Increased salivary prostaglandins are seen during and after XRT-induced oral mucositis, suggesting a role for proinflammatory mediators and providing a possible therapeutic target. Clinical trial information: NCT01252498. [Table: see text]
Patient-reported sources of breast cancer survivorship care four years after diagnosis.
Authors: Friese Christopher Ryan , Hawley Sarah T. , Griggs Jennifer J. , Hamilton Ann S. , Graff John , Katz Steven J.
Published: March 2020

e20511

Background: Breast cancer survivors remain “lost in transition” after active treatment due to changing needs and fragmented care. We sought to describe the patterns of breast cancer survivorship care in a diverse sample to identify factors associated with receipt of survivorship care by medical oncologists (med onc). Methods: We conducted a mailed survey to 2,290 women who resided in the Los Angeles and Detroit SEER registry catchment areas with a confirmed invasive breast cancer case from 6/05-2/07. Women were then surveyed approximately 4 years after diagnosis (n=1,536). On the follow-up survey, women were asked to identify their main provider of breast cancer follow up care: med onc, surgeon, primary care physician (PCP)/other physician. We examined the relationship between report of med onc as main provider of survivor care and: age, race/ethnicity, insurance, tumor stage, receipt of chemotherapy, and care by med onc reported on the baseline survey. Bivariate analyses and logistic regression were used to examine med onc-led survivorship care and the factors above. Results were weighted to account for sample selection and non-response. Results: 858 women had invasive disease at time of diagnosis: 65.2% reported med oncs as the main provider of survivorship care, followed by PCP/other physicians (24.3%) and surgeons (10.5%). Of the women who did not receive chemotherapy, 56% reported med onc-led survivorship care, compared with 79% of chemotherapy recipients. In multivariable logistic regression, black women were less likely than white women to report med onc-led survivorship care (OR 0.49, 95% CI 0.34-0.71). Privately-insured patients were more likely than Medicaid recipients to report med onc-led care (OR 2.00, 95% CI 1.16-3.45). Women with higher disease stage, those who received chemotherapy, and those who saw a med onc at baseline were significantly more likely to report med onc-led survivorship care. Conclusions: The oncology workforce shortage compels the identification of optimal and efficient survivorship care models. A mismatch may exist between chemotherapy receipt and med onc-led care. Our data suggest clear guidelines are needed to direct patients to the providers most appropriate to manage their care.
Association between musculoskeletal symptoms and serum vitamin D levels in women receiving aromatase inhibitor treatment.
Authors: Shapiro Alice C. , Swenson Karen K , Nissen MaryJo , Adlis Susan , Maybon Laura , Anderson Elsie , Zwicky Karen E
Published: March 2020

e20560

Background: Up to 40% of women with estrogen positive (ER+) breast cancer treated with aromatase inhibitors (AIs) experience musculoskeletal symptoms (AIMSS) such as bone pain, joint pain, joint stiffness, and muscle weakness that negatively impact functional ability. Previous reports indicate that vitamin D insufficiency is common in this patient population and that D supplementation might attenuate AIMSS by affecting muscle, bone and/or nerve metabolism. To test the association between AIMSS and serum 25(OH)D levels, we analyzed data collected as part of a pilot prospective study assessing instrument effect sizes to measure AIMSS. Methods: Data were analyzed from 58 women, age 61 ± 10 y with a history of ER+ breast cancer stage I-IIIa. AIMSS symptoms were measured at baseline (pre AI) and 6 mo using the Breast Cancer Prevention Trial Musculoskeletal Subscale (BCPT-MS), the Western Ontario and McMaster Universities Arthritis Index (WOMAC), and the Australian-Canadian Hand Osteoarthritis Index (AUSCAN). Serum 25(OH)D was measured by radioimmunoassay (Diasorin liaison, Stillwater, MN). Linear regression analysis was used to determine the association between changes in AIMSS scores (dependent variables) and changes in serum 25(OH)D from baseline to 6 mo, adjusting for age and season. Results: From baseline to 6 mo there were significant increases on all AIMSS measures (BCPT-MS, WOMAC and AUSCAN p<0.02). These increases in AIMSS measures were not associated with the change in serum 25(OH)D from baseline to 6 mo (Δ =11 ng/ml ± 12; p<0.001). Conclusions: Worsening of symptoms during the initial 6 months of AI therapy was not associated with changes in serum 25(OH)D levels. These results suggest that short-term supplementation with 25(OH)D does not attenuate the symptoms of AIMSS in post-menopausal women with ER+ breast cancer during the first 6 mo of AI therapy. However vitamin D insufficiency was uncommon in this study population (mean 25(OH)D at baseline 31 ng/ml ± 10 and 42± 13 ng/ml at 6 mo). Well controlled clinical trials are needed to further our understanding of these relationships. Clinical trial information: NCT01074320.
Hexafil: Individualized or guideline-concordant G-CSF usage—Is there a bridge?
Authors: Tesch Hans , Chang DeLi Tilly , Ottillinger Bertram
Published: March 2020

e20563

Background: G-CSF is frequently used to prevent/treat chemotherapy (CT)-induced neutropenia (CIN) in cancer patients. The non-interventional observational study HEXAFIL on the use of biosimilar filgrastim (EP-2006) was conducted to provide further insight into G-CSF usage with respect to guidelines (EORTC, ASCO) in Germany. Methods: Patients who signed informed consents were enrolled. Data were documented for up to 3 consecutive G-CSF-supported CT-cycles. Rates of modified CT-treatments (dose modification/discontinuation of drug) were calculated by the number and percentage of patients affected; data presented are based on the first CT-cycle. In/Exclusion criteria: www.germanctr.de . Results: A total of 709 breast cancer patients were included in this interim analysis (9/2012). Only 2.0% of all patients experienced febrile neutropenia (FN) and 8.7% neutropenic complications. A majority of patients received primary (49.4%, PP) or secondary prophylaxis (33.6%, SP) with the biosimilar G-CSF. However, 17.1% were treated interventional (TX). Median G-CSF treatment duration was 4d with median start on day 6 after CT. Of all documented patients, 96.3% received CT without modifications; in 3.0% of the patients dose of CT was modified and in 0.8% CT drug was discontinued. To investigate potential effects of guideline-concordant G-CSF treatment the following populations were selected: patients with FN-risk > 20% and (1) G-CSF initiation < day 5 after CT (ie, “guideline-concordant” GL; N=104) or (2) G-CSF initiation starting > day 6 after CT (ie, “individualized” IND; N=169). As expected, IND-patients experienced FN twice as often as GL-patients (4.1% vs 1.9%). Moreover, CT treatment had to be modified in 6.5% of IND-patients compared with only 1.0% of GL-patients. Conclusions: A total of 96.3% of all analyzed patients receiving biosimilar G-CSF-supported CT-cycles had no modification to their CT-regimen. Data indicate that IND-patients showed a higher rate of CT disturbances/FNs and, as a consequence, should “cross the bridge” to potentially benefit from guideline-concordant treatment. However, further data are required to detail the impact of individualized G-CSF treatment. Clinical trial information: DRKS00000313.
Differences in pain, symptom burden, and opioid use among cancer pain patients with active versus non-active disease.
Authors: Bouffard Karina J , Koyyalagunta Lakshmi , Abdi Salahardin , Hernandez Mike , Novy Diane M.
Published: March 2020

e20568

Background: Many cancer survivors with non-active disease suffer with pain and other symptoms. This study investigated differences in symptoms and opioid use among cancer pain patients with active versus non-active disease. Methods: Data were obtained from 518 consecutive new patients seen at the Pain Management Center of MD Anderson Cancer Center from 01/01/09 to 06/30/09. Measures: Usual pain was rated on the Brief Pain Inventory. The Edmonton Symptom Assessment Scale (ESAS) was used for ratings of fatigue, shortness of breath, poor appetite, depression, anxiety, drowsiness, difficulty thinking clearly and insomnia. Opioid use was calculated in morphine equivalency daily dose (MEDD) milligrams based on the sum of long- and short-acting opioids used per day. Analyses of Data: Independent samples t-tests were used to make comparisons between patients with active versus non-active disease on continuous variables. Chi-square tests were used to make comparisons across disease status on categorical variables. Results: 349 patients had active disease; 169 patients had non-active disease. Patients with active disease received significantly higher MEDD (125.6 ± 158.8 mg) versus patients with non-active disease (74.4 ± 87.0 mg). Patients with active disease reported significantly higher mean scores on fatigue, poor appetite, and drowsiness. Average weekly pain scores were comparable and moderately high for both groups of patients. Other symptoms and clinical characteristics were not significantly different across disease status. Conclusions: Plausible explanations for the higher opioid use and symptom burden among patients with active disease are cancer treatments and disease progression. A higher level of pain medication is often needed to achieve pain management during active treatment or following recent surgery. The finding of higher fatigue, poor appetite, and drowsiness among those with active disease is also consistent with the symptom burden expected from treatment. Although patients with active disease have a greater symptom burden and need for pain medication, there is a need for pain and symptom management among patients in the non-active disease phase of survivorship.
Weight loss in solid tumors: Clinical features and prognostic importance.
Authors: Shrotriya Shiva , Aktas Aynur , Estfan Bassam N. , Rybicki Lisa A. , Walsh Declan
Published: March 2020

e20572

Background: Large cancer databases provide valuable information on weight change and its impact on different clinical parameters. Body weight change in adults with solid tumors was examined in outpatients. The objective was to determine if demographics, clinical and biochemical indices are predictive of weight loss (WL). The effect of WL and other parameters on survival were also assessed. Methods: Electronic medical records (EMR) for outpatient visits from a tertiary cancer center were retrospectively reviewed. Body weight and other clinical parameters on first visit (V1) - within a year post diagnosis - last visit (V2) ≥3 weeks after V1. WL at V2 from V1 categorized as: ≤5%, 5.01-10%, >10%. Results summarized by descriptive statistics, level of association and survival analysis. Results: N = 5901; Mean age (±SD): 61 ± 12 years; 82% were Caucasians; 16% African Americans. Common cancers were genitourinary (GU) 31%; gastrointestinal (GI) 16%; breast 15%; lung 15%; head and neck 6%; brain 5% and others 12%. Metastatic disease in 18%. Bone, brain, lymph nodes – common. 45% had radiotherapy and 41% chemotherapy. Median (min, max) weight, kgs: V1=81(32.0, 223), V2=79.4(34, 221). Median duration (min, max), days V1→V2: 195 (22, 1080). Weight loss V1→V2: ≤5% (73%), 5.01-10% (13%) and >10% (14%). Median change in BMI V1→V2: -0.2 (-19, 13). Median change systolic/diastolic blood pressure (BP) V1→V2: -3(-99, 80)/-1(-57, 47). Change in REE V1→V2: -13(-890, 365). Median survival for 5.01-10.0% WL= 9.4 months, >10.0% = 5.3 months and not observed for ≤ 5%. Conclusions: Majority lost ≤ 5% of body weight by V2. WL maximum for head and neck cancer and GI. High BMI predicted greater WL compared to normal or underweight. ≤5% WL had a survival advantage 5.01-10% and >10%. WL remained prognostic for survival even after adjusting for other prognostic factors.
Assessment of communication about palliative care between physicians and their cancer patients prior to admission to the palliative care unit (PCU).
Authors: Storek Benjamin , Nickel Sebastian , Markwordt Janett , Behzadi Asita , Thuss-Patience Peter C. , Sturm Isrid
Published: March 2020

e20575

Background: Discussions on palliative care are particularly challenging for both cancer patients (pts) and their treating physicians. From the pts perspective, prior to their admission to the PCU, information about palliative care is often lacking and their opinions are not adequately respected. In our study, we evaluated 1) whether pts were satisfied with the received information about palliative care prior to admission to the PCU, 2) the pts level of understanding about palliative care options and 3) pts wishes for their stay at the PCU. Methods: n=180 from n=273 pts participated in the study (time period: 12 months). A standardized palliative care assessment was performed on the day of admission. Study interview was performed within 48h after admission; the questionnaire contained free response and multiple-choice questions. Analysis: Likert scaling method with descriptive statistics using SPSS. Results: Baseline characteristics: n=92 male, n=88 female, median age 64 (range 26-89), 53% with an ECOG 3, n=25 hematological and n=155 oncological malignancies. Symptoms: 56% had 8-14 physical symptoms, 36% had 3-4 emotional problems, 38% had high levels of distress. Prior knowledge about palliative care: 38% did not know what a PCU was and 31% believed it was a unit for dying patients. 44% received none, 26% some information about palliative care prior admission. 42% did not feel well informed, 34% felt they received some information on palliative care. Prior information about the disease: 27% felt minimally, 64% felt well informed about their current disease state. The following points were not addressed from the physicians: living will 57%, health care proxy 59%, home care supply 70%, hospice 70%, psychooncological care 52%, prognosis 43%. Wishes of pts on the PCU: improvement in their general condition 47%, pain relief 30%. Conclusions: Our study shows that the majority of pts do not feel sufficiently informed about palliative care prior to the admission at the PCU. A communication barrier between physicians and their pts may explain patient’s views. The data confirm the importance of early integration of palliative care in addition to oncological care.
Modified Khorana risk score for prediction of venous thromboembolic events in cancer patients receiving chemotherapy: An Australian single institution experience.
Authors: Heller Wolfgang H , Khalafallah Alhossain A , Li Rebecca Yuan , Arora Anurag , Latif Maimoona , Nepal Sujana , Loi Sie Wuong , Grabek Daniel , Robertson Iain K
Published: March 2020

e20610

Background: Venous thromboembolic events (VTEs) are a common complication in cancer. The Khorana Score (KS) is widely used for the prediction of VTEs in malignancy. The KS is composed of 5 items: cancer entity, platelet count >350/nL, white cell count (WCC) >11/nL, Hb <100 g/L and body mass index ≥35 (BMI). Scores are grouped into 3 categories indicating the VTE-risk (0=low, 1-2= intermediate, 3 or more points= high-risk). Methods: All ambulatory cancer patients at our institution starting chemotherapy from January 2010 to December 2011 were included. We applied the KS and then modified by adding further cancer subtypes and metastatic status. Results: In 658 of 766 chemotherapy patients, all the data were available for calculating the KS, of whom 52 had a VTE. In multivariate analysis, associations between KS and VTE were found (P≤0.05) in pancreas (p<0.001), lung (p=0.002), stomach (p=0.008), gynaecological cancers (p=0.037), and BMI ≥35 (p=0.004), but not found in lymphoma (p=0.14), high platelet count (p=0.6) and high WCC (p=0.8), or low Hb (p=0.53). There was an increased risk for VTE in some cancers not included in the KS: breast (p=0.01), colorectal (CRC)(p<0.001), prostate (p=0.003) and oesophageal cancer (p= 0.041). The original KS score did not significantly predict VTEs. When adding cases of neoadjuvant/adjuvant (n/a) and/or metastatic (met) CRC, breast, and prostate cancer, significant associations were found, as shown in the Table. Conclusions: The original KS showed only a weak association with VTE occurrence. However, the association was improved by including other cancer entities and / or metastatic status. Major differences between our and other cohorts, such as different proportions of cancer entities and general referral patterns, could explain the discrepancies with other studies. [Table: see text]
Understanding the experience of living with non-small cell lung cancer (NSCLC): A qualitative study.
Authors: Buzaglo Joanne S. , Gayer Christopher , Mallick Rajiv , Micco Ellyn , Morris Anne , Ferris Andrea Stern , Golant Mitch , Langer Corey J. , Mullins C. Daniel , Cella David
Published: March 2020

e20618

Background: As non-small cell lung cancer (NSCLC) treatments improve and patients live longer, it is increasingly important to develop interventions to help patients live fuller lives. We sought to identify key components of quality of life (QOL) and social support in determining therapeutic decision-making and overall value of life-extension, in patients with NSCLC. Methods: Three semi-structured focus groups (n=16) and telephone interviews (n=15) were conducted and recorded with NSCLC patients (N=31), to explore the full range of symptoms that patients considered important to QOL. A tradeoff format assessed the value of life-extension relative to QOL. Patients were asked to consider a hypothetical treatment option that offered on average a 3 month life extension. Results: Mean age was 61.6 years, 67.6% were female, 77.4% white, 61.3% were not employed/retired, 58.1% were living with a spouse/other, 93.5% had health insurance, and 48.4% were Stage III/IV. Sixty-Eight percent of patients conceptualized emotions and attitudinal orientation as symptoms of NSCLC. Key symptoms/concerns changed over time – 74% of patients reported shock and fear at diagnosis, 55% felt fear or loneliness during the beginning of therapy, 52% successfully connected with other NSCLC patients (peers) and support groups, and reported a positive shift in feelings with social/emotional support from all social networks. 26% of patients reported confusion and isolation during treatment due to education gaps. Financially, 23% of patients reported being adversely impacted by co-pays, 36% by unexpected gaps in coverage, 39% by other bills, and 52% accepted help from any/all sources. The most important factor driving treatment-decision making about life-extending therapy was the somatic (i.e., physical symptom) dimension (84% cited as important), followed by functional (32%), relational (23%), and emotional (10%) factors. Conclusions: Patients with advanced NSCLC tend to conflate emotional well-being post diagnosis with symptoms of their cancer and treatment toxicities. However, somatic QOL concerns, ahead of functional, emotional and relational QOL, emerge as the dominant driver of therapeutic decision-making.
The use of intravenous morphine for breakthrough pain in terminal cancer patients admitted to hospice center.
Authors: Chung Ik-Joo , Cho Sang-Hee , Hwang Jun-Eul , Ahn Jae-Sook , Choi Won-young , Shim Hyun-Jeong
Published: March 2020

e20621

Background: The adequate opioid dose to be administered for breakthrough pain(BTP) is still controversial. Dosing recommendations are based on patient’s(pts) total daily opioid dose. Intravenous morphine(IV-M) has been found to be effective and safe for the management of BTP. However, physicians are often reluctant in using large doses of IV-M because of the possible adverse events in terminal cancer pts. The aim of this study was to evaluate whether pts were treated appropriately for their BTP in hospice setting. Methods: A total of 94 consecutive terminal cancer pts who were admitted in the Hospice and Palliative Care Clinic at Jeonnam Regional Cancer Center from June 2012 to Nov 2012 were analyzed in this study. Results: In total, 1,213 BTP events treated by IV-M were recorded and the mean number of events per pts was 13.6 (95% confidence interval (CI) 10.5-15.4). The mean dose of IV-M was 13.9mg (95% CI 12.5-14.5mg, range 3-90mg) and was equivalent to 7.1% of the total daily opioid dose. For each episode, pain intensity and opioid-related symptoms were recorded at the base (T0) and within 30 minutes after (T1). Pain intensity decreased from a mean of 5.1(on a 0-10 numeric scale) at base to 1.8 at T1. A decrease in pain of more than 30%, 50% and 70% was observed in 1179 (97.2%), 958 (78.9%) and 460 (37.9%) BTP events, respectively. In 21 episodes, no changes in pain intensity were observed and a further dose of IV-M was given. Doses of more than 10mg, 30mg and 50mg of IV-M were given for 456 (37.6%), 200 (16.5%) and 104(8.6%). No differences in age, sex and pain location were found. Adverse effects were uncommon, moderate nausea/vomiting in 32 episodes, drowsiness in 15 episodes, and confusion in one episode. Conclusions: In the current study, IV-M was safe and effective for almost all episodes of BTP. This study shows that IV-M did not result in life-threatening adverse effects in terminal cancer pts, including older pts and those requiring relatively large doses.
Daily assessment of quality of life during 100 courses of radiation: Pain, anxiety, problems or concerns, and need to see physician.
Authors: Howell David D.
Published: March 2020

e20625

Background: Patients (Pts) undergoing radiation therapy (RTRx) may have pain, anxiety, distress or other symptoms impacting on quality of life (QOL) at the time of initiation of RTRx. Pts may also develop (or have an exacerbation of) one or more of the above during RTRx. During RTRx, pts are seen at least weekly by the treating physician (MD), and are seen daily by the treating radiation therapy technologists (RTT). Pts may develop problems between weekly MD visits which may benefit from MD interventions. A system was developed where pts would be asked four questions (4?) to assess QOL each treatment day by the RTT: 1) Are you having pain, and if so, how would you rate it on a scale of zero to 10? (PainQ); 2) Are you having anxiety or distress today? (ADQ); 3) Are you having new problems or concerns? (ProConQ); 4) Do you want to see the physician today? (CMDQ). This information was used in pts management. Methods: 100 RTRx courses were reviewed for demographics including gender, age, primary malignancy, region treated, # of visits and total RTRx dose, as well as detailed information from the 4? instrument. Results: Of the 100 pts, 56 were male. Disease distribution: Breast-22; Prostate-20; Head and Neck-20; Lung-13; Brain-7; Other-18. For the ADQ, 83 did not report anxiety or distress; 17 reported anxiety on one or two occasions. For the ProConQ, 35 reported none, 34 reported yes on 1 or 2 occasions, 22 reported yes on 3 to 5 occasions, and 9 reported yes on greater than five occasions; 29 reported yes on 2 days in a row, and 15 reported yes to problems or concerns on 3 days in a row. For the PainQ, 31 reported no pain throughout RTRx, with 22, 23, and 25 reporting pain of any magnitude for 1 to 5, 6 to 10, and greater than ten days, respectively. 22 reported pain greater than 6 on at least one occasion. For CMDQ, 26 of pts did not request additional visits, 71 and 3 requested to see the MD an additional 1 to 5, and 6 to 10 times. Conclusions: A simple instrument prompting a 4? QOL query to pts undergoing RTRx may prompt the need for further evaluation and interventions between scheduled MD visits. This may facilitate more expeditious interventions for RTRx related toxicity as well as for treatment dependent or independent QOL symptoms and needs.
Paulinia CUPANA (PC) (GUARANÁ) dry extract for breast cancer (BC) women with HOT flashes (HFS): Results of a PILOT study.
Authors: Del Giglio Auro , del Giglio Adriana Braz , silva Oliveira Saulo , Zanellato Rebecca Melo , Cavicchioli Livia tiemi , Reifur Lucas , Lerner Tatiana Goberstein
Published: March 2020

e20631

Background: HFs are very disturbing for BC patients, affecting about two thirds of them. PC is an amazonic plant that was shown to have anti-fatigue activity for BC women undergoing chemotherapy. Methods: we included BC women at least 3 months after finishing their treatment with at least 14 HFs per week. Patients received 50 mg PO of PC dry extract twice daily for 6 weeks. We assessed both HF frequency and its severity and patients graded their own toxicities weekly. We employed a phase II Simon design in which 9 out of 15 patients would be required to have at least a 50% decrease in their HF severity score. Results: We included 24 women with a median age of 50.2(36-65). Only 18 started PC and 15 completed the 6 weeks of the study. Three patients declined participation right after starting PC for difficulty in participation and for noncompliance. Ten out of 15 patients had a more than 50% decrease in their HF severity score. Throughout the 6 weeks of treatment we observed statistically significant decreases in HFs number (p =0.0331) and Severity Scores (p=0,0039). As compared to week 0, patients reported worsening of anorexia (1), insomnia (1), nausea (1), fatigue (1), sweating (1), constipation (1), anxiety (1), humor change (1) and headache (1). None of these toxicities warranted discontinuation of the study. Conclusions: We conclude that PC was effective for HF control achieving the pre-specified threshold with acceptable toxicity and warrants further confirmatory studies.