Optimizing the use of Ki-67 proliferative index as a prognostic biomarker in meningiomas using digital analysis.

Objective: Ki-67 immunohistochemistry is widely used as a prognostic marker in meningiomas, but visual estimations tend to be imprecise. Whether the average Ki-67 over an entire slide, a particular block, or areas of high staining (hotspots) is prognostic for recurrence-free survival (RFS) and overall survival (OS) is unknown. This study aimed to generate evidence-based recommendations for the optimal use of Ki-67 immunohistochemistry in the workup of meningiomas.

Long-term antiseizure medication use in patients after meningioma resection: identifying predictors for successful weaning and failures.

Objective: To define risk factors for meningioma-related seizures and predictors of successful weaning of antiseizure medications following meningioma resection.

Methods: This is a retrospective study of 95 patients who underwent meningioma resection at a single institution. Primary outcome analyzed was ability to achieve seizure freedom without the use of anti-seizure medication at 6-months, 1-year, and last known follow up.

Genomic Tumor Correlates of Clinical Outcomes Following Organ-Sparing Chemoradiation Therapy for Bladder Cancer.

Purpose: There is an urgent need for biomarkers of radiation response in organ-sparing therapies. Bladder preservation with trimodality therapy (TMT), consisting of transurethral tumor resection followed by chemoradiation, is an alternative to radical cystectomy for muscle-invasive bladder cancer (MIBC), but molecular determinants of response are poorly understood.

Experimental Design: We characterized genomic and transcriptomic features correlated with long-term response in a single institution cohort of patients with MIBC homogeneously treated with TMT.

Patterns of Antiseizure Medication Use Following Meningioma Resection: A Single-Institution Experience.

Objective: To investigate antiseizure medication (ASM) practice behavior for patients who present with seizures before meningioma resection and to review postoperative ASM management.

Methods: A retrospective study was performed of 112 consecutive patients with meningiomas who underwent resection at a single institution between October 2016 and January 2020. Data were collected through detailed chart review.

Postoperative risk of IDH-mutant glioma-associated seizures and their potential management with IDH-mutant inhibitors.

Seizures are a frequent complication of adult-type diffuse gliomas, and are often difficult to control with medications. Gliomas with mutations in isocitrate dehydrogenase 1 or 2 (IDHmut) are more likely than IDH-wild type (IDHwt) gliomas to cause seizures as part of their initial clinical presentation. However, whether IDHmut is also associated with seizures during the remaining disease course, and whether IDHmut inhibitors can reduce seizure risk, are unclear.

Impact of Postoperative Stereotactic Body Radiation Therapy on Survival of Patients with Spinal Metastases in the Context of Additional Systemic Adjuvant Therapy.

Background: Stereotactic body radiotherapy (SBRT) has been established as a safe and effective treatment modality for control of long-term pain and tumor growth. However, few studies have investigated the efficacy of postoperative SBRT versus conventional external beam radiation therapy (EBRT) in extending survival within the context of systemic therapy.

Methods: A retrospective chart review of patients who underwent surgery for spinal metastasis at our institution was conducted.

Determining venous thromboembolism risk in patients with adult-type diffuse glioma.

Venous thromboembolism (VTE) is a life-threating condition that is common in patients with adult-type diffuse gliomas, yet thromboprophylaxis is controversial because of possible intracerebral hemorrhage. Effective VTE prediction models exist for other cancers, but not glioma. Our objective was to develop a VTE prediction tool to improve glioma patient care, incorporating clinical, blood-based, histologic, and molecular markers.

The efficacy of an unrestricted cycling ketogenic diet in preclinical models of IDH wild-type and IDH mutant glioma.

Infiltrative gliomas are the most common neoplasms arising in the brain, and remain largely incurable despite decades of research. A subset of these gliomas contains mutations in isocitrate dehydrogenase 1 (IDH1mut) or, less commonly, IDH2 (together called "IDHmut"). These mutations alter cellular biochemistry, and IDHmut gliomas are generally less aggressive than IDH wild-type (IDHwt) gliomas.

Differences in Quality of Life Between Men and Women who Undergo Bladder Preservation with Trimodality Therapy.

Purpose: Sex-specific differences exist in muscle invasive bladder cancer (MIBC): men have a higher incidence; women present with more advanced disease; and surgical options differ between men and women. Health related quality of life (HRQoL) for male versus female patients with MIBC is not well understood and limited data exists in patients who undergo bladder preservation with trimodality therapy (TMT). The purpose of this study was to compare long-term HRQoL between men and women who have undergone TMT.

Complications and Outcomes of Salvage Cystectomy after Trimodality Therapy.

Purpose: Salvage cystectomy is required for some patients with intravesical recurrence after trimodality therapy. We compared postoperative outcomes between salvage cystectomy post-trimodality therapy, primary cystectomy and primary cystectomy with prior history of nontrimodality therapy abdominal or pelvic radiotherapy.

Materials And Methods: We included 265 patients who underwent radical cystectomy at Massachusetts General Hospital for cT1-T4 bladder cancer between 2003 and 2013.

Extensive brainstem infiltration, not mass effect, is a common feature of end-stage cerebral glioblastomas.

Background: Progress in extending the survival of glioblastoma (GBM) patients has been slow. A better understanding of why patient survival remains poor is critical to developing new strategies. Postmortem studies on GBM can shed light on why patients are dying.

Methylation and transcription patterns are distinct in IDH mutant gliomas compared to other IDH mutant cancers.

Mutations in isocitrate dehydrogenases 1 and 2 (IDH) are present in a variety of cancers, including glioma, acute myeloid leukemia (AML), melanoma, and cholangiocarcinoma. These mutations promote hypermethylation, yet it is only a favorable prognostic marker in glioma, for reasons that are unclear. We hypothesized that the patterns of DNA methylation, and transcriptome profiles, would vary among IDH cancers, especially gliomas.

Impact of Immune and Stromal Infiltration on Outcomes Following Bladder-Sparing Trimodality Therapy for Muscle-Invasive Bladder Cancer.

Background: Bladder-sparing trimodality therapy (TMT) is an alternative to radical cystectomy (RC) for muscle-invasive bladder cancer (MIBC), and biomarkers to inform therapy selection are needed.

Objective: To evaluate the prognostic value of immune and stromal signatures in MIBC treated with TMT.

Design, Setting, And Participants: We used a clinical-grade platform to perform transcriptome-wide gene expression profiling of primary tumors from 136 MIBC patients treated with TMT at a single institution.

Long-term impact of a faculty mentoring program in academic medicine.

The authors conducted a prospective longitudinal study from 2009 to 2016 to assess the short and long-term impact of a formal mentorship program on junior faculty satisfaction and productivity. Junior faculty mentees enrolled in the program and junior faculty without formal mentorship were administered surveys before and after the program to assess satisfaction with their mentoring experiences. Long-term retention, promotion, and funding data were also collected.

Methylation-dependent Tissue Factor Suppression Contributes to the Reduced Malignancy of IDH1-mutant Gliomas.

Purpose: Gliomas with mutations (IDH1) are less aggressive than IDH1 wild-type (IDH1) gliomas and have global genomic hypermethylation. Yet it is unclear how specific hypermethylation events contribute to the IDH1 phenotype. Previously, we showed that the gene encoding the procoagulant tissue factor (TF), , is among the most hypermethylated and downregulated genes in IDH1 gliomas, correlating with greatly reduced thrombosis in patients with IDH1 glioma.

PARP-1 inhibition with or without ionizing radiation confers reactive oxygen species-mediated cytotoxicity preferentially to cancer cells with mutant TP53.

Biomarkers and mechanisms of poly (ADP-ribose) polymerase (PARP) inhibitor-mediated cytotoxicity in tumor cells lacking a BRCA-mutant or BRCA-like phenotype are poorly defined. We sought to explore the utility of PARP-1 inhibitor (PARPi) treatment with/without ionizing radiation in muscle-invasive bladder cancer (MIBC), which has poor therapeutic outcomes. We assessed the DNA damaging and cytotoxic effects of the PARPi olaparib in nine bladder cancer cell lines.

Incidence, Clinicopathological Risk Factors, Management and Outcomes of Nonmuscle Invasive Recurrence after Complete Response to Trimodality Therapy for Muscle Invasive Bladder Cancer.

Purpose: We describe the incidence, clinicopathological risk factors, management and outcomes of recurrent nonmuscle invasive bladder cancer after a complete response to trimodality therapy of muscle invasive bladder cancer.

Materials And Methods: We retrospectively reviewed the records of 342 patients with cT2-4aN0M0 muscle invasive bladder cancer and a complete response after trimodality therapy from 1986 to 2013. Using competing risks analyses we examined the association between baseline clinicopathological variables and nonmuscle invasive bladder cancer outcomes.

Risk Factors for Disease Progression After Postprostatectomy Salvage Radiation: Long-term Results of a Single-institution Experience.

Background: Salvage radiotherapy (SRT) has been successfully used for recurrent prostate cancer after radical prostatectomy; however, the optimal timing of SRT remains controversial. Our objective was to identify the risk factors for disease progression after SRT, with a focus on the pre-SRT prostate-specific antigen (PSA) levels in the modern era of PSA testing.

Patients And Methods: We performed a retrospective review of 551 consecutive patients who had undergone postradical prostatectomy SRT for recurrent prostate cancer from 2000 to 2013.

Long-term quality of life after definitive treatment for prostate cancer: patient-reported outcomes in the second posttreatment decade.

Definitive treatment for prostate cancer includes radical prostatectomy (RP), external beam radiation therapy (EBRT), and brachytherapy (BT). The different side effect profiles of these options are crucial factors for patients and clinicians when deciding between treatments. This study reports long-term health-related quality of life (HRQOL) for patients in their second decade after treatment for prostate cancer.

Long-term results of adjuvant versus early salvage postprostatectomy radiation: A large single-institutional experience.

Purpose: The purpose of this study was to evaluate freedom from biochemical failure (FFBF), freedom from androgen deprivation therapy (FFADT), freedom from distant metastases (FFDM), and overall survival (OS) after adjuvant radiation therapy (ART) versus early salvage radiation therapy (ESRT) in men with prostate cancer and adverse pathologic features (pT3 and/or positive surgical margins).

Methods And Materials: Of 718 patients consecutively treated with postoperative radiation therapy (RT) for prostate cancer between 1992 and 2013, we retrospectively identified 171 men receiving ART and 230 receiving ESRT (RT delivered at a prostate-specific antigen level ≤0.5 ng/mL) who had adverse pathologic features.