bluuebunny/crossref_metadata_2025_split huggingface dataset:
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.