bluuebunny/crossref_metadata_2025 huggingface dataset:
Targeted agents matched with tumor molecular aberrations: Review of 160 patients with advanced melanoma treated in a phase I clinic.
Authors: Henary Haby Adel , Hong David S. , Falchook Gerald Steven , Tsimberidou Apostolia Maria , George Goldy , Wheler Jennifer J. , Fu Siqing , Naing Aung , Piha-Paul Sarina Anne , Janku Filip , Kim Kevin B. , Hwu Patrick , Kurzrock Razelle
Published: March 2020

8551

Background: Identification of activating mutations in melanoma has increased the number of novel targeted agents for this disease. Methods: Weretrospectively reviewed clinical outcomes of 160 consecutive metastatic melanoma patients (pts) treated in the Dept of Investigational Cancer Therapeutics (Phase I program) at M. D. Anderson since 2008, and compared their median progression free survival (PFS) to their first and last standard systemic therapy PFS. In addition, we compared those pts’ outcomes tested for tumor molecular aberrations on a phase I trial with a matched targeted agent with those of pts who were treated without regard for their molecular profiles. Results: Of 160 pts treated on 35 different phase 1 clinical trials, 110 pts (69%) had ≥ 1 molecular aberration. Of those pts who had adequate tissue for molecular analysis, 63% (85/134) pts had BRAF mutation, 20% (22/109) NRAS mutation, 20% (1/5) GNAQ mutation, 11% (1/9) P53 mutation, 2.5% (1/39) PIK3CA and 1.3% (1/76) had KIT mutation. 77 (48%) pts were treated on a phase I trial with a matched targeted agent and 83 (52%) pts were treated on a non-matched phase 1 trial. The overall response rate was 39% (complete response [CR], 9%; partial response [PR], 30%) in the 77 pts treated with matched therapy and 9% (all PRs) in the 83 pts treated without matched therapy (P = 0.0018). 139 (87%) pts received at least one systemic therapy before referral to phase I, median PFS was longer on phase 1 therapy than on last line standard therapy prior to referral to phase 1 (4.2 vs. 2.8 months, P = 0.002). Median PFS was greater for pts on matched vs. non-matched therapy (5.3 vs. 3.7 months, log rank P = 0.004). Also, median PFS was longer on phase 1 matched trial than on first standard treatment (5.3 vs. 3.9 months, log rank P = 0.045).PFS did not differ between first standard and non-matched phase 1 study. Univariate analyses with the log rank test revealed that matched therapy (P = 0.004) was positively associated with longer PFS on phase I clinical trials. Conclusions: Matching melanoma pts with targeted drugsbased on specific molecular aberrations in the phase I setting can be associated with superior outcomes compared to prior standard systemic therapies.
Everolimus in combination with paclitaxel and carboplatin in patients with advanced melanoma: A phase II trial of the Sarah Cannon Research Institute (SCRI).
Authors: Hauke Ralph J. , Infante Jeffrey R. , Shih Kent C. , Rubin Mark S. , Arrowsmith Edward , Whorf Robert C. , Hainsworth John D.
Published: March 2020

8556

Background: The PI3k/AKT pathway is activated in most metastatic melanomas; mTOR is a critical component of this pathway. Everolimus, an mTOR inhibitor, has demonstrated single-agent activity in patients with advanced melanoma. We evaluated the efficacy and toxicity of everolimus in combination with paclitaxel/carboplatin in patients with advanced melanoma. Methods: Eligible patients had stage IV or unresectable stage III melanoma, unselected for braf status, previously untreated with chemotherapy or targeted agents. Previous immunotherapy was allowed. Additional eligibility criteria: ECOG PS 0 or 1; measurable disease; no active brain metastases; adequate bone marrow, kidney, and liver function; informed consent. All patients received paclitaxel 175mg/m2, 1-3 hour IV infusion, and carboplatin AUC 6.0 IV on day 1 of each 21-day cycle. Everolimus 5mg PO was given daily. Patients were evaluated for response every 6 weeks; treatment continued until progression or undue toxicity. Median progression-free survival (PFS) for paclitaxel/carboplatin treatment is 4 months; we looked for a median PFS of 6 months with this novel combination. Results: Seventy patients were treated between 2/2010 and 2/2011; median age 63, 90% had stage IV melanoma. 91% of patients received at least 2 cycles of therapy; median cycles received: 4 (range: 1-25+). Twelve patients (17%) had partial responses; an additional 42 patients (60%) had stable disease at first reevaluation. After a median 13 months of followup, the median PFS for the entire group was 4 months (95% CI: 2.8 – 5.0 months); 96% had progressed during the first 12 months. Median survival was 10 months (95% CI: 7.3 – 10.9 months). Toxicity was as previously described with these agents; neutropenia was the most common grade 3/4 toxicity (27%). Only 3 patients stopped treatment due to toxicity. Conclusions: The addition of everolimus to paclitaxel/carboplatin was feasible and well-tolerated; however, efficacy results were similar to those reported with paclitaxel/carboplatin alone. Further development of this combination regimen for treatment of metastatic melanoma is not recommended.
mTOR pathway activation in KIT-mutated melanoma with acquired imatinib resistance.
Authors: Si Lu , Xu Xiao wei , Kong Yan , Flaherty Keith T. , Chi Zhi Hong , Cui Chuan Liang , Sheng Xi Nan , Li Si Ming , Tang Bi Xia , Guo Jun
Published: March 2020

8562

Background: c-Kit mutation is a common genetic abnormality in certain melanoma subtypes, and is a target for treatment. However, the mechanisms of secondary (acquired) resistance and how to treat patients in the second line are unknown. Methods: Tissuesamples were obtained from c-Kit-mutated melanoma patients who failed of imatinib after having PR or SD for at least 6 months pre- and post-imatinib therapy. Somatic mutations in genes in MAP kinase (c-Kit, BRAF, NRAS, etc) and PI3K-AKT-mTOR (AKT1, TSC1, PTEN, etc) pathways were detected by DNA sequencing. The expression of pS6RP, p4E-BP1, pAKT and pERK1/2 were examined by immunohistochemistry (IHC) assays. Results: Four paired samples (formalin-fixed, paraffin-embedded) were analyzed. 1) Laboratory results: No secondary mutations in addition to the c-Kit mutations identified at baseline were identified. However, IHC showed increased pS6RP and p4E-BP1 (two targets of mTOR activation) as well as increased pAKT and pERK1/2 in imatinib-resistant samples, suggested that mTOR signaling pathway was selectively activated in these secondary imatinib-resistant melanomas. 2) Treatment: Everolimus is an orally administered inhibitor of mTOR. The four patients received everolimus (10 mg/day) by continuous daily dosing. The tumor response revealed 1 PR and 3 SD (all >3 months) with grade 1-2 toxicities consisting of myelosupression, hyperglycemia, hypercholesterolemia and hypertriglyceridemia, consistent with previously reported toxicities for everolimus. Conclusions: The case series provides an important clue that activation of the mTOR signal pathway may be one of the mechanisms for secondary imatinib resistance in c-Kit-mutated melanomas. The results also show that everolimus may be effective and safe for melanoma patients who develop resistance to imatinib and could be investigated in combination with c-Kit inhibitors in treatment-naive patients.
Outcomes of patients with malignant melanoma treated with immunotherapy prior to or after vemurafenib.
Authors: Ackerman Allison , McDermott David F. , Lawrence Donald P. , Gunturi Anasuya , Flaherty Keith T. , Giobbie-Hurder Anita , Hodi F. Stephen , Ibrahim Nageatte , Atkins Michael B. , Cho Daniel C. , Sullivan Ryan J.
Published: March 2020

8569

Background: Treatment of patients (pts) with BRAF mutant malignant melanoma (MM) with vemurafenib (vem), a BRAF inhibitor (BRAFi), is associated with a high response rate (RR) and improvement in progression free survival (PFS) and overall survival (OS) compared to standard chemotherapy. Responses to vem are typically not durable and most pts require additional therapy. However, there is little data to guide sequencing of vem with other standard therapies such as ipilimumab (ipi) or interleukin 2 (IL-2). Methods: 43 pts treated with vem as part of clinical trials from 2009-2012 were retrospectively identified. RR of vem was calculated for all pts as well as for pts treated with immunotherapy (IT) prior to vem. The OS from first systemic and vem treatment, duration of vem therapy, OS from when pts came off vem, and PFS and OS for post-vem ipi was determined using Kaplan-Meier estimates. Results: Of the 43 pts, 11 remain on vem and 32 are off vem (19 deceased) with a median follow up of 19 mo. Pre-vem LDH was elevated in 46% (17/37 evaluable pts). The RR to vem was 52% (22/42 evaluable pts), the median duration of therapy 5.6 months (mo), and the median OS 19.3 mo, similar to results in trials. The median OS from initiation of any treatment was 27 mo. 16 pts received IT (11 IL-2, 4 ipi, 1 IL-2 then ipi) prior to vem with a median OS of 31.2 mo; the RR of vem following IT was 75% (12/16). At time of vem discontinuation 50% of pts (12/24 evaluable) had an elevated LDH, and the median OS of the 32 pts who stopped vem was 4 mo from last vem dose. 10 of these pts then received single-agent ipi; six of whom had an elevated LDH. Five pts died within 3 mo of last vem dose, and all 10 pts had disease progression (PD) at 6 months with a median PFS of 0.7 mo and OS of 2.2 mo. The 3 pts who lived beyond 1 year following vem and then ipi were subsequently treated with a BRAFi following PD on ipi. Conclusions: Response to vem following IT appears similar to that seen in previously untreated pts. Median PFS and OS for pts receiving ipi after discontinuation of vem are poor, possibly due to rapid PD at the time of vem discontinuation. Prolonged OS is primarily seen with resumption of BRAF inhibition. Our data suggests that in appropriately selected pts, IT should be considered prior to BRAFi.
Use of Cobas 4800 BRAF mutation test for the analysis of BRAF V600 mutations in cytological samples (CS) from metastatic melanoma (MM).
Authors: Martin-Algarra Salvador , Labiano Tania , Echeveste Jose Ignacio , Gomez Nerea , Montañana Myriam , Aguirre Mercedes , Echarri Mari­a Eugenia , Sanmamed Miguel F. , Gurpide Alfonso , Perez-Gracia Jose Luis , Idoate Miguel A. , Lozano Maria D.
Published: March 2020

8572

Background: Vemurafenib is currently the most active first-line treatment in MM patients that harbor BRAF-V600E mutations. The Cobas 4800 BRAF V600 Mutation Test is an FDA-approved, CE-marked test that identifies formalin-fixed-paraffin-embedded samples (FFPE) carrying the BRAF V600E mutation. Fine needle aspirates are frequently the only samples available in MM patients, but the use of CS has not been validated in this platform. We have evaluated the capability to identify BRAF-V600E mutations in CS of MM with the Cobas 4800 BRAF Mutation Test, and results have been compared to the conventional Sanger direct sequencing method. Methods: BRAF mutations have been studied in 117 samples from 98 MM patients with the conventional Sanger method: 37 (32%) FFPE and 80 (68%) CS. DNA was extracted from 4-micron sections in FFPE and from stained smears in CS. All CS contained >50% of tumor cells. In a second step, 57 out of the 117 samples have been studied using Cobas (25 CS and 32 FFPE). In CS, Nucleospin Tissue (Macherey-Nagel) DNA extraction was used in 17 cases and the Cobas procedure in 8. FFPE and CS paired samples were available in 9 patients. Results were compared using the Kappa coefficient. Results: There was 93% (53/57) agreement between Cobas and direct sequencing. All V600E+ cases were detected with both methods. Four V600R+ cases were negative using Cobas. Mean DNA concentrations using Nucleospin and Cobas procedures were 55.20 ng/µl and 11.37 ng/µl respectively. Concordance using Cobas in FFPE and CS paired samples was 100%. The table shows the results with Cobas and direct sequencing in 25 CS. One V600R+ case was not detected with Cobas. Conclusions: The Cobas 4800 BRAF Mutation Test results using CS containing >50% of tumor cells are identical to those obtained with FFPE. In our experience, DNA concentrations from CS with the Cobas method are lower than those obtained with Nucleospin procedure. These results provide a strong rationale for a larger validation study. [Table: see text]
Evaluation of the absolute lymphocyte count as a biomarker for melanoma patients treated with the commercially available dose of ipilimumab (3mg/kg).
Authors: Postow Michael Andrew , Yuan Jianda , Panageas Katherine , Bogatch Kita , Callahan Margaret , Cheng Michael , Schroeder Sebastian Edoardo Artur , Kendle Ryan F. , Harding James J. , Dickson Mark Andrew , D'Angelo Sandra P. , Carvajal Richard D. , Schwartz Gary K. , Wolchok Jedd D.
Published: March 2020

8575

Background: Ipilimumab (ipi) has demonstrated an overall survival (OS) benefit in 2 phase III trials. Only ~30% of patients (pts) achieve clinical benefit, and factors that determine which pts benefit are unclear. For pts treated with 10mg/kg of ipi, we previously reported that an absolute lymphocyte count (ALC) ≥1000/μL prior to dose 3 [week (wk) 7] was associated with improved OS. Since the mean increase in ALC during ipi treatment correlates with dose, we investigated if ALC is also associated with improved OS at 3mg/kg, the currently FDA approved, commercially available dose. Methods: In an IRB-approved analysis, we evaluated landmark survival data from 137 pts treated with 3mg/kg of ipi at Memorial Sloan-Kettering Cancer Center. 67 pts were treated on an expanded access protocol (CA 184-045). 70 pts were treated per FDA approval (commercial ipi) with 4 standard induction doses. These 2 groups were analyzed separately because some pts in CA 184-045 received re-induction ipi. ALC was determined at first ipi dose (baseline, wk 1) and at subsequent doses (wks 4, 7, and 10). Results: Pts treated with 3mg/kg on CA 184-045 with a wk 7 (prior to dose 3) ALC ≥1000/µL had significantly improved OS compared to pts with an ALC at wk 7 <1000/μL (Median OS: not reached vs. 4.24 mos, p<0.001). This OS difference was also seen for pts treated with commercial ipi (Median OS: not reached vs. 4.44 mos, p<0.01). This difference remained significant in a multivariable model accounting for Karnofsky performance score, LDH, M-stage, and number of prior therapies for pts in the CA 184-045 group and commercial ipi group (p=0.01 and p=0.05, respectively). Baseline ALC ≥1000/µL was associated with improved OS (p=0.02) for pts in the commercial ipi group, though follow-up is limited. Conclusions: At the FDA approved dose of ipi, 3mg/kg, ALC at wk 7 remains significantly associated with improved OS. Our preliminary finding of improved OS for pts treated with commercial ipi whose pre-treatment baseline ALC ≥1000/µL deserves confirmation with longer follow-up and prospective validation. Baseline or on treatment ALC may be a marker of overall prognosis, regardless of therapy.
Efficacy and safety of the hedgehog pathway inhibitor vismodegib in patients with advanced basal cell carcinoma (BCC): ERIVANCE BCC study update.
Authors: Sekulic Aleksandar , Migden Michael R , Oro Anthony E , Lewis Karl D , Hainsworth John D , Yoo Simon , Dirix Luc , Hou Jeannie , Yue Huibin , Hauschild Axel ,   on behalf of the ERIVANCE BCC Study Investigators
Published: March 2020

8579

Background: The ERIVANCE BCC study is the pivotal trial of vismodegib (GDC-0449), a first-in-class small-molecule inhibitor of Hedgehog signaling, for treatment of locally advanced (laBCC) and metastatic BCC (mBCC), for whom there are no other effective therapy options. The study met the primary endpoint of overall response rate by independent review (Sekulic, Melanoma Res 2011). Here we report a 6-mo update of investigator-assessed (I-A) efficacy and safety endpoints as of May 26, 2011. Methods: This multicenter, international, nonrandomized 2-cohort study enrolled patients (pts) with laBCC (deemed inoperable or for whom surgery would be significantly disfiguring), and mBCC pts with RECIST-measurable disease. Pts received 150 mg oral vismodegib daily. Results: 104 pts (71 laBCC/33 mBCC) enrolled at 31 sites in the US, Europe, and Australia. I-A efficacy endpoints are shown in the table. One-year survival rate was 77.3% (95% CI 62.48–92.09%) for mBCC and 93.1% (95% CI 86.49–99.63%) for laBCC. Adverse events (AEs) in >30% of pts were muscle spasms, alopecia, dysgeusia, weight decrease, fatigue, nausea, and amenorrhea (33.3%; 2/6 pts). Serious AEs were reported in 32 pts (31%). No additional fatal AEs were reported since the prior data cut (n=7, 7%; none considered related to vismodegib). Conclusions: This 6-mo update of I-A efficacy and safety endpoints from the ERIVANCE BCC study supports the significant clinical benefit of vismodegib in both laBCC and mBCC reported at the primary analysis. Median DOR and PFS increased numerically with follow-up. The AE profile was consistent with the prior data cut. These results further support the efficacy of vismodegib for treatment of advanced BCC. [Table: see text]
Correlation of BRAF and NRAS mutation status with tumor characteristics and treatment outcomes in melanoma patients with brain metastasis.
Authors: Koay Eugene Jon , Bucheit Amanda Dawn , Jakob John Andrew , Hyun Eric D. , Settle Stephen H , Brown Paul D. , Davies Michael A. , Sulman Erik P.
Published: March 2020

8584

Background: The management of melanoma has evolved rapidly with the identification of activating mutations in the majority of patients (pts). We reviewed characteristics and outcomes of molecularly characterized melanoma pts with brain metastasis (BM) to help design and interpret future clinical trials. Methods: We reviewed clinical and pathologic features of melanoma pts with known BRAF and NRAS mutation status and BM. Pt demographics, intra- (IC) and extra-cranial (EC) tumor characteristics, and IC/EC disease treatments were correlated to BM treatment outcomes (local and distant brain control [LC, DC]) and overall survival (OS). Univariate and multivariate analyses were performed to identify significant associations between mutation status and outcome. Results: We identified 296 pts with melanoma BM and known BRAF/NRAS mutation status diagnosed from 2005 to 2011. Mutation prevalence was BRAF 57%, NRAS 17%, and wild-type for both genes (WT) 26%. The initial treatments given for BM were surgery/radiosurgery (SRS) 60%, surgery/SRS + whole brain radiation (WBRT) 7%, WBRT alone 19%, systemic therapy alone 9%, and no treatment 5%. Mutation status was not significantly associated with sex, performance status, EC disease status, number of brain lesions, or BM treatment. Pts with mutations were younger (p<0.0001) and more likely to have symptomatic BM (p=0.0003) than WT pts. In univariate analysis, BM treatment strategy (p<0.001) and mutation status predicted for poor LC, with 6 month LC rates of 70% for any mutation and 88% for WT (HR=1.86, p=0.048). Compared to systemic agents alone, use of radiation (SRS or WBRT) improved LC for pts with a mutation (HR 0.23, p=0.0006). Subsequent multivariate analysis identified mutation status and radiation treatment as independent predictors of LC (HR 2.5 and 0.25, respectively). Mutation status did not predict for DC or OS. Conclusions: The presence of BRAF and NRAS mutations predicts worse LC following conventional treatments for melanoma BM. Radiation may improve LC in pts with a mutation. This data suggest a role for combining radiation with targeted therapies in melanoma pts with activating BRAF or NRAS mutations in the treatment of BM.
KIT, NRAS, BRAF, and PTEN alterations in acral lentiginous melanomas.
Authors: Zebary Abdlsattar , Omholt Katarina , Hoiom Veronica , Johansson Carolina , Linden Diana , Vassilaki Ismini , Hansson Johan
Published: March 2020

8588

Background: Acral lentiginous melanoma (ALM) accounts for ~5% of all melanomas. ALMs are often located on palms, soles and under nails. Patients with ALM are significantly older at diagnosis and have a poorer prognosis than patients with other types of cutaneous melanoma. We analyzed a large series of ALMs from Swedish patients to better define the frequency of KIT, BRAF, NRAS, and PTEN mutations in ALM. The effect of mutation status on tumor and patients characteristics was also studied. Methods: A total of 77 primary ALMs and 8 paired metastases were analyzed. Laser capture microdissection was used to dissect tumor cells from formalin-fixed paraffin-embedded tissue. Tumors were screened for mutations in the KIT (exons 11, 13, 17 and 18), NRAS (exons 1 and 2), BRAF (exons 11 and 15) and PTEN (exons 1, 3-6, 10, 11 and 12) genes by direct sequencing. Results: There were 42 females and 35 males with a median age at diagnosis of 71 years. The most common location was the feet (60.5%), followed by subungual sites (34.2%). Overall, mutations in KIT, NRAS and BRAF were detected in 11.8%, 14.5% and 16.0% of the ALMs, respectively. In no case were KIT, NRAS and BRAF mutations detected in the same tumor. For 8 primary ALMs the corresponding metastases were available for analysis. In five metastases the same KIT (n=3) or BRAF (n=2) mutation was detected as in the primary ALMs, suggesting that the KIT and BRAF mutations had occurred before metastasis. BRAF and NRAS mutations were significantly more common in females (P=0.044). ALMs with NRAS and BRAF mutations were more commonly located on the feet compared with KIT mutated ALMs which were more frequent on subungual sites (P=0.041). Other clinicopathological features such as age at diagnosis, thickness, ulceration, histological subtype and Clark’s level showed no significant correlation with the mutation status. A subset of 25 tumors was evaluated for mutations in the PTEN tumor suppressor gene. One tumor was found to carry a nonsense mutation (W111X). To our knowledge, this is the first description of a PTEN mutation in ALM. Conclusions: Our results confirm the presence of KIT, NRAS and BRAF mutations in ALM. KIT, NRAS and BRAF mutation status associated significantly with anatomical site. PTEN mutations seem to be rare in ALMs.
TILs in metastatic melanoma tumors: A biomarker for immunotherapy?
Authors: Chandra Sunandana , Ding Yi , Ma Michelle W. , Bannan Michael , Darvishian Farbod , Berman Russell S. , Shapiro Richard , Krogsgaard Michelle , Osman Iman , Pavlick Anna C.
Published: March 2020

8589

Background: Increased tumor infiltrating lymphocytes (TILs) in primary (P) and locoregional melanoma tissue correlate with improved clinical outcome. Our recent data have suggested that matrix metalloproteinase 23 (MMP 23) expression (exp) in P result in lower prevalence of TILs and correlate with poor clinical outcome. On this basis, we examined P and metastatic (M) melanoma tissues to assess for concordance between the presence of TILs, MMP 23 protein levels and clinical response(resp) to anti-cytotoxic T-lymphocyte antigen 4 (CTLA4) therapy (tx). Methods: 21 melanoma patients (pts) with M specimens were analyzed. 17 matched P specimens were also evaluated. Immunohistochemical (IHC) staining for TILs of the pre-anti-CTLA4 specimens were conducted and confirmed by 2 pathologists. IHC TILs were graded- 2+: >10% TILs present in multiple foci in both peri- and through the tumor; 1+: 1-10% TILs present in one or more foci in the tumor and predominantly peri-tumor; 0: no TILs were present or if the lymphocytes did not infiltrate the tumor. TILs in P and M were analyzed for concordance and potential for predictability of resp to anti-CTLA4 tx. Staining to identify lymphocyte subtypes and MMP 23 exp in M is being completed. Results: 20 pts received anti-CTLA4 tx. M analysis- 6 pts with 0 TILs in M (5 no response [NR], 1 partial response[PR]); 8 pts with 1-2+ TILs in M (1 complete response [CR], 5 PR, 2 progressive disease [PD]); 6 pts with 2+ TILs in M ( 3 CR, 2 PR, 1PD). 1 pt with 2+ TILs in M resected, no tx and 4 years disease free. TILs present in 13 P, absent in 4 P and not evaluable in 4 pts with unknown P melanoma. MMP 23 protein scores in P (range 2-4) correlated with melanoma recurrence. MMP 23 exp in M will be reported. Conclusions: TILs in P do not appear to correlate with TILs in M or predict for resp to anti-CTLA4 tx. TILs in M may be an indicator of responsiveness to anti-CTLA4 tx. Identification of the type of M TIL subsets may further refine tx recommendations.
Patterns of care in adjuvant systemic therapy of patients with stage III melanoma: A U.S. population-based study.
Authors: Hu Boyu , Koon Henry B. , Kim Julian
Published: March 2020

8595

Background: Use of adjuvant systemic therapy in patients with stage III melanoma is widely known to be variable based upon multiple factors such as patient age and comorbidities as well as the preference and even geographic location of the oncologist and patient. The purpose of this study was to compare the use of adjuvant therapy among patients treated in teaching hospitals and community hospitals. Methods: The study population consisted of patients with stage III melanoma enrolled into the National Cancer Database (NCDB) between 2000-2008. Patients were selected based upon surgery as the first course of therapy which resulted in a total of 27,353 eligible for analysis. The study population was then categorized into those who were treated at Teaching Hospitals (TH) including National Cancer Institute-designated cancer centers or Community Hospitals (CH). Multiple variables including age, median household income, insurance status, race and overall survival were compared between patients in the two hospital groups. Results: The overall proportion of stage III patients who received adjuvant systemic therapy was approximately 30%. There was no difference in the proportion of patients receiving adjuvant systemic therapy between patients treated in TH as compared to CH, and there was no obvious trend towards increased use over time. Of interest was that the cohort of patients designated as being treated at TH had a higher proportion of patients less than 70 years old as compared to CH. Median household income was found to be higher in patients treated at TH. Finally, despite the observation that the proportion of patients who received adjuvant therapy was not different, there a significantly higher 5-year overall survival in patients treated at TH as compared to CH. Conclusions: Although the proportion of patients who received adjuvant systemic therapy was comparable in TH and CH, there was a significant increase in 5-year overall survival within TH. Additional factors such as age, lesser comorbidities, more favorable socioeconomic factors or other unmeasured factors such as type of adjuvant therapy or whether adjuvant therapy was completed may have contributed to the improved survival in patients treated at TH.
Comparison of sun protection modalities in parents and children.
Authors: Mortier Laurent , Saiag Philippe , Robert Caroline , Sassolas Bruno , Lhomel Christine , Lebbe Celeste , Grange Florent
Published: March 2020

8601

Background: Routine sun protection is recommended to prevent skin cancer. Our aims were to examine and compare, in an observational survey, modalities of sun protection in parents and their children. Methods: This French nationwide observational survey, EDIFICE melanoma, was conducted through phone interviews among a representative sample of 1502 subjects aged ≥ 18 years old, using the quota method. The survey took place shortly after summer, from 28 Sep 2011 to 20 Oct 2011. Results: 1502 subjects were interviewed. Among them 1067 reported that they were sun-exposed (SE) at least ten days per year, 748 were parents, and 319 had no children. Sun protection measures seemed well done both in “parents” and “nonparents” groups: 74% used clothing; 43% used sunscreen, which was regularly renewed in 57% of cases. Sun protection measures used by SE parents for SE children were superior, both qualitatively and quantitatively to those used for themselves, ie 50% of parents reported using clothing, sunglasses and hat for their children vs 23% for themselves. In 87% of cases, parents reported regular re-application of sunscreen for their children vs 44% for themselves. The sunscreen SPF (Sun Protection Factor) was significantly lower for parents than for their children. Such data are in accordance with Buller et al. (Oncol Nurs Forum 1995), but contrast with the findings of Riordan et al. (J Pediatr 2003) with children being significantly less likely to wear sunglasses and to adopt sun avoidance habits than their parents. Conclusions: Sun protection awareness seems globally satisfying in the French population, with no difference between adult parents and nonparents, and is similar to that reported in Germany (Gambicher JEADV 2010), but seems better than in the US (Buller et al. JAAD 2011). Furthermore, French parents use sun protective measures qualitatively and quantitatively more efficiently for their children than for themselves.
EXCAP exercise to improve fatigue, cardiopulmonary function, and strength: A phase II RCT among older prostate cancer patients receiving radiation and androgen deprivation therapy.
Authors: Mustian Karen Michelle , Sprod Lisa , Janelsins Michelle Christine , Peppone Luke Joseph , Mohile Supriya Gupta , Trevino Lara Anne , Gewandter Jennifer S. , Chandwani Kavita Dayal , Heckler Charles E , Morrow Gary R.
Published: March 2020

9010

Background: Radiation therapy (RT) and androgen deprivation therapy (ADT) result in cancer-related fatigue (CRF), decreased cardiopulmonary function (CPF) and decreased strength. Research suggests exercise can improve CRF during RT and ADT, through physical conditioning responses that improve CPF and strength. We explored the influence of an individually-tailored, home-based exercise intervention (EXCAP), including progressive resistance and aerobic training, on CRF, CPF and strength. Methods: Older prostate cancer patients (N=58; mean age=67), receiving RT (47%) or ADT (53%), were randomized to 6 wks of EXCAP (7 days/wk) or standard care (RT or ADT with no exercise). CPF (VO2 max) was assessed via graded exercise testing (GXT) or a 6-minute walk test when GXT was contraindicated. Muscular strength was assessed using multiple repetition maximum testing (chest press and leg extension). CRF was assessed via valid self-report questionnaires (BFI, POMS-FI, MFSI). All assessments were pre- and post-intervention. Results: ANCOVAs, controlling for baseline, revealed significant differences between groups in mean levels of CRF on the BFI and POMS-FI (all p<0.05), and a trend toward differences on the MFSI (p<0.10) with significant baseline interactions (all p<0.05) post-intervention: exercisers decreased CRF while controls increased. ANCOVAs revealed a trend toward differences between groups in mean levels of CPF (VO2 max) and strength (all p<0.10): exercisers improved while controls declined in performance. Pearson correlations revealed significant inverse associations between changes in CRF (BFI) and CPF (p<0.05;r=-0.0.36), and CRF and strength (p<0.05;r=-0.0.31). MANOVA revealed that changes in CPF and strength significantly predicted changes in CRF (p<0.05, r=0.67) and accounted for 45% of the variance. Conclusions: Exercise improves CRF and these improvements may be mediated, in part, by improvements in CPF and strength. Future phase III RCTs with prostate cancer patients receiving RT and ADT are needed to confirm these relationships. Funding: DOD W81XWH-07-1-0341, NCI K07CA120025, NCI 1R25CA102618.
Prognostic factors of the loss of autonomy (LoA) in older patients with cancer receiving first-line chemotherapy.
Authors: Soubeyran Pierre-Louis , Fonck Marianne , Hoppenreys Laurent , Hoppe Stephanie , Bellera Carine , Blanc-Bisson Christele , Blanc Jean-Frédéric , Ceccaldi Joel , Mertens Cecile , Imbert Yves , Cany Laurent , Vogt Luc , Dauba Jérôme , Houede Nadine , Floquet Anne , Chomy François , Brouste Veronique , Ravaud Alain , Mathoulin-Pelissier Simone , Rainfray Muriel
Published: March 2020

9012

Background: Actual data on prognostic geriatric factors of health outcomes are lacking. We aimed to examine whether a decrease in autonomy for activities of daily living (ADL) after a first cycle of chemotherapy influences elderly cancer pts prognosis, and to determine prognostic factors of this LoA from a range of biological and geriatric evaluation factors. Methods: Pts> 70 years receiving 1st-line chemotherapy for a range of cancers were included in this multicentre prospective study. A LoA was defined as a decrease of 0.5 or more points on the ADL scale between the beginning of treatment and the 2nd cycle (ADL scored 6 to 0). The association between a LoA and OS was examined and prognostic factors were sought from the pre-treatment Geriatric Assessment data (CIRS-G, IADL, MNA, MMSE, GDS et Get up and Go) and from baseline biological and clinical information (age, sex, tumor extension and localization, performance status, BMI, weight loss, albumin, CRP, haemoglobin levels, leucocyte and platelet count, creatinine clearance). Pts completely dependent at baseline (ADL score 0) were excluded as a LoA was not possible. Results: Among 364 pts included, 299 pts were evaluable and 50 experienced a LoA. A LoA was significantly associated with an increased risk of death (RR 1.518, 95%CI[1.079-2.135]). Biological and clinical factors were not associated with LoA but pre-treatment low GDS15, dependencies on the IADL, low MMS, slow Get Up and Go, low ECOG-PS and poor MNA were found to be prognostic of a LoA in univariate analyses. In the multivariate model, low GDS (OR 2.4, p=0.01, 95%CI [1.23-4.66]) and dependencies on the IADL (OR 3.0, p= 0.027, 95%CI = [1.13-9.09]) were independently associated with an increased risk of LoA. Conclusions: Our study underlines the close link between LoA during treatment and poorer prognosis of elderly pts with cancer. Pts with a pre-treatment low GDS15 and IADL-dependent were the most likely to experience LoA after the 1st chemotherapy cycle. This research suggests that the GDS15 and IADL should be included as part of any screening for elderly pts before treatment.
Rates and risks of suicidality in young adults (YAs) with advanced cancer.
Authors: Trevino Kelly Marie , Fasciano Karen , Prigerson Holly Gwen
Published: March 2020

9015

Background: Suicide rates in YA cancer patients are higher than in the general population. Although cancer is associated with a four-fold increase in the likelihood of a suicide attempt, little is known about suicidality in YAs with cancer. This study examined rates and clinical risk factors associated with suicidality in a sample of YAs with advanced cancer. Methods: Structured interviews were conducted between 4/2010 and 9/2011 with 70 YA advanced cancer patients (range 20-40 yrs, M=33.97, SD=5.61) receiving care at the Dana-Farber Cancer Institute. Validated measures assessed suicidality (i.e., Yale Evaluation of Suicidality), quality of life, major depressive disorder, grief over cancer-related losses, and social support. Scores on the suicidality measure were dichotomized into positive screen = 1 and negative screen = 0. Chi-square, t-test, and logistic regression analyses evaluated the relationship between suicidality and participant characteristics and psychosocial variables, controlling for confounding variables. Results: Over one-fifth (21.4%) of the sample screened positive for suicidality. Female gender χ2(1, N = 70) = 4.95, p = .026), breast compared with other cancer diagnosis χ2(1, N = 70) = 5.66, p = .017), and better performance status (t(68) = 3.13, p < .01) were associated with lower rates of suicidality. Participants who met criteria for current (OR [95% CI] 8.67 [1.78, 42.22]) or lifetime major depressive disorder (5.38 [1.60, 18.12]) endorsed higher rates of suicidality. Better overall (.97 [.94, .99]), psychological (.93 [.87, .94]), and existential quality of life (.91 [.85, .98]) were associated with reduced suicidality risk. More severe grief was associated with greater risk (1.15 [1.04, 1.28]) whereas greater social support was associated with lower suicidality risk (.85 [.74, .97]). Conclusions: YAs with advanced cancer reported higher rates of suicidality than observed in other age groups. Developmentally targeted interventions that promote physical function, effectively treat depression, improve quality of life and reduce grief, and provide opportunities for social support may reduce rates of and risk for suicidality in this population.
Patterns of antidepressant use in cancer patients (pts): An analysis from SOAPP (ECOG E2Z02: Symptom Outcomes and Practice Patterns).
Authors: Manola Judith , Zhao Fengmin , Miller Andrew H. , Pirl William F. , Wagner Lynne I. , Fisch Michael
Published: March 2020

9016

Background: Antidepressant (AD) use is common in outpatient oncology, but the pattern and determinants of prescribing for commonly used AD are unknown. Methods: 3106 pts with cancer of the breast, prostate, colon/rectum, or lung were enrolled from multiple sites in a study of symptoms. Five depression case-finding methods were explored : 3 based on MDASI items reported by patients (1) sadness/ depression>=4, (2) distress>=4, (3) interference with mood>=7 or enjoyment>=7; 2 based on clinician’s report (4) presence of psychological distress, (5) depression being listed as one of top 3 symptoms. AD use (excluding tricyclic antidepressants and psychostimulants) was examined by depression status. Logistic regression models were used to examine the effect of demographic and clinical characteristics on AD use. Results: Rates of depressive symptoms varied by casefinding method (1=29%, 2=28%, 3=14%, 4=24%, 5=11%); 47% (1457) pts were defined as having depressive symptoms by at least one method. AD were prescribed in 25% of depressed pts compared to 14% of non-depressed pts. After adjusting for other covariates, factors associated with greater use of AD included depression (OR=1.7, P<0.01), family history of depression (OR=2.2, P<0.01), female sex (OR=1.8, P<0.01), younger age (OR=1.2, P=0.04), non-Hispanic White race (OR=2.0, P<0.01), prior chemo/immune/ hormonal treatment (OR=1.5, P<0.01), more concurrent medication use (OR=3.3, P<0.01), anxiolytics use (OR=2.0, P<0.01), sedative use (OR=2.1, P<0.01), receiving counseling (OR=1.6, P=0.04), patient’s perception of poor QOL (OR=1.3, P=0.02), duration of current treatment >1 year (OR=1.6, P<0.01), and being enrolled by a CCOP (OR=1.8, P=0.01). These significant associations remained regardless of the case-finding method used for depression, with only slight changes in the magnitude of ORs. Conclusions: Depressive symptoms are common in outpatients with cancer. One-fourth of solid tumor pts with depressive symptoms are taking an AD. Antidepressant prescribing varies by type of institution, race/ethnicity, age, concomitant medication exposure and several other clinical factors.
Low-level laser therapy for chemotherapy-induced peripheral neuropathy.
Authors: Lee John Muzi , Look Regan M. , Turner Crystal , Gardiner Stuart K , Wagie Terry , Douglas Jeremy , Sorenson Leslie , Evans Laura , Kirchner Sandra , Dashkoff Cyd , Garrett Karen , Johnson Nathalie
Published: March 2020

9019

Background: Chemotherapy induced peripheral neuropathy (CIPN) is a common and serious side effect from chemotherapy agents. Low-level laser light therapy (LLLT) devices were approved in 2002 for pain management. Studies suggest a local release of serotonin, increased mitochondrial ATP production, or anti-inflammatory effects as a mechanism of action. We then questioned whether LLLT would show efficacy in mitigating symptoms caused by CIPN. Methods: In a single center prospective randomized trial, participants were randomized to receive either treatment with LLLT twice a week for 8 weeks or placebo LLLT twice a week for 4 weeks followed by actual treatment twice a week for 4 weeks. FACT/GOG-NTX, Brief Pain Inventory (BPI -Severity and Interference), SF-36 Quality of Life (Physical and Mental Score), monofilament and function testing (buttoning, coin use and walking) were conducted prior to initiation of therapy, during, at completion, and 2 months after treatment. 20 participants, 16 women and 4 men (average age 58 and 63 respectively), were enrolled between October 2009 and June 2010. 10 patients were randomized to each group. Average time from end of chemotherapy to enrollment was 32.6 months (range 2 - 120 mo). All patients had neuropathic involvement of the feet. 14 patients had additional involvement of the hands. Results: Compared to baseline, patients receiving any amount of active treatment showed significant improvement at 8 weeks in NTX, BPI, function testing, and SF36 Mental score. Those receiving 4 weeks of placebo treatment showed improvement in only BPI, NTX and SF36 Mental score. At 2-month follow up, all 20 patients showed a significant improvement in walking and SF 36 mental score, suggesting 4 weeks of active treatment improved function. No significant difference in monofilament testing was observed throughout the study in either group. Direct comparison between 4 or 8 weeks of treatment vs. placebo showed a statistically significant difference in walking function at 2-months. All patients tolerated therapy well without side effects. Conclusions: Low-level laser light therapy improved functional test over placebo and may be a viable option for non-medical management of CIPN. Further study of LLLT in CIPN is warranted.
Patient-reported cognitive impairments among women with breast cancer randomly assigned to hormonal therapy (HT) alone versus chemotherapy followed by hormonal therapy (C+HT): Results from the Trial Assigning Individualized Options for Treatment (TAILORx).
Authors: Wagner Lynne I. , Gray Robert James , Sledge George W. , Whelan Timothy Joseph , Hayes Daniel F. , Geyer Charles E. , Dees Elizabeth Claire , Cella David , Sparano Joseph
Published: March 2020

9020

Background: Cognitive impairment is a complication of chemotherapy. Perceived cognitive impairments (PCI) were prospectively assessed among TAILORx participants randomized to HT alone versus chemotherapy followed by HT (C+HT). Methods: TAILORx participants with an OncoType DX Recurrence Score 11-25 were randomly assigned to HT or C+HT. PCI, fatigue, endocrine symptoms and health-related quality of life (HRQL) were assessed at baseline, 3, 6, 12, 24, and 36 months, using the Functional Assessment of Cancer Therapy (FACT) in 455 patients enrolled after 1/15/10. PCI change scores > 4.5 from baseline were defined a priori as clinically meaningful. Linear regression (LR) was used to model PCI scores on baseline PCI, treatment and other factors. Results: PCI scores were significantly worse at 3, 6, and 12 months compared to baseline for both groups (Table). The decline was greater for C+HT than HT at 3 months, but scores were similar at 12 months. Tests of an interaction between menopausal status and treatment were non-significant. PCI correlated with fatigue (r = 0.57-0.64) but not FACT Emotional well-being (EWB; r = 0.28-0.38); controlling for EWB did not account for differences in PCI change scores between treatment arms. Conclusions: Our study is the first to examine PCI among breast cancer patients randomized to receive C+HT vs. HT alone. C+HT was associated with greater declines in PCI at 3 months, but at 12 months PCI was similar in the C+HT and HT groups. PCI was associated with fatigue but not EWB. Pre- and post-menopausal groups demonstrated the same pattern of change. Since this study did not include a control group of patients not treated with HT, further study is required to determine if and to what extent HT contributes to PCI. [Table: see text]
Palliative cancer therapy during end of life at a regional cancer center in Norway in 2005 and 2009.
Authors: Gynnild Mari Aas , Anshushaug Malin , Kaasa Stein , Kvikstad Anne , Grønberg Bjørn Henning
Published: March 2020

9040

Background: With increasing number of available therapies, there is a risk that patients (pts) are overtreated. Palliative cancer therapy is mostly recommended for pts with good Performance Status (PS). In one study, 42 % of pts received chemotherapy (CTx) during the last 30 days of life – suggesting that this may not always be the case. Methods: All pts who, according to the national registry, died from cancer in our region in 2005 and 2009 were analyzed. Data were collected from individual medical records. Endpoints: Time from the end of palliative cancer therapy until death. Whether there were differences depending on age; type of cancer; year of death or if they were seen at a palliative care unit (PCU). PS when the last cancer therapy was initiated. Results: 616 pts died in 2005; 599 in 2009. We excluded 495 pts: No cancer therapy (n=260); no information of cancer (n=101); last therapy with curative intention (n=83); hematological malignancy (n=51). Median age 71 (6 - 99); 49 % men; median overall survival from diagnosis: 16.9 mos. Last therapy was radiotherapy (RT): 31 %; CTx: 40 %; hormonal: 15 %; surgery: 11 %. 4 % died from treatment complications. Median time from start of last CTx or RT until death: 100 days; from end of last CTx or RT: 63 days. Younger pts received more CTx and RT in the last 30 days: Age < 60: 28 %; 60-70: 23 % and 70+: 12 % (p<.001). The table shows the use of CTx and RT the last 30 and 14 days for the most common cancers. Among those who got CTx in the last 30 days (n=74); 54 % had PS 2; 14 % PS 3-4. Among those who got RT in the last 30 days (n=61), 31 % had PS 2; 54 % PS 3-4. Of the 49 % referred to the PCU, fewer received CTx or RT in the last 30 days (PCU: 14 %, no PCU: 22 %; p=.002) and 14 days (PCU: 5 %, no PCU: 12 %; p<.001). Conclusions: Many pts received cancer therapy the last month of life. The percentage varies with age, cancer type and was lower in 2009 than in 2005. Pts seen at the PCU received less CTx and RT. Many pts had a poorer PS at the start of last cancer therapy than recommended. [Table: see text]
Predictors of resilience in women treated for breast cancer: A prospective study.
Authors: Bennett Barbara Kaye , Lloyd Andrew R. , Webber Kate , Friedlander Michael , Goldstein David ,   FolCan Study Group
Published: March 2020

9044

Background: Because a cancer diagnosis may be regarded as a potentially traumatic event with untoward consequences, much research has focussed on negative aspects of cancer diagnosis and treatment, emphasising psychological outcomes. A recent paradigm shift recognises that such a psycho-pathological approach discounts the human capacity for resilience "the ability to maintain relatively stable functioning following an aversive life event" (Bonanno GA Curr Direct in Psychol Science 2005 14(3) 135). Predictors of resilience in women who recovered uneventfully from surgical and adjuvant treatment for early stage breast cancer were investigated in a prospective study. Methods: Validated self-report measures of mood, somatic symptoms, temperament, illness attitudes, and social support were completed post-surgery. Clinical, tumor and treatment details were recorded. At end treatment and subsequently at 1, 3, 6, 9 and 12 months, self-report measures of mood and somatic symptoms were completed. Resilience was defined as: no evidence of protracted psychological or somatic distress in the 12 months following treatment completion. Identified resilient and non-resilient groups were compared and predictors sought by logistic regression. Results: Of 218 women evaluated, 106 (49%) were classified as "resilient." They either reported no clinically significant psychological or other distress post-surgery (34%) and 12months following adjuvant treatment or recovered promptly (15%) and remained well. There were no significant differences in age (52 years); marital status; tumor size; treatment; treatment toxicity (nadir hemoglobin and neutrophil count) or mortality at 5 years post treatment (8 confirmed deaths in each group). Logistic regression identified low neuroticism (temperament or personality trait) as the most significant predictor of resilience. Conclusions: These findings suggest that without any intervention almost half the women treated for breast cancer adapt well to diagnosis and treatment. These outcomes warrant further research, to provide further insight into how individuals cope with major illness and to facilitate development of programs to aid those in whom outcomes are protracted.