Three-year Progression-free Survival Rates Research Articles

Harmonizing cancer care delivery for AYAs with osteosarcoma: Comparison of pediatric and medical oncology approaches in a single center.

10039 Background: Osteosarcoma (OS) has a peak incidence amongst adolescents and young adults (AYA). Nuances in chemotherapeutic regimens are largely influenced by the training of pediatric or medical oncologists. MAP is the standard chemotherapy regimen used by pediatric oncologists. Chemotherapy regimens used by medical oncologists vary; our center uses preoperative doxorubicin/cisplatin (AP) followed by either doxorubicin/ifosfamide (AI) or a combination of HD methotrexate and HD ifosfamide. We undertook this analysis to characterize the treatment response, toxicity, and survival outcomes for AYAs with OS treated with pediatric vs medical oncology regimens as an initial step towards harmonizing our institutional approach to the treatment of AYA patients with bone sarcomas. Methods: We retrospectively reviewed the records of AYAs with OS receiving primary treatment at our center. Clinicopathologic characteristics and outcomes for patients treated with MAP vs. AP+ were compared. Progression-free survival (PFS) was defined as the time from either MAP/AP+ initiation or surgery to the time of first recurrence or death. Overall survival was defined as the time from MAP/AP+ initiation or surgery to death. The distributions of PFS and overall survival were estimated by the Kaplan-Meier method. Log-rank test was performed to test the difference in survival between groups. Regression analyses of survival data based on the Cox proportional hazard (PH) model were conducted on the time to event outcomes. Results: Between 2016-2022, 209 OS patients were seen at our center for initial diagnosis and treatment recommendations including 124 AYAs (59%). Amongst AYAs, 41 patients (median age 22y, range 14-38y) initiated and received the majority of their chemotherapy at our center and were included in analysis. Of the 41 AYAs, 17 were treated on MAP; 24 were treated using AP+. Ten patients < 20 years received MAP; one patient >30 years received MAP. The median time from initiation of therapy to surgery for those receiving MAP was 87.5 days vs 95.5 days for AP (p = 0.0052). Percent tumor necrosis varied widely with both regimens (range 0-99%) and was not statistically different (p = 0.11). There was no statistically significant difference in PFS between AYAs treated with MAP as compared to AP+ (Three-year PFS rates 80% vs 66%, p = 0.40). Evaluation of treatment related toxicity and late effects is ongoing. Conclusions: We had insufficient data to compare survival outcomes in this limited retrospective series. This limited retrospective study did not show a statistically significant difference in PFS for AYA patients with OS treated with a standard pediatric vs. adult type regimen containing at least 3-drug chemotherapy. Further study is needed to refine treatment for this patient population. These data support prospective efforts to harmonize AYA treatment paradigms in osteosarcoma.

Comparing Clinical Efficacy of Different Bacillus Calmette-Guérin Strains in Patients With T1 High Grade Bladder Cancer.

This study aimed to compare the clinical efficacy of two different Bacillus Calmette-Guérin (BCG) strains, TICE strain (OncoTICE) and Connaught strain (ImmuCyst), as a first line intravesical instillation therapy in patients with T1 high grade bladder cancer. Patients with newly diagnosed T1 high-grade bladder cancer who underwent transurethral resection of bladder tumor (TURBT) followed by intravesical instillation therapy were enrolled. The effects of BCG strain on recurrence, progression, and side effects were analyzed using Kaplan-Meier and Cox proportional hazards models. Among 147 patients, 53 patients received Connaught strain and 94 patients received TICE strain. The completion rate of induction instillation was 92.45% in the Connaught group and 91.49% in the TICE group (p=1.00). The three-year recurrence-free survival rate was 71.7% in the Connaught group and 63.83% in the TICE group (p=0.33), whereas the three-year progression-free survival rate was 96.23% in the Connaught group and 89.36% in the TICE group (p=0.21). On Cox regression test, carcinoma in situ and ≥eight lesions were significant predictors for recurrence. No significant difference was observed in recurrence and progression between the two BCG regimens. The complication rates according to the Cleveland Clinic grading system showed no significant difference between the two groups (p=0.13). Both the Connaught and TICE strains of BCG demonstrated comparable three-year recurrence-free survival rates and three-year progression-free survival rates for T1 high grade bladder cancer, as well as comparable adverse events. Due to the global BCG shortage, further strain comparisons are essential for clinical validation.

Radiofrequency ablation for pediatric recurrent hepatocellular carcinoma: a single-center experience

PurposeTo summarize our single-center experience with percutaneous ultrasound (US)-guided radiofrequency ablation (RFA) for pediatric recurrent hepatocellular carcinoma (RHCC).MethodsFrom September 2007 to September 2021, patients under 18 who underwent percutaneous US-guided RFA for RHCC were retrospectively enrolled in this study. Local effectiveness, complications, local tumor progression (LTP), progression free survival (PFS), and overall survival (OS) were evaluated.ResultsA total of 10 patients (9 male and 1 female; mean age, 11.7 ± 4 years ; age range, 6–17 years) with 15 intrahepatic RHCC lesions were enrolled in this study. Complete ablation (CA) was achieved in 14 out of 15 lesions (93.3%) after the first RFA. During the follow-up (mean, 63.1 ± 18 months; range, 5.3-123.3 months), LTP did not occur. Five patients died including three with tumor progression and one with liver failure. The accumulative one- and three-year PFS rates were 30% and 10%, respectively. The accumulative one- and three-year OS rates were 77.8% and 44.4%, respectively.ConclusionsOur single-center experience suggests the safety and feasibility of percutaneous US-guided RFA for pediatric RHCC.

Outcomes for patients with high-risk endometrial cancer undergoing sentinel lymph node assessment versus full lymphadenectomy

ObjectiveThe objective of this study was to determine the progression free survival (PFS) and overall survival (OS) among patients with high-risk endometrial cancer (EC) who underwent sentinel lymph node (SLN) mapping and dissection compared to patients who underwent pelvic +/− para-aortic lymphadenectomy (LND). MethodsPatients with newly diagnosed high-risk EC were identified. Inclusion criteria included patients who underwent primary surgical management from January 1, 2014 to September 1, 2020 at our institution. Patients were categorized into either the SLN or LND group based on their method of planned lymph node assessment. Patients in the SLN group had dye injected followed by successful bilateral lymph node mapping, retrieval, and processing per our institutional protocol. Clinicopathological and follow-up data were extracted from patient's medical records. The t-test or Mann-Whitney test was used to compare continuous variables and Chi-squared or Fisher's exact test were used for categorical variables. Progression-free survival (PFS) was calculated from the date of initial surgery to the date of progression, death, or last follow-up. Overall survival (OS) was calculated from the date of surgical staging to the date of death or last follow-up. Three-year PFS and OS were calculated using the Kaplan-Meier method, and the log-rank test was used to compare cohorts. Multivariable Cox regression models were used to assess the relationship between nodal assessment cohort and OS/PFS while adjusting for age, adjuvant therapy, and surgical approach. A result was considered statistically significant at the p < 0.05 level of significance and all statistical analysis was done using SAS version 9.4 (SAS Institute, Cary, NC). ResultsOut of 674 patients diagnosed with EC during the study period, 189 were diagnosed with high-risk EC based on our criteria. Forty-six (23.7%) patients underwent SLN assessment and 143 (73.7%) underwent LND. No difference was observed between the two groups in regards to age, histology, stage, body mass index, tumors myometrial invasion, lymphovascular space invasion, or peritoneal washing positivity. Patients in the SLN group underwent robotic-assisted procedures more frequently than those in the LND group (p < 0.0001). The three-year PFS rate was 71.1% (95% CI 51.3–84.0%) in the SLN group and 71.3% (95% CI 62.0–78.6%) in the LND group (p = 0.91). The unadjusted hazard ratio (HR) for recurrence in the SLN versus LND group was 1.11 (95% CI 0.56–2.18; p = 0.77), and after adjusting for age, adjuvant therapy, and surgical approach, the HR for recurrence was 1.04 (95% CI 0.47–2.30, p = 0.91). The three-year OS rate was 81.1% (95% CI 51.1–93.7%) in the SLN group and 95.1% (95% CI 89.4–97.8%) in the LND group (p = 0.009). Although the unadjusted HR for death was 3.74 in the SLN vs LND group (95% CI 1.39–10.09; p = 0.009), when adjusted for age, adjuvant therapy, and surgical approach, it was no longer significant with a HR of 2.90 (95% CI 0.94–8.95, p = 0.06). ConclusionsThere was no difference in three-year PFS in patients diagnosed with high-risk EC who underwent SLN evaluation compared to those who underwent full LND in our cohort. The SLN group did experience shorter unadjusted OS; however, when adjusting for age, adjuvant therapy and surgical approach, there was no difference OS in patients who underwent SLN compared to LND.

Preoperative Platelet-Lymphocyte Ratio (PLR) as a prognostic inflammation biomarker in Asian HIV-infected patients with gastric cancer: a single-center study

BackgroundThe serum systemic inflammation biomarkers have been established as predictors of prognosis in gastric cancer (GC) patients, but their prognostic value in human immunodeficiency virus (HIV)-infected patients with GC has not been well studied. This retrospective study aimed to evaluate the prognostic value of preoperative systemic inflammation biomarkers in Asian HIV-infected patients with GC.MethodsWe retrospectively analyzed 41 HIV-infected GC patients who underwent surgery between January 2015 and December 2021 at the Shanghai Public Health Clinical Center. Preoperative systemic inflammation biomarkers were measured and patients were divided into two groups based on the optimal cut-off value. Overall survival (OS) and progression-free survival (PFS) were measured using the Kaplan–Meier method and the log-rank test. Multivariate analysis of variables was performed using the Cox proportional regression model. As a comparison, 127 GC patients without HIV infection were also recruited.ResultsThe median age of the 41 patients included in the study was 59 years, with 39 males and two females. The follow-up period for OS and PFS ranged from 3 to 94 months. The cumulative three-year OS rate was 46.0%, and the cumulative three-year PFS rate was 44%. HIV-infected GC patients had worse clinical outcomes compared to the normal GC population. The optimal cut-off value for preoperative platelet to lymphocyte ratio (PLR) was 199 in HIV-infected GC patients. Multivariate Cox regression analysis revealed that a low PLR was an independent predictor of better OS and PFS (OS: HR = 0.038, 95% CI: 0.006–0.258, P < 0.001; PFS: HR = 0.027, 95% CI: 0.004–0.201, P < 0.001). Furthermore, higher preoperative PLR in HIV-infected GC was significantly associated with lower BMI, hemoglobin, albumin, CD4 + T, CD8 + T, and CD3 + T cell counts.ConclusionThe preoperative PLR is an easily measurable immune biomarker that may provide useful prognostic information in HIV-infected GC patients. Our findings suggest that PLR could be a valuable clinical tool for guiding treatment decisions in this population.

The MEMORY Study: MulticentEr study of Minimally invasive surgery versus Open Radical hYsterectomy in the management of early-stage cervical cancer: Survival outcomes

ObjectiveThe Laparoscopic Approach to Cervical Cancer (LACC) trial found that minimally invasive radical hysterectomy compared to open radical hysterectomy compromised oncologic outcomes and was associated with worse progression-free survival (PFS) and overall survival (OS) in early-stage cervical carcinoma. We sought to assess oncologic outcomes at multiple centers between minimally invasive (MIS) radical hysterectomy and OPEN radical hysterectomy. MethodsThis is a multi-institutional, retrospective cohort study of patients with 2009 FIGO stage IA1 (with lymphovascular space invasion) to IB1 cervical carcinoma from 1/2007–12/2016. Patients who underwent preoperative therapy were excluded. Squamous cell carcinoma, adenocarcinoma, and adenosquamous carcinomas were included. Appropriate statistical tests were used. ResultsWe identified 1093 cases for analysis—715 MIS (558 robotic [78%]) and 378. OPEN procedures. The OPEN cohort had more patients with tumors >2 cm, residual disease in the hysterectomy specimen, and more likely to have had adjuvant therapy. Median follow-up for the MIS and OPEN cohorts were 38.5 months (range, 0.03–149.51) and 54.98 months (range, 0.03–145.20), respectively. Three-year PFS rates were 87.9% (95% CI: 84.9–90.4%) and 89% (95% CI: 84.9–92%), respectively (P = 0.6). On multivariate analysis, the adjusted HR for recurrence/death was 0.70 (95% CI: 0.47–1.03; P = 0.07). Three-year OS rates were 95.8% (95% CI: 93.6–97.2%) and 96.6% (95% CI: 93.8–98.2%), respectively (P = 0.8). On multivariate analysis, the adjusted HR for death was 0.81 (95% CI: 0.43–1.52; P = 0.5). ConclusionThis multi-institutional analysis showed that an MIS compared to OPEN radical hysterectomy for cervical cancer did not appear to compromise oncologic outcomes, with similar PFS and OS.

Improved diagnostics of “concealed” metastases in patients with сТ1–2N0М0 oral squamous cell carcinoma

Introduction. Oral squamous cell carcinoma is associated with a high risk of regional metastasis even in early stages (T1–2N0M0). Morphological examination reveals concealed metastases in 20 % of removed clinically unaffected lymph nodes.Objective – to evaluate the effectiveness of flow cytometry for detection of concealed metastases in sentinel lymph nodes as an indication for cervical lymph node dissection in patients with stage сT1–2N0M0 oral squamous cell carcinoma.Materials and methods. This study included 27 patients, including 13 patients (48.1 %) with stage T1N0M0 cancer and 14 patients with stage T2N0M0 cancer (51.9 %). At the first stage, all participants underwent primary tumor removal and cervical lymph node dissection with sentinel lymph node examination. After mobilization, half of these lymph nodes was used for routine morphological examination followed by immunohistochemical examination, while the second half of them was analyzed using flow cytometry. Then we compared the results obtained.Results. We examined 46 removed sentinel lymph nodes from 27 patients. Conventional histological examination revealed 4 concealed metastases (8.7 %). Polymerase chain reaction allowed us to detect another 16 metastases (37.8 %). Levels I, II, and III lymph nodes were most frequently affected. Flow cytometry demonstrated that 20 % of patients with a &lt;4 mm invasion had concealed metastases, whereas patients with a 4 to 8 mm invasion had concealed metastases in 60 % of cases. Median follow-up time was 20.4 ± 11.7 months (range: 2.2 to 42.5 months; median 19.5 months). All participants were alive during this time. Seventeen out of 27 patients with stage T1–2N0M0 disease (63 %) were found to have concealed metastases, while the remaining ten patients (37 %) had no metastasis. One patient with stage T1N0M0 oral floor squamous cell carcinoma underwent the removal of the primary tumor and sentinel lymph node. Morphological examination and flow cytometry showed no metastatic lesions. After 14.8 months, the patient developed ipsilateral regional CN3 metastasis. The three-year progression-free survival rate was 94.7 ± 5.1 %.Conclusion. Highly sensible and rapid flow cytometry can become the method of choice in the diagnosis of metastases and deciding on cervical lymph node dissection in patients with cN0 disease. The study is still ongoing.

First-line nivolumab plus ipilimumab versus chemotherapy in patients with unresectable malignant pleural mesothelioma: 3-year outcomes from CheckMate 743

In the phase III CheckMate 743 study (NCT02899299), first-line nivolumab plus ipilimumab significantly improved overall survival (OS) versus chemotherapy in patients with unresectable malignant pleural mesothelioma (MPM). We report updated data with 3-year minimum follow-up. Adults with previously untreated, histologically confirmed, unresectable MPM and Eastern Cooperative Oncology Group performance status of ≤1 were randomized 1 : 1 to nivolumab (3 mg/kg every 2 weeks) plus ipilimumab (1 mg/kg every 6 weeks) for up to 2 years, or six cycles of platinum plus pemetrexed chemotherapy. This report includes updated efficacy and safety outcomes, exploratory biomarker analyses including four-gene inflammatory expression signature score, and a post hoc efficacy analysis in patients who discontinued treatment due to treatment-related adverse events (TRAEs). With a median follow-up of 43.1 months, nivolumab plus ipilimumab continued to prolong OS versus chemotherapy. Median OS was 18.1 versus 14.1 months [hazard ratio (95% confidence interval), 0.73 (0.61-0.87)], and 3-year OS rates were 23% versus 15%, respectively. Three-year progression-free survival rates were 14% versus 1%, and objective response rates were 40% versus 44%. At 3 years, 28% versus 0% of responders had an ongoing response. Improved survival benefit with nivolumab plus ipilimumab versus chemotherapy was observed across subgroups, including histology. A high score of the four-gene inflammatory signature appeared to correlate with improved survival benefit with nivolumab plus ipilimumab. No new safety signals were observed with nivolumab plus ipilimumab, despite patients being off therapy for 1 year. In patients who discontinued nivolumab plus ipilimumab due to TRAEs, median OS was 25.4 months, and 34% of responders maintained their responses for ≥3 years after discontinuation. With 3 years' minimum follow-up, nivolumab plus ipilimumab continued to provide long-term survival benefit over chemotherapy and a manageable safety profile, supporting the regimen as standard-of-care treatment for unresectable MPM, regardless of histology.

RBIO-05. THE IMPACT OF STEREOTATIC RADIOSURGERY (SRS) FOR THE RESIDUAL LESIONS OF PINEAL NON-GERMINOMATOUS GERM CELL TUMORS (NGGCTS) FOLLOWING CONVENTIONAL RADIOTHERAPY: A RETROSPECTIVE STUDY

Abstract OBJECTIVE To evaluate the safety and efficacy of stereotatic radiosurgery (SRS) in treating residual lesions of pineal non-germinomatous germ cell tumors (NGGCTs) after conventional radiotherapy. METHODS The patients admitted to Guangdong Sanjiu Brain Hospital from 1 January 2008 to 31 December 2018 who diagnosed with pineal NGGCTs pathologically or clinically were retrospectively analyzed. Among those, the patients received conventional radiotherapy with or without SRS were included. The residual lesions after radiotherapy were defined with a maximum diameter &amp;gt; 10mm. Prognosis related parameters such as local control rate, progress-free survival, overall survival and treatment-related toxicity were determined. RESULTS The median follow-up time was 34 months (range 8-142 months). The objective response rate and disease control rate were 71.4% and 95.2%, respectively. Three-year progression-free survival rate was 85.2% and 3-year total survival rate was 88.0%. The univariate analysis revealed that both age and concurrent chemotherapy were not correlated with the prognosis (P=0.286, 0.824). Partial tumor resection before radiotherapy and chemotherapy, AFP &amp;gt;500ng/ml, and no more than 4 cycles of adjuvant chemotherapy were poor prognostic factors (P=0.037, 0.010, 0.006). Moreover, no acute radiation response was observed after treatment with SRS. Only 1 out of 27 patients (3.7%) had brain neurotoxicity related to a prolonged course of radiochemotherapy. CONCLUSION SRS for residual lesions of NGGCTs following conventional radiotherapy appears to be well tolerant and improved local control. However, the therapeutic efficacy of conventional radiotherapy combined with SRS warrants further investigations in a large-scale randomized controlled clinical trials.

Testicular, Spermatic Cord, and Scrotal Soft Tissue Sarcomas: Treatment Outcomes and Patterns of Failure.

Introduction Paratesticular sarcomas are defined as tumors that arise within the scrotum and include the subsites of epididymis, spermatic cord, and tunica vaginalis and represent the most common type of GU sarcoma. The mainstay of treatment is often surgical resection, combined with histology specific chemotherapy and radiotherapy. Due to the rare nature of the disease, there are limited data to guide management. We present our single-institution retrospective experience regarding the management and treatment of paratesticular sarcomas. Materials and Methods We queried our oncology registry database for patients treated for testicular, spermatic cord, and scrotal soft tissue sarcomas between 1971 and 2017. Patients in this series had pathological confirmation of a sarcoma diagnosis by a sarcoma-specialized pathologist. Only patients with localized disease were included in this analysis with the exception of patients with a diagnosis of rhabdomyosarcoma where patients with both localized and metastatic disease were included on this study. Results A total of 34 patients were included in this retrospective analysis. The median was 24 (range, 5–78), and the median tumor size was 6.25 cm. Twenty-six patients had localized disease (76.6%) at the time of diagnosis. A predominance of patients had tumors involving the spermatic cord (45.5%), and the most common histology was rhabdomyosarcoma (35.3%), leiomyosarcoma (26.5%), and well-differentiated liposarcoma (23.5%). The median follow-up was 71.0 months (range, 2.5–534.4 months). A total of 7 patients experienced an isolated local failure (20.6%), four patients developed distant metastatic disease (11.8%), and one patient (2.9%) with synovial sarcoma of the spermatic cord experienced a regional recurrence. The median progression-free survival (PFS) was 99.6 months, 95% CI (45.8–534.3 months), with a three-year PFS rate of 71%, 95% CI (53%–83%), and a 5-year PFS rate of 64% (range, 46%–78%). We did not find any statistically significant associations based on surgery type (p=0.15), the use of chemotherapy, (p=0.36), or final margin status (p=0.21). Two patients who were treated with preoperative radiotherapy had significant wound healing complication with chronic sinus tracts, though these patients did not experience a local recurrence. Conclusions We provide a characterization of the natural history and treatment patterns of paratesticular sarcomas. While effective at reducing a local recurrence, preoperative radiotherapy was associated with significant toxicity. As a result, we prefer the use of postoperative radiotherapy in patients as clinically indicated. We did not find any specific treatment patterns associated with an improvement in clinical outcomes.

Stereotactic Body Radiotherapy for Lymph Node Oligometastases: Real-World Evidence From 90 Consecutive Patients.

AimsTo evaluate the efficacy and toxicity of extracranial stereotactic body radiotherapy (SBRT) in the treatment of oligometastatic lymph node involvement in the mediastinum, retroperitoneum, or pelvis, in a consecutive group of patients from real clinical practice outside clinical trials.MethodsA retrospective analysis of 90 patients with a maximum of four oligometastases and various primary tumors (the most common being colorectal cancers). The endpoints were local control of treated metastases (LC), freedom from widespread dissemination (FFWD), progression-free survival (PFS), overall survival (OS), and freedom from systemic treatment (FFST). Acute and delayed toxicities were also evaluated.ResultsThe median follow-up after SBRT was 34.9 months. The LC rate at three and five years was 68.4 and 56.3%, respectively. The observed median FFWD was 14.6 months, with a five-year FFWD rate of 33.7%. The median PFS was 9.4 months; the three-year PFS rate was 19.8%. The median FFST was 14.0 months; the five-year FFST rate was 23.5%. The OS rate at three and five years was 61.8 and 39.3%, respectively. Median OS was 53.1 months. The initial dissemination significantly shortened the time to relapse, death, or activation of systemic treatment—LC (HR 4.8, p < 0.001), FFWD (HR 2.8, p = 0.001), PFS (HR 2.1, p = 0.011), FFST (HR 2.4, p = 0.005), OS (HR 2.2, p = 0.034). Patients classified as having radioresistant tumors noticed significantly higher risk in terms of LC (HR 13.8, p = 0.010), FFWD (HR 3.1, p = 0.006), PFS (HR 3.5, p < 0.001), FFST (HR 3.2, p = 0.003). The multivariable analysis detected statistically significantly worse survival outcomes for initially disseminated patients as well as separately in groups divided according to radiosensitivity. No grade III or IV toxicity was reported.ConclusionOur study shows that targeted SBRT is a very effective and low toxic treatment for oligometastatic lymph node involvement. It can delay the indication of cytotoxic chemotherapy and thus improve and maintain patient quality of life. The aim of further studies should focus on identifying patients who benefit most from SBRT, as well as the correct timing and dosage of SBRT in treatment strategy.

Volumetric PET Parameters Predict Prognosis after Definitive Chemoradiotherapy with Cisplatin/Docetaxel for Stage III Non-Small Cell Lung Cancer.

The aim of this study was to investigate whether volumetric positron emission tomography (PET) parameters are prognostic predictors in stage III non-small cell lung cancer patients receiving definitive concurrent chemo-radiotherapy (CCRT) with cisplatin/docetaxel. Cases involving definitive CCRT were reviewed retrospectively, and the maximum standardized uptake value, metabolic tumor volume (MTV) and total lesion glycolysis (TLG) were calculated. The relationships between these PET parameters and prognosis were analyzed. MTV and TLG were significant predictors of distant metastasis-free survival (DMFS) (p = 0.0003 and 0.0005, respectively) and progression-free survival (PFS) (p = 0.001 and 0.0007, respectively). The three-year DMFS rates in patients with low and high MTV were 13.3% and 64.6%, respectively, and the corresponding values in those with low and high TLG were 13.3% and 65.2%, respectively. The three-year PFS rates in patients with low and high MTV were 13.3% and 57.8%, respectively, and the corresponding values in patients with low and high TLG were 13.3% and 57.8%, respectively. However, MTV and TLG were not predictors of local control or overall sur-vival. We demonstrated that volumetric PET parameters were predictors of patients receiving definitive CCRT. Our findings contradict the findings of previous reports and warrant further research to validate them.

Vertical Lamina Propria Invasion Diagnosed by En Bloc Transurethral Resection is a Significant Predictor of Progression for pT1 Bladder Cancer.

T1 bladder cancer is characterized by high recurrence and aggressive progression. Muscularis mucosae invasion may be a prognostic factor for progression, but the limitations of conventional transurethral resection of bladder tumors make diagnosis difficult. We correlated degree of invasion with oncologic outcome and evaluated the utility of pathological diagnosis following en bloc resection of bladder tumors. We retrospectively analyzed the records of 123 consecutive patients diagnosed with pT1 bladder cancer between November 2013 and December 2018. Transurethral resection was conducted in 91 patients, and en bloc resection in 32 patients. All specimens were analyzed for invasion depth and pT1 substaging (T1a/b: invasion above or into/beyond muscularis mucosae, pT1m/e: microinvasive or extensively invasive). Primary end points were prognostic values of pT1 substaging and invasion depth. The secondary end point was the pathological diagnostic utility of en bloc resection. Median followup was 23 months. Three-year progression-free survival rate differed significantly depending on muscularis mucosae invasion (pT1a: 97.3%, pT1b: 72.8%; p=0.003) and invasion depth from basal membrane (<2 mm: 90.6%, ≥2 mm: 77.9%; p=0.03). Multivariate analysis showed that sessile tumor and invasion depth from basal membrane ≥2 mm were independent prognostic factors for progression. Diagnostic rates for pT1a/b and invasion depth were 77.6% and 85.9%, respectively, with transurethral resection, but 100% and 100% with en bloc resection (p=0.01 and p=0.03). Vertical lamina propria invasion is predictive of progression in T1 bladder cancer, underlining the importance of accurately diagnosing the degree of vertical lamina propria invasion with en bloc resection.

RADT-44. STEREOTATIC RADIOSURGERY FOR RESIDUAL LESIONS OF PINEAL NON-GERMINOMATOUS GERM CELL TUMORS AFTER CONVENTIONAL RADIOTHERAPY: A RETROSPECTIVE STUDY

Abstract OBJECTIVE To evaluate the safety and efficacy of stereotatic radiosurgery (SRS) in treating residual lesions of pineal non-germinomatous germ cell tumors (NGGCTs) after conventional radiotherapy. METHODS The patients admitted to Guangdong Sanjiu Brain Hospital from 1 January 2008 to 31 December 2018 who diagnosed with pineal NGGCTs pathologically or clinically were retrospectively analyzed. Among those, the patients received conventional radiotherapy with or without SRS were included. The residual lesions after radiotherapy were defined with a maximum diameter &amp;gt; 10mm. Prognosis related parameters such as local control rate, progress-free survival, overall survival and treatment-related toxicity were determined. RESULTS The median follow-up time was 34 months (range 8-142 months). The objective response rate and disease control rate were 71.4% and 95.2%, respectively. Three-year progression-free survival rate was 85.2% and 3-year total survival rate was 88.0%. The univariate analysis revealed that both age and concurrent chemotherapy were not correlated with the prognosis (P=0.286, 0.824). Partial tumor resection before radiotherapy and chemotherapy, AFP＞500ng/ml, and no more than 4 cycles of adjuvant chemotherapy were poor prognostic factors (P=0.037, 0.010, 0.006). Moreover, no acute radiation response was observed after treatment with SRS. Only 1 out of 27 patients (3.7%) had brain neurotoxicity related to a prolonged course of radiochemotherapy. CONCLUSION SRS for residual lesions of NGGCTs following conventional radiotherapy appears to be well tolerant and improved local control. However, the combination of conventional radiotherapy and SRS warrants further investigations in a large-scale randomized controlled clinical trials.

Single-agent carboplatin AUC10 in metastatic seminoma: A multi-centre UK study of 216 patients

BackgroundRadiotherapy and cisplatin-based combination chemotherapy are accepted standard-of-care treatments for metastatic seminoma with excellent survival outcomes but with established short- and long-term morbidity. Carboplatin monotherapy may be a less toxic alternative; however early historic studies at AUC7 showed inferior outcomes. ObjectivesTo evaluate multi-institutional data on and toxicity and longer-term survival for metastatic seminoma patients treated with the single-agent carboplatin AUC10. MethodsWe undertook a multi-institutional analysis incorporating all men with the International Germ Cell Cancer Collaborative Group good-prognosis metastatic seminoma treated until 2018. Carboplatin AUC10 was given every 21 days. Toxicity, progression-free survival (PFS), disease-specific survival (DSS) and overall survival were noted. Variables predictive of progression were identified. Results and limitations216 patients were treated. The three-year PFS rate was 96.5%, and five-year DSS was 98.3%. There were seven relapses, of which 5 were successfully salvaged with further chemotherapy ± surgery, and three non-seminoma–related deaths. There were no treatment-related deaths. Of 148/216 evaluable patients for toxicity, 37% and 27% suffered >/ = grade III neutropenia and thrombocytopenia, respectively. Twelve percent of patients needed a platelet or blood transfusion (or both). The incidence of febrile neutropenia was 5%. ConclusionFor metastatic seminoma, carboplatin AUC10 harbours a similar oncological efficacy to established therapies, with a low failure risk. The major acute toxicity was myelosuppression. Our study establishes carboplatin AUC10 as another standard-of-care treatment option for good-prognosis metastatic seminoma, with a potentially lower toxicity profile than other therapies.

Analysis of treatment outcomes in patients with progressive locally advanced non-resectable and disseminated medullary thyroid cancer receiving vandetanib outside of clinical trials (Russian experience)

The study objective is to perform retrospective analysis of the efficacy and safety of vandetanib for metastatic and non-resectable medullary thyroid cancer in routine clinical practice. Materials and methods. We analyzed treatment outcomes in 46 patients treated with vandetanib. We also evaluated progression-free survival, overall survival, time to progression, and frequency of adverse events. Results. At a median follow-up time of 27.4 months (range: 2.5–106.5 months) and median duration of vandetanib therapy of 21 months, disease progression was registered in 32.6 % of cases, whereas stable disease was observed in 28.3 % of cases and 8.7 % of study participants demonstrated partial response. One patient had complete response to treatment. Almost one-third of patients (28.2 %) died, including 2 individuals whose death was not associated with cancer. The one-year and three-year progression-free survival rates were 67.3 % and 33.3 %, respectively; the two-year and five-year overall survival rates were 82.4 % and 29.4 %, respectively. The efficacy of therapy was confirmed by a 79.4 % decrease in the serum level of calcitonin after treatment initiation. Side effects were observed in 33.9 % of patients (primarily skin and gastrointestinal toxic reactions) and were easily managed in most of the cases. Eight individuals (17.4 %) required cessation of vandetanib due to adverse events. Conclusion. Our findings suggest high efficacy and acceptable safety profile of vandetanib in the treatment of progressive locally advanced non-resectable and disseminated medullary thyroid cancer

Clinical characteristics and prognostic analysis of advanced-stage extranodal NK/T cell lymphoma

目的探讨非局限期结外鼻型NK/T细胞淋巴瘤（ENKTL）患者的临床特征及预后影响因素。方法回顾性分析北京协和医院2012年1月至2019年12月收治的51例Ⅲ~Ⅳ期ENKTL患者的临床资料。分析其临床特征、疗效、生存情况及预后影响因素，依据起病时是否存在鼻咽部受累分为鼻型与非鼻型，对比分析二者的差异，探讨EB病毒DNA（EBV-DNA）在疗效监测及预后评价中的意义。结果所有患者的中位发病年龄为42（14~67）岁，男女比例为2.9∶1。中位随访时间为30（1~78）个月，非局限期患者中位总生存（OS）时间为7个月，1年及3年无进展生存（PFS）率分别为34.1%和24.6%，1年及3年OS率分别为39.9%和26.6%。鼻型与非鼻型患者的比例为1.6∶1。非鼻型患者合并噬血细胞综合征的比例较鼻型患者高（65.0%对35.5%，P=0.039），非鼻型患者一线化疗的完全缓解（CR）率较鼻型患者低（10.0%对45.2%，P=0.008）。非局限期鼻型与非鼻型患者的中位OS时间分别为9个月和4个月，3年PFS率分别为36.0%和10.0%（P=0.029），3年OS率分别为37.9%和11.4%（P=0.050）。EBV-DNA的变化趋势与疗效有良好的相关性。基线EBV-DNA阴性与阳性患者生存曲线的差异无统计学意义。1个疗程化疗后EBV-DNA阴性与阳性患者的3年OS率分别为77.9%和8.1%，差异有统计学意义（P=0.002）。多因素分析结果显示，1个疗程化疗后EBV-DNA阳性为OS不良的独立预后因素。结论应用以培门冬酶为基础化疗方案的非局限期ENKTL患者的治疗有效率及远期生存仍较差。非鼻型患者在临床特征、化疗疗效及远期预后方面均较鼻型患者差。1个疗程化疗后EBV-DNA阳性为OS不良的独立预后因素，可用于早期预测疗效及预后。

Comparison between radiofrequency ablation and sublobar resections for the therapy of stage I non-small cell lung cancer: a meta-analysis.

BackgroundSublobar resection (SLR) and radiofrequency ablation (RFA) are the two minimally invasive procedures performed for treating stage I non-small cell lung cancer (NSCLC). This study aimed to compare SLR and RFA for the treatment of stage I NSCLC using the meta-analytical method.MethodsWe searched PubMed and Embase for articles published till December 2019 to evaluate the comparative studies and assess the survival and progression-free survival rates and postoperative complications (PROSPERO registration number: CRD42018087587). A meta-analysis was performed by combining the outcomes of the reported incidences of short-term morbidity and long-term mortality. The fixed or random effects model was utilized to calculate the pooled odds ratios (OR) and the 95% confidence intervals.ResultsFour retrospective studies were considered in the course of this study. The studies included a total of 309 participants; 154 were assigned to the SLR group, and 155 were assigned to the RFA group. Moreover, there were statistically significant differences between the one- and three-year survival rates and one- and three-year progression-free survival rates for the two groups, which were in favor of the SLR group. Among the post-surgical complications, pneumothorax and pleural effusion were more common for the SLR group, while cardiac abnormalities were prevalent in the RFA group. There was no difference in prevalence of hemoptysis between SLR and RFA groups, which might be attributed to the limited study sample size.ConclusionConsidering the higher survival rates and disease control in the evaluated cases, surgical resection is the preferred treatment method for stage I NSCLC. RFA can be considered a valid alternative in patients not eligible for surgery and in high-risk patients as it is less invasive and requires shorter hospital stay.

Stereotatic radiosurgery for residual lesions of pineal nongerminomatous germ cell tumors after conventional radiotherapy: A retrospective study.

e14516 Background: To evaluate the safety and efficacy of stereotatic radiosurgery (SRS) in treating residual lesions of pineal non-germinomatous germ cell tumors (NGGCTs) after conventional radiotherapy. Methods: The patients admitted to Guangdong Sanjiu Brain Hospital from 1 January 2008 to 31 December 2018 who diagnosed with pineal NGGCTs pathologically or clinically were retrospectively analyzed. Among those, the patients received conventional radiotherapy with or without SRS were included. The residual lesions after radiotherapy were defined with a maximum diameter &gt; 10mm. Prognosis related parameters such as local control rate, progress-free survival, overall survival and treatment-related toxicity were determined. Results: The median follow-up time was 34 months (range 8-142 months). The objective response rate and disease control rate were 71.4% and 95.2%, respectively. Three-year progression-free survival rate was 85.2% and 3-year total survival rate was 88.0%. The univariate analysis revealed that both age and concurrent chemotherapy were not correlated with the prognosis (P = 0.286, 0.824). Partial tumor resection before radiotherapy and chemotherapy, AFP&gt;500ng/ml, and no more than 4 cycles of adjuvant chemotherapy were poor prognostic factors (P = 0.037, 0.010, 0.006). Moreover, no acute radiation response was observed after treatment with SRS. Only 1 out of 27 patients (3.7%) had brain neurotoxicity related to a prolonged course of radiochemotherapy. Conclusions: SRS for residual lesions of NGGCTs following conventional radiotherapy appears to be well tolerant and improved local control. However, the combination of conventional radiotherapy and SRS warrants further investigations in a large-scale randomized controlled clinical trials.

Ibrutinib Selects for Cells with Elevated Reactive Oxygen Species and Downregulated Phosphatases

Signals from the B-cell receptor are inappropriately activated in B-cell malignancies, including Chronic lymphocytic leukemia (CLL), Mantle cell lymphoma (MCL), and Diffuse large B-cell lymphoma (DLBCL). In CLL, 90% of patients respond to treatment with ibrutinib, an inhibitor of Bruton's Tyrosine Kinase (BTK), with a mean three-year progression free survival rate of approximately 60%. Despite these promising numbers, patients who do not initially respond to ibrutinib have extremely poor outcomes, and nearly all patients eventually become resistant to ibrutinib due to mutations in BTK and its downstream effector Phospholipase C gamma 2 (PLCG2), with a median survival time of 23 months. In order to identify salvage therapies for ibrutinib-resistant patients, we employed several quantitative proteomic methods to identify signaling pathways and proteins that are essential in ibrutinib-resistant patient cells and cell lines. Total proteomic analysis of lymphoma cell lines selected with ibrutinib in vitro revealed that multiple mitochondrial proteins are increased in B cells exposed to ibrutinib. Next, we found that ibrutinib-treated B cells also exhibited increases in reactive oxygen species (ROS), which potently inhibit several protein phosphatases, including B cell receptor signaling regulators PTPN6 and INPP5D. We next looked at tyrosine phosphorylation in patient B cells collected at several time points during ibrutinib treatment and found decreased phosphorylation of both PTPN6 (Y536) and INPP5D (Y944 and Y865) during treatment. Furthermore, total levels of PTPN6 are decreased in patients within 3 months of initiating treatment, and disruption of PTPN6 in cell lines by CRISPR provided a selective advantage in ibrutinib-treated cell populations. Finally, we found that ibrutinib-treated and ibrutinib-naïve primary CLL cells are sensitive to compounds that prevent reactive oxygen species generation (SOD and PHOX inhibitors). Combined, we propose a mechanism by which ibrutinib treatment leads to increased levels of ROS and decreased phosphatase activity, ultimately leading to a growth advantage in the presence of ibrutinib without concomitant mutations in PLCG2 and BTK. We hypothesize that targeting proteins important for reactive oxygen species generation would also be useful in patients and could result in regained disease control and/or prevention of acquired resistance. Disclosures Gopal: Seattle Genetics, Pfizer, Janssen, Gilead, Sanofi, Spectrum, Amgen, Aptevo, BRIM bio, Acerta, I-Mab-pharma, Takeda, Compliment, Asana Bio, and Incyte.: Consultancy; Teva, Bristol-Myers Squibb, Merck, Takeda, Seattle Genetics, Pfizer, Janssen, Takeda, and Effector: Research Funding; Seattle Genetics, Pfizer, Janssen, Gilead, Sanofi, Spectrum, Amgen, Aptevo, BRIM bio, Acerta, I-Mab-pharma, Takeda, Compliment, Asana Bio, and Incyte: Honoraria.