Comparison of the safety between cervical conization and hysterectomy for patients with cervical adenocarcinoma in situ.

OBJECTIVE: To compare the safety between cervical conization (CC) alone and hysterectomy for patients with adenocarcinoma in situ (AIS) of the cervix. METHODS: Patients diagnosed with AIS after CC during 2007-2021 were identified by computerized databases at Women's Hospital of Zhejiang University School of Medicine. A total of 453 AIS patients were divided into 2 groups according to uterus preservation: hysterectomy group (n=300) and CC(s) alone group (n=153). The prevalence of residual disease and disease recurrence was compared between patients treated by CC(s) alone and hysterectomy. The prevalence of residual disease in specimens from women who had a hysterectomy and repeat CC were compared between positive and negative margins of CC. The factors influencing residual disease and disease recurrence were assessed. RESULTS: Among 310 specimens from women who had a hysterectomy or repeat CC, the prevalence of residual disease was 50.6% (45/89) for a positive margin and 2.3% (5/221) for a negative margin (p=0.000). Four patients had recurrence of vaginal intraepithelial neoplasia in those treated by hysterectomy and one had recurrence of cervical squamous intraepithelial neoplasia in those treated by CC(s) alone. The prevalence of recurrence was 0.7% (1/153) for CC(s) alone and 1.3% (4/300) for hysterectomy (p=0.431). Hysterectomy did not influence residual disease or disease recurrence. CONCLUSION: CC is an efficacious and safe option for patients with AIS of the cervix provided the margin is negative.

Residual melanoma in wide local excision specimens after 'complete' excision of primary cutaneous in situ and invasive melanomas.

Wide local excision (WLE) to achieve adequate clearance margins is the standard initial definitive treatment for patients with biopsy-proven primary cutaneous melanoma. Residual melanoma in WLE specimens after prior complete excision-biopsy (CEB) is reported in 0-6.3% of cases. However, studies evaluating the prevalence, clinicopathological features and relevance of persistent disease in WLE specimens are limited. This study sought to determine the frequency of and clinicopathological characteristics associated with residual melanoma in WLE specimens performed after a CEB of primary cutaneous or acral melanoma (in situ or invasive) with clinically and histologically tumour-free margins, and assess its relevance. A review of the research database and pathology archives of a large Australian tertiary referral melanoma treatment centre was performed. Eligible patients were those for whom a definitive WLE was performed after CEB of a primary melanoma (in situ or invasive) with negative clinical and histological margins, between May 2013 and May 2015. All partial biopsies were excluded. Of 640 eligible patients, 510 (79.7%) had invasive melanoma and 130 (20.3%) had melanoma in situ. Residual disease was identified in 20 cases (20/640, 3.1%), of which three (15%) were melanoma in situ on CEB and 17 (85%) were invasive melanoma. On univariate analysis, the presence of residual disease in WLE specimens was associated with lentigo maligna (LM)/LM melanoma (LMM) subtype [odds ratio (OR) 10.33; 95% confidence interval (CI) 2.84-37.54; p=0.004], nodular melanoma (NM) subtype (OR 4.92; 95% CI 1.53-15.85; p=0.0076) and, for invasive tumours, higher tumour mitotic rate (mean 7.7, SD 7.51 vs 3.4, SD 4.83; OR 1.11; 95% CI 1.04-1.18; p=0.0014). Breslow thickness >4 mm was associated with a higher risk of residual disease (OR 7.30; 95% CI 1.88, 28.26; p=0.004). Cases with residual disease had primary tumours with a significantly larger diameter (median 14 mm, range 4-25) than those without residual disease (median 9 mm, range 2-60), (OR 1.07; 95% CI 1.03-1.11; p≤0.001) and were also more likely to be amelanotic (38% vs 14%), (OR 3.69; 95% CI 1.17, 11.60; p=0.026). Residual disease was associated with assessment of >3 slides of tissue (OR 6.98; 95% CI 1.54-31.62; p=0.0118) and complete blocking of the scar (OR 31.69; 95% CI 3.98-252.21; p=0.0011). Residual melanoma in WLE specimens is an infrequent occurrence. Risk factors for residual disease are LM/LMM and NM melanoma subtypes, higher mitotic rate, larger lesion diameter and amelanosis. Tumours with these features warrant more extensive pathological sampling. WLE after CEB for melanoma remains an important procedure to reduce local recurrence; however, limited pathological sampling of the WLE scar is probably appropriate for cases lacking high risk features.

Association of minimal residual disease with clinical outcomes in Philadelphia chromosome positive acute lymphoblastic leukemia in the tyrosine kinase inhibitor era: A systemic literature review and meta-analysis.

Minimal residual disease (MRD) appeared to be a potent prognostic indicator in patients with Philadelphia chromosome positive acute lymphoblastic leukemia (Ph+ ALL), with potential value in informing individualized treatment decisions. Hence, we performed herein a systemic literature review and meta-analysis to comprehensively address the prognostic value of MRD in Ph+ ALL. Systematic literature review was conducted in PubMed, Embase, and Cochrane databases with the data access date up to September 23, 2020. Pooled hazard ratios (HRs) with 95% confidence intervals (CIs) were calculated with fixed-effects or random-effects models. Furthermore, subgroup analyses were performed to assess the robustness of the associations. 27 studies with a total number of 3289 patients were eligible for this meta-analysis. Combined HRs suggested that MRD positivity was associated with inferior event-free survival (EFS) (HR = 2.00, 95% CI 1.77-2.26) and overall survival (OS) (HR = 2.34, 95% CI 1.86-2.95). The associations remained statistically significant in subgroup analyses including age group, MRD timing, disease status at MRD, MRD cutoff level, et al. Our findings suggested MRD as a potent clinical tool for assessing the prognosis of Ph+ ALL. Further studies using MRD-based risk stratification might help optimize individualized treatment strategies for Ph+ ALL patients.

Application of the Euro Clonality next-generation sequencing-based marker screening approach to detect immunoglobulin heavy chain rearrangements in mantle cell lymphoma patients: first data from the Fondazione Italiana Linfomi MCL0208 trial.

Minimal residual disease (MRD) determined by classic polymerase chain reaction (PCR) methods is a powerful outcome predictor in mantle cell lymphoma (MCL). Nevertheless, some technical pitfalls can reduce the rate of of molecular markers. Therefore, we applied the EuroClonality-NGS IGH (next-generation sequencing immunoglobulin heavy chain) method (previously published in acute lymphoblastic leukaemia) to 20 MCL patients enrolled in an Italian phase III trial sponsored by Fondazione Italiana Linfomi. Results from this preliminary investigation show that EuroClonality-NGS IGH method is feasible in the MCL context, detecting a molecular IGH target in 19/20 investigated cases, allowing MRD monitoring also in those patients lacking a molecular marker for classical screening approaches.

Optimal Volume of the Residual Tumor to Predict Long-term Tumor Control Using Stereotactic Radiosurgery after Facial Nerve-preserving Surgery for Vestibular Schwannomas.

BACKGROUND: Intended subtotal resection (STR) followed by adjuvant gamma knife radiosurgery (GKRS) has emerged as an effective treatment option for facial nerve (FN) preservation in vestibular schwannomas (VSs). This study aimed to identify the optimal cut-off volume of residual VS to predict favorable outcomes in terms of both tumor control and FN preservation. METHODS: This retrospective study assessed the patients who underwent adjuvant GKRS for residual VS after microsurgery. A total of 68 patients who had been followed up for ≥ 24 months after GKRS were included. Tumor progression was defined as an increase in tumor volume (TV) of ≥ 20%. House-Brackmann grades I and II were considered to indicate good FN function. RESULTS: The median residual TV was 2.5 cm³ (range: 0.3-27.4). The median follow-up period after the first adjuvant GKRS was 64 months (range: 25.7-152.4). Eight (12%) patients showed tumor progression. In multivariate analyses, residual TV was associated with tumor progression (P = 0.003; hazard ratio [HR], 1.229; 95% confidence interval [CI], 1.075-1.405). A residual TV of 6.4 cm³ was identified as the cut-off volume for showing the greatest difference in progression-free survival (PFS). The 5-year PFS rates in the group with residual TVs of < 6.4 cm³ (54 patients) and that with residual TVs of ≥ 6.4 cm³ (14 patients) were 93.3% and 69.3%, respectively (P = 0.014). A good FN outcome was achieved in 57 (84%) patients. Residual TV was not associated with good FN function during the immediate postoperative period (P = 0.695; odds ratio [OR], 1.024; 95% CI, 0.908-1.156) or at the last follow-up (P = 0.755; OR, 0.980; 95% CI, 0.866-1.110). CONCLUSION: In this study, residual TV was associated with tumor progression in VS after adjuvant GKRS following STR. As preservation of FN function is not correlated with the extent of resection, optimal volume reduction is imperative to achieve long-term tumor control. Our findings will help surgeons predict the prognosis of residual VS after FN-preserving surgery.

Safety and efficacy of obinutuzumab alone or with chemotherapy in previously untreated or relapsed/refractory chronic lymphocytic leukaemia patients: Final analysis of the Phase IIIb GREEN study.

The manageable toxicity profile of obinutuzumab (GA101; G) alone or with chemotherapy in first-line (1L; fit and non-fit) and relapsed/refractory (R/R) patients with chronic lymphocytic leukaemia (CLL) was established in the primary analysis of the Phase IIIb GREEN trial (Clinicaltrials.gov: NCT01905943). The final analysis (cut-off, 31 January 2019) is reported here. Patients received G (1000 mg) alone (G-mono; fit and non-fit patients) or with chemotherapy [fludarabine and cyclophosphamide (FC; fit patients); chlorambucil (non-fit patients); bendamustine (any patient)]. Study endpoints were safety (primary) and efficacy (secondary). Subgroup analyses were performed on prognostic biomarkers in 1L CLL. Overall, 630 patients received 1L and 341 received R/R CLL treatment. At the final analysis, no new safety signals were observed [Grade ≥ 3 adverse events (AEs): 1L 82·7%, R/R 84·5%; serious AEs: 1L 58·1%, R/R 62·5%]. Neutropenia (1L 50·5%, R/R 53·4%) and thrombocytopenia (1L 14·6%, R/R 19·1%) were the most common Grade 3-5 AEs. G-mono-, G-bendamustine and G-FC-treated patients with unmutated immunoglobulin heavy chain trended towards shorter progression-free survival. Achievement of minimal residual disease negativity was greatest in 1L patients treated with G-FC. In this final analysis of the GREEN trial, the safety profile of G was consistent with current risk management strategies. Biomarker analyses supported efficacy in the specific subgroups.

Prognostic impact of minimal residual disease at the end of consolidation in NCI standard-risk B-lymphoblastic leukemia: A report from the Children's Oncology Group.

The 5-year disease-free survival (DFS) of National Cancer Institute (NCI) high-risk (HR) B-lymphoblastic leukemia (B-ALL) patients with end of induction (EOI) minimal residual disease (MRD) ≥0.1% and end of consolidation (EOC) MRD ≥0.01% is 39 ± 7%, warranting consideration of hematopoietic stem cell transplant (HSCT). However, the impact of EOC MRD in NCI standard-risk (SR) B-ALL patients using COG regimens is unknown. We found that SR patients with MRD ≥0.01% at both EOI and EOC have a 4-year DFS/overall survival (OS) of 72.9 ± 19.0%/91.7 ± 10.8% versus 90.7 ± 2.9%/95.5 ± 2.0% (p = .0019/.25) for those with EOI MRD ≥0.01% and EOC MRD <0.01%. These data suggest that routine use of HSCT may not be warranted in EOC MRD ≥0.01% SR patients.

Next-generation sequencing improves BCR-ABL1 mutation detection in Philadelphia chromosome-positive acute lymphoblastic leukaemia.

BCR-ABL1 kinase domain mutation testing in tyrosine kinase inhibitor (TKI)-resistant Philadelphia chromosome-positive (Ph+) acute lymphoblastic leukaemia (ALL) patients is routinely performed by Sanger sequencing (SS). Recently, next-generation sequencing (NGS)-based approaches have been developed that afford greater sensitivity and straightforward discrimination between compound and polyclonal mutations. We performed a study to compare the results of SS and NGS in a consecutive cohort of 171 Ph+ ALL patients. At diagnosis, 0/44 and 3/44 patients were positive for mutations by SS and NGS respectively. Out of 47 patients with haematologic resistance, 45 had mutations according to both methods, but in 25 patients NGS revealed additional mutations undetectable by SS. Out of 80 patients in complete haematologic response but with BCR-ABL1 ≥0·1%, 28 (35%) and 52 (65%) were positive by SS and NGS respectively. Moreover, in 12 patients positive by SS, NGS detected additional mutations. NGS resolved clonal complexity in 34 patients with multiple mutations at the same or different codons and identified 35 compound mutations. Our study demonstrates that, in Ph+ ALL on TKI therapy, NGS enables more accurate assessment of mutation status both in patients who fail therapy and in patients with minimal residual disease above 0·1%.

International harmonization in performing and reporting minimal residual disease assessment in multiple myeloma trials.

Minimal residual disease (MRD) assessment is incorporated in an increasing number of multiple myeloma (MM) clinical trials as a correlative analysis, an endpoint or even as a determinant of subsequent therapy. There is substantial heterogeneity across clinical trials in how MRD is assessed and reported, creating challenges for data interpretation and for the design of subsequent studies. We convened an international panel of MM investigators to harmonize how MRD should be assessed and reported in MM clinical trials. The panel provides consensus on which MM trials should include MRD, the recommended time points for MRD assessment, and expected analytical validation for MRD assays. We subsequently outlined parameters for reporting MRD results implementing the intention-to-treat principle. The panel provides guidance regarding the incorporation of newer peripheral blood-based and imaging-based approaches to detection of residual disease. Recommendations are summarized in 13 consensus statements that should be followed by sponsors, investigators, editors, and reviewers engaged in designing, performing, and interpreting MM trials.

The Association of Vestibular Schwannoma Volume With Facial Nerve Outcomes After Surgical Resection.

OBJECTIVE: To explore the relationship between tumor size and facial nerve outcomes following vestibular schwannoma (VS) resection. STUDY DESIGN: Single institutional retrospective chart review of all adult patients with untreated sporadic VS who underwent surgical resection from 2008 to 2018 with preoperative magnetic resonance imaging (MRI) and 1 year of follow-up. The primary outcome measure was facial nerve outcome as assessed by the House-Brackmann facial nerve grading system. RESULTS: One hundred sixty-seven patients, 54.5% female, with a median age of 49 years (20-76 years), were identified who underwent VS resection. Surgical resection was performed by translabyrinthine (76.7%), middle cranial fossa (14.4%), retrosigmoid (7.2%), and transpromontorial (1.8%) approaches. The median tumor diameter and volume were 25.3 mm (range: 4.1-47.1 mm) and 3.17 cm3 (range: 0.01-30.6 cm3 ), respectively. The median follow-up was 24.2 months (range: 12-114.2 months). Gross total resection was performed in 79% of cases, with residual tumor identified on MRI in 17% of cases. For patients with tumors <3 cm3 , 92.7% had grade 1 or 2 facial function after at least 1 year follow-up, compared to 81.2% for those with tumors >3 cm3 (univariate logistic regression OR = 2.9, P = .03). Tumor volume >3 cm3 was predictive of facial weakness on multivariate regression analysis (OR = 7.4, P = .02) when controlling for surgical approach, internal auditory canal extension, anterior extension, age, gender, and extent of resection. CONCLUSIONS: Tumor volume >3 cm3 is associated with worse facial nerve outcomes 12 months following surgical resection. LEVEL OF EVIDENCE: IV Laryngoscope, 131:E1328-E1334, 2021.

Clinicoepidemiologic Profile and Outcome Predicted by Minimal Residual Disease in Children With Mixed-phenotype Acute Leukemia Treated on a Modified MCP-841 Protocol at a Tertiary Cancer Institute in India.

INTRODUCTION: Mixed-phenotype acute leukemia (MPAL) accounts for 1.2% to 5% of acute leukemia across age groups with intermediate prognosis. We evaluated clinicoepidemiologic profiles and outcomes of MPAL. METHODS: Records of children younger than 15 years of age with acute leukemia from January 2010 to December 2016 were reviewed on the basis of the MPAL WHO 2008 criteria. Treatment was uniform with a modified MCP-841 protocol. Descriptive analysis tools were used. Outcomes were measured by the Kaplan-Meier method on MedCalc, version 14.8.1. RESULTS: Among 3830 children with acute leukemia in the study period, 2892 received treatment from our center, of whom 24 (0.83%) had MPAL, median age 9 years, with a male:female ratio of 3:1, and median white blood cell of 13.4×10/L. Common immunophenotypes were B/myeloid-12 (50%), T/myeloid-9 (37.5%), and B/T-lymphoid-3 (12.5%). Some B/myeloid cases had abnormal cytogenetics. Seventeen patients were evaluable for outcome. Sixteen patients underwent postinduction bone marrow and 13 (81%) achieved morphologic remission. Thirteen patients underwent flow cytometry-based minimal residual disease evaluation; 9 (69%) were <0.01% (4 postinduction, 5 postconsolidation), and 67% of these had sustained remission till the last follow-up. None underwent bone marrow transplant. The projected 3-year event-free and overall survival rates were 40% and 48%, respectively (median follow-up: 22 mo). CONCLUSION: MPAL represented <1% of childhood acute leukemia. acute lymphoblastic leukemia-type chemotherapy that incorporated high-dose cytarabine was effective in achieving an minimal residual disease-negativity rate of 69% in evaluated patients, which was also predictive of better outcome.

Impacto de la resección no planificada y la reintervención de sarcomas de partes blandas en su pronóstico / Impact of unplanned resection and re-excision of a soft tissue sarcoma on prognosis

INTRODUCCIÓN: Hasta un 40% de los sarcomas de partes blandas (SPB) son resecados de forma no planificada, dejando tumor residual en más del 50% de los casos. La implicación pronóstica de estas resecciones no está claramente definida, dado que existen escasos estudios comparativos que demuestren cómo afecta a la tasa de recurrencia local, de metástasis y de supervivencia. MÉTODOS: Revisión retrospectiva de pacientes intervenidos de un SPB de enero de 2000 a enero de 2016 clasificándolos respecto a intervención planificada o no planificada. Se compararon las tasas de recurrencia y metástasis en global y por estadios. RESULTADOS: Ceintitrés pacientes con SPB fueron tratados de forma planificada y 16 de forma no planificada, con 13 reintervenciones. El 40% del grupo planificado presentó un estadio avanzado respecto al 20% del grupo no planificado. El 77% de los pacientes con resección no planificada reintervenidos presentaron tumor residual en la pieza. La tasa de recidiva local en el grupo de no planificados fue considerablemente más alta (73,5% frente al 43,8%). La tasa de metástasis en no planificados fue del 45,5%, frente al 56,3% en planificados (p > 0,05). En el grupo de no planificados el patrón de recidiva fue más errático con peores resultados en estadios precoces. Concusiones: La resección no planificada de los SPB asocia mayores tasas de recurrencia local y peores resultados funcionales a pesar del manejo oncológico posterior. En las lesiones de partes blandas es fundamental reconocer los signos de alarma que sugieren malignidad para llevar a cabo un estudio diagnóstico específico y evitar resecciones inadecuadas

INTRODUCTION: Up to 40% of all initial operations for soft tissue sarcoma (STS) are unplanned, which would leave residual macroscopic tumor in more than 50% of the cases. The effect this has on local recurrence rate, metastases rate and survival has never been fully established, due to the lack of randomized studies. METHODS: Retrospective review of patients with STS treated in our unit between January 2001-January 2016. We classified them whether they had been treated by initial planned or unplanned operation. Outcomes were compared in both groups globally and stage-matched. Endpoints were local recurrence and distant metastases. RESULTS: Twenty-three patients of STS underwent a planned excision and 16 an unplanned excision, 13 of them underwent further re-excision.40% of patients with planned excision had an advanced stage in regard to the unplanned excision group which presented earlier stages.77% of patients with unplanned excision had residual tumor identified after surgical re-excision. Local recurrence rate in the unplanned excision group was considerably higher 73,5% vs.43,8%. Metastases rate was lower in planned excision group, 45,5% vs 56,3% (P > .05). The recurrence pattern in the unplanned excision group was unstable, with worse outcomes in earlier stages. CONCLUSION: The unplanned excision of a soft tissue sarcoma may compromise disease local control, with higher rates of local recurrence and metastases, and worse functional out- comes, despite further oncological treatment. We need to recognize the clinical features for malignancy risk in soft tissue lumps for a safe diagnosis to avoid inadequate resections

Prognostic value of posttreatment FEDG-PET imaging following combined chemoradiation therapy in locally advanced cervical cancer.

OBJECTIVES: To evaluate the performances of posttreatment FEDG-PET to predict the prognosis of patients treated with concurrent chemoradiotherapy (CT/RT) for locally advanced cervical cancer. MATERIALS AND METHODS: The medical records of 131 patients treated in 9 French academic institutions for IB2-IIB cervical cancer and for which a posttherapy FEDG-PET was performed were reviewed. All patients received CT/RT, possibly completed with vaginal brachytherapy (VBT) and completion surgery. Posttreatment FEDG-PET was performed within 3 months after completion of CT/RT or VBT. Incomplete metabolic response (IMR) was defined as the persistence of FEDG uptake. RESULTS: An IMR was identified in 44 (33.6 %) cases. IMR was associated with higher risk of recurrence (aHR = 2.8; 95 %CI: 1.3-5.7; p = 0.006) and death (aHR = 4.5 ;95 %CI: 1.4-13.8; p = 0.009). Completion surgery was performed in 61 (46.9 %) patients with histologic cervical residual disease identified in 31 (50.8 %). FEDG-PET sensitivity and specificity in predicting cervical residual disease following CT/RT was 48.4 % (95 %CI: 30.8-66) and 80 % (95 %CI: 65.7-94.3), respectively. CONCLUSIONS: In patients treated with CT/RT for locally advanced cervical cancer, despite limited performances to predict cervical residual disease, posttreatment FEDG-PET is predictive of patients' prognosis and long-term outcome.

Patient-reported outcomes from KATHERINE: A phase 3 study of adjuvant trastuzumab emtansine versus trastuzumab in patients with residual invasive disease after neoadjuvant therapy for human epidermal growth factor receptor 2-positive breast cancer.

BACKGROUND: The phase 3 KATHERINE trial demonstrated significantly improved invasive disease-free survival with adjuvant trastuzumab emtansine (T-DM1) versus trastuzumab in patients with HER2-positive early breast cancer and residual invasive disease after neoadjuvant chemotherapy plus HER2-targeted therapy. METHODS: Patients who received taxane- and trastuzumab-containing neoadjuvant therapy (with/without anthracyclines) and had residual invasive disease (breast and/or axillary nodes) at surgery were randomly assigned to 14 cycles of adjuvant T-DM1 (3.6 mg/kg intravenously every 3 weeks) or trastuzumab (6 mg/kg intravenously every 3 weeks). The European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (QLQ-C30) and breast cancer module (QLQ-BR23) were completed at screening, at day 1 of cycles 5 and 11, within 30 days after study drug completion, and at 6- and 12-month follow-up visits. RESULTS: Of patients who were randomly assigned to T-DM1 (n = 743) and trastuzumab (n = 743), 612 (82%) and 640 (86%), respectively, had valid baseline and ≥1 postbaseline assessments. No clinically meaningful changes (≥10 points) from baseline in mean QLQ-C30 and QLQ-BR23 scores occurred in either arm. More patients receiving T-DM1 reported clinically meaningful deterioration at any assessment point in role functioning (49% vs 41%), appetite loss (38% vs 28%), constipation (47% vs 38%), fatigue (66% vs 60%), nausea/vomiting (39% vs 30%), and systemic therapy side effects (49% vs 36%). These differences were no longer apparent at the 6-month follow-up assessment, except for role functioning (23% vs 16%). CONCLUSION: These data suggest that health-related quality of life was generally maintained in both study arms over the course of treatment.

Argon plasma coagulation for superficial squamous cell carcinoma in the residual esophagus after esophagectomy.

BACKGROUND: Patients after esophagectomy for esophageal squamous cell carcinoma (SCC) occasionally develop metachronous SCC in the residual esophagus. Although most of these second primary lesions are detected as superficial cancer at follow-up endoscopy, it is often difficult to perform endoscopic resection for these lesions near the site of anastomosis. METHODS: The objective of this study was to evaluate the effectiveness of argon plasma coagulation (APC) for superficial SCC in the residual esophagus after esophagectomy. Twelve patients (involving 15 s primary lesions) received APC for superficial SCC in the residual esophagus after esophagectomy. These lesions were difficult to perform endoscopic resection and they were treated using APC. RESULTS: There was no treatment-related complication. Complete remission (CR) was achieved in 13 (86.6%) of the 15 lesions: CR was achieved in 11 lesions (73.3%) after the first APC course, and in another 2 lesions (13.3%) after two or more APC courses. Of the 2 patients with persisting residual tumor, 1 patient received 12 times repeated-APC courses over 6 years, and eventually achieved local control without metastasis, the other patient received radiotherapy and cervical esophagectomy after treatment failure with APC. All patients survived except for one patient who died of old age and another patient who died of tongue cancer. CONCLUSIONS: APC was a safe treatment that was easy to perform. APC was concluded to be an effective treatment for superficial SCC in the residual esophagus after esophagectomy when endoscopic resection was difficult.

Outcomes of Endoscopic Submucosal Dissection for Subepithelial Lesions Localized Within the Submucosa, Including Neuroendocrine Tumors: A Multicenter Prospective Study.

BACKGROUND AND AIMS: Endoscopic submucosal dissection (ESD) seems to be a reasonable option for gastrointestinal subepithelial lesions (SELs) localized within the submucosa. Indications for ESD include small neuroendocrine tumors (NETs) and indeterminate SELs. However, the prospective data regarding ESD and surveillance remain unclear. This study was performed to prospectively investigate the outcomes of ESD, including organ-specific outcomes and the mid-term prognosis. METHODS: This prospective multicenter study included 57 patients who underwent ESD for SELs localized within the submucosa [definite NETs (n = 42) and indeterminate SELs (n = 15)]. The efficacy and safety of ESD were evaluated in the whole cohort and in subgroups (NETs and indeterminate SELs). All patients were followed up. RESULTS: The rates of en bloc resection, curative resection, and complications were 98.2%, 66.7%, and 7.7% for the overall population (n=57); 100%, 61.9%, and 2.4% for NETs (n=42); and 93.3%, 80.0%, and 20.0% for indeterminate SELs (n=15), respectively. The rates of curative resection for NETs were poorer in the stomach (20%, n=5) and duodenum (33%, n=3) than in the rectum (71%, n=34). Including 11 of 16 patients with NETs who underwent a conservative approach resulting in non-curative resection, no patients developed tumor recurrence during the follow-up period (median, 24.5 months; range, 1-60 months). ESD followed by surveillance demonstrated acceptable mid-term outcomes for non-curative NETs. CONCLUSIONS: ESD can be an efficient therapy for SELs localized within the submucosa. However, gastric and duodenal ESD for NETs may be limited in terms of its curative and technical aspects. Clinicians should be aware of the potential complications of ESD for indeterminate SELs.

Significance of minimal residual disease in pediatric mixed phenotype acute leukemia: a multicenter cohort study.

The rarity of mixed phenotype acute leukemia (MPAL) has precluded adequate data to incorporate minimal residual disease (MRD) monitoring into therapy. Fluidity in MPAL classification systems further complicates understanding its biology and outcomes; this includes uncertainty surrounding the impact of shifting diagnostic requirements even between iterations of the World Health Organization (WHO) classification. Our primary objective was to address these knowledge gaps. To do so, we analyzed clinicopathologic features, therapy, MRD, and survival in a centrally-reviewed, multicenter cohort of MPAL uniformly diagnosed by the WHO classification and treated with acute lymphoblastic leukemia (ALL) regimens. ALL induction therapy achieved an EOI MRD negative (<0.01%) remission in most patients (70%). EOI MRD positivity was predictive of 5-year EFS (HR = 6.00, p < 0.001) and OS (HR = 9.57, p = 0.003). Patients who cleared MRD by EOC had worse survival compared with those EOI MRD negative. In contrast to adults with MPAL, ALL therapy without transplantation was adequate to treat most pediatric patients. Earlier MRD clearance was associated with better treatment success and survival. Prospective trials are now necessary to validate and refine MRD thresholds within the pediatric MPAL population and to identify salvage strategies for those with poor predicted survival.

How to measure tumour response in rectal cancer? An explanation of discrepancies and suggestions for improvement.

Various methods categorize tumour response after neoadjuvant therapy, including down-staging and tumour regression grading. Response categories allow comparison of different treatments within clinical trials and predict outcome. A reproducible response categorization could identify subgroups with high or low risk for the most appropriate subsequent treatments, like watch and wait. Lack of standardization and interpretation difficulties currently limit the usability of these approaches. In this review we describe these difficulties for the evaluation of chemoradiation in rectal cancer. An alternative approach of tumour response is based on patterns of residual disease, including fragmentation. We summarise the evidence behind this alternative method of response categorisation, which explains a number of very relevant clinical discrepancies. These issues include differences between downstaging and tumour regression, high local regrowth in advanced tumours during watchful waiting procedures, the importance of resection margins, the limited value of post-treatment biopsies and the relatively poor outcome of patients with a near complete pathological response. Recognition of these patterns of response can allow meaningful development of novel biomarkers in the future.

Facial nerve function and hearing after microsurgical removal of sporadic vestibular schwannomas in a population-based cohort.

BACKGROUND: Vestibular schwannoma (VS) is a benign tumor originating from the vestibulocochlear nerve. The optimal treatment strategy is debated, since surgery may result in iatrogenic facial nerve injury. We report the results of VS surgery in a population-based unselected cohort in a center with access to Cyber Knife (CK) radiosurgery. METHODS: We reviewed 117 consecutive operations and found 95 patients who had their primary operation due to vestibular schwannoma between 2001 and 2017. Facial nerve function was evaluated with the House-Brackmann (HB) scale and hearing with the EU classification. RESULTS: The population consisted of 37 males and 58 females with a median age of 54 years (range 19-79). One year after surgery 67% of patients had a good outcome (HB 1-2). The rate of good outcome was 90% if no facial nerve damage was observed during intraoperative monitoring, the size of the tumor was under 30 mm and no hydrocephalus was present. During the study period, the treatment strategy changed from total to near-total resection after the introduction of CK radiosurgery, which could be used as a second-line treatment in case of residual tumor regrowth. This resulted in an improvement of outcomes (0% HB 5-6) despite the larger tumor sizes (25 ± 14 mm vs. 31 ± 9 mm, p < 0.05). Hearing preservation rates did not increase. CONCLUSIONS: Near-total resection and subsequent CK radiosurgery in case of residual tumor regrowth during follow-up seems to provide a good outcome of facial nerve function even in large VSs.