Presence Of High-risk Features Research Articles

Adjuvant endocrine therapy choices in premenopausal patients with hormone receptor-positive early breast cancer: Insights from the prospective GIM23-POSTER study

BackgroundMost premenopausal patients with early breast cancer (eBC) are diagnosed with hormone receptor-positive disease and therefore candidate for adjuvant endocrine therapy (ET). Patients and methodsThe Gruppo Italiano Mammella (GIM) 23-POSTER (GIM23) is a multicenter, prospective, observational study conducted in 26 Italian institutions, aiming to evaluate ET choices for premenopausal patients affected by hormone receptor-positive eBC in a real-world setting. Here we report also the results in terms of type of ET prescribed according to the definition of high-risk patients by monarchE and NATALEE trials. ResultsBetween October 2019 and June 2022, 600 premenopausal patients were included, with a median age of 46 years. Almost half (271, 45.2 %) of the patients had stage I disease, while 254 (42.3 %) and 60 (10.0 %) patients had stage II and III, respectively. Overall, 149 (25.1 %) patients received tamoxifen alone, 83 (14.0 %) tamoxifen with ovarian function suppression (OFS), while 361 (60.9 %) received aromatase inhibitor (AI) with OFS. Patients treated with AI and OFS had higher number of metastatic axillary nodes, higher grade and more often received chemotherapy (all p < 0.001). According to the inclusion criteria of the monarchE and NATALEE trials, 81 patients (15.6 %) were considered high-risk for the monarchE and received AI with OFS in 88.9 % of the cases, while 231 patients (44.4 %) were considered high-risk for the NATALEE trial and received AI with OFS in 74.5 % of cases. ConclusionsAI with OFS is the most prescribed adjuvant ET among premenopausal patients, especially in the presence of high-risk features.

Clinical management of typical and atypical carcinoids/neuroendocrine tumors in ENETS centres of excellence (CoE): Survey from the ENETS lung NET task force.

Lung carcinoid tumours are neuroendocrine neoplasms originating from the bronchopulmonary tract's neuroendocrine cells, accounting for only 1%-3% of all lung cancers but 30% of all neuroendocrine tumours. The incidence of lung carcinoids, both typical and atypical, has been increasing over the years due to improved diagnostic methods and increased awareness among clinicians and pathologists. The most recent WHO classification includes a subgroup of lung carcinoids with atypical morphology and higher mitotic count and/or Ki67 labelling index. Despite appropriate surgery, the 5-year survival rate for atypical carcinoids barely exceeds 50%-70%. The role of adjuvant therapy in lung carcinoids is not well-defined, and clinical decisions are generally based on the presence of high-risk features. Long-term follow-up is essential to monitor for recurrence, although the optimal follow-up protocol remains unclear. To address the lack of consensus in clinical management decisions, the European Neuroendocrine Tumor Society (ENETS) initiated a survey among 20 expert centres. The survey identified varied opinions on approaches to imaging, surgery, use of adjuvant therapy, and follow-up protocols. Notably, the absence of dedicated multidisciplinary lung neuroendocrine tumour boards in some centres was evident. Experts agreed on the need for a prospective adjuvant trial in high-risk patients, emphasizing the feasibility of such a study. In conclusion, the study highlights the need for a more uniform adoption of existing guidelines in the management of lung carcinoid tumours and emphasizes the importance of international collaboration to advance research and patient care. Close collaboration between healthcare providers and patients is vital for effective long-term surveillance and management of these rare tumours.

Inadequate Lymph Node Yield: An Inadequate Indication for Adjuvant Chemotherapy in Stage II Colon Cancer.

Optimal therapy for stage II colon cancer remains unclear, and national guidelines recommend "consideration" of adjuvant chemotherapy (ACT) in the presence of high-risk features, including inadequate lymph node yield (LNY, <12 nodes). This study aims to determine whether the survival benefit of ACT in stage II disease varies based on the adequacy of LNY. We used the National Cancer Database (NCDB) to identify adults who underwent resection for a single primary T3 or T4 colon cancer between 2006 and 2018. Multivariable logistic regression tested for associations between ACT and prespecified demographic and clinical characteristics, including the adequacy of LNY. We used Cox proportional hazards models to assess overall survival and restricted cubic splines to estimate the optimal LNY threshold to dichotomize patients based on overall survival. Unadjusted 5- and 10-year survival rates were 84% and 75%, respectively, among patients who received ACT and 70% and 50% among patients who did not (log-rank P < 0.01). Inadequate LNY was independently associated with both receipt of ACT (odds ratios, 1.50; P < 0.01) and decreased overall survival [hazard ratio (HR), 1.56; P < 0.01]. ACT was independently associated with improved survival (HR, 0.67; P < 0.01); this effect size did not change based on the adequacy of LNY (interaction P = 0.41). Results were robust to re-analysis with our cohort-optimized threshold of 18 lymph nodes. Consistent with contemporary guidelines, patients with inadequate LNY are more likely to receive ACT. LNY adequacy is an independent prognostic factor but, in isolation, should not dictate whether patients receive ACT.

The diagnostic accuracy of local staging in colon cancer based on computed tomography (CT): evaluating the role of extramural venous invasion and tumour deposits.

The shift from adjuvant to neoadjuvant treatment in colon cancer demands the radiological selection of patients for systemic therapy. The aim of this study was to evaluate the accuracy of the CT-based TNM stage and high-risk features, including extramural venous invasion (EMVI) and tumour deposits, in the identification of patients with histopathological advanced disease, currently considered for neoadjuvant treatment (T3-4 disease). All consecutive patients surgically treated for non-metastatic colon cancer between January 2018 and January 2020 in a referral centre for colorectal cancer were identified retrospectively. All tumours were staged on CT according to the TNM classification system. Additionally, the presence of EMVI and tumour deposits on CT was evaluated. The histopathological TNM classification was used as reference standard. A total of 176 patients were included. Histopathological T3-4 colon cancer was present in 85.0% of the patients with CT-detected T3-4 disease. Histopathological T3-4 colon cancer was present in 96.4% of the patients with CT-detected T3-4 colon cancer in the presence of both CT-detected EMVI and CT-detected tumour deposits. Histopathological T0-2 colon cancer was present in 50.8% of the patients with CT-detected T0-2 disease, and in 32.4% of the patients without CT-detected EMVI and tumour deposits. The diagnostic accuracy of CT-based staging was comparable with previous studies. The presence of high-risk features on CT increased the probability of histopathological T3-4 colon cancer. However, a substantial part of the patients without CT-detected EMVI and tumour deposits was diagnosed with histopathological T3-4 disease. Hence, more accurate selection criteria are required to correctly identify patients with locally advanced disease.

Combined therapy with ibrutinib and bortezomib followed by ibrutinib maintenance in relapsed or refractory mantle cell lymphoma and high-risk features: a phase 1/2 trial of the European MCL network (SAKK 36/13)

The Bruton's tyrosine kinase inhibitor ibrutinib and the proteasome inhibitor bortezomib have single-agent activity, non-overlapping toxicities, and regulatory approval in mantle cell lymphoma (MCL). Invitro, their combination provides synergistic cytotoxicity. In this investigator-initiated phase 1/2 trial, we established the recommended phase 2 dose of ibrutinib in combination with bortezomib, and assessed its efficacy in patients with relapsed or refractory MCL. In this phase 1/2 study open in 15 sites in Switzerland, Germany and Italy, patients with relapsed or refractory MCL after ≤2 lines of chemotherapy and both ibrutinib-naïve and bortezomib-naïve received six cycles of ibrutinibb and bortezomib, followed by ibrutinib maintenance. For the phase 1 study, a standard 3+3 dose escalation design was used to determine the recommended phase 2 dose of ibrutinib in combination with bortezomib. The primary endpoint in phase 1 was the dose limiting toxicities in cycle 1. The phase 2 study was an open-label, single-arm trial with a Simon's two-stage min-max design, with a primary endpoint of overall response rate (ORR) assessed by CT/MRI. This study was registered with ClinicalTrials.gov, NCT02356458. Between August 2015 and September 2016, nine patients were treated in the phase 1 study, and 49 patients were treated between November 2016 and March 2020 in the phase 2 of the trial. The ORR was 81.8% (90% CI 71.1, 89.8%, CR(u) 21.8%) which increased with continued ibrutinib (median 10.6 months) to 87.3%, (CR(u) 41.8%). 75.6% of patients had at least one high-risk feature (Ki-67>30%, blastoid or pleomorphic variant, p53 overexpression, TP53 mutations and/or deletions). In these patients, ibrutinib and bortezomib were also effective with an ORR of 74%, increasing to 82% during maintenance. With a median follow-up of 25.4 months, the median duration of response was 22.7, and the median PFS was 18.6 months. PFS reached 30.8 and 32.9 months for patients with a CR or Cru, respectively. The combination of ibrutinib and bortezomib shows durable efficacy in patients with relapsed or refractory MCL, also in the presence of high-risk features. SAKK (Hubacher Fund), Swiss State Secretariat for Education, Research and Innovation, Swiss Cancer Research Foundation, and Janssen.

Reevaluating the role of adjuvant chemotherapy in early-stage, resectable NSCLC with high-risk clinical and pathologic features.

8572 Background: The preferred treatment for early-stage non-small cell lung cancer remains surgical resection with the consideration of adjuvant chemotherapy for tumors with certain high-risk features. It is commonly cited that such treatments confer a meager 5% 5-year survival benefit compared to observation alone. We sought to reassess the benefit of adjuvant chemotherapy using modern, real-world datasets. Methods: We performed a retrospective cohort study using a dataset from the National Cancer Database. All patients with early-stage stage NSCLC (3-5cm, node-negative) who would be eligible for adjuvant chemotherapy based on National Comprehensive Cancer Network guidelines were included (i.e., presence of at least 1 high-risk feature). High-risk clinical and pathologic features were defined as poor differentiation, tumor size (≥4cm), non-anatomic wedge resection, inadequate lymph node evaluation, vascular invasion, and visceral pleural involvement. We employed average treatment effect on the treated (ATT) weighting to match patients with similar demographic, tumor, and treatment-related variables to compare outcomes between chemotherapy versus observation groups. The primary outcome was overall survival. These findings were further validated in an independent cohort from the US Veteran Health Administration (VHA). Results: The study included 10,812 patients with early-stage NSCLC who had at least 1 high-risk feature. The frequencies of high-risk features were as follows: tumor size ≥4cm (n = 3,271, 30.3%), poor differentiation (n = 9,454, 87.4%), visceral-pleural invasion (n = 2,542, 23.5%), vascular invasion (n = 1,742, 16.11%), non-anatomic wedge resection (n = 781, 7.2%), and inadequate nodal sampling (n = 6,306, 58.3%). Despite the presence of high-risk features, only 1,427 (13.2%) patients received adjuvant chemotherapy. In the ATT weighted analysis, 1,261 (49.7%) patients received adjuvant chemotherapy and 1,278 (50.3%) patients received observation. The 5-year overall survival was 70.0% (95% CI 67.1-72.7) in the chemotherapy group versus 62.0% (95% CI 60.2-63.7%) in the observation group (absolute 5-year survival difference 8.0%). In the VHA cohort, 11.3% of patients received adjuvant chemotherapy. Similarly, the 5-year overall survival was 64.0% (95% CI 51.4-74.2) in the chemotherapy group versus 56.2% (95% CI 48.3-63.4) in the observation group (absolute 5-year survival difference 7.8%). Conclusions: These data suggest a notably larger benefit of adjuvant chemotherapy in eligible patients with high-risk clinical pathologic features compared to commonly cited statistics. With the addition of more robust treatment options in early-stage disease, adherence to adjuvant and neoadjuvant treatment guidelines may disproportionately improve early-stage NSCLC outcomes following curative-intent resection.

Axicabtagene Ciloleucel in the Management of Follicular Lymphoma: Current Perspectives on Clinical Utility, Patient Selection and Reported Outcomes.

Axicabtagene ciloleucel (axi-cel) is an autologous anti-CD19 chimeric antigen receptor T-cell therapy (CAR-T) that has shown efficacy in B-cell non-Hodgkin's lymphoma. It has shown high efficacy in relapsed/refractory follicular lymphoma (FL) even in the presence of high risk features (early relapse, heavily pretreated patients and bulky disease). Treatment options for R/R follicular lymphoma do not offer long-term remissions, especially in the third-line setting. Axi-cel was studied in R/R FL in the ZUMA-5 study, which showed high response rates with durable remissions. Axi-cel was associated with anticipated but manageable toxicities. Long-term follow up may be able to inform the potential for cure of FL. Axi-cel should be part of the standard of care options for R/R FL beyond second line.

Association of Surgical Margin Distance With Survival in Patients With Resected Head and Neck Squamous Cell Carcinoma

Clear surgical margins reduce the risk of local recurrence, improve survival, and determine decision-making with regard to adjuvant treatment of squamous cell carcinoma of the head and neck (SCCHN). However, the definitions of clear, close, or positive surgical margins vary in both the literature and in practice. To examine whether the association between surgical margin distance and survival varies by primary tumor site. This was a secondary analysis of a multi-institutional, multinational randomized clinical trial. The trial enrolled patients from January 22, 2007, to March 29, 2013, with stage II to IVA resected SCCHN with extranodal extension (ENE) or positive margins (<5 mm from invasive tumor to the resected margin). The current analysis included those patients with known ENE and margin status and was conducted from April 29, 2022, to December 19, 2022. Patients received adjuvant chemoradiotherapy plus either placebo or lapatinib. Overall survival (OS) was calculated to examine association with surgical margin distance, primary site, and survival, with stratification by ENE status. Among 688 patients enrolled in the trial, 630 patients with known ENE and margin status were included. Exact patient ages were not made available; 523 (83%) patients were male, and 415 (66%) patients were White. Patients with 1 high-risk feature (positive margins or ENE) had significantly better OS vs 2 high-risk features (hazard ratio [HR], 0.65; 95% CI, 0.49-0.87), although most other results were not statistically significant. For example, in the cohort with ENE-negative disease, multivariable adjusted analysis showed nonsignificant improvements with shorter surgical margin distance (1- to 5-mm margins), and no association with OS was found in the cohort with ENE-positive status (either >5 mm margins or 1-5 mm margins). The association between survival and margin distance varied based on primary site, human papillomavirus (HPV) status, and ENE status. For example, HPV-positive status was associated with a significant and clinically meaningful increase in survival (adjusted HR, 0.33; 95% CI, 0.11-0.97). The improvement was greatest, although not significantly so, in patients with ENE- and HPV-negative oropharynx (OP), hypopharynx (HP), and larynx cancer (HR, 0.57; 95% CI, 0.30-1.10). No survival benefit was seen in ENE-negative oral cavity cancer (HR, 0.89; 95% CI, 0.45-1.77), nor was an association observed between margins and OS in HPV-positive OP cancer. In this secondary analysis of a randomized clinical trial, the presence of high-risk features (extranodal extension, positive margins, or both) was associated with worse survival; longer survival was observed with greater surgical margin distance among patients with oral cavity tumors and human papillomavirus-negative tumors of the OP, larynx, or HP. No other significant differences were found. These findings support variable interpretation of surgical margin distance based on the primary site and HPV status. ClinicalTrials.gov Identifier: NCT00424255.

De-escalation of Radiation in Positive Axilla for Breast Cancer Radiation de escalation breast cancer

Introduction: There has been a trend towards de-escalation in the management of axilla over the last two decades in the form of shift from axillary lymph node dissection to sentinel lymph node dissection in early stage breast cancer. This de-escalation has main advantage in terms of reducing the incidence of lymphedema without compromising the local control. However, when it comes to axillary radiation, there is lack of consensus regarding its use . In this context we reviewed our prospectively maintained data base for axillary recurrences, without radiation to axilla in axillary node positive patient cohort. Materials and methods: The data of breast cancer patients treated at Medanta, Cancer Institute from 2010 till 2020 was analyzed by querying the electronic health records. Minimum follow up was 2 years after completion of radiation treatment. During follow up, patients were assessed clinically and underwent yearly mammogram, bi-annual ultrasound abdomen and annual chest X-Ray. In case of clinically palpable or suspicious lymph nodes in axilla, a histopathological confirmation was required. The axilla was not irradiated intentionally except in very few cases where the decision was individualized as per surgical and pathological findings after discussion in the tumour board meeting. Results: Of the 2400 breast cancer patients treated from 2010-2020, final analysis included 1422 patients as per the inclusion criteria. Pathological node positive cases were 827(58.15%). Of which 446/827(53.9%) had N1, 283/827(34.2%) were N2 and 98/827(11.8%) were with N3 disease status. 69.19% patients had undergone axillary dissection. A total of 35 patients received axillary radiation, 7 of them had early stage disease, underwent sentinel lymph node biopsy and were treated before 2013, and rest of them had advanced local disease, post axillary dissection with high axillary burden and presence of high risk features. None (0%) of the patients developed ipsilateral axillary relapse. Conclusion: The results of this study are a step further in de-escalation of axillary management in terms of radiation, and provide robust data in support of omitting the axillary radiation for breast cancer patients even when sentinel node biopsy shows (1-2) positive nodes for early stage breast disease and in locally advanced breast disease when adequate axillary dissection (even with heavy axillary node burden) has been performed.

Radiotherapy after radical prostatectomy

Local treatment following radical prostatectomy used in prostate cancer patients with risk factors of recurrence or with biochemical recurrence and/or local recurrence consists of adjuvant and salvage radiotherapy. The postprostatectomy biochemical failure, according to some studies based on ten years of follow-up, is estimated at one-third of patients. It remains challenging to extract those patients who may benefit from implementing radiotherapy while minimizing the risk of overtreatment. Adjuvant radiotherapy is considered in a situation of the absence of biochemical recurrence with the presence of high-risk features in pathological staging defined as positive surgical margins (R1), extraprostatic extension (pT3a), or seminal vesicle invasion (pT3b) and Gleason score 8-10. Failure rate after RP is found approximately in 50% of men diagnosed with adverse pathologic features. It is recommended to implement adjuvant radiotherapy in case of very aggressive form of prostate cancer (pT3b, Gleason 8-10) without awaiting biochemical recurrence. However, salvage radiotherapy represents a therapeutic option for patients experiencing biochemical recurrence in case of no distant metastasis. Monitoring of serum PSA levels in each individual is crucial in deciding whether salvage radiotherapy is needed. The effectiveness of treatment increases along with early initiation of radiation therapy. Current guidelines developed by NCCN and EAU regard conversion of PSA from undetectable to detectable level as a sign of cancers’ recurrence. In addition, prostate-specific membrane antigen (PSMA) PET should be used as a part of modern imaging diagnostics for a precise determination of disease extent.

Abstract B013: Loss of the extracellular domain of human epidermal growth factor receptor 2 (HER2) p95 isoform is common in large DCIS lesions

Abstract Background/Aim: Testing for human epidermal growth factor receptor 2 (HER2) positivity in women diagnosed with ductal carcinoma in situ (DCIS) is not performed routinely, although the frequency of HER2+ DCIS is at least 30%. HER2+ DCIS lesions may be at higher risk of progression to invasive carcinoma, and specific isoforms of HER2 may lead to different malignant potential. Loss of the HER2 extracellular domain engineered in mouse models demonstrates rapid progression to invasive behavior. Evaluating isoforms of HER2 may aid in classifying DCIS lesions as higher or lower risk, and may provide insight for novel treatment and prevention approaches. Methods: A cohort of high risk DCIS cases were assembled, enriched for the presence of high risk features, including large size (&amp;gt;5 cm) and palpable. Immunohistochemistry (IHC) and FISH were used to identify cases that were HER2 positive. MultiplexIHC was used to detect extracellular and intracellular domains of HER2, with imaging analysis performed to identify HER2 isoforms of HER2+ specimens. Isoforms were characterized as 1) full-length/extracellular domain (ECD) intact, 2) pure/complete loss of ECD (p95 isoform), 3) subclonal populations of both full-length ECD and p95 and 4) gradient/representing partial loss of ECD per cell (reflecting post-translational cleavage). Results: Out of 51 cases, 34 (67%) cases were HER2+. In multiplexIHC analysis for HER2, 51% displayed gradient (partial) or focal (subclonal) loss of the extracellular domain. 33% displayed pure p95 isoform (complete loss of ECD). Only 16% of the cohort displayed full-length HER2 extracellular domain. Conclusions: HER2 expression is much more common in large in situ lesions than in invasive lesions. This suggests that HER2 positivity may play a role in protecting against invasion. Investigation of HER2 Isoform testing using multiplex staining reveals heterogeneity with partial or complete loss of the HER2 extracellular domain being most common. Loss of the extracellular domain of human epidermal growth factor receptor 2 (HER2) p95 isoform is predominant among patients diagnosed with HER2 positive ductal carcinoma in situ (DCIS). Citation Format: Nicole F. Schindler, Alexa Glencer, Hidetoshi Mori, Gillian Hirst, Cristian Maldonado Rodas, Michael Campbell, Laura Esserman, Alexander Borowsky. Loss of the extracellular domain of human epidermal growth factor receptor 2 (HER2) p95 isoform is common in large DCIS lesions [abstract]. In: Proceedings of the AACR Special Conference on Rethinking DCIS: An Opportunity for Prevention?; 2022 Sep 8-11; Philadelphia, PA. Philadelphia (PA): AACR; Can Prev Res 2022;15(12 Suppl_1): Abstract nr B013.

Survival outcome and treatment response of patients with young-onset locally advanced rectal cancer (YO-LARC) receiving total neoadjuvant therapy (TNT).

44 Background: Despite an alarming rise in incidence, data on survival outcome and treatment response of young-onset (age &lt; 50 years) locally advanced rectal cancer (YO-LARC) patients receiving total neoadjuvant therapy (TNT) are sparse. We retrospectively compared the outcome between YO-LARC and later-onset (aged 50 years or older) LARC (LO-LARC) patients treated with TNT. Methods: After the institutional review board approval, electronic medical records of the LARC (T3/T4 or node-positive) patients treated with TNT at a tertiary care cancer center between January 1, 2015, and June 30, 2020, were reviewed for data collection. TNT consisted of systemic chemotherapy with oxaliplatin-based regimens for 16 weeks followed by long-course radiation with concurrent capecitabine or 5-fluorouracil (CRT). Patients receiving only preoperative CRT were excluded. Most patients underwent surgical resection following the TNT. Non-operative management was offered to patients if TNT resulted in clinical complete response (cCR). The following comparisons between the YO-LARC and the LO-LARC patients were performed: patient characteristics, pathological complete response (pCR) rate, combined pCR + cCR rate, disease-free survival (DFS), and overall survival (OS). Results: Of 72 patients included in the analysis, 44(61%) were male, 49 (68%) were Caucasian, and 62 (86%) had clinical stage III disease. The study included 26 (36%) patients with YO-LARC (median age, 43 years) and 46 (64%) patients with LO-LARC (median age, 64 years). The comparison of patient characteristics that included gender, clinical stage, baseline carcinoembryonic antigen level, the distance of the tumor from the anal verge, presence of high-risk features, and histologic grade did not differ significantly between the groups. There were no statistically significant differences in pCR and combined pCR+cCR rates (p = 0.16) between the groups: YO-LARC, 12 % (3/26) and 15 % (4/26), respectively; LO-LARC, 22% (10/46) and 30% (14/46), respectively. Either group did not reach median DFS and OS after a median follow-up of 38 months for survivors. The estimated 5-year OS rates in patients with YO-LARC and LO-LARC were 86 % (95% confidence interval [CI], 69% to 100%) and 84% (95% CI, 68% to 100%), respectively (p = 0.92). The estimated 3-year DFS rates in patients with YO-LARC and LO-LARC were 67 % (95% CI, 50% to 89%) and 83% (95% CI, 72% to 95%), respectively (p = 0.19). Conclusions: The current retrospective analysis did not demonstrate significant differences in the pCR rates, combined pCR +cCR rates, DFS, or OS between the YO-LARC and LO-LARC patients treated with TNT.

The Utility of Standard, Diastolic Phase, Cardiac Computed Tomography (dCCT) in Diagnosing and Identifying High-risk features in Apical Hypertrophic Cardiomyopathy (ApHCM)

Apical hypertrophic cardiomyopathy (ApHCM) is increasingly prevalent and not as benign as previously thought. Cardiac magnetic resonance imaging (CMR) has been the gold-standard for diagnosing ApHCM, however certain factors preclude their use prompting the use of other modalities i.e cardiac computed tomography (CCT). The utility of CCTs in ApHCM however is still limited. We aimed to assess the sensitivity of a standard, diastolic phase, cardiac computed tomography (dCCT) compared to CMR in identifying ApHCM by comparing left ventricular (LV) wall thickness, LV wall ratio, & presence of high-risk features, i.e apical aneurysm and cardiac thrombus, in addition to coronary artery disease (CAD) severity. We conducted a retrospective analysis of 38 patients from a multicentre database who had a dCCT, CMR, and a confirmed diagnosis of ApHCM. ApHCM was defined as apex thickness of ≥15 mm & apex:basal posterior wall thickness ratio≥1.3. LV wall measurements, presence of apical aneurysm and cardiac thrombus were obtained for both dCCT and CMR. CAD severity was assessed. Standard dCCTs were highly sensitive (94.7%) at diagnosing ApHCM compared to CMR, with good correlation (R=0.8; p <0.05) between dCCT & CMR measurements. 44.7% patients had mild CAD and 5.3% patients had severe CAD. 3 patients had apical aneurysm on dCCT compared to 4 in the CMR group, conferring a specificity of 97.1% and sensitivity of 80%. Standard dCCT performed for coronary artery assessment has a potential role in diagnosing ApHCM, identifying high-risk features and delineating CAD relative to dedicated ‘gold standard’ CMR.Figure 1Apical aneurysm on Cardiac CT (left) vs Cardiac MR (right).View Large Image Figure ViewerDownload Hi-res image Download (PPT)

Risk Benefit Analysis of Routine Thymectomy for Differentiated Thyroid Cancers: A Systematic Review.

Background Central compartment lymph node dissection (CLND) is a part of the surgical management of differentiated thyroid cancer (DTC). Therapeutic CLND is done to address clinically significant central compartment nodes in patients with DTC, while prophylactic CLND is performed in the presence of high-risk features in the absence of clinically significant neck nodes. Removal of thymus—unilateral or bilateral—during CLND to achieve complete clearance of level VI and VII lymph node stations and address thymic metastasis is debatable. Objective The present systematic review was conducted to summarize the evidence, delineating the role of thymectomy during CLND in patients with DTC. Methods Electronic databases of PubMed, Embase, and Cochrane were searched from their inception to July 2020 using keywords—thyroid neoplasms or tumors, thyroidectomy, and thymectomy—to identify the articles describing the role of thymectomy during CLND in DTC. A pooled analysis of surgicopathological outcomes was performed using metaprop command in STATA software version 16. Result A total of three studies and 347 patients—total thyroidectomy (TT) with bilateral thymectomy in 154, TT with unilateral thymectomy in 166, and TT alone in 27 patients with DTC—were included in the systematic review. The pooled frequency of thymic metastasis was a mere 2% in patients undergoing either unilateral or bilateral thymectomy. The routine addition of thymectomy does not result in better lymph node clearance. Unilateral and bilateral thymectomy were associated with high chances of transient hypocalcemia (12.0% and 56.1%, respectively). Conclusion Routine thymectomy is not warranted during CLND, considering minimal oncological benefit and high risk of postoperative hypocalcemia.

Reintervention and Spinal Cord Ischemia After Thoracic Endovascular Aortic Repair for Acute Type B Aortic Dissection With a Zone 3 Entry Tear

Treatment of acute type B aortic dissections (TBADs) using thoracic endovascular aortic repair (TEVAR) is influenced by the location and extent of the pathology, the presence of high-risk features, and complication status. The technical aspects of TEVAR for TBAD (specifically the location of the proximal seal zone [PSZ], the need to cover the left subclavian artery [LSA], distal seal zone [DSZ; length of aortic coverage]), the benefits of LSA revascularization, and prophylactic lumbar spinal drainage are still debated.

Impact of Donor Type on Long-Term Outcomes of Hematopoietic Cell Transplantation for Adult Acute Lymphoblastic Leukemia during First Remission

Background: Standard therapy for adult patients with high-risk acute lymphoblastic leukemia (ALL) consists of hematopoietic cell transplantation (HCT) including autologous-HCT (AUTO) and allogeneic-HCT from a matched-sibling donor (MSD) or matched unrelated donor (MUD). When a conventional donor is not available, HCT from a partially-mismatched unrelated donor (MMUD), cord blood transplantation (CBT) or a familial haploidentical donor (HID) is considered.Aim: Although HCT outcomes of those alternative strategies are advancing with optimization of pre-conditioning regimens with immunosuppressive agents, there are still subjects to debate. We tried to analyze the long-term HCT outcomes according to the donor types including MMUD, double CBT (DCBT) and AUTO as an alternative choice compared to the conventional donors.Methods: We enrolled 661 adult ALL patients who underwent transplantation from 1995 to 2015 in their first remission (CR1). Patients with acute undifferentiated leukemia (AUL, n=5) and mixed phenotype acute leukemia (MPAL, n=52) in the same department were also enrolled and median age was 33 years old (range, 15-65). Before 2010, our treatment strategy for ALL patients in CR1 was to offer allogeneic or autologous HCT according to the donor availability and the presence of high-risk features. After 2010, DCBT was mainly used for patients who were not available with conventional donors. For myeloablative regimen, we administered cyclophosphamide (120 mg/kg) combined with TBI (1320 cGy), and reduced intensity regimen was applied for elderly or patients with comorbid conditions which consisted of fludarabine (150 mg/m2 in total) and melphalan (140 mg/m2 in total). Conditioning regimen for AUTO was TBI (1200 cGy), ARA-C (9g/m2 in total) and melphalan (100mg/m2 in total), and fludarabine (150mg/m2 in total) was used for DCBT instead of melphalan. Graft-versus-host disease (GVHD) prophylaxis was attempted by administering calcineurin inhibitors (cyclosporine for MSD, tacrolimus for others) plus methotrexate or mycophnolate mofetil (for DCBT). Antithymocyte globulin (ATG) was administered to the patients who received grafts from MMUD.Results: Engraftment was successful in all donor types, but neutrophil and platelet recovery was significantly delayed only after DCBT (median recovery for neutrophil and platelet was 25 and 33.5 days respectively). After median follow-up of 80.4 months (range, 6.5-259.1), 7-year OS for the entire 661 patients was 57.0%. In detail, 7-year OS for MSD, MUD, MMUD, DCBT, and AUTO was 56.9%, 56.8%, 62.6%, 65.1% and 48.6% (p=0.423). MSD, MUD and MMUD showed similar relapse rate (27.5%) and non-relapse mortality (NRM) rate (20.6%), but DCBT showed significantly higher NRM rate (29.6%) and AUTO showed significantly higher relapse rate (41.6%). In contrast, DCBT showed lower relapse rate (7.2%) and AUTO showed lower NRM rate (9.7%). Interestingly, 7-year GVHD and relapse-free survival (GRFS) for MSD, MUD, MMUD, and DCBT was 34.1%, 15.0%, 40.9%, and 50.3%, respectively, which was related with higher incidence of severe chronic GVHD in MUD (27.6%) and MSD (14.1%) compared to DCBT (4.2%, p < 0.001). In high-risk subgroup (n=517) including 233 Philadelphia chromosome (Ph)-positive ALL, 7-year OS for MSD, MUD, MMUD, DCBT, and AUTO was 54.9%, 58.1%, 57.8%, 60.7%, and 33.3%, respectively. But the 7-year GRFS for MSD, MUD, MMUD, and DCBT was 30.7%, 14.5%, 35.3%, and 47.7%, respectively, which revealed lower relapse rate (8.7%) and low severe chronic GVHD (2.6%) of DCBT. Multivariate analysis showed that old age and AUTO was related with poor OS in high-risk ALL patients group, and old age and poor-risk karyotype and MUD transplant without ATG were related with poor GRFS.Conclusion: Our data showed similar transplant outcomes of alternative donors such as DCBT and ATG-applied MMUD compared to conventional donor transplants in ALL patients in CR1. In addition, GRFS was rather superior in patients treated with DCBT. Our long-term transplantation outcome results revealed that DCBT might be a good alternative choice for patients who are not available with conventional allogeneic donors, and AUTO may be considered for selected standard-risk patients with low NRM rate without a risk of GVHD. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Skin shop: long-term management and follow-up of narrowly and incompletely excised non-melanomatous skin cancer.

'Skin Shop' is a model of care at a high-volume tertiary centre that describes a registrar-lead skin cancer service under consultant supervision. Ninety-two percent of lesions are completely excised, 4.2% are narrowly excised and 3.2% are incompletely excised. Current international guidelines suggest re-excision of incompletely excised non-melanomatous skin cancer (NMSC); however, there is a lack of robust evidence to suggest how these lesions should be optimally managed. We describe how narrow and incompletely excised NMSC are managed in the 'Skin Shop' and present rates of recurrence. Retrospective analysis of all lesions excised between December 2014 and June 2019. Lesion type, histological margin, presence of high-risk features, management, presence of residual tumour in re-excision and follow-up duration were recorded. Rates of clinical recurrence were documented. From 5821 lesions excised, a total of 394 NMSC (245 basal cell carcinoma (BCC), 128 squamous cell carcinoma (SCC) and 21 Basosquamous cell carcinoma) were narrowly or incompletely excised. A total of 135 (34.3%) lesions were observed in clinic for recurrence, 133 (33.8%) lesions underwent re-excision, 81 (20.6%) lesions underwent GP surveillance and 14 (3.6%) lesions received radiotherapy. Mean specialist clinic follow-up was 12.4 months. Fourteen lesions recurred (3.5%, 10 BCC, 3 SCC, 1 basosquamous) of which 12 underwent re-excision. The risk of recurrence for narrow and incompletely excised BCC was 2.9% and 10%, respectively. The corresponding rates for SCC were 2.2% and 3.3%, respectively. Skin Shop is an effective model with low rates of narrow and incompletely excised NMSC. Risk of recurrence of these lesions is low with our current practice.

Progression of choriocapillaris flow deficits in clinically stable intermediate age-related macular degeneration.

To evaluate the choriocapillaris (CC) flow deficit (FD) in eyes with stable intermediate age-related macular degeneration (AMD) eyes over 12 months of follow-up. Thirty four patients with intermediate AMD were prospectively enrolled and evaluated by swept-source optical coherence tomography (SS-OCT) and OCT-angiography (OCTA) using the PLEX-Elite 9000. A 6 × 6 mm foveal-centered scan was used for both modalities and the study eyes were scanned twice to allow subsequent averaging. En face OCTA CC slabs (31-41 µm below the RPE-band) were exported and compensated for signal attenuation. Two compensated CC en-face images were registered and averaged prior to binarization and CC FD computation. The CC FD of the entire 6 × 6 macular region was quantified at baseline and at 12-months. The presence of high-risk features, namely intraretinal hyper-reflective foci (HRF), subretinal drusenoid deposits (SDD), and hyporeflective-core-drusen, were evaluated using SS-OCT volume scans. Among the 34 eyes, 25 eyes from 25 patients were noted on exam and OCT to remain stable as intermediate AMD at 12-months without the development of late AMD. Eleven eyes had high-risk features at baseline compared to 14 eyes at the end of the follow-up (p = 0.094). The mean ± SD FD% across the whole 6 × 6 macular region at baseline was 19.32 ± 4.64% and significantly increased to 28.62 ± 4.71% at the end of the study (p = 0.001). The CC FD progressed significantly both in non-HR and HR-eyes. Choriocapillaris flow impairment significantly deteriorated over one year in relatively stable intermediate AMD. This might suggest that underlying progression of CC dysfunction occurs before structural changes appears on OCT and lead to the progression to late-stage AMD.

Colorectal malignant polyps: a modern approach.

Colorectal malignant polyps (MP) are polyps with invasive cancer into the submucosa harboring a variable risk of lymph node involvement, which can be estimated through evaluation of morphological, endoscopic, and histologic features. The recent advances in imaging endoscopic techniques have led to the possibility of performing an optical diagnosis of T1 colorectal cancer, allowing the selection of the best therapeutic modality to optimize outcomes for the patient. When MP are diagnosed after endoscopic removal, their management can be challenging. Differentiating low- and high-risk histologic features that influence the possibility of residual tumor, the risk of recurrence and the risk of lymph node metastasis, is crucial to further optimize treatment and surveillance plans. While the presence of high-risk features indicates a need for surgery in the majority of cases, location, comorbidities and the patient’s preference should be taken in account when making the final decision. This is a particularly important issue in the management of low rectal MP presenting with high-risk features, where chemoradiotherapy followed by a watch-and-wait strategy has demonstrated promising results. In this review we discuss the important prognostic features of MP and the most modern approaches regarding their management.

Accuracy of pelvic magnetic resonance imaging in local staging for rectal cancer: a single local health district, real world experience.

Neoadjuvant chemoradiotherapy plays a key role in reducing local recurrence rates for locally advanced rectal cancer. Pelvic magnetic resonance imaging (pMRI) is the gold standard for local clinical staging which allows clinicians to decide the treatment patients receive. A more advanced tumour or the presence of high-risk features on pMRI mean that neoadjuvant therapy will be offered to these patients. Understanding the accuracy of pMRI in local staging for rectal cancer is therefore crucial. A retrospective cohort analysis of the accuracy of pMRI staging in a subgroup of patients who had primary rectal cancer surgery without neoadjuvant therapy was performed. Specificity and sensitivity for T-staging, N-staging and presence of high-risk features (threatened circumferential resection margin and extramural venous invasion) were calculated. Patients who had previous pelvic surgery, previous pelvic radiotherapy and previous surgery for continence were excluded. A total of 114 patients were included in the analysis. MRI accurately predicts T-stage in 56.6% and N-stage in 55.8%. Prediction of extramural disease was accurate in 51%. A negative circumferential resection margin was accurately predicted in 98.6% of patients. Overall adherence to reporting proforma was 15.8%. Overall, this study provided valuable information about the clinical staging of patients with rectal cancer who are at an early stage within a large regional catchment area in Australia with pMRI. These results allow us to assess the accuracy of our local staging with ramifications to the clinical decisions being made in the context of the more recent trials which questioned the need for neoadjuvant chemo-radiotherapy in all node positive patients.