bluuebunny/crossref_metadata_2025 huggingface dataset:
Analysis of patterns of care and benefit of thoracic radiotherapy for patients with stage IV NSCLC in the immunotherapy-era from a national hospital-based registry.
Authors: Kharouta Michael , Gross Andrew Jonathan , Kelley Kevin , Choi Serah , Biswas Tithi
Published: June 2021

9123

Background: Metastatic non-small cell lung cancer (mNSCLC) has classically been treated with platinum-doublet chemotherapy. Recent studies have established immunotherapy as an integral part of therapy for mNSCLC without targetable mutations. There are limited data on the role of consolidative thoracic radiotherapy (TRT) for patients with mNSCLC in the immunotherapy-era. A secondary analysis of KEYNOTE-001 showed significant improvement in overall survival in patients who received radiotherapy with pembrolizumab compared to patients not previously receiving radiotherapy. Methods: We queried the National Cancer Database (NCDB) for patients with metastatic presentation, stage IVA/IVB non-small cell lung cancer between the ages of 18-90 years treated between 2012-2017 with a combination of chemotherapy, immunotherapy, and thoracic radiotherapy. Patients with unknown treatment status, follow up time, or vital status were excluded. Overall survival (OS) was estimated using the Kaplan-Meier method and compared between treatment groups utilizing log-rank testing. A 3:1 nearest-neighbor propensity-score matching was performed utilizing clinical and demographic covariates to reduce the impact of potential confounders of overall survival on the probability of receipt of TRT. Cox proportional hazards regression was used to identify predictors of overall survival. Results: A total of 81,382 patients were identified that met inclusion criteria. The median age was 68 (18-90) years. The majority of patients (n = 51,681, 64%) had chemotherapy, while 7,929 (10%) patients received immunotherapy, and 15,984 (20%) received TRT. The median follow-up was 6.18 (range 0-76.9) months. For the entire cohort of patients receiving immunotherapy, 2 year OS was 29.4% with TRT compared to 32.7% without. Following propensity matching by age, sex, race, and comorbidity score, a total number of 4,264 patients receiving immunotherapy were matched. The 2 year OS was 27.7% in patients receiving TRT and immunotherapy vs. 22.2% in patients with immunotherapy alone (p = 0.004). On multivariable analysis receipt of TRT was a significant predictor of OS after adjustment for age, race, comorbidity score, sex, and median income (p = 0.0003, HR 0.87, 95% CI 0.80 - 0.94). For patients receiving BED10 > 39 Gy (equivalent to 30 Gy in 10 fractions), 2 year OS was significantly improved at 37.0% vs 18.1% (p < 0.0001). Conclusions: In patients with mNSCLC, the addition of TRT to immunotherapy is associated with improved overall survival at 2 years. Receipt of a higher BED10 is associated with further improved survival. Selection of mNSCLC patients receiving immunotherapy for TRT approaching definitive doses warrants further investigation. Data from prospective, randomized trials may better elucidate this benefit and identify a potential mechanism.
TMB and BRAF mutation status are independent predictive factors in stage IIIC/D/IV melanoma patients receiving adjuvant PD-1 antibodies.
Authors: Forschner Andrea , Eckardt Julia , Martus Peter , Armeanu-Ebinger Sorin , Ossowski Stephan , Bonzheim Irina , Eigentler Thomas , Amaral Teresa Maria Santos , Flatz Lukas , Garbe Claus , Schroeder Christopher
Published: June 2021

9524

Background: High tumor mutational burden (TMB) is associated with a favorable outcome in metastatic melanoma patients treated with immune checkpoint inhibitors. However, data are limited in the adjuvant setting. As BRAF mutated patients have an alternative with targeted adjuvant therapy, it is important to identify predictive factors for relapse and recurrence-free survival (RFS) in patients receiving adjuvant PD-1 antibodies. Methods: We systematically evaluated all melanoma patients who started adjuvant PD-1 antibody therapy at our center between March 2018 and September 2019 to identify predictive factors for outcome. The median follow-up time from start of adjuvant anti-PD-1 therapy was 22 months. Tumor and normal tissue of all stage IIIC/D/IV patients and of stage IIIA/B patients with relapse were sequenced using a 700 genes panel. Predictive factors for relapse and RFS were identified using univariate and multivariate logistic and Cox regression analysis. RFS was estimated by the Kaplan-Meier method. TMB high was defined as the top 20 % of the cohort, corresponding to TMB values ≥ 20 Var/Mb. Results: A total of 165 patients were included in this study. According to AJCC 8th the initial tumor stages at the beginning of adjuvant anti-PD-1 therapy were as follows: N = 80 stage IIIA/B (48 %), N = 85 stage IIIC/D/IV (52 %). 72/165 patients (44 %) suffered a relapse, 44/72 (61 %) with loco regional and 28/72 (39 %) with distant metastases. Sequencing results were available from 79 / 85 patients with stage IIIC/D/IV. Here we present the results of this cohort. TMB low (OR 17.46, 95%CI 4.03-75.55; p < 0.0001) or absence of BRAF V600E/K mutation (OR 4.13, 95%CI 1.36-12.53; p = 0.012) were statistically significant, independent predictive factors for relapse. Also, with regard to RFS, BRAF mutation status and TMB were statistically significant and independent predictive factors. In the table below we display results for the combined variables. Patients with BRAF V600E/K mutation and TMB high had the best outcome. Conclusions: We identified TMB high as positive predictive marker in stage IIIC/D/IVmelanoma patients with adjuvant PD-1 antibody therapy. In tumors with BRAF V600E/K mutation and concurrent low TMB, adjuvant targeted therapy with BRAF- and MEK-inhibitors may be an alternative. This is also supported by the data on adjuvant dabrafenib and trametinib, which showed a greater advantage in patients with low TMB, presumably due to less tumor heterogeneity.[Table: see text]
Patterns and management of progression on first-line ipilimumab combined with anti-PD-1 (IPI+PD1) in metastatic melanoma (MM) patients.
Authors: Pires Da Silva Ines , Versluis Judith M. , Ahmed Tasnia , Johnson Douglas Buckner , Soon Jennifer , Allayous Clara , Gerard Camille Lea , Mangana Joanna , Klein Oliver , Zimmer Lisa , Robert Caroline , Vitale Maria Grazia , Yeoh Hui-Ling , Michielin Olivier , Lebbe Celeste , Sandhu Shahneen Kaur , Blank Christian U. , Carlino Matteo S. , Menzies Alexander M. , Long Georgina V.
Published: June 2021

9533

Background: First line IPI+PD1 induces long-term response in 36% of MM patients (pts); however, the majority of pts will progress and may require further treatment, which is yet to be established. We studied the patterns of progressive disease (PD) on 1st line IPI+PD1, and the management and outcomes in MM pts. Methods: Demographics, disease characteristics, nature of PD, subsequent treatments and outcomes were examined in MM pts with PD on 1st line IPI+PD1. Multivariable analyses (MVA) identified factors associated with patterns of PD: innate resistance (IR) = PD as best response or stable disease (SD) < 6 mo; acquired resistance (AR) = PD after initial response or SD ≥ 6 mo. Results: 310 MM pts from 14 melanoma centres were included; 208 (67%) had PD during and 102 (33%) after ceasing IPI+PD1. Overall med. progression-free survival (mPFS) was 2.8 mo (CI 95% 2.7 – 3.0); 187 pts (60%) had IR (mPFS 2.2 [2.1 – 2.5]), 112 pts (36%) had AR (mPFS 8.5 [7.2 – 10.2]) and 11 pts (4%) had pseudoprogression, i.e. PD followed by response without changing treatment (mPFS 2.7 mo [1.4 – NA]). On MVA, pts with ECOG PS ≥ 1 were more likely to have IR vs AR; and within IR pts, those with head & neck primary melanomas and lung metastases were more likely to have PD < 1.5 mo. Most pts with IR (68%) had PD in multiple sites, while 61% AR pts had PD in a single site. Brain was most common site of single organ PD; 49% of IR and 41% of AR. Med. follow-up from PD was 32.7 mo (28.1 – 36.8). After PD, 61 pts (20%) had best supportive care (26% of IR and 11% of AR pts). 259 pts (80%) received further treatment: 39% IR pts had systemic treatment (ST) only and 27% had ST + local; 31% AR pts had ST only and 39% had ST + local. Of 200 pts (65%) who had ST(+/-local), 54% had 1 line of ST and 46% had ≥ 2; 1st line ST (ST1) was BRAF/MEKi in 36% of pts, PD1 in 32%, IPI+PD1 in 7%, investigational drugs in 11%, chemotherapy in 9% and others in 5%. ORR in IR pts was lower than in AR pts for every type of ST1 (see Table). Med. OS from PD was 11.4 mo (CI 95% 9.6 – 16.1); IR 6.4 mo (CI 95% 5.6 – 10.2) and AR 26.1 mo (CI 95% 17.1 – NA). Conclusions: These data suggest longer OS from PD for AR vs IR pts independent of ST type. BRAF/MEKi, rechallenge with PD1+/-IPI and investigational drugs showed activity after PD on IPI+PD1, while chemotherapy has no role in this context.[Table: see text]
Apatinib in combination with camrelizumab, a humanized immunoglobulin G4 monoclonal antibody against programmed cell death-1, in patients with metastatic acral melanoma.
Authors: Wang Xuan , Cui Chuanliang , Lian Bin , Si Lu , Chi Zhihong , Sheng Xinan , Kong Yan , Mao Lili , Bai Xue , Tang Bixia , Yan Xieqiao , Li Siming , Zhou Li , Guo Jun
Published: June 2021

9539

Background: Patients(pts) with metastatic acral melanoma respond poorly to anti–PD-1 monotherapy. Apatinib, a vascular endothelial growth factor (VEGF) inhibitor, is a kind of anti-angiogenic drugs which have shown synergistic therapeutic effects in combination with PD-1 blockade. We conducted this single-center, open label phase trial to evaluate the safety and efficacy of camrelizumab in combination with apatinib in advanced treatment-naïve acral melanoma pts. Methods: Eligible participants were adult pts (aged 18 to 75) with histologically confirmed unresectable stage or distant metastatic acral melanoma. Exclusion criterion included unknown primary melanoma, brain metastatic disease or previous use of anti PD-1 ab. Pts received camrelizumab at 200mg intravenous infusion every 2 weeks, in combination with apatinib 250 mg orally once a day. The primary endpoint was ORR according to RECIST 1.1 criteria, and the secondary endpoints were safety and RFS. Results: Thirty pts were enrolled from April 2019 to January 2021. Basic characteristics: the mean age was 56.7 years, 22 pts were at stage, 33.3% had an elevated LDH level. Median tumor burden was 45mm (10-187). Gene mutation: Nras 4, cKit 3, Braf 2. Up to January 2021, 27 pts could be evaluated, in which 2 pts got CR, 4 pts achieved PR, and 63% experienced tumor shrinkage. The ORR and DCR were 22.2% and 77.8%, respectively. With a median follow up time of 8.3 months, the median PFS was 8.0 months (95% CI, 3.68, 10.19), the one-year durable response rate was 83.3% and the duration of response time was still not reached. Univariate analysis showed high LDH level was negatively associated with PFS. Whole exome data of baseline tumor biopsies revealed a positive correlation between high copy number variation (CNV) plus high mutational load (TMB) and efficacy，and all of the 4pts with MDC1 gene mutation got tumor shrink and 2 got PR. 96.7% pts experienced treatment-related AEs (TRAEs), including hand foot syndrome in 40%, proteinuria in 40%, liver dysfunction in 36.7%, and hypothyroidism in 30%. The grade 3-4 TRAEs were 33.3%. AE-related permanent discontinuation occurred in only 13.3% pts. 6 pts had delays of treatment due to the COVID-19 epidemic. No dose-limiting toxicities and suspected unexpected AEs were observed in the combination. Conclusions: The combination of apatinib plus camrelizumab was tolerable and showed promising antitumor activities and PFS improvement in pts with treatment-naïve metastatic acral melanoma. The survival is still in follow up. Clinical trial information: NCT03955354.
Durability of response to immune checkpoint inhibitors (ICI) in metastatic Merkel cell carcinoma (mMCC) after treatment cessation.
Authors: Weppler Alison Margaret , Da Meda Laetitia , Silva Ines , Xu Wen , Grignani Giovanni , Menzies Alexander M. , Carlino Matteo S. , Long Georgina V. , Nordman Ina , Steer Christopher , Lyle Megan , Trojaniello Claudia , Ascierto Paolo Antonio , Lebbe Celeste , Sandhu Shahneen Kaur
Published: June 2021

9543

Background: mMCC is a rare, aggressive neuroendocrine cancer which often occurs in older patients (pts) with multiple comorbidities. While initial response rates to ICI are high, optimal treatment duration, durability of response after treatment cessation and response to retreatment with ICI is unknown. Methods: mMCC pts from 12 international centres who received at least one dose of ICI and subsequently stopped treatment without progression for a minimum of 12 weeks were studied. Demographics, disease characteristics and treatment course were examined. Results: 40 pts with mMCC were included. Pt characteristics are summarised in Table. Median time on treatment was 13.5 months (range 1 to 35). Median time to best response was 4.5 months (range 1 to 17) and median time receiving treatment after best response was 8 months (range 0 to 29). 25 pts (63%) stopped primarily due to being in a complete or partial response (CR or PR), 9 (23%) due to toxicity and 6 (15%) due to other reasons, primarily pt choice or comorbidities. At time of discontinuation, 30 pts (75%) were in a CR, 8 (20%) in a PR and 2 pts (5%) had stable disease (SD). After a median follow up of 12 months from discontinuation, 14 pts (35%) have progressed (PD); 5 (36%) at a previous site, 5 (36%) at a new site and 4 (29%) at both. PD occurred after a median of 5.5 months (range 4 to 29) off treatment. 4 pts (29%) had a CNS recurrence, none of whom previously had CNS involvement. Pts in CR at time of discontinuation were less likely to progress (CR: 26% PD vs non-CR: 67% PD, p=0.044), but still had a considerable rate of PD (CR: 26%, PR: 57%, SD: 100%). Those who progressed had numerically less cycles of ICI prior to treatment cessation (17 vs 32, p>0.05). Baseline disease factors, time to best response and duration of treatment after best response were not associated with PD. ICI was restarted in 8 of 14 pts (57%) with PD, with response rate to retreatment of 75% (4 CR, 2 PR, 1 SD, 1 PD – pt with leptomeningeal disease). Median time to best response at retreatment was 3 months (range 2 to 7), with all responses ongoing after a median of 10 months back on treatment. 3 pts had an isolated site of PD successfully treated with radiation therapy and remain in remission off ICI. Conclusions: ICI responses in mMCC do not appear as durable off treatment as in other cancers, including in patients who achieve a CR. Ongoing treatment should be considered, though initial data on response to retreatment is promising.[Table: see text]
External validation of a Dutch predictive nomogram for complete response to T-VEC in an independent American patient cohort.
Authors: Stahlie Emma H.A. , Carr Michael , Zager Jonathan S. , Van Akkooi Alexander Christopher Jonathan
Published: June 2021

9563

Background: Talimogene Laherparepvec (T-VEC) is a genetically modified herpes simplex type 1 virus and known as an effective oncolytic immunotherapy for injectable cutaneous, subcutaneous, and nodal melanoma lesions in stage IIIB-IVM1a patients. Recently, Stahlie et al. published (Cancer Immunol Immunother '21) a model for predicting a complete response (CR) to T-VEC based on 3 easily accessible tumor characteristics identified using univariable and multivariable logistic regression analysis. The aim of this study was to externally validate this model in an independent, American patient cohort. Methods: A total of 76 patients with stage IIIB-IVM1a melanoma treated with T-VEC at Moffitt Cancer Center were included. A second nomogram was built incorporating the same predictive factors: tumor size (diameter of largest metastasis in mm), type of metastases (cutaneous, subcutaneous and nodal) and number of metastases (cut-off: <20 and >20). Predictive accuracy was assessed through calculation of overall performance, discriminative ability, and calibration. Outcomes and previously published outcomes were compared. Statistical analyses were done using R software. Results: Overall performance of the validation dataset nomogram was calculated with the Brier score and found to be 0.195, demonstrating good overall performance and similar to the original model Brier score of 0.182. Discriminative power, assessed by calculating the area under the receiver operating characteristic (ROC) curve was similar for both models, 0.767 and 0.755 for the NKI and Moffitt, respectively, resulting in a fair discriminative ability. The calibration curve showed mostly slight underestimation for predicated probabilities >0.37 and slight overestimation <0.37. Conclusions: An independent dataset externally validated a recently published predictive nomogram for CR to T-VEC in stage IIIB-IVM1a melanoma, with both models resulting in overall performances that were comparable and good. The second model reinforces the conclusion that for the best response to T-VEC, it should be used early on in the course of the disease, when the patient’s tumor burden is cutaneous with smaller diameter and fewer of metastases.[Table: see text]
Postoperative radiotherapy in Merkel cell carcinoma (MCC).
Authors: Levy Sonja , Blankenstein Stephanie , Grunhagen Dirk J. , Jalving Mathilde , Hamming-Vrieze Olga , Been Lukas B. , Tans Lisa , Van Akkooi Alexander Christopher Jonathan , Tesselaar Margot Et
Published: June 2021

9575

Background: MCC is a rare and aggressive neuroendocrine malignancy of the skin. Postoperative radiotherapy (PORT) is recommended by current guidelines to reduce recurrences and improve survival in patients with locoregional MCC. However, evidence supporting these recommendations is conflicting and deviations from the protocol occur frequently, due to the generally elderly and frail patient population. We aim to evaluate the influence of PORT on survival in stage I-III MCC patients treated in the Netherlands. Methods: All patients with stage I-III MCC treated in three referral centers between 2013 and 2018 were included retrospectively. Recurrence free survival (RFS) and disease specific survival (DSS, including death from unknown causes) were compared between patients with and without PORT. Prognostic factors for DSS were analyzed using Kaplan-Meier curves, logrank test and cox regression. Since sentinel node biopsies (SN) are frequently omitted in this patient population, analyses were performed in patients with clinical (SN not performed) stage I/II (c-I/II-MCC), pathologic (SN negative) stage I/II (p-I/II-MCC) and stage III MCC (III-MCC), separately. Propensity score matching (PSM) was performed to assess possible confounding by indication. Results: In total 219 patients were included, of whom 54 had p-I/II-MCC, 82 had c-I/II-MCC and 83 had III-MCC. Median follow up time was 53.4 (IQR 32.8-62.4), 28 (11.8-43.3) and 30.8 (19.5-50.0) months, respectively. PSM identified no confounding by indication, analyses were therefore performed in the unmatched cohort. Majority of recurrences were regional in p-I/II-MCC (77.8%) and c-I/II-MCC (74.2%), and distant in III-MCC (61.7%). RFS was significantly different across all stages (p<0.001), DSS was similar for patients with c-I/II-MCC and III-MCC, which was significantly worse compared to patients with p-I/II-MCC (p=0.003). Survival times are shown in table. PORT did not improve RFS and DSS in patients with p-I/II-MCC and c-I/II-MCC. In patients with III-MCC, PORT was associated with improved RFS, but not with DSS. Multivariable analysis identified male gender (hazard ratio (HR) 1.94, p=0.030), performance status (PS) of 3 (HR 3.87, p=0.014) and an unknown PS (HR 5.45, p=0.004), primary tumor on the trunk (HR 2.67, p=0.008), c-I/II-MCC (HR 5.38, p=0.001) and III-MCC (HR 6.44, p<0.001) as predictors for DSS. Effect of PORT was not significant. Conclusions: In this retrospective cohort PORT did not show a DSS benefit in patients with stage I-III MCC. RFS was improved by PORT in III-MCC. PSM showed no confounding by indication.[Table: see text]
The effect of non-oncology drugs on clinical and genomic risk in early luminal breast cancer.
Authors: Waissengrin Barliz , Wolf Ido , Zahavi Tamar , Salmon‐Divon Mali , Sonnenblick Amir
Published: June 2021

e12505

Background: In women with ER-positive, HER2-negative early stage breast cancer (BC), treatment decisions for adjuvant chemotherapy are based on genomic risk and clinical risk. Recently, an effect of non-oncology medications on cancer cell lines and cancer outcome have been suggested. In this study we aimed to systematically examine the impact of non- oncology drugs on clinical risk and genomic risk (based on OncotypeDx recurrence score [RS]) in early BC. Methods: We collected data from 1385 files of ER positive HER2 negative breast cancer patients regarding their clinical risk (stage and grade), genomic risk (OncotypeDx RS) as well as data regarding medications the patients received during the month before their surgery. Statistical analysis was applied to identify the influence of various medications on OncotypeDx RS. Results: Out of the various medications we examined, we found that Levothyroxine was significantly associated with high median OncotypeDx RS (RS median = 25 ;p < 0.0001) and Metformin was associated with low median OncotypeDx RS (RS median = 12 p < 0.0011) in comparison to patients not receiving these medications (RS median = 17). By contrast there were no differences in the clinical risk between patients who received Metformin or Levothyroxine. Notably, Levothyroxine and metformin did not impact proliferation marker (Ki67) levels but did impact progesterone-related features, suggesting they influence genomic risk through estrogen dependent modules. Indeed, scores of other genomic tests (PAM50, Mammaprint), which are determined largely by proliferative features, were not influenced by Levothyroxine or Metformin. Finally, by using contemporary guidelines to recommend adjuvant chemotherapy based on clinical risk and genomic risk (OncotypeDx ) we show that patients (Age > 50) who received Metformin treatment had 14.5% chance to be recommended adjuvant chemotherapy while patients who received Levothyroxine had 49% (p = 0.0001). Conclusions: The results of this study indicate significant impact of Metformin and Levothyroxine on clinical decisions with potential impact on early BC patients.
Five-day accelerated partial breast irradiation (APBI) using intensity modulated radiation therapy (IMRT) in stage 0-II breast cancer: A report of 214 cases with up to 39 month follow-up.
Authors: Mark Rufus J. , Gorman Valerie , Wolski Michal , McCullough Steven
Published: June 2021

e12508

Background: Randomized trials in stage 0-II breast cancer have proven that APBI given via HDR implant in 5 days is equivalent to whole breast irradiation (WBI) given in 5-6 weeks in regard to breast tumor local recurrence (LR). However, complications have been significant. Recently APBI using non-invasive IMRT given in 5 fractions has been shown in another randomized trial with 10 year follow-up to be equivalent to WBI in 6 weeks, with respect to LR. IMRT was superior in regard to acute effects, late effects, and cosmesis. In the randomized clinical trial of APBI IMRT, the Clinical Target Volume (CTV) was defined by the injection of individual fiducial markers bordering the surgical cavity. We have used the Biozorb fiducial system to localize the CTV for IMRT. We sought to confirm the APBI IMRT results with this simpler less labor intensive fiducial placement system. Methods: Between 2017 and 2021, 214 patients have undergone IMRT targeted to a Biozorb defined CTV with the walls of the surgical cavity sewn to the Biozorb device. Eligible patients were older than age 40, had tumor sizes < 3 cm, negative surgical margins, and negative sentinel node dissections. IMRT dose was 30 Gy given in 5 fractions. Dose Constraints were as follows : V-30 Gy < 105%, Ipsilateral Breast V-15 Gy < 50%, Ipsilateral Lung V-10 Gy < 20%, Contralateral Lung V-5 Gy < 10%, Heart V-3 Gy < 20%, Contralateral Breast Dmax < 2 Gy and Skin Dmax < 27 Gy. The Planning Target Volume (PTV) ranged from 27 to 355 cc with a median of 80 cc. PTV = CTV + 1-2 cm. Results: Follow-up ranged from 1-39 months with a median of 20 months. LR has been 0% (0/214). There have been no skin reactions or seromas. Infection has occurred in one patient (0.5%). Four (1.9%) patients developed pain around the Biozorb site. This resolved on a short courses of steroids in all cases. Cosmetic results as rated by the Surgeon, Radiation Oncologist, and Nurse, were rated excellent in 99.0% (212/214) of cases. Conclusions: Non-invasive APBI with IMRT given qd over 5 days targeted to Biozorb has resulted in LR, complications, and cosmetic results which compare favorably to invasive APBI given bid with HDR implant. At last follow-up, there have been no LR, skin reactions, or significant complications. Cosmesis has been excellent in 99.0% of patients.
OncotypeDx scores according to race/ethnicity and age in a diverse cohort of breast cancer patients.
Authors: Chen Eileen , Jones Corinne , Pagano Ian , Fukui Jami Aya
Published: June 2021

e12512

Background: Breast cancer incidence and mortality rate differ across racial/ethnic populations in the US, but little is known about the relationship between Oncotype DX scores and race/ethnicity. Oncotype DX scores are used in early stage, hormone positive breast cancers to estimate the likelihood of breast cancer recurrence and benefit from receiving chemotherapy. Most available literature assesses disparities between race and receipt of an Oncotype DX score, with only some assessing distribution of scores by race. Populations previously studied mainly focus on Black compared to White women, with very few including Asian and Native Hawaiian/Pacific Islander subpopulations. When included, they are often grouped together as Asian/Pacific Islander. Current studies suggest there is a similar distribution of scores among Black and White women, but some studies report that Black women may be more likely to have high-risk scores. Methods: We examined 476 unique breast cancer cases in the Hawaii Pacific Health system diagnosed in 2018-2020. We used univariable and multivariable analyses on all of those cases that received an Oncotype DX score to determine correlation to age and race. Results: In 328 breast cancer cases that received an Oncotype DX score, age of diagnosis ranged from 29 to 84 with race/ethnicity including Japanese (n = 90, 27%), White (n = 78, 24%), Filipino (n = 54, 17%), Native Hawaiian (n = 52, 16%), Chinese (n = 24, 7%), and other (n = 30, 9%) populations. Cases with age at diagnosis between 60-69 (n = 118, 36%) were found to have a mean Oncotype DX score of 13.91 (CI 12.19-15.62, p = 0.04) which was statistically lower than other ages groups on both univariable and multivariable analysis. We found no other significant relationships between Oncotype DX score and race or age at diagnosis on our analyses. Conclusions: These findings contribute more information about Oncotype DX scores within Asian and Native Hawaiian populations to the available literature.
Weight changes according to treatment in a diverse cohort of breast cancer patients.
Authors: Fukui Jami Aya , White Kami , Frankland Timothy , Oshiro Caryn , Wilkens Lynne
Published: June 2021

e12513

Background: Weight changes are common among breast cancer patients. The majority of studies to date have focused on weight gain after a breast cancer diagnosis and its implications on health in survivors. Fewer studies have examined weight loss and its related characteristics. Weight changes have been reported to be influenced by several factors such as age, treatment, stage and pre-diagnostic weight. We evaluated weight changes during key treatment time points in early stage breast cancer patients. Methods: We characterized 389 female patients diagnosed in Hawaii with early stage breast cancer from 2003-2017 in the Multiethnic Cohort (MEC) linked with Kaiser Permanente Hawaii electronic medical record data. We evaluated weight changes from surgery to 4 years post-diagnosis with six time points along a patient’s treatment trajectory (chemotherapy, radiation, endocrine, or surgery alone) and annually thereafter, adjusting for age, race/ethnicity and initial body mass index (BMI). Results: We found key time points of significant weight change for breast cancer patients according to their adjuvant treatment. In patients who had surgery alone (S), surgery-radiation (SR), or surgery-endocrine therapy (SE), the percentage of patients with stable weight, while generally comprising the majority, consistently decreased over time. However, the percentages of patients with weight loss and weight gain during this time steadily increased up to 4 years after initial surgery. Weight loss was more common than weight gain by about 2 fold in these treatment groups (weight loss 33.2%-42% vs weight gain 11.6%-21.4%). For patients with surgery-chemotherapy (SC), there was significant increase in patients with weight loss seen within the first 3 months after surgery (16.2% to 43.7%), during the time when patients receive chemotherapy. And this weight loss trend persisted until year 4. Weight gain was less commonly seen in this treatment group. Conclusions: We identified key time points during breast cancer treatment that may provide a therapeutic window to positively influence outcomes. Tailored weight management interventions should be utilized to promote overall health and long term survivorship.
Breast cancer as seen at the Nairobi Hospital.
Authors: Othieno-Abinya Nicholas Anthony , Kiarie Gladwell Wanjiru Kamere , Musibi Alice , Kidee Amina Habib , Nyaboga Tom , Wanjohi Ruth , Baraza Richard
Published: June 2021

e12514

Background: Breast cancer is the most common cancer and the second leading cause of death among women globally. The Nairobi Hospital has a comprehensive cancer centre, with various practitioners treating cancer patients individually. To document breast cancer diagnosis, treatment and outcome at the Nairobi Hospital. Methods: A retrospective cohort study involving records of breast cancer patients between Jan 2014 and Dec 2019 inclusive. Details included, demographic details, comorbidities, pathology, stage, treatment and outcome. The study was approved by the hospital’s Ethics and Research Committee. Results: 591 patients; 580 (98.1%) women and 11(1.9%) men. Age group 41-60 years had 330 patients(57.2%). Mean parity was 3. Fifteen (2.5%) were smokers, 73 (12.4%) took alcohol, 159 (12.4%) used hormonal contraceptives, 4(0.7%) had been exposed to iatrogenic radiation. Family history of cancer was present in 112 (19%), 25 (4.2%) had personal history of cancer, breast cancer in 8 (1.4%). Diagnosis was by core needle biopsy in 301 (50.9%), excision biopsy in 238 (40.3%), and fine needle aspiration cytology in 52 (8.8%). Pathology was invasive ductal carcinoma in 502(84.9%), invasive lobular in 12(2%). Oestrogen receptors were expressed in 329 (55.7%), progesterone receptors in 264 (44.7%), and Her2 in 129(21.8%). Triple negative were 86( 18%). T1 tumors were 84 (14.2%), T2 were 197 (33.3%), T3 were 126 (15.9%,) and T4 in 94 (15.9%), 126 (21.3%) had distant metastases. Neoadjuvant combination of doxorubicin and cyclophosphamide (AC) was in 109(18.4%) of patients, a taxane following AC (AC-T) in 79 (13.4), and 5-FU with doxorubicin and cyclophosphamide (CAF) in 105 (17.8%). Adjuvant AC was administered to 59 (10%), AC-T to 65 (11%), and CAF to 105 (17.8%), adjuvant tamoxifen to 160 (27.1%). Overall 93 patients (15.7%) received trastuzumab. Adjuvant radiotherapy was completed in 367 (62.1%). At a median follow-up of 36 months, patients 33 (5.6%) were recorded dead. The younger patients had worse survival. Conclusions: Ductal carcinoma constituted 85% of cases and metastatic disease was in 21.3 %. Triple negative cancer were 18%. Younger patients had higher risk of early death.
Thromboembolism (TE) and adjuvant endocrine therapy (AET) in hormone receptor positive (HR+) early breast cancer (EBC): Did the evolution of treatment change the incidence of the adverse event? A metanalysis.
Authors: Moscetti Luca , Omarini Claudia , Sperduti Isabella , Canino Fabio , Barbolini Monica , Nasso Cecilia , Toss Angela , Dominici Massimo , Piacentini Federico
Published: June 2021

e12516

Background: The AET of HR+ EBC has been changing in the recent years. Aromatase inhibitors (AI) as upfront, or in a planned switch strategy after Tamoxifen (T), have been added to the choice of T alone. An increased risk of TE is well known in the T treated patients while AIs have showed a reduced rate of TE. Recently, adding the cyclin dependent kinase 4/6 inhibitors (CDK4/6) abemaciclib to AIs, has showed a positive impact in the high risk HR+ EBC subgroups, but we are seeing an increase of the TE rate. We conducted this meta-analysis to evaluate the impact of the new AETs on the incidence of TE if compared to the standard monotherapy. Methods: We performed a meta-analysis of the randomized phase III trials comparing the experimental AETs and the endocrine standard therapy. A random-effect model to find differences in the rate of TE events between the experimental treatments and the standard therapy has been used. Results: Twelve phase III trials were included. Five trials evaluated the upfront strategy, 6 studies the switch and one the combination with a CDK4/6inhibitor (i.e. abemaciclib). Overall, the new AETs did not significantly modify or affect the rate of TE events (OR 0.708, 0.444-1.130, p = 0.148) with high heterogeneity among studies (I2 87, p < 0.0001). Excluding the abemaciclib trial, the incidence of TE is reduced (OR 0.609, 0.462-0.802, p < 0.0001) with a moderate heterogeneity among the studies (I2 59, p < 0.006). Considering the upfront strategies with AIs, the TE events are reduced (OR 0.507, 0.394-0.651, p < 0.0001) but they are not if we consider the trials in which T is used upfront before AIs (OR 0.762, 0.546-1.065, p = 0.112). Conclusions: Overall, the new treatments (AIs alone or plus CDK4/6 inhibitors) did not affect the rate in TE events. AIs as upfront strategy is the safest AETs of HR+ EBC, being associated to the lowest incidence of TE. The switch strategy increases the TE rate whereas the addition of abemaciclib to the standard AET showed to significantly increase the TE events. The results of the currently ongoing trials with the CDK4/6 inhibitors will help to obtain additional data to evaluate any differences among the different CDK4/6 inhibitors and to clarify the weight of the TE adverse events in the balance of benefit/risk of this new adjuvant strategy.
Comparing practice patterns and outcomes for early-stage hormone receptor-positive and node-positive breast cancer patients with high-intermediate-risk Oncotype Dx scores in the National Cancer Database.
Authors: Tamragouri Keerthi , Ritz Ethan M. , Rao Ruta D. , O'Donoghue Cristina
Published: June 2021

e12520

Background: Oncotype Dx (ODX) is a commercial diagnostic test primarily used to predict the likely benefit from chemotherapy in ER+, HER2-, and node negative breast cancer. The prognostic value (recurrence risk) has also been demonstrated to apply to early stage lymph node positive (LN+) disease in a number of retrospective and prospective studies. The ongoing RxPONDER trial aims to clarify the predictive value of RS in LN+ population. In light of the initial results, we analyzed the practice patterns and outcomes for HR+/Her2 -/node positive breast cancer patients receiving ODX testing in the years from 2010-2017 with RS 14-25 in a retrospective observational study of the NCDB. Methods: Women with HR+/Her2 -/node positive breast cancer receiving ODX testing from 2010-2017 were identified in the NCDB using TAILORx and RxPONDER patients’ inclusion criteria: ages 18-75, 6-50mm invasive tumors, N1, M0, ER+/HER2 -. The impact of ODX results in the high-intermediate range (14-25) and other clinico-pathologic variables on the receipt of chemotherapy were compared. Additionally, we examined the impact of chemotherapy on overall survival (OS). Frequencies, Kaplain-Meier analysis, and changepoint analysis using the Contal and O’Quigley method were utilized. Results: There were 109,652 T1-2 and N1 patients of whom 32,506 (29.6%) received ODX testing. 13,461 (41.4%%) women had scores in the high-intermediate (14-25) range. The majority tended to have only 1 LN involved (1LN: 77.2%, 2LNs: 17.5%, 3LNs: 5.3%), had a mean age of 57.8y, were Caucasian (86.4%), and were preferentially tested at academic or comprehensive community cancer programs (79.2%). 6,610 (49.3%) patients were recommended chemotherapy, the median ODX score for all women who were recommended chemotherapy was 20 compared to 17 for those whom chemotherapy was not recommended. 5,068 (76.7%) women had documentation of receiving chemotherapy which correlated with improved OS regardless of age. Conclusions: In the group of women with HR+/Her2 -/node positive breast cancer, clinicians appear to utilize ODX testing in less than one-third of patients, possibly finding RS to be most useful in guiding adjuvant therapy recommendations when only 1LN is involved. Both the recommendation and receipt of chemotherapy correlated linearly with increasing RS, as expected based on the current NCCN guideline recommendations. We identified an OS benefit when chemotherapy was administered, regardless of patient age. Long-term follow-up in the RxPONDER trial will likely continue to clarify the predictive value of RS < 25 in the ER+/HER2-/node positive breast cancer population.
Trends in use of ovarian suppression (OS) for premenopausal patients with early-stage hormone positive breast cancer and Intermediate Risk (IR) Oncotype Recurrence Scores (RS) from 2006-2020: A retrospective database analysis.
Authors: Hovstadius Sara Malin , Zimmerman Brittney Shulman , Berwick Shana , Blanter Julia , Berger Natalie F , Moshier Erin , Berkalieva Asem , Jaffer Shabnam , Cascetta Krystal Pauline , Tiersten Amy
Published: June 2021

e12522

Background: Oncotype RS is a 21-gene assay used to predict the risk of recurrence and benefit from chemotherapy in early-stage, hormone positive (HR+), node-negative breast cancer (BC). The TAILORx trial showed that many patients with RS<25 can avoid chemotherapy and the small absolute benefit may be due to chemotherapy-induced menopause in premenopausal patients. The SOFT-TEXT trials found that premenopausal women have higher rates of freedom from recurrence and 8-year survival when receiving OS with endocrine therapy (ET). These studies suggest that premenopausal women with IR RS (16-25) benefit from aggressive ET with OS but trends in OS use have not been adequately studied. We predict that OS use has increased in premenopausal patients over time. Methods: We identified 87 premenopausal patients with early-stage, HR+ BC with IR Oncotype RS (16-25) who were treated with ET between 2006-2020 at our large NYC academic cancer center. The Cochran-Armitage test was used for trends in the proportions of patients receiving OS and chemotherapy over time. The log-rank test was used to compare distributions of recurrence rates between RS groups. Results: Median age was 46 years and median RS was 19. Overall, 23 (26%) patients received chemotherapy and 30 (34%) received OS (via leuprolide, goserelin or surgical oophorectomy) with ET. 55 (63%) received tamoxifen alone, 10 (11%) tamoxifen + OS, and 20 (23%) aromatase inhibitor (AI) + OS. Between 2006-2010, 2 (17%) patients received OS and 2 (17%) received chemotherapy compared to 9 (24%) and 12 (32%) between 2011-2015, and 19 (51%) and 9 (24%) between 2016-2020, respectively (Table). There was a significant increasing proportion of patients receiving OS; p=0.0064, but no significant trend in chemotherapy receipt; p=0.8910. There were 8 (9%) patients that recurred, with a borderline significant difference in secondary invasive breast event rates in patients receiving tamoxifen alone (8, 15%) compared to those on tamoxifen + OS or AI + OS (0, 0%), (p=0.0520). There were no significant differences in recurrence rates based on chemotherapy receipt (p=0.1868) or RS group 16-20 vs 21-25 (p= 0.1836). Conclusions: There has been a significant increase in the use of OS with ET in premenopausal women with IR RS in our study population. This study shows how the results of the SOFT-TEXT trial have been adapted into current practice. Future studies are needed to evaluate real-world recurrence rates with the use of increased OS and whether chemotherapy rates have decreased over time.[Table: see text]
Impact of RxPONDER on breast cancer treatment in an academic-community hospital.
Authors: Saito Be , Johnson Cathryn , Sizer Lina , Carruthers Catherine , Lamb Elena , Carter W. Bradford , Frazier Thomas G.
Published: June 2021

e12524

Background: The introduction of Oncotype Dx set the stage for targeting chemotherapy treatment to only patients who would derive a benefit. RxPONDER trial then demonstrated that postmenopausal women with 1-3 positive lymph nodes, could forego chemotherapy if the recurrence score (RS) was ≤25. The most common chemotherapy regimens for breast cancer are taxotere and cytoxan or dose dense adriamycin/cytoxan followed by taxol. Chemotherapy can have many side effects and can increase risk of hospitalization due to complications. In addition, the financial cost can be considerable. Four cycles of TC will approximately cost $59,000, and most patients likely receive doses of growth factor support (neulasta is $12,565 per dose), totaling at minimum to $100,000 per patient. The purpose of this study was to look at the impact of RxPONDER on our patients. We reviewed patients who had RS at our institution in the last 5 years to see if we were appropriately treating patients with chemotherapy and hormonal therapy, or if a large group could be treated with hormonal therapy alone. Methods: This was an IRB approved retrospective chart review of patients at an academic-community hospital from 2015-2019. We identified patients ≥50 years old diagnosed with ER+/HER2- node positive breast cancer. Exclusion criteria included: M1, pN2, pN3. Univariate analysis used to compare patients that had RS vs those that did not. Student’s t-test was used to analyze whether there was a difference in rate of patients getting chemotherapy based on RS. Results: 216 patients were identified with ER+/Her2- breast cancer and 1-3 positive lymph nodes. 142 had RS (65.7%). Of those with RS, 140 were T1-T2 (98.6%), 131 had 1-2 positive LNs (92.3%), 115 had RS≤25 (80.9%), and 56 received chemotherapy (39.4%). Of the 74 patients without RS, 60 were T1-T2 (94.6%), 69 had 1-2 positive LNs (93.2%), and 51 received chemotherapy (68.9%). 30 patients who met the RxPONDER criteria (postmenopausal, 1-3 positive lymph nodes, and RS ≤25) still received chemotherapy. Conclusions: If we apply the RxPONDER trial recommendations, 30 patients would have been spared chemotherapy. In addition, 54.2% RxPONDER patients had RS ≤25. Extrapolated by percentage, 40 of the 74 patients who did not get RS in our study may have also been spared the side effects and cost of chemotherapy. This would be a savings of at least $3-7 million dollars to the health care system. RxPONDER makes a significant impact, not only in appropriately deescalating breast cancer treatment, but also to counter the increasing cost of medical care.[Table: see text]
An analysis of lines of treatment and survival analysis in older Indigenous and Nonindigenous women of Western Australia with breast cancer.
Authors: Khan Azim , Spalding Lisa , Martin Hilary Laura , Redfern Andrew David
Published: June 2021

e12529

Background: Indigenous women with breast cancer (BrCa) have markedly higher mortality and are more likely to be diagnosed with more advanced disease compared with non-indigenous women. However, it is unknown if Indigenous older adults receive same lines of treatment as non-indigenous older adults with breast cancer. Methods: We retrospectively examined data from WA cancer registry from 2001 to 2016 with BrCa by Indigenous status. Indigenous were considered older adults aged above 55 years and non-indigenous aged above 65 years. Cases with confirmed breast cancer, where chemotherapy was indicated in adjuvant and metastatic setting were included for analysis. Overall survival was compared between treatment arms of indigenous and non-indigenous cohort using log-rank analysis and demonstrated by Kaplan Meier curve. Chi-square was employed as well. Results: At time of writing, results were available for 75 indigenous and non-indigenous older adults identified for analysis from cohort of 315 older adults. 79% Indigenous received treatment in adjuvant setting, 14% was not offered and 7% declined adjuvant treatment compared to 89% non-indigenous patients received adjuvant chemotherapy, 7% were not offered and 4% declined therapy. In first line metastatic setting, only 65% older indigenous group received chemotherapy compared to 76% non-indigenous patients. In second line, only 48% patients received treatment compared to 61% non-indigenous patients. In third line, 23% indigenous women received chemotherapy compared to 51% non-indigenous women with significant p-value 0.012. The rate of decline was higher in indigenous cohort. Kaplan meier curve of 10-year survival analysis favors the Non-Indigenous group. The difference between groups was 55 vs 68%. When comparing groups, the median survival of Indigenous group was 79 months and mean survival of Non-Indigenous cohort was 97 months. Log-rank testing p value 0.0025. Conclusions: In this study, indigenous patients have shown reduced survival outcomes and with drop in lines of treatment in the course of disease, highlighting a potential area to address and improve survival outcomes, along with addressing barriers that lead to treatment disparity in older adults.