Intermediate Risk Of Recurrence Research Articles

Survival benefit of postoperative radioiodine therapy among patients with intermediate-risk differentiated thyroid carcinoma.

The 2015 American Thyroid Association (ATA) guidelines proposed the use of the ATA Risk Stratification System and American Joint Committee on Cancer Tumor-Node-Metastasis (AJCC/TNM) Staging System for postoperative radioiodine decision-making. However, the management of patients with intermediate-risk differentiated thyroid carcinoma (DTC) is not well defined. In this study, we aimed to evaluate the therapeutic efficacy of radioactive iodine therapy (RAIT) among various subgroups of patients with intermediate-risk DTC after surgery. This was a retrospective study based on the Surveillance, Epidemiology, and End Results (SEER) database (2010-2015). The DTC patients with intermediate risk of recurrence were divided into two groups (treated or not treated with radioactive iodine (RAI)). As the treatment was not randomly assigned, stabilized inverse probability treatment weighting (sIPTW) was used to reduce selection bias. We used the Kaplan-Meier method and log-rank test to analyze overall survival (OS) and cancer-specific survival (CSS). Kaplan-Meier analysis after sIPTW found a significant difference in OS and CSS between no RAIT and RAIT (log-rank test, P < 0.0001; P = 0.0019, respectively). The Kaplan-Meier curves of CSS in age cutoff of 55 years showed a significant association between no RAIT and RAIT (log-rank test, P = 0.0045). Univariate and multivariate Cox regression showed RAIT was associated with a reduced risk of mortality compared with no RAIT (hazard ratio [HR] 0.59, 95% confidence interval [95% CI 0.44-0.80]). Age (≥ 55) years showed a worse CSS regardless of whether or not a patient was treated or not treated with RAI ([HR] 8.91, 95% confidence interval [95% CI 6.19-12.84]). RAIT improves OS and CSS in patients with intermediate-risk DTC after surgery. 55 years is a more appropriate prognostic age cutoff for the relevant classification systems and is a crucial consideration in RAI decision-making. Therefore, we need individualized treatment plans.

Abstract PO2-18-09: A phase 3 randomized open-label study of extended adjuvant therapy with camizestrant vs standard endocrine therapy in patients with ER+/HER2– early breast cancer and an intermediate or high risk of recurrence (CAMBRIA 1)

Abstract Background: Definitive locoregional (surgery ± radiotherapy) and standard adjuvant endocrine therapy (ET) (± chemotherapy or cyclin-dependent kinase 4/6 inhibitor [CDK4/6i]) can achieve cure in many patients (pts) with estrogen receptor-positive/human epidermal growth factor receptor 2-negative (ER+/HER2–) early breast cancer (BC). Nevertheless, a significant proportion of pts with stage I–III disease will experience recurrence to metastatic, incurable disease (5- and 10-year cumulative incidences of recurrence of 8.3% and 14.0%, respectively). There is evidence that incorporating a more effective endocrine therapy after 2 years of standard adjuvant ET can result in clinical benefit for high-risk individuals. Camizestrant is a next-generation oral selective ER degrader and pure ER antagonist. In SERENA-2, camizestrant 75 mg and 150 mg significantly prolonged progression-free survival vs fulvestrant in postmenopausal women with ER+/HER2– advanced BC with disease recurrence or progression after ET. The CAMBRIA-1 study (NCT05774951) is evaluating the potential of extended adjuvant therapy with camizestrant to improve outcomes in pts with ER+/HER2– early BC with an intermediate or high risk of recurrence after definitive locoregional therapy and standard adjuvant ET. Trial design: This phase 3 randomized, open-label study is enrolling women (pre- or postmenopausal) and men with ER+/HER2– (immunohistochemistry 0/1+/2+/in situ hybridization-negative) early BC who have completed definitive locoregional therapy and standard adjuvant ET (± CDK4/6i) for ≥2 and ≤5 years (+ 3 months) without disease recurrence. Pts must be considered at intermediate or high risk of recurrence based on clinical, biological, and genomic factors. Pts are randomized (1:1) to continue standard ET of the investigator’s choice (tamoxifen or aromatase inhibitor ± luteinizing hormone-releasing hormone [LHRH] agonist) or camizestrant ± LHRH agonist for up to 60 months. The primary endpoint is invasive BC-free survival (STEEP 2.0 criteria). Secondary endpoints include invasive disease-free survival and distant relapse-free survival (STEEP 2.0 criteria), overall survival, safety, and health-related quality of life. Primary endpoint analysis will use a stratified log-rank test adjusting for stratification factors, assuming a two-sided significance level of 5%. Approximately 4300 pts will be randomized; enrollment is ongoing. Clinical trial identification: NCT05774951 Editorial acknowledgment: Writing assistance was provided by Alison Lovibond, PhD, of BOLDSCIENCE Inc., funded by AstraZeneca. Legal entity responsible for the study: AstraZeneca Funding: This study was supported by AstraZeneca. Citation Format: Erika Hamilton, Sibylle Loibl, Naoki Niikura, Priya Rastogi, Kamal S. Saini, Ioanna Gioni, Teresa Klinowska, Ingrid A. Mayer, Mary Stuart, Emilia Syta, Andrew Walding, Thomas Bachelot. A phase 3 randomized open-label study of extended adjuvant therapy with camizestrant vs standard endocrine therapy in patients with ER+/HER2– early breast cancer and an intermediate or high risk of recurrence (CAMBRIA 1) [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO2-18-09.

Abstract PO2-16-08: Adjuvant Treatment Selection for County-Level Patients with HR+/HER2- Early Breast Cancer in a Real-Life Setting in China

Abstract Background: CHASE001 (NCT05544123), a prospective, non-interventional multicenter study exploring real-world treatment and referral behavior of Chinese county patients (pts) with HER2+ or HR+/HER2– breast cancer is ongoing since September 2022. A prespecified interim analysis (IA) on 750 HER2+ and HR+/HER2- early breast cancer (eBC) was reported at the ESMO Congress 2023. In the 2nd IA from CHASE001, adjuvant treatment selection for patients with HR+/HER2- eBC will be evaluated. Methods: The study was designed to enroll 2500 pts, including four cohorts (HER2+ eBC, HR+/HER2-eBC, HER2+ advanced BC, and HR+/HER2- aBC). In this IA, HR+/HER2- eBC pts after surgery were included. Descriptive statistics reported patient demographics, clinical and disease characteristics and treatment patterns. To investigate the factors associated with chemotherapy-free regimen, non-anthracycline chemotherapy regimen and ovarian function suppression (OFS), univariate and multivariate logistic regression analyses were conducted. Results: At data cutoff (May 17, 2023), 697 HR+/HER2- eBC pts (median age 52 years, 45.77% pT2, 50.93% pN0, 56.10% G2) were included from 26 institutions in China county areas, 338 (48.49%) were premenopausal. 584 (83.79%) received adjuvant chemotherapy, with a few (47/584, 8.05%) initially developing their treatment plan at a higher level hospital (national or provincial tertiary hospital). AC-T (309/584, 52.91%) was the most commonly used regimen. 181 (30.99%) pts received non-anthracycline chemotherapy regimen (mainly TC), and pts with N0, age≥65 years and ki67 &amp;lt; 20% had the strongest association to this regimen (multivariate OR=0.082, 95%CI [0.037,0.179], OR=0.463, 95%CI [0.250,0.859], and OR=0.642, 95%CI [0.418,0.985], respectively). Interestingly, on univariate analysis pts initially diagnosed in a higher level hospital were significantly associated with non-anthracycline regimen (P=0.0109), however on multivariate analysis it was no longer significant. 483 pts received endocrine therapy, including 234 (48.45%) premenopausal pts. The most commonly used endocrine regimen for premenopausal pts was OFS/OFS+ (122/234, 52.14%) ,of which half (61, 50%) were prescribed OFS+TAM/TOR; followed by TAM/TOR monotherapy (69/234, 29.49%). The proportions of patients classified as low, intermediate, and high clinical risk for recurrence (investigator assessed)were 33.62%, 42.67% and 23.71%. The OFS rate were 39.74% in low, 61.62% in intermediate and 70.91% in high risk pts, respectively. Multivariable analyses found that high clinical risk, age &amp;lt; 45 years and ki67 &amp;lt; 20% were strongly associated with the use of OFS (OR=0.210, 95%CI [0.066,0.674], OR=0.327, 95%CI [0.165,0.649], and OR=0.405, 95%CI [0.194,0.845], respectively). For postmenopausal pts, AI monotherapy (84.74%) was the most commonly used endocrine regimen. Conclusions: To our knowledge, this is the first real-world study evaluating the treatment patterns and referral behavior of BC pts in China counties. The 2nd IA results presented showed the current systemic adjuvant treatment preferences and influence factors from a large sample of HR+/HER2- eBC pts in China counties, which were generally consistent with China BC treatment guidelines. Table 1. Utilization of adjuvant systemic therapy regimens in 697 HR+/HER2− eBC pts, China counties AC-T: (dd)doxorubicin/epirubicin, cyclophosphamide, followed by (dd)paclitaxel/docetaxel; TC: paclitaxel/docetaxel, cyclophosphamide; AC: doxorubicin/epirubicin, cyclophosphamide; TAC: docetaxel, doxorubicin/epirubicin, cyclophosphamide; TAM: tamoxifen; OFS: ovarian function suppression; AI: aromatase inhibitors; TOR: toremifene; CDK4/6i: cyclin-dependent kinase 4/6 inhibitors; “Other” category includes various therapies used in &amp;lt;1% of patients each Citation Format: Yinghua Ji, Honglan Qu, Feidu Zhou, Juan Wang, Qianfu Wu, Guohua Dai, Mengyou Liu, Wenbo He, Wei Liang, Qiuli Meng, Yun Ren, Guoxiang Luo, Hongjian Wang, Hui Liu, Zien Qin, Yingguo Tian, Huali Tang, Hongmei Liu, Jun Luo, Zengfeng Yu, Guinv Hu, Jianzhi Gao, Xiang Tan, Yi Liu, Yuanjiang Zhang, Ming Wang, Min Zhang, Ping Lu. Adjuvant Treatment Selection for County-Level Patients with HR+/HER2- Early Breast Cancer in a Real-Life Setting in China [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO2-16-08.

Intermediate-risk endometrial cancer treated with adjuvant brachytherapy using single dosimetric planning: long-term outcome and toxicity assessment

ObjectiveBrachytherapy of the vaginal dome is the recommended adjuvant treatment for intermediate-risk endometrial cancer. This study assessed the results of dosimetric planning of high-dose-rate brachytherapy exclusively in the first treatment session.Study design: This retrospective study included all patients who underwent hysterectomy for endometrial cancer followed by adjuvant brachytherapy of the vaginal dome between 2012 and 2015. Local recurrence rates, overall survival (OS) rates, recurrence-free survival (RFS) rates, and related acute and late toxicity rates were evaluated. ResultsThis analysis included 250 patients, of whom 208 were considered to be at high–intermediate risk of disease recurrence. After a median follow-up of 56 months, the cumulative incidence of local recurrence was 4.8% at 3 years [95% confidence interval (CI) 2.8–8.3] and 7.8% at 5 years (95% CI 4.8–12.6). The 5-year OS rate was 86.2% (95% CI 80.6–90.3), and the 5-year RFS rate was 77.5% (95% CI 71.1–82.7). Acute toxicity occurred in 20 (8%) patients, of which two patients had grade ≥3 toxicity. Only one patient (0.4%) presented with late grade ≥3 toxicity. ConclusionThese findings confirm the tolerability of this brachytherapy approach, indicating minimal cases of late grade ≥3 toxicity, associated with a good 5-year OS rate. With the advent of molecular prognostic factors, the current focus revolves around discerning those individuals who gain the greatest benefit from adjuvant therapy, and tailoring treatment more effectively.

Tailored anticoagulant treatment after a first venous thromboembolism: protocol of the Leiden Thrombosis Recurrence Risk Prevention (L-TRRiP) study - cohort-based randomised controlled trial

IntroductionPatients with a first venous thromboembolism (VTE) are at risk of recurrence. Recurrent VTE (rVTE) can be prevented by extended anticoagulant therapy, but this comes at the cost of an...

Assessment of Background Parenchymal Enhancement at Dynamic Contrast-enhanced MRI in Predicting Breast Cancer Recurrence Risk.

Background Background parenchymal enhancement (BPE) at dynamic contrast-enhanced (DCE) MRI of cancer-free breasts increases the risk of developing breast cancer; implications of quantitative BPE in ipsilateral breasts with breast cancer are largely unexplored. Purpose To determine whether quantitative BPE measurements in one or both breasts could be used to predict recurrence risk in women with breast cancer, using the Oncotype DX recurrence score as the reference standard. Materials and Methods This HIPAA-compliant retrospective single-institution study included women diagnosed with breast cancer between January 2007 and January 2012 (development set) and between January 2012 and January 2017 (internal test set). Quantitative BPE was automatically computed using an in-house-developed computer algorithm in both breasts. Univariable logistic regression was used to examine the association of BPE with Oncotype DX recurrence score binarized into high-risk (recurrence score >25) and low- or intermediate-risk (recurrence score ≤25) categories. Models including BPE measures were assessed for their ability to distinguish patients with high risk versus those with low or intermediate risk and the actual recurrence outcome. Results The development set included 127 women (mean age, 58 years ± 10.2 [SD]; 33 with high risk and 94 with low or intermediate risk) with an actual local or distant recurrence rate of 15.7% (20 of 127) at a minimum 10 years of follow-up. The test set included 60 women (mean age, 57.8 years ± 11.6; 16 with high risk and 44 with low or intermediate risk). BPE measurements quantified in both breasts were associated with increased odds of a high-risk Oncotype DX recurrence score (odds ratio range, 1.27-1.66 [95% CI: 1.02, 2.56]; P < .001 to P = .04). Measures of BPE combined with tumor radiomics helped distinguish patients with a high-risk Oncotype DX recurrence score from those with a low- or intermediate-risk score, with an area under the receiver operating characteristic curve of 0.94 in the development set and 0.79 in the test set. For the combined models, the negative predictive values were 0.97 and 0.93 in predicting actual distant recurrence and local recurrence, respectively. Conclusion Ipsilateral and contralateral DCE MRI measures of BPE quantified in patients with breast cancer can help distinguish patients with high recurrence risk from those with low or intermediate recurrence risk, similar to Oncotype DX recurrence score. © RSNA, 2024 Supplemental material is available for this article. See also the editorial by Zhou and Rahbar in this issue.

New Score for Predicting Results after Catheter Ablation for Atrial Fibrillation: VAT-DHF.

Catheter ablation (CA) for atrial fibrillation (AF) has been proven to have the highest efficacy in maintaining sinus rhythm. Several studies have proposed different scores for predicting post-procedural success, but most have not been validated in prospective cohorts. Further research is required to determine the optimal formulae. This study aimed to identify independent predictors of AF recurrence after CA and develop a composite score. Consecutive patients with persistent and paroxysmal AF who underwent CA were retrospectively analyzed. The independent predictors of recurrence were used to create a new predictive score. The cohort included 263 patients with a follow-up of 37.6 ± 23.4 months. Persistent AF, f-waves < 0.1 mV, indexed left atrium volume, the presence of type 2 diabetes, and smaller height were independent predictors of recurrence and were used to create a new scoring model, VAT-DHF (V = Volume, AT = AF Type, D = Diabetes, H = Height, F = f waves). The ROC curve for this new score showed an AUC of 0.869, p < 0.0001, 95% CI [0.802-0.936], while those for APPLE and CHA2DS2-VASc showed an AUC of 0.765, 95% CI [0.637-0.893] and an AUC of 0.655, 95% CI [0.580-0.730], respectively. Patients who had a VAT-DHF score between 0 and 3.25, 3.25 and 6, and ≥6, had success rates of 95.7%, 76.3%, and 25% (p < 0.0001), respectively. The novel VAT-DHF score is easy to calculate and may be a useful clinical tool for identifying patients with a low, intermediate, or high risk of AF recurrence after CA.

Benefit and harm of lymphadenectomy in intermediate risk prostate cancer: comparison of five nomograms

BackgroundPelvic lymph node dissection (PLND) is recommended method for detecting prostate cancer (PCa) nodal metastases although associated with serious complications. In this study, we aimed to assess benefit/harm of routine PLND in intermediate risk PCa patients and to compare diagnostic yield of five different nomograms in predicting lymph node invasion (LNI).MethodsRetrospective analysis of consecutive PCa patients with intermediate risk of biochemical recurrence who underwent open radical prostatectomy (RP) with bilateral PLND between January 2017 and December 2019 at our institution. Partin, 2012-Briganti, 2018-Briganti, Cagiannos and Memorial Sloan Kettering Cancer Center (MSKCC) values were calculated. To compare accuracy, sensitivity, specificity, and area under receiver-operating curve (AUC) were calculated and then optimal cutoff values were estimated, analyses repeated and compared. To assess benefit and harm of PLND, relative risk (RR) and number need to treat (NNT) with LNI and complications set as outcome were calculated.ResultsTotal 309 subjects. Average age 62.2 years, average PSA 7.2 ng/mL; 18 (5.8%) had LNI; 88 (28.5%) suffered Clavien-Dindo grade 3–5 complication. AUC for predicting LNI: 0.729 for 2012-Briganti, 0.660 for MSKCC, 0.521 for 2018-Briganti, 0.486 for Cagiannos, and 0.424 for Partin. None of pairwise AUC comparisons based on default and newly established cutoff values were statistically significant. Lowest NNT was for Partin and Cagiannos with default cutoff (≥ 5%). Risks of serious complications between higher/lower than cutoff values were non-significant across nomograms.Conclusions2012-Briganti nomogram outperforms, although not significantly, MSKCC, 2018-Briganti, Cagiannos, and Partin nomograms in classifying LNI in intermediate risk PCa patients. Routine PLND in these patients should be avoided, due to high rate and severity of complications.

Partial Thyroidectomy With Incidental Metastatic Lymph Nodes

The need for completion thyroidectomy in patients with incidental metastatic lymph nodes after partial thyroidectomy is unclear. To investigate the outcomes of patients with incidental metastatic lymph nodes following partial thyroidectomy. A retrospective review of a prospectively maintained thyroid cancer database from 1985 to 2015 was carried out at a head and neck surgery practice at a tertiary referral cancer center. A total of 74 patients who underwent thyroid lobectomy or thyroid isthmusectomy between 1985 and 2015 and were found to have incidental metastatic lymph nodes on final pathologic analysis and were selected to be observed without immediate completion thyroidectomy were included. A separate group of additional 11 patients who underwent immediate completion thyroidectomy was also identified and reviewed. Analysis took place from February to May 2022. Recurrence-free survival outcomes of patients found to have incidental metastatic lymph nodes on final pathologic analysis following partial thyroidectomy with no immediate completion thyroidectomy. A total of 74 patients were observed, with a median (IQR) age of 39 (28-49) years; 44 (59%) were women. Sixty-four patients underwent thyroid lobectomy and 10 patients had isthmusectomy. Classic papillary thyroid carcinoma was the most common histologic type (34 [46%]). Vascular invasion and microscopic extrathyroidal extension were present in 11 patients (16%) and 22 patients (30%), respectively. Positive margins were identified in 5 patients (7.8%). Size of metastatic lymph nodes ranged between 0.07 cm and 1.2 cm. No extranodal extension was reported. A total of 52 patients (70%) were classified as intermediate risk for recurrence based on the American Thyroid Association risk stratification system. The median (IQR) follow up was 48.15 (15.4-86.1) months, during which only 1 patient had a regional recurrence. Another patient underwent delayed completion thyroidectomy for a contralateral lobe malignant abnormality. Recurrence-free survival, disease-specific survival, and overall survival were 97.4%, 100%, and 96.2%, respectively. A separate group of 11 patients who underwent immediate completion thyroidectomy were reviewed. These patients were more likely to have tall-cell papillary thyroid carcinoma (6 [55%] vs 13 [18%]), multifocality (9 [82%] vs 28 [41%]), microscopic extrathyroidal extension (8 [73%] vs 22 [30%]), and positive margins (3 [30%] vs 5 [7.8%]) compared with patients who were under observation only. Completion thyroidectomy may not be necessary in appropriately selected patients who are found to have incidental metastatic lymph nodes (N1a) after partial thyroidectomy for localized well-differentiated thyroid cancer.

Molecular landscape and clinical significance of exon 11 mutations in KIT gene among patients with gastrointestinal stromal tumor: a retrospective exploratory study.

This aim of this study was to investigate the prognostic significance of KIT exon 11 mutation subtypes in patients with GISTs. A total of 233 consecutive patients diagnosed with GISTs at the First Affiliated Hospital of Zhengzhou University from January 2013 to August 2018 were included in this study. The prevalence and mutation landscape of exon 11 in KIT was presented. The clinicopathological characteristics and prognosis among the different mutation subtypes were analyzed. All the statistical analyses were performed by SPSS22.0. Somatic mutational analysis indicated that point mutations were the most frequently detected mutations followed by deletions & compound mutations and insertion and tandem duplication mutations in the stomach. Point mutations showed a low mitotic count and a high risk of recurrence, and deletions and compound mutations have a high mitotic count while insertions and tandem duplication mutations showed a low mitotic count with an intermediate recurrence risk. Point mutations and deletions frequently occurred in sequence region codons 550-560 of exon 11, while compound mutations, insertion, and tandem duplication were mainly detected in codons 557-559, 572-580, and 577-581, respectively. The multi-variation analysis demonstrated that tumor diameter and high recurrence risk groups had worse prognostic values. However, mutation types were not significant predictors of relapse-free survival (RFS) in GISTs. Survival analysis suggested no significant difference in RFS between the 557/558 deletion and the other deletions. This study suggested that mutations in exon 11 of the KIT gene were common with intermediate/high recurrence risk in GISTs patients. Tumor diameter ≥5 cm, and deletions mutations might predict a worse prognosis.

354TiP A phase III randomised open-label study of extended adjuvant therapy with camizestrant vs standard endocrine therapy (ET) in patients with ER+/HER2– early breast cancer (BC) and an intermediate or high risk of recurrence (CAMBRIA-1)

354TiP A phase III randomised open-label study of extended adjuvant therapy with camizestrant vs standard endocrine therapy (ET) in patients with ER+/HER2– early breast cancer (BC) and an intermediate or high risk of recurrence (CAMBRIA-1)

Impact of lymphovascular invasion on otherwise low-risk papillary thyroid carcinomas: a retrospective and observational study

PurposePresence of venous vascular invasion is a criterion of intermediate risk of recurrence in papillary thyroid carcinoma (PTC). However, the presence and type of vascular invasion (lymphatic or venous) is often underreported and its impact on PTCs without other risk features remains unknown. The aim of this study was to evaluate the impact of both lymphatic and venous invasion on the risk of recurrence/persistence on otherwise low-risk PTCs.MethodsRetrospective study including patients with otherwise low-risk PTCs but with vascular invasion, diagnosed between 2013 and 2019. The persistence/recurrence during the follow-up was evaluated. Pathology was reviewed to confirm the presence of lymphovascular invasion and determine the type of invasion.ResultsA total of 141 patients were included. Lymphovascular invasion was confirmed in 20.6%. After surgery, 48.9% (N = 69) of the patients received radioactive iodine (RAI). The median follow-up time was 4 [3–6] years. Overall, 6 (4.2%) patients experienced persistent/recurrent disease in the neck, including 3 with lymphovascular invasion, confirmed as “only lymphatic”. Overall, patients with tumors harboring lymphovascular invasion had sensibly more persistent/recurrence disease compared with those without lymphovascular invasion (10.3% vs 2.7%, p = 0.1), especially in the subgroup of patients not treated with RAI (20% vs 1.6%, p = 0.049) [OR 15.25, 95% CI 1.24-187.85, p = 0.033].ConclusionLymphovascular invasion, including lymphatic invasion only, is associated with a sensibly higher risk of persistent/recurrent disease in otherwise low-risk PTCs, namely in patients not treated with RAI. Lymphatic invasion could have a role in risk-stratification systems for decision making.

Adjuvant mitotane versus surveillance in low-grade, localised adrenocortical carcinoma (ADIUVO): an international, multicentre, open-label, randomised, phase 3 trial and observational study

Adjuvant treatment with mitotane is commonly used after resection of adrenocortical carcinoma; however, treatment remains controversial, particularly if risk of recurrence is not high. We aimed to assess the efficacy and safety of adjuvant mitotane compared with surveillance alone following complete tumour resection in patients with adrenocortical carcinoma considered to be at low to intermediate risk of recurrence. ADIUVO was a multicentre, open-label, parallel, randomised, phase 3 trial done in 23 centres across seven countries. Patients aged 18 years or older with adrenocortical carcinoma and low to intermediate risk of recurrence (R0, stage I-III, and Ki67 ≤10%) were randomly assigned to adjuvant oral mitotane two or three times daily (the dose was adjusted by the local investigator with the target of reaching and maintaining plasma mitotane concentrations of 14-20 mg/L) for 2 years or surveillance alone. All consecutive patients at 14 study centres fulfilling the eligibility criteria of the ADIUVO trial who refused randomisation and agreed on data collection via the European Network for the Study of Adrenal Tumors adrenocortical carcinoma registry were included prospectively in the ADIUVO Observational study. The primary endpoint was recurrence-free survival, defined as the time from randomisation to the first radiological evidence of recurrence or death from any cause (whichever occurred first), assessed in all randomly assigned patients by intention to treat. Overall survival, defined as time from the date of randomisation to the date of death from any cause, was a secondary endpoint analysed by intention to treat in all randomly assigned patients. Safety was assessed in all patients who adhered to the assigned regimen, which was defined by taking at least one tablet of mitotane in the mitotane group and no mitotane at all in the surveillance group. The ADIUVO trial is registered with ClinicalTrials.gov, NCT00777244, and is now complete. Between Oct 23, 2008, and Dec 27, 2018, 45 patients were randomly assigned to mitotane and 46 to surveillance alone. Because the study was discontinued prematurely, 5-year recurrence-free and overall survival are reported instead of recurrence-free and overall survival as defined in the protocol. 5-year recurrence-free survival was 79% (95% CI 67-94) in the mitotane group and 75% (63-90) in the surveillance group (hazard ratio 0·74 [95% CI 0·30-1·85]). Two people in the mitotane group and five people in the surveillance group died, and 5-year overall survival was not significantly different (95% [95% CI 89-100] in the mitotane group and 86% [74-100] in the surveillance group). All 42 patients who received mitotane had adverse events, and eight (19%) discontinued treatment. There were no grade 4 adverse events or treatment-related deaths. Adjuvant mitotane might not be indicated in patients with low-grade, localised adrenocortical carcinoma considering the relatively good prognosis of these patients, and no significant improvement in recurrence-free survival and treatment-associated toxicity in the mitotane group. However, the study was discontinued prematurely due to slow recruitment and cannot rule out an efficacy of treatment. AIFA, ENSAT Cancer Health F2-2010-259735 programme, Deutsche Forschungsgemeinschaft, Cancer Research UK, and the French Ministry of Health.

Photodynamic Diagnosis-guided Transurethral Resection of Bladder Tumour in Participants with a First Suspected Diagnosis of Intermediate- or High-risk Non–muscle-invasive Bladder Cancer: Cost-effectiveness Analysis Alongside a Randomised Controlled Trial

BackgroundRecurrence of non–muscle-invasive bladder cancer (NMIBC) is common after transurethral resection of bladder tumour (TURBT). Photodynamic diagnosis (PDD) may reduce recurrence. PDD uses a photosensitiser in the bladder that causes the tumour to fluoresce to guide resection. PDD provides better diagnostic accuracy and allows more complete tumour resection. ObjectiveTo estimate the economic efficiency of PDD-guided TURBT (PDD-TURBT) in comparison to white light–guided TURNT (WL-TURBT) in individuals with a suspected first diagnosis of NMIBC at intermediate or high risk of recurrence on the basis of routine visual assessment before being scheduled for TURBT. Design, setting, and participantsThis is a health economic evaluation alongside a pragmatic, open-label, parallel-group randomised trial from a societal perspective. A total of 493 participants (aged ≥16 yr) were randomly allocated to PDD-TURBT (n = 244) or WL-TURBT (n = 249) in 22 UK National Health Service hospitals. Outcome measurements and statistical analysisCost effectiveness ratios were based on the use of health care resources associated with PDD-TURBT and WL-TURBT and quality-adjusted life years (QALYs) gained within the trial. Uncertainties in key parameters were assessed using sensitivity analyses. Results and limitationsOn the basis of the use of resources driven by the trial protocol, the incremental cost effectiveness of PDD-TURBT in comparison to WL-TURBT was not cost saving. At 3 yr, the total cost was £12 881 for PDD-TURBT and £12 005 for WL-TURBT. QALYs at three years were 2.087 for PDD-TURBT and 2.094 for WL-TURBT. The probability that PDD-TURBT is cost effective was never >30% above the range of societal cost-effectiveness thresholds. ConclusionsThere was no evidence of a difference in either costs or QALYs over 3-yr follow-up between PDD-TURBT and WL-TURBT in individuals with suspected intermediate- or high-risk NMIBC. PDD-TURBT is not supported for the management of primary intermediate- or high-risk NMIBC. Patient summaryWe assessed overall costs for two approaches for removal of bladder tumours in noninvasive cancer and measured quality-adjusted life years gained for each. We found that use of a photosensitiser in the bladder was not more cost effective than use of white light only during tumour removal.

Relapse Rate in Patients Avoiding Adjuvant Chemotherapy Based on Oncotype DX Score – Real-world Data from the Kent Oncology Centre

Purpose: Oncotype DX is an approved gene expression assay that aids decision-making regarding adjuvant chemotherapy for node-negative ER+/HER2– breast cancers with intermediate recurrence risk [1]. TAILOR-X data demonstrated no significant evidence of chemotherapy benefit with scores ≤25 if age >50, or ≤20 if age ≤50, guiding cut-offs for chemotherapy avoidance recommendations [2]. Our principle aim was to determine distant relapse rates for Kent Oncology Centre patients with >5 years follow-up for ER+/HER2– breast cancer who avoided adjuvant chemotherapy based on their Oncotype DX score.

Relationship between Proclarix and the Aggressiveness of Prostate Cancer.

Proclarix is a CE-marked test that provides the risk of clinically significant prostate cancer (csPCa), ranging from 0% to 100%, based on the serum measurement of Thrombospondin-1, cathepsin D, prostate-specific antigen (PSA), and percentage of free PSA in addition to age. We hypothesize that Proclarix could be correlated with PCa aggressiveness. We analyzed the association of this new biomarker with four surrogates of aggressiveness: grade group (GG) in the biopsy, clinical stage, risk of biochemical recurrence after primary treatment of localized PCa, and pathology in the surgical specimen. This is a retrospective study from 606 men with suspicion of PCa [PSA of ≥3.0ng/mL and/or abnormal digital rectal examination (DRE)], in whom Proclarix was assessed (0-100%). The GG was defined by the International Society of Urological Pathology categories. The TNM was used for clinical staging (cT based on DRE, whereas cN and cM were established with computed tomography and 99-technetium bone scintigraphy). The risk of biochemical recurrence of localized PCa after primary treatment was defined by combining PSA, GG, and cT. Finally, an unfavorable pathology in a surgical specimen was defined as GG> 2 or pT≥ 3. The median age of the cohort was 67yearsold, with a median PSA of 7ng/mL and a rate of abnormal DRE of 23.3%. CsPCa was detected in 254 men (41.9%), with a median Proclarix of 60.1% compared with 37.3% obtained in patients with insignificant PCa and 20.7% in men without PCa. Among patients with GG > 3, Proclarix was significantly higher (58.2%) than in those with GG of 3 or lower (33.1%, p< 0.001). Men with localized tumors exhibited a Proclarix median of 37.3% compared with those with advanced disease (60.1%, p< 0.001). Proclarix levels among 197 patients with low and intermediate risk of biochemical recurrence were 24.9% and 35.0%, respectively, significantly lower compared with patients with high-risk disease (58.7%, p< 0.001). Unfavorable pathology was observed in 35 patients out of the 79 who underwent radical prostatectomy, with a Proclarix median of 35.7% compared with 23.7% obtained in patients with favorable pathology (p= 0.013). Proclarix and magnetic resonance imaging were independent predictors of the four surrogates of aggressiveness analyzed. There is a correlation between Proclarix and the aggressiveness of PCa.

Abstract 5839: Novel stroma-derived prostate cancer subtypes are associated with risk of clinical progression

Abstract The tumor microenvironment influences prostate cancer aggressiveness, and by focusing on how different changes to the microenvironment can affect the cancer, we aimed to identify novel stromal subtypes in localized prostate cancer (LPC), characterize these subtypes, and utilize subtypes to increase accuracy in prostate cancer risk stratification. Subtype identification was conducted using non-negative matrix factorization with consensus clustering on a stroma-specific expression signature in RNA sequencing data. A discovery cohort (127 LPC patients) and two independent validation cohorts (406 LPC &amp; 126 LPC patients) were used for subtype identification. All three cohorts were subsequently used for subtype characterization and prognostic evaluation. Identified subtypes were characterized by evaluation of clinical characteristics, by gene set enrichment analysis, and by cell-type deconvolution analysis. Survival differences between subtypes were assessed using Kaplan-Meier and univariate Cox regression analyses with biochemical recurrence (BCR) as endpoint. Lastly, a high-risk stromal subtype was investigated for its ability to improve risk stratification for intermediate risk prostate cancer using hazard ratio changes from univariate Cox regression analysis. We identified three stromal subtypes (S1-S3) in prostate cancer. Of these, subtype S3 showed characteristics of a highly reactive stromal environment with significantly (adj. p &amp;lt; 0.05) decreased cell polarity and stroma related functions, significantly (adj. p &amp;lt; 0.05) reduced fibroblast infiltration, and a significantly (adj. p &amp;lt; 0.05) increased immune cells infiltration compared to the other subtypes. Survival analysis also revealed significant (p &amp;lt; 0.05) association of S3 with BCR in all three cohorts (HR = 3.2, 2.1, and 3.4 in cohorts 1, 2 and 3 respectively). Lastly, S3 significantly (p &amp;lt; 0.05) improved the risk prediction for patients with intermediate recurrence risk according to the clinical nomogram CAPRA-S (cohort 1, delta HR = 1.4; cohort 2, delta HR = 2.3; cohort 3, delta HR = 4.2). In conclusion, by focusing on the stromal alteration in prostate cancer, this study sheds new light on the influence of tumor microenvironment on LPC aggressiveness. A stromal subtype characterized by dysregulated stromal functions and changes in stroma and immune cells infiltration predicted adverse outcome in patients with a high prognostic ambiguity. This utilization of stromal information to improve risk assessment for clinically intermediate risk PC indicates a potential use in future evaluation of PC aggressiveness. Citation Format: Martin Rasmussen, Jacob Fredsøe, Paul V. Salachan, Marcus P. Blanke, Benedicte P. Ulhøi, Michael Borre, Karina D. Sørensen. Novel stroma-derived prostate cancer subtypes are associated with risk of clinical progression. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 5839.

Incidence of Disease Recurrence in Patients With Colon and Upper Rectum Adenocarcinoma Stage II and III Receiving Adjuvant Capecitabine Monotherapy: Do Number of Chemotherapy Cycles and Relative Dose Intensity of the Drug Play a Role?

Introduction/BackgroundAdjuvant capecitabine monotherapy is an option for colon and upper rectum adenocarcinoma patients, providing they have stage II disease with an intermediate risk of recurrence, or stage III but they are above 70’s or they have comorbidities. We wanted to examine whether the number of chemotherapy cycles and the relative dose intensity (RDI) of capecitabine monotherapy in the adjuvant setting are affecting disease recurrence. Patients and MethodsWe included patients with completely resected stage II and III colon and upper rectum cancer who received adjuvant capecitabine monotherapy, from 2003 until May 2020. Patients with early relapse, i.e. during chemotherapy or within 6 months after the completion of adjuvant chemotherapy, and those with rectal cancer who received radiotherapy were excluded. Patients were divided into 3 groups based on the number of chemotherapy cycles received and the RDI. Group A included patients with ≤4 cycles of chemotherapy, group B patients with >4 cycles of chemotherapy and RDI ≤80%, and group C patients with >4 cycles of chemotherapy and RDI >80%. Study’s endpoint, was recurrence free survival (RFS). ResultsTwo hundred twenty six patients with stage II and III disease (164 and 62 respectively) were included. Sixteen, 166 and 44 were included in groups A, B and C respectively. After a median follow-up of 41 months, 21 patients (9,3%) had relapsed. Patients belonging to group C were found to have a trend for lower relapse rate compared to patients belonging to group A or group B. ConclusionNumber of adjuvant capecitabine cycles and RDI might play a role in RFS in patients with stage II and III colon and upper rectum adenocarcinoma.

Abstract P4-07-17: Follow-up in breast cancer care: guidelines and individual risks

Abstract The aim of this study was to investigate how breast cancer follow-up in the Netherlands changed during the COVID-19 pandemic, compared to 2018-2019, and to what extent follow-up during the pandemic corresponded to the patient risk of recurrence. During the early phase of the pandemic the Dutch Society for Surgical Oncology (NVCO) issued a report with recommendations on how follow-up could be postponed, as a guidance for the pandemic, based on a low, intermediate or high risk of recurrence. In this study we investigated to what extent this advice was followed. A dataset of 33160 women diagnosed with primary invasive breast cancer between January of 2017 and July of 2021 was selected from the Netherlands Cancer Registry (NCR) and Dutch Hospital Data (DHD). The pandemic, 2020 and weeks 1-32 of 2021, was divided into six periods (A to F), based on the number of hospitalized COVID patients in the Netherlands. The five-year risk of locoregional recurrence (LRR) was determined for each patient with the INFLUENCE nomogram. The LRR risk was compared to the risk groups from the NVCO report with a Kruskal-Wallis test. The percentage of patients who received a mammogram during period A to F was compared to the same periods of 2018-2019 with a chi-squared test. Correlation between the LRR risk, and if patients had a mammogram, was investigated with logistic regression. This analysis was repeated separately for the risk groups. Correlation between the LRR risk, and time intervals between surgery and the first and second mammogram was analyzed using cox proportional hazard models, this was also repeated for the risk groups. There was a significant difference in LRR risk between the NVCO risk groups. In the low-risk group (n=7673), 86 patients (1.1%) had a risk &amp;gt;5%. In the intermediate risk group (n=19197), 18364 patients (95.7%) had a risk of &amp;lt; 5%, and 65 patients (0.34%) had a risk of &amp;gt;10%. In the high-risk group (n=2674), 2365 patients (88.4%) had a risk &amp;lt; 10%. The percentage of patients who received a mammogram was significantly lower in periods B to F of the pandemic. Logistic regression showed a negative correlation between the risk of LRR and if patients had a mammogram in 2020 (OR 0.93) and 2021 (OR 0.93). There was also a negative correlation between the risk groups and mammography in 2020 (OR 0.92 for intermediate and 0.80 for high), and for the risk groups and mammography in 2021 (OR 0.98 for intermediate and 0.95 for high). There was no significant impact of LRR risk, or risk group, on time intervals between mammograms. During the pandemic, patients with a higher LRR risk, or a higher risk according to NVCO advice, had lower odds of having a mammogram. If the advice would have been followed, in 0.5% of the patients scheduled for follow-up, the recommendation was to postpone in contrast to a high estimation of the individual risk. For 62.7%, a follow-up was recommended, despite a low estimated individuals risk. Because the number of high-risk patients is relatively low, individual risk prediction could be supportive, in case of future restrictions. This way the high-risk patients can be identified and prioritized for follow-up, and can also be encouraged to come to the hospital. Citation Format: Lotte Van Dongen, Joyce Meijer, Jolanda Van Hoeve, Desiree van den Bongard, Marielle Hendriks, Aafke Honkoop, Luc Strobbe, Cristina Guerrero Paez, Sabine Siesling. Follow-up in breast cancer care: guidelines and individual risks [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P4-07-17.

Role of Genomic and Molecular Biology in the Modulation of the Treatment of Endometrial Cancer: Narrative Review and Perspectives

Endometrial cancer (EC) is one of the most common gynecological malignancies in Western countries. Traditionally, loco-reginal dissemination and histological characteristics are the main prognostic factors. Nowadays, molecular and genomic profiling showed exciting results in terms of prognostication. According to the data provided by The Cancer Genome Atlas and other studies, molecular and genomic profiling might be useful in identifying patients al low, intermediate, and high risk of recurrence. However, data regarding the therapeutic value are scant. Several prospective studies are ongoing to identify the most appropriate adjuvant strategy in EC patients, especially for those with positive nodes and low volume disease. The molecular classification has offered the possibility to improve the risk stratification and management of EC. The aim of this review is to focus on the evolution of molecular classification in EC and its impact on the research approach and on clinical management. Molecular and genomic profiling might be useful to tailor the most appropriate adjuvant strategies in apparent early-stage EC.