bluuebunny/crossref_metadata_2025_split huggingface dataset:
Population-based validation of the melanoma institute australia (MIA) and the memorial sloan-kettering cancer center (MSKCC) predictive tool for sentinel node status in patients with melanoma.
Authors: Mikiver Rasmus , Olofsson Bagge Roger , Marchetti Michael A. , Van Akkooi Alexander Christopher Jonathan , Coit Daniel G. , Ingvar Christian , Isaksson Karolin , Scolyer Richard A. , Thompson John , Varey Alexander , Lyth Johan , Bartlett Edmund 
Published: June 2023

9571 Background: Patients with primary cutaneous melanoma are selected for sentinel lymph node biopsy (SLNB) based upon their risk of a positive SLN being identified. To improve upon stage-based categorization, the Memorial Sloan Kettering Cancer Center (MSKCC) and Melanoma Institute Australia (MIA) developed predictive models. Which model is more clinically useful is currently unclear. Methods: Consecutive patients undergoing SLNB from 2007-2021 were identified from the Swedish Melanoma Registry (SweMR), which covers 99% of patients with invasive cutaneous melanoma in Sweden. The predicted probability of SLN positivity was calculated using the MSKCC and limited MIA models (using mitotic rate as absent/present instead of count and excluding the optional variable lymphovascular invasion) for each patient. The operating characteristics of the models were assessed and compared. The “clinical utility” of each model was assessed using decision curve analysis (DCA) and compared with a strategy of performing SLNB on all patients. Results: In total 10,089 patients were included; the median Breslow thickness was 1.8 mm, 33.7% were ulcerated, and 1,802 patients had a positive SLN (17.9%). Both the MSKCC and limited MIA models were well calibrated across the full range of predicted probabilities, and had similar external area under curve (AUC), MSKCC 70.8% (95% CI 69.5-72.1%) and MIA 70.3% (95% CI 68.9-71.7%). When new models were constructed to compare the incremental value of the additional parameters of either nomogram over Breslow thickness alone, the AUCs were 70.1%, 71.6% and 72.0% for Breslow alone, MIA parameters and MSKCC parameters, respectively. At a risk threshold of 5%, DCA indicated no added net benefit for either model compared to performing SLNB for all patients. At risk thresholds of 10% or higher, both models added net benefit compared to SLNB for all. The greatest benefit was observed from use of the models in patients with T2 melanomas when a threshold of 10% was used to select patients for SLNB. In that setting, use of the nomograms led to a net reduction in seven avoidable SLNBs per 100 patients for the limited MIA nomogram and eight for the MSKCC nomogram, when compared to a strategy of SLNB for all. Conclusions: This study confirms the statistical performance of both the MSKCC and limited MIA models in a large, nationally-representative dataset. However, clinical utility as assessed by DCA demonstrated that using the models only improved selection for SLNB when a risk threshold of at least 10% was employed, and then mainly for T2 melanomas. Either further development of the nomograms, or other strategies, are needed to improve selection at lower risk thresholds.
Tumor-informed circulating tumor DNA (TI-ctDNA) based molecular residual disease (MRD) detection and relapse risk for patients with stage II-IV melanoma in surgical remission: A single center experience.
Authors: Rhea Logan , Daniels Megan , Sabo Roy , Poklepovic Andrew Stewart 
Published: June 2023

9572 Background: Melanoma is associated with significant risk of relapse after surgery. While the odds of relapse increase with advancing stage, long term relapse free survival (RFS) is possible without adjuvant therapy in a significant subset of patients as shown by AJCC v8 staging long term survival data. TI-ctDNA (Signatera™) is a non-invasive biomarker for MRD detection and functions by sequencing the patient’s own tumor for the creation of a customized panel of PCR probes based upon a tumor’s unique mutational profile. Positive TI-ctDNA testing is significantly associated with relapse after surgical resection in colorectal cancer and may help inform treatment decision-making, allowing for intensification or de-intensification of patient management. This study describes the operating characteristics of TI-ctDNA in monitoring for relapse in patients with resected melanoma. Methods: This is a single center retrospective analysis of patients with stage IIb-IV melanoma in surgical remission. Between January 2021 and January 2023, male and female patients presenting in surgical remission were monitored with TI-ctDNA at 6- or 12-week intervals. Surveillance imaging for relapse was performed according to standard of care guidelines appropriate for tumor stage. Patients were treated with immunotherapy, targeted therapy, or melanoma specific anti-tumor vaccine. Duration of RFS from surgery to detectable TI-ctDNA was recorded, along with duration of RFS from surgery to confirmed melanoma relapse. Results: 45 eligible patients were included in the analysis. 10 patients had detectable TI-ctDNA during the study period. 7 patients had confirmed relapse, 6 of whom were TI-ctDNA positive and 1 who was TI-ctDNA negative. The total relapse rate in TI-ctDNA positive patients (6/10) was significantly higher than the relapse rate in TI-ctDNA negative patients (1/35) [p = 0.0002]. Time to detection of positive TI-ctDNA was variable and ranged from 0 to 664 days (median 73 days). Conclusions: TI-ctDNA testing demonstrated preliminary ability to differentiate melanoma patients at the highest risk of relapse. Prospective evaluation of TI-ctDNA monitoring for determination of patients at high versus low risk of relapse is warranted and may help to inform future clinical trial designs by allowing for patient stratification to low risk (undetectable TI-ctDNA) and high risk (detectable TI-ctDNA) disease states.
Discovery and validation of AMBLor as a prognostic biomarker for non-ulcerated cutaneous AJCC stage I/II melanoma.
Authors: Lovat Penny , Ewen Tom , Podlipnik Sebastian , Puig Susana , Malvehy Josep , Clark Priscilla , Lewis Claire , Paragh Gyorgy , Bogner Paul , Mailer Sonia , McArthur Grant A. , Husain Akhtar , Stefanos Niki , Barrett Paul , Labus Marie , Sloan Philip 
Published: June 2023

9573 Background: Cutaneous melanoma incidence continue to increase, with a particular increase in the number of patients diagnosed with thin, < 1mm tumours with reduced probability of recurrence-free survival. The inability of current AJCC staging criteria to identify genuinely low risk subsets of patients with AJCC stage I/II tumours thus emphasises the acute need for credible prognostic biomarkers to stratify patient follow-up based on personalised risk. The combined immunohistochemical (IHC) expression of AMBRA1 and Loricrin (AMBLor) in the epidermis overlying non-ulcerated AJCC stage I melanomas has recently been identified as a prognostic biomarker and valuable pre SLNB test. The aim of the present study was to evaluate the potential for AMBLor as a prognostic biomarker for both AJCC stage I and II non-ulcerated melanoma. Methods: Prospective analysis of AMBLor was performed in two independent retrospective cohorts of non-ulcerated AJCC (8th edition) stage I and II cutaneous melanomas derived from the USA and Australia (discovery cohort) and Spain and the UK (Validation cohort) following validated automated immune-histological staining and binary scoring analysis to define at risk vs low risk subgroups. Each cohort was powered to represent rates of 10% or up to 20% metastasis for stage I or stage II disease respectively. Results: Data revealed retention of AMBLor in the discovery cohort of 541 melanomas correlated with significantly increased recurrence-free survival (RFS) of 96% compared to 87% for patients with stage I/II melanomas in which AMBLor was lost (P = 0.06; HR 3.6, 95% CI 1.99-6.84, NPV 96%). Subsequent AMBLor analysis in the validation cohort of 303 tumours, further confirmed retention of AMBLor was associated with increased RFS of 98% compared to 81% for patients with stage I/II tumours in which AMBLor was lost (P = 0.01; HR 8.16, 95% CI 3.68-18.07). Conclusions: Collectively data from this multi-international study confirm AMBLor as a prognostic biomarker marker able to identify genuinely low risk subsets of AJCC stage I/II melanomas. Inclusion of AMBLor into clinical melanoma management may therefore aid stratification of patient follow up, enable significant savings on healthcare resources and improve patient anxiety.
Melanoma disparities in urban vs rural communities in the era of immunotherapy: An NCDB analysis.
Authors: Akers Rachel , Coogan Alison , Kasper Laura , Krishnan Vaishnavi , Tan Alan , O'Donoghue Cristina 
Published: June 2023

9578 Background: Several barriers to care exist for melanoma patients including distance to specialty care, transportation, and cost. Additionally, differences in rural and urban melanoma incidence have not been fully investigated. Using a large nationwide database, we aim to investigate the relationship between urban and rural locations in stage of melanoma presentation and access to adjuvant systemic treatment. Methods: The National Cancer Database (NCDB) was queried for all adult patients (≥ 18 years old) with diagnosis of cutaneous melanoma from 1/1/2011 – 12/31/2020. For receipt of adjuvant immunotherapy, diagnosis from only 1/1/2017 - 12/31/2020 was analyzed. Demographic, socioeconomic, tumor-related, and treatment-related factors were analyzed using SPSS Statistics, with Chi-square analysis performed for categorical variables and ANOVA performed for continuous. Results: Between 2011 and 2020, 558,445 patient cases were identified and included in the analyses. The average age was 63.7 years, and patients predominantly identified as White (97.6%) and non-Hispanic (96.2%). Patients in urban areas were more likely to present with melanoma of the extremities (40.8% vs 36.2%, p < 0.001), while patients in rural areas presented with head and neck melanoma (26.2% vs 31.0%, p < 0.001). Additionally, patients in urban areas were more likely to have an early-stage melanoma (0, 1, or 2) melanoma (51.4% vs 48.5%, p < 0.001). Patients in rural areas traveled an average of 68 miles for care, in contrast to urban patients who traveled an average of 20 miles (p < 0.001). There was no significant difference when comparing receipt of immunotherapy for stage 3 or stage 4 patients. Conclusions: In rural areas, patients with melanoma tended to present with a higher portion of head and neck melanoma and of later stage. Rural patients also had to travel farther for care. However, these differences did not result in fewer patients in rural areas receiving immunotherapy for appropriate treatment. Further studies are needed to evaluate how these presentation differences influence care outcomes.
A pilot study of the neoadjuvant use of vemurafenib plus cobimetinib in patients with BRAF-mutant melanoma with palpable lymph node metastases: Survival results.
Authors: Petrella Teresa M. , Mihalcioiu Catalin Liviu Dragos , Nessim Carolyn , Spatz Alan , Watson Ian , Wright Frances Catriona 
Published: June 2023

9579 Background: Melanoma patients with palpable nodal metastases have a very poor prognosis with the majority recurring within the first 2-3 years post-resection with survival ranging from 20-50% at 5 years. We aimed to ascertain if patients with a BRAF V600 mutation that receive vemurafenib and cobimetinib before surgery (neoadjuvantly) have a higher probability of resectability, pathologic complete response (pCR), and a lower risk of local recurrence and a longer disease free survival (DFS), distant metastatic free survival (DMFS) and overall survival (OS). Methods: This was a single arm, prospective, multi centre phase II study in patients with histologically confirmed, BRAF V600 mutated Stage IIIB and IIIC melanoma (AJCC 7th Edition) with palpable nodal disease. Patients received vemurafenib 960mg PO BID and cobimetinib 60mg PO OD for 4 months prior to resection followed by 8 months of adjuvant therapy post-surgery. CTscans were performed at baseline and before resection and every 6 months for the first 3 years and yearly in year 4 and 5. Biopsies for correlative studies and diagnosis were performed at baseline prior to starting therapy. The primary outcomes were the proportion of patients achieving resectability, radiologic response as per RECIST and the proportion of patients achieving a pCR. Presented here are the LRFS, DMFS, DFS and OS. Results: Twenty-four patients were enrolled and received neoadjuvant vemurafenib and cobimetinib and 21 underwent resection. Following resection and pathological evaluation 12 (57%; 95% CI 34.02-78.18)) patients achieved a pCR, 8 (38%; 95% CI 18.11-61.56) had a partial pathologic response and 1 had no pathologic response. Of the 24 patients, 2 patients (8%) developed local recurrence, 6 patients (25%) developed distant metastasis, and 8 patients (33%) had either local or distant recurrences. 7 patients (29%) died due to metastatic disease. At 60 months, LRFS was 89.5% (76.7-100%), DMFS was 75.0% (59.5-94.5%), DFS was 85.7% (72.0-100%), and OS was 63.9% (95% CI 43.5-93.8). Among total 20 evaluable patients, 17 patients had CR/PR and 3 had PD/SD as best response. There was no significant difference between patients with CR/PR or SD/PD (log-rank p-value = 0.0548) with 48 month survival of 82.4% for CR/PR population compared to 33.3% with SD or PD. Conclusions: In this small phase II study, neoadjuvant vemurafenib and cobimetinib led to a higher LRFS, DMFS, DFS and OS of all resected patients with bulky nodal disease compared to historical survival rates. Clinical trial information: NCT02036086 .
Longitudinal circulating tumor DNA monitoring for detection of molecular residual disease in patients with surgically resected stage II/III melanoma.
Authors: Kollipara Revathi , Budde Griffin , Aushev Vasily N. , Brunsgaard Elise Kornreich , Kuzel Timothy , O'Donoghue Cristina , Riddell Timothy , Palsuledesai Charuta C. , Krainock Michael , Liu Minetta C. , Tan Alan 
Published: June 2023

9582 Background: Over the past decade, advances in immunotherapy (IO) have dramatically improved overall survival (OS) for patients with metastatic melanoma. Immune checkpoint inhibitors and BRAF/MEK inhibitors also became standard of care for surgically resected stage III melanoma, and most recently pembrolizumab was approved for stage IIB/C patients. Although the phase III trials that led to their respective approvals met their primary endpoints for relapse-free survival, no benefit in OS has been observed. Given that a large proportion of early-stage melanoma patients are cured with surgery alone, the decision to proceed with adjuvant therapy should be weighed against the risk of potential life-altering toxicity. There is a high unmet need to develop biomarkers to accurately select patients who are most likely to benefit from adjuvant IO while sparing a group of low risk patients from unnecessary treatment. In this study, we evaluated the prognostic value of personalized, tumor-informed circulating tumor DNA (ctDNA) testing in patients with resectable stage II/III melanoma. Methods: In this real-world study, longitudinal plasma samples (n = 159) were analyzed in real-time from 45 stage IIA-IIID cutaneous melanoma patients treated at Rush University between 03/30/2021 and 01/12/2023. A personalized, tumor-informed ctDNA assay (Signatera bespoke, mPCR-NGS assay) was used for detection and quantification of ctDNA in plasma samples. Results: Personalized, tumor-informed ctDNA assays were successfully designed for 93% (42/45) of patients using tissue samples from either surgical resection (14/42, 33%) or biopsy (26/42, 67%; 16 shave, 10 excisional, 1 punch, 1 core). ctDNA was detectable at one or more time points in 36% (15/42) of patients. We observed a higher ctDNA-positivity rate in stage III patients (11/20, 55%) compared to stage II patients (4/22, 18%). Twelve of the 15 ctDNA-positive patients received adjuvant IO/treatment escalation after a positive ctDNA result; 6 patients had sustained ctDNA clearance, 2 had transient clearance, and 4 continue to receive adjuvant IO and follow-up ctDNA testing. Radiographic recurrence was observed in 7/42 patients, 6 of whom were ctDNA-positive. Ninety-six percent (26/27) of patients with persistent ctDNA-negativity remain clinically and radiographically progression-free. Conclusions: Our data suggest that molecular residual disease detection using a personalized, tumor-informed ctDNA assay is highly prognostic in melanoma patients undergoing curative resection. Sustained clearance of ctDNA was achieved with adjuvant therapy in a subset of this cohort. Prospective studies evaluating the utility of ctDNA to aid clinical decision-making regarding adjuvant treatment intensification or de-escalation are warranted.
Correlation of breast arterial calcification with overall survival in patients with breast cancer.
Authors: Dusi Vidya Sagar , Attili Suresh VS , Vutukuru Anuradha , Peri Soumya V , Sharma Rakesh 
Published: June 2023

e12501 Background: Calcifications in breast tissue are common and indicate an array of conditions. Based on pattern of calcifications it indicate cancerous/ precancerous changes. Similarly vascular calcifications indicate a systemic vasculopathy. Aim of this study is to correlate Breast Arterial Calcification (BAC) with overall survival/all cause mortality in patients with breast cancer. Methods: It is a retrospective analysis of all breast cancer patients diagnosed across 3 specialty hospitals In the period of 2013-2017 with at least 5 years of follow up. All cause mortality, breast cancer specific mortality were measured. The comparison was made between the patients with no calcifications (Gr I), vascular calcifications (GrII) ductal calcifications (Gr III), and any breast calcification (Gr IV). Results: The baseline characters of all these groups and the treatment received were balanced. The median survival of the Groups were 43.6+22.6 mo vs 28.6+14.2 mo vs38.5+20.2 mo vs41.6+22.3 months (p=<0.02). Presence of vascular calcifications confers shorter overall survival and the main reason being death due to cardiovascular events. The risk is more in presence of co-morbid conditions (>2 have increased risk of 2.8 fold compared to less than 2), which were defined as diabetes, hypertension, dyslipidemia, history of cardiac illness in family, obesity. Those who received Adriamycin based therapy have 1.16 times higher risk than those who did not. Those who smoke are 3.2 times at higher risk than non smokers to have cardiovascular event in presence of breast arterial calcification. Alcohol did not have any impact. Conclusions: BAC is an important marker to predict underlying vasculopathy and risk of coronary cardiac diseases. It confers poor prognosis and reduced overall survival compared to those who do not have it. The challenges to assess CAD risk through CT/angio on community basis is high. Mammograms are being done annually across nations as a routine basis. Risk factors of breast cancer and CAD are common. The cancer detection rates of mammo as <0.2% compared to arterial calcifications, which is almost 12.8%. A simple extra attention towards BAC could help in preventing cardiac related mortality in women both with and without cancer. [Table: see text] [Table: see text]
Possible advantage of granulocyte colony-stimulating factor in breast cancer chemotherapy during COVID-19 pandemic: A single center experience in Japan.
Authors: Yokoyama Kioto 
Published: June 2023

e12505 Background: The COVID-19 pandemic seems to be ongoing in many countries, including Japan. ASCO and ESMO guidelines recommend treatment with during chemotherapy, and their use also reduces the risk of febrile neutropenia. On the other hand, there is a report that use of granulocyte colony-stimulating factor (G-CSF) increases the risk of admission and mortality due to COVID-19, so appropriate G-CSF use is still under discussion. Methods: Breast cancer patients treated with chemotherapy at our hospital from October 2020 to December 2022 were included in this study. We retrospectively collected patient data, including chemotherapy regimens, G-CSF use, COVID-19 infection, and COVID-19 severity, from electronic medical records. Results: Twenty-four patients (two bilateral breast cancers) received chemotherapy during this period. Twenty-three patients were female (95.8%) and one was male (4.2%), the mean age was 58.7 (34–79) years; 11 (45.8%) had early-stage breast cancer and 14 (58.3%) had advanced or recurrent breast cancer (one patient with early-stage breast cancer developed recurrent breast cancer during the study period). Seventeen cases (65.4%) were ER positive and nine cases (34.6%) were negative, 15 cases (57.7%) were PgR positive and 11 cases (42.3%) were negative, and six cases (23.1%) were HER2 positive and 20 cases (76.9%) were negative. The major chemotherapy regimens were ddAC in three patients (12.5%), AC in eight patients (33.3%), wPTX in 11 patients (45.8%), DTX in four patients (16.7%), TC in one patient (4.2%) and S-1 in eight patients (33.3%). Some patients also received treatment with anti-HER2 or anti-VEGF drugs or an immune check-point inhibitor but we did not consider these. Of the 13 patients who received AC, DTX and TC, 11 patients received PEG-GCSF in all their cycles. Among all patients receiving, COVID-19 symptoms were suspected on four occasions, and the COVID-19 antigen test was conducted, but all were negative, so no cases of COVID-19 were observed. Of the 46 cycles of AC, DTX, and TC, the proportion of patients with suspected COVID-19 symptoms who underwent antigen testing tended to be lower in the PEG-GCSF group (37 cycles) than in the no PEG-GCSF group (nine cycles) (2.7% vs. 22.2%; p = 0.0933, Fisher’s exact test). Conclusions: In this study, we did not find any cases of COVID-19 infection during chemotherapy, and so were unable to analyze the association between G-CSF use and COVID-19 infection severity. However, we did observe a trend toward a lower rate of potential COVID-19 with administration of PEG-GCSF. This might reflect a better quality of life for breast cancer chemotherapy patients.