bluuebunny/crossref_metadata_2025_split huggingface dataset:
Complete responders to checkpoint inhibitors in advanced melanoma: Relapse risk factors, and patients' outcomes.
Authors: Dutheil Amelie , Belkadi Djaouida , Antigny Marine , Roy Severine , Lupu Jeremy , Vallet Anaïs , Routier Emilie , Robert Caroline 
Published: June 2021

9550 Background: Since the development of immune checkpoint inhibitors (ICI) for advanced melanoma, a small group of patients with an excellent and durable response has emerged. Complete response (CR) is achievable in about 10-20% of the patients and seem to have an excellent prognosis. However, 10 to 15% of them might relapse eventually. Our main objective was to determine factors associated with relapse after a CR to ICI in advanced melanoma. The second objective was to describe relapse modalities and tumor response to subsequent treatments. Methods: We performed a single-center, retrospective study, in 141 patients with a CR to ICI for advanced melanoma, treated at Gustave Roussy (France) from January 2010 to June 2020. CR was confirmed on two consecutive CT-scanner or PET-CT at least 3 months apart. Characteristics of the patients at diagnosis, during and after treatment were compared in both groups: CR with relapse and CR without relapse. The LASSO analysis, a statistical analysis using lambda penalization coefficient for prognostic studies, was performed regarding the many statistical variables analysed. Results: At data analysis, immunotherapy was interrupted in 94.3% of the patients and the median follow-up was 3.5 years since immunotherapy discontinuation. Eventually, 18 of 141 patients (12.8%) had relapsed and 126 (87.2%) had not. The statistical analysis identified three factors associated with melanoma recurrence: prior lines of therapy, the type of melanoma and the mutation status. Indeed, relapse risk was higher in patients with wild type melanoma (as opposed to BRAF or NRAS mutant melanoma), with a mucosal, acral or unknown primitive melanoma and who received prior lines of treatment. Other factors such as demographical characteristics, tumor burden, metastasis localization, type or grade of toxicity, pseudo progression, type of ICI, treatment duration, use of a complementary local treatment and pursuit/discontinuation of immunotherapy were not statistically associated with the duration of the complete response. In case of melanoma recurrence, reintroduction of immunotherapy provided tumor response in half of our patients: 13 of the 18 relapsing patients received immunotherapy after melanoma recurrence; allowing 3 CR, 2 partial responses and 1 stable disease. One third of the relapsing patients eventually died of disease progression. Conclusions: This study confirmed the excellent prognosis of CR to ICI in advanced melanoma, even after treatment discontinuation and identified 3 baseline factors associated with a risk of relapse: absence of BRAF or NRAS mutation, primary of acral, mucosal or unknown origin, and previous lines of therapy. Rechallenge with ICI was effective in 50% of the patients.
Efficacy of cetuximab after immunotherapy (IO) in advanced cutaneous squamous cell carcinoma (CSCC).
Authors: Marin-Acevedo Julian Andres , Withycombe Bethany , Kim Youngchul , Eroglu Zeynep , Markowitz Joseph , Brohl Andrew S. , Tarhini Ahmad A. , Tsai Kenneth Yee , Khushalani Nikhil I. 
Published: June 2021

9562 Background: Anti-PD1 (aPD1) monotherapy with cemiplimab-rwlc or pembrolizumab is now considered standard of care for first-line management of advanced CSCC not amenable to surgery or curative radiotherapy. Previously chemotherapy or anti-EGFR agents were commonly used for these patients albeit with modest efficacy and limited duration of response. In prospective evaluation, the overall response rate (ORR) to cetuximab was 28% with disease control rate (DCR) of 69% at 6 weeks. The efficacy of second-line treatment following primary or acquired resistance to aPD1 therapy is not known. We investigated the activity of cetuximab in patients who progressed on previous IO therapy. Methods: We performed a single institution retrospective review from 9/28/18 (US approval date of cemiplimab-rwlc for CSCC) through 11/30/20 of patients with locally advanced or metastatic CSCC who received cetuximab after prior IO therapy. We identified patients who received cetuximab either immediately following IO therapy (cohort A) or as a subsequent line not immediately following IO therapy (cohort B). Primary endpoint was ORR with secondary endpoints of DCR, survival and toxicity. Median follow-up and survival times were calculated using the Kaplan-Meier method. Results: Thirteen patients, median age 72 years (62-82), all Caucasian, and 11 males (85%) were included in this study. Eleven pts received cetuximab immediately post-IO progression; two had additional intervening therapy post-IO before receiving cetuximab. Three patients received concurrent radiotherapy (palliative or definitive) with cetuximab. The ORR to cetuximab was 54% (7/13) including 1 complete and 6 partial responses. The cumulative 6-month DCR was 77%. All responses were observed in cohort A; both patients in cohort B had progressive disease as best response. Six of 7 initial responses are ongoing, including 3 in whom cetuximab was discontinued. At a median follow-up of 9.1 months, the median PFS has not been reached for the entire cohort. There were no unanticipated toxicities to cetuximab with rash (77%) and hypomagnesemia (54%) being the most common adverse events. Conclusions: In advanced CSCC, cetuximab used immediately after progression on aPD1 therapy yields notably higher and durable overall response than previously reported in the pre-IO therapy era. If validated in a larger dataset, this should be the preferred therapy for second-line treatment in advanced CSCC. Further exploration into the mechanism of this high efficacy of anti-EGFR therapy post aPD1 therapy is warranted.
Propensity weighted indirect treatment comparison of nivolumab (NIVO) versus placebo (PBO) as adjuvant therapy for resected melanoma: A number needed to treat and overall survival analysis.
Authors: Weber Jeffrey S. , Poretta Tayla , Stwalley Brian , Sakkal Leon , Du Ella X. , Wang Travis , Chen Yan , Wang Yan , Betts Keith A. , Shoushtari Alexander Noor 
Published: June 2021

9572 Background: The CheckMate 238 trial demonstrated that NIVO improved recurrence free survival (RFS) vs. ipilimumab (IPI). The EORTC 18071 trial demonstrated that IPI improved RFS and overall survival (OS) vs. PBO. The current study pooled data from these two trials to indirectly assess the RFS and OS of NIVO vs. PBO and the numbers needed to treat (NNTs) for one additional recurrence-free survivor and survivor over 4 years. Methods: Patients with resected AJCC 7th edition stage IIIB/C cutaneous melanoma from CheckMate 238 (NIVO vs. IPI) and EORTC 18071 (IPI vs. PBO) were pooled together with inverse probability weighting to balance between-trial differences in baseline characteristics. NNTs were calculated for RFS and OS comparing NIVO vs. IPI and PBO over 4 years. To account for improved post-recurrence survival over time, a sensitivity analysis that adjusted for post-recurrence survival in the PBO arm of EORTC 18071 was performed. Results: A total of 278, 643, and 365 patients treated with NIVO, IPI, and PBO, respectively, were included. In the weighted samples, patients treated with NIVO had consistently higher RFS rates than those treated with IPI (HR [95% CI]: 0.69 [0.56, 0.85]) and PBO (HR: 0.49 [0.39, 0.61]). NIVO was associated with similar OS as IPI (HR: 0.80 [0.60, 1.08]) and superior OS compared to PBO (HR: 0.45 [0.33, 0.60]). At 4 years, the weighted RFS rate was 53.1% for NIVO, 41.8% for IPI, and 29.1% for PBO. The NNT to achieve one additional recurrence-free survivor was 4.2 for NIVO vs. PBO and 8.9 for NIVO vs. IPI. The NNT to obtain one additional survivor was 4.8 for NIVO vs. PBO and 22.2 for NIVO vs. IPI. The OS rate for PBO after adjusting for differences in post-recurrence treatments at 4 years was 64.1%, and the corresponding NNT of OS comparing NIVO vs. adjusted PBO was 8.5. Conclusions: In patients with resected AJCC 7th edition stage IIIB/C cutaneous melanoma, this indirect comparison showed that NIVO improved RFS and OS vs placebo, with OS improvement maintained after adjustment for post-recurrence therapy.[Table: see text]
Efficacy of adjuvant radiotherapy in recurrent melanoma after adjuvant immunotherapy.
Authors: Bhave Prachi , Hong Angela M. , Johnson Rebecca , Menzies Alexander M. , Long Georgina V. , Mangana Joanna , Johnson Douglas Buckner , Eroglu Zeynep , Dulgar Ozgecan , Yeoh Hui-Ling , Haydon Andrew Mark , Lodde Georg , Livingstone Elisabeth , Khattak Muhammad Adnan , Kähler Katharina C. , Hauschild Axel , Wang Wei , Carlino Matteo S. 
Published: June 2021

9578 Background: Adjuvant (adj) radiotherapy (RT) halves the risk of locoregional (LR) recurrence in patients (pts) with high risk stage III melanoma after lymphadenectomy (CLND), however its role in the adj immunotherapy (IO) era without CLND is unknown. Methods: Pts with resected stage III melanoma who received adj IO and recurred with resectable LR only disease were studied. After resection of this 1st recurrence, adj RT may or may not have been administered. Disease characteristics, treatment at relapse and outcomes were examined. Results: 71 pts from 9 centres were included. Prior to adj IO, median age was 60y, 59% male, 56% BRAF mutant, 61% stage IIIC (AJCC V8), 52% underwent CLND and 17% had in-transit (IT) only disease. Adj IO included: 90% single agent anti-PD1, 8% ipilimumab-nivolumab (IN) and 1% nivolumab or IN (blinded on trial). Median duration of adj IO was 5 months. 21(30%) pts had high risk stage III disease at diagnosis, per previously established TROG criteria; 3 (4%) received upfront adj RT prior to recurrence. Median time to 1st recurrence was 7 months. 49 (69%) pts recurred during and 22 (31%) after cessation of adj IO. At 1st recurrence, 9 (13%) pts had stage IIIB disease, 55 (77%) IIIC, 7 (10%) IIID and 8 (11%) continued prior adj IO, 31 (44%) commenced therapy and 32 (45%) had no systemic therapy. 24 (34%) pts received adj RT after resection of 1st recurrence and 47 (66%) did not (Table). Adj RT was associated with a reduced risk of any 2nd recurrence (7/24, 29% vs 26/47, 55%, p=0.03) and LR 2nd recurrence (2/24, 8% vs 17/47, 36%, p=0.012). Whilst pts who received adj RT at 1st recurrence were more likely to have LN only disease, extra nodal extension and involved surgical margins, these factors did not significantly affect overall risk of 2nd recurrence on multivariate analysis. Of note, 70% of pts who did not receive adj RT at 1st recurrence had IT only disease, and though this did not significantly affect rate of 2nd recurrence (p=0.19), this likely reflects an inherent selection bias in this study. RT toxicity occurred in 16 (67%) pts, 10 with dermatitis only, and all grade 1 or 2. Median follow up was 22 months. Median recurrence free survival to 2nd recurrence was 23 months for all pts, not reached for those who had adj RT at 1st recurrence and 19 months for those who did not have adj RT (p=0.047). Median overall survival was not reached. Conclusions: Whilst adj RT appears to reduce 2nd recurrences, this may have been influenced by an unavoidable selection bias in the data, particularly an imbalance in the percentage of pts with IT disease. Prospective data with larger cohorts is needed to validate our results.[Table: see text]
The prognostic value of the interferon-gamma (IFNγ) signature in patients with macroscopic stage III melanoma treated with and without adjuvant systemic therapy.
Authors: Versluis Judith M. , Blankenstein Stephanie , Dimitriadis Petros , Sanders Joyce , Hoefakker Willem , Broeks Annegien , van Houdt Winan J. , Schrage Yvonne M. , Wouters Michel W.J.M. , Van Akkooi Alexander Christopher Jonathan , Blank Christian U. 
Published: June 2021

9579 Background: Recently, trials have shown the benefit of adjuvant aPD-1 therapy in macroscopic stage III melanoma patients. This treatment has been incorporated in daily clinical practice, however, a substantial part of patients still does not benefit from this therapy, as they develop recurrences. The aim of this study is to evaluate the results of adjuvant aPD-1 therapy and the potency of the IFNγ signature as a prognostic or predictive marker, as it has proven to be predictive of response in neoadjuvant trials. Methods: Patients participating in an ongoing biobank study and naïve for systemic therapy were included, between 10-2017 and 06-2020, after complete resection of macroscopic stage III melanoma. Approval and reimbursement of adjuvant therapy in the Netherlands started in 12-2018, resulting in 2 cohorts of similar high risk patients: prior to availability of adjuvant aPD-1 (cohort A) and thereafter (cohort B). Data cut-off for clinical data was January 1st 2021. Transcriptome sequencing was performed on samples of stage III melanoma by CeGaT GmbH, IFNγ signature was determined on these data with the median as cut-off. Clinical data were compared between cohort A and B as intention-to-treat population, including patients with a recurrence before adjuvant therapy start (n=10). Results: In total, 99 patients were included: 50 in cohort A and 49 in cohort B. Majority of included patients had thick primary melanomas (Breslow >2mm in 59.6%) and stage IIIC/IIID disease (83.3%) according to AJCC 8th edition. At a median follow-up of 20.6 months (95% confidence interval [CI] 16.6-24.7), median recurrence-free survival (RFS) was 6.1 months (95%CI 3.9-8.4) versus 22.8 months (95%CI 8.7-36.9), significantly in favor of cohort B (p=0.011). Median overall survival (OS) was not reached in both patient groups, but was overall significantly different (p=0.040), favoring cohort B. RNA sequencing was performed in 25 patients who received adjuvant therapy and in 24 who did not, excluding patients with an early recurrence (<12 weeks). In both treatment groups median (p=0.003) and 12-months RFS (p<0.001) was significantly higher for IFNγ high patients, but both IFNγ low and high patients show higher RFS rates when receiving adjuvant aPD-1 therapy (Table). Conclusions: Our study confirms RFS and OS benefit of adjuvant aPD-1 for patients with macroscopic stage III melanoma. IFNγ has shown to be a prognostic marker in both patients who were and were not treated with adjuvant therapy, as both patients with IFNγ high and low signatures show benefit from adjuvant therapy.[Table: see text]
Advanced breast cancer at presentation (ABC-p) in octogenarian women (OW): Specific elderly-devoted risk tests(SEDRT) (CARG+CRASH) as new tools to prevent serious/irreversible adverse reactions (AR) in frail patients.
Authors: Carreca Ignazio Ugo , Bazan Viviana , Galvano Antonio , Carreca Anna Paola , Cusenza Stefania , Russo Antonio 
Published: June 2021

e12510 Background: Due to current lengthening of average lifespan and progressive increase of malignant tumors in mankind, more new strategies must be constantly sought especially for thirdage neoplasms. Nevertheless because severe toxicity developed in the majority of frail patients, administration of therapy may cause high risk of life-threatening AIM: We have considered in this paper ABC in frail patients like OW. Purpose of the study is preliminary detection of the overall toxicity (OTox) through the possible use of specifics tests adopted specially in frail patients such as OW, to ensure greater control in drugs administration with good effectiveness. AIM: We have considered in this paper ABC in frail patients like OW. Methods: Sixty-two patients with advanced breast cancer at presentation ABC-p were enrolled between January 2018 and December 2019. Eligibility criteria: • women aging eighty or older; • acquired written consensus; • confirmed diagnosis of ABC; • one or two measurable lesions (bone or visceral or both); • no brain secondarisms; • Charlson’s Comorbidity Scale 1-3 score points; CGA Evaluation permissive for treatment. CARG-TS (Cancer and Aging Research Group-Test Score) and CRASH-TS (Chemotherapy Risk Assessment Scale for High-Age Patients Test S) are rated for predictive assessment of the risk of severe chemotox in all patients. Further Evaluations tools: Clinical Benefit according to ESMO CB scale v2a; Tox Profile CTCAE v3.0 Criteria; QoL by EORTC QLQ-C20 Results: CARG-TS predicts severe OTox; CRASH-TS predicts hematologic non-hematologic toxicity. Using a combination of CGA-ES+CARG-TS+CRASH-TS, we were able to divide patients into three categories: • LR -Low risk (score0-5); • MR-Medium risk (score 5-10); • HR High risk (score over 10). On this basis HR people was directed to receive endocrine therapy (if ER+PGR+) or RT alone. The MR group experienced a reduced schedule of eribulin (0.90mg/sqm d1,d28 until P-progression or INT-intolerable toxicity). Finally LR group received a schedule with eribulin alone(E 0.96-1.1 mg/sqm IV on d1, d21 dosage depending on creatinine clearance value according to the Kintzel-Dorr’s method and until P or INT-toxicity). Conclusions: With contemporary use of CGA-ES, CARG-TS, CRASH-TS we obtained two diagrams: the first “predicted risk” ; the second “observed risk” for each patient. The first curve was almost perfectly in line (p<0.001) with that of the “observed risk”. This allowed to have extremely personalized treatments, negligible OTox, and very good values for both CB and QoL.
Transcriptomic mapping on Notch signaling in A luminal phenotype breast cancer.
Authors: Rojas Katerin Ingrid , Martín M Rocio , Rojo Federico , Gámez-Pozo Angelo , De Castro Francisco J. , Filipovich Elena , Ceballos Jaime , Hernández M. Rosario , Ales-Martinez Jose 
Published: June 2021

e12539 Background: The Notch signaling pathway plays an important role in cell-differentiation, survival, proliferation, stem-cell renewal, and in determining cell fate during development and morphogenesis. The dysregulation of the Notch pathways contributes to carcinogenesis, cancer stem cell renewal, angiogenesis, and chemo-resistance. Elevated levels of Notch receptors and ligands have been associated with cancer-progression and poor survival. A less explored function of Notch pathways in cancer is their role in leukocyte homing and activation. Understanding their role and relationship with immune infiltrates is an area of interest in cancer research. Methods: The expression of four different Notch genes (Notch1, Notch2, Notch3 and Notch4) was explored in relation with A luminal breast cancer patient outcome using transcriptomic data (Affymetrix dataset, exploratory cohort) and the METABRIC study (validation cohort). The TIMER online tool was used to explore the association of the identified notch and immune infiltration, and the TCGA and METABRIC studies to analyze the correlation between notch1 - 4 expression and genomic signatures of immune activation. Results: We identified 2 individual genes called Notch1 and Notch2, which predict favorable prognosis in luminal A breast cancer. Their expression positively correlated with the presence of immune infiltrates within the tumor (dendritic cells, CD4+ T cells, neutrophils, CD8+ T cells and B cells), with markers of T cell activation and antigen presentation, and with gene signatures of immune surveillance (cytotoxic T lymphocyte activation and IFN gamma signature). By contrast Notch3 and Notch4 which predicted for detrimental outcome were not associated with any of these parameters. Conclusions: Our analysis identifies a Notch signature composed of 2 genes with potential to recognize immune infiltrated and activated A luminal phenotype breast cancers with favorable prognosis.
Final report of Breast Cancer Care Registry at the Kenyatta National Hospital, Nairobi.
Authors: Othieno-Abinya Nicholas Anthony , Musibi Alice , Nyongesa Catherine , Njihia Benjamin , Gachii Andrew , Kiarie Gladwell Wanjiru Kamere , Nyawira Beatrice , Onyango Ochieng' Noel 
Published: June 2021

Retraction The abstract by Othieno-Abinya et al entitled, “Final report of Breast Cancer Care Registry at the Kenyatta National Hospital, Nairobi,” published in the Journal of Clinical Oncology 39, no. 15 suppl (May 20, 2021) e12552-e12552, was retracted by the authors as it did not meet the study sponsor's prior scientific verification and approval. This abstract was retracted on June 29, 2021. e12552 Background: Breast cancer is the commonest cancer among women in Kenya. We wanted to examine breast cancer seen at the Kenyatta National Hospital in relation to local factors that influence prognosis and quality of life, local variations in treatment and outcomes; describe the clinical care patterns, monitor the safety of the therapies provided to patients in a routine clinic setting. Methods: A prospective study of patients with breast cancer between 11.08.2011 and 11.09.2014 inclusive. Data included demographic details, diagnostic and staging procedures, stage, treatment and outcome. Estimates of relative survival used period approach. hi-square tests and analysis of variance (ANOVA) were utilised to make comparisons. Cross sectional data are presented in proportions, means and medians. Results: Four hundred patients were included, age range 20 to 83, median 49 years. Out 312, 65 (20.8%) were obese. Eight of 397 (2%) were smokers and 22(5.5%) took alcohol. Early disease was diagnosed in 269 out of 354 (76%) and metastatic disease in 85(24%). Breast lump presented in 388 out of 400 (97%), breast pain in 104 out of 388 (26.8%). Fifteen of 394 (3.8%) had second breast cancer, 4 (1%) had had ovarian cancer and 9 (2.3%) had had had other malignancy. History of breast cancer in first and second-degree relative was elicited in 41 out of 394 (10.4%). Ductal carcinoma NOS was commonest in 343 (88.2%), lobular carcinoma in 9(2.5%). Cases by T stage were T1 - 25(7.2%), T2 -130(37.4%), T3 - 96(27.6%), T4 - 87(25%). Of 322 cases, 187(58.1%) were ER positive and 175 (54.4%) PR positive. Her2 positive cases were 78 out of 322 (24.2%). Neo adjuvant and adjuvant chemotherapy mainly consisted of combinations of cyclophosphamide and doxorubicin [AC] +/- a taxane[AC→T] ( mainly by medical oncologists) or AC+ 5-FU [CAF] (mainly by clinical oncologists). Of 305 cases 272 (89.2%) completed adjuvant therapy, 8(2.6%) died during treatment. Median overall survival was 57.1 months (95% CI; 55.6 to 59.5 months). For metastatic disease, median PFS was worse for patients < 40 years. Conclusions: Pathology and biology mirrored global situation, over 75% of patients had non metastatic disease. A significant proportion of early disease patients did not complete treatment.