Pediatric Myeloid Sarcoma of the Testes Treated With Surgery and Adjuvant Radiation Therapy.

Myeloid sarcoma (MS) is a rare extramedullary tumor of immature granulocytic cells and is most often associated with acute myeloid leukemia (AML). Myeloid sarcomas can occur anywhere in the body but are seldom present in the testicles, especially in the pediatric population. The treatment of MS, especially testicular myeloid sarcoma (TMS) is not well defined in the literature and the role of radiation therapy in the treatment of TMS is even less well defined. In this case report, we discuss the treatment for TMS in a pediatric patient, review the literature, and discuss the role of radiation therapy in the treatment.

Phase II Trial of Concurrent Nivolumab and Radiation Therapy for Muscle-Invasive Bladder Cancer of Older or Chemotherapy-Ineligible Patients.

PURPOSE: Bladder cancer is predominantly a disease of older individuals. Concurrent chemotherapy and radiation is a bladder-sparing strategy for management of muscle-invasive bladder cancer; however, many patients are not candidates for chemotherapy due to comorbidities or impaired performance status. We conducted a study in a chemotherapy-ineligible patient population with the objectives of evaluating the safety, efficacy, and quality-of-life effect of the combination of nivolumab and radiation therapy in patients with localized/locally advanced urothelial cancer. METHODS AND MATERIALS: Eligible patients had muscle-invasive bladder cancer and were not candidates for standard chemoradiation strategy due to at least one of the following: performance status of 2, creatinine clearance ≤60 mL/min, cardiac disease, neuropathy, and intolerance to previous treatment. Creatinine clearance ≥40 mL/min, normal marrow, and liver function were required. The primary endpoint was progression-free survival at 12 months. Nivolumab was started within 3 days of radiation therapy and administered at a dose of 240 mg intravenously every 2 weeks for a maximum of 6 months. Radiation therapy was per standard of care for bladder cancer. Imaging and cystoscopy and biopsy evaluation were required at months 3, 6, and 12 and then annually until progression. RESULTS: Twenty patients were enrolled, with a median age of 78.5 years (range, 58-95 years); 80% of patients were >70 years of age, and 8 (40%) were >80 years of age. Median creatinine clearance was 52 mL/min. Nine patients (48%) were progression free at 12 months. Median progression-free survival was 11.4 months (90% CI, 7.5-23.7 months), and median overall survival was 15.6 months (90% CI, 9.1-26.1 months). CONCLUSIONS: Concurrent nivolumab and radiation therapy is tolerable but demonstrated limited efficacy in an older population with multiple comorbidities. Immune correlates demonstrated that patients with baseline programmed cell death ligand 1 combined prognostic score ≥5% had numerically longer progression-free survival.

A preliminary report assessing the feasibility and effectiveness of amniotic bladder therapy in patients with chronic radiation cystitis.

INTRODUCTION: Chronic radiation cystitis (CRC) can develop between 6 months and 20 years after radiation therapy that presents with symptoms of urinary frequency, urgency, bladder pain, and nocturia. Amniotic membrane (AM) is known to contain pro-regenerative properties and could thereby be a potential therapeutic modality for radiation-induced tissue injury of the bladder. MATERIALS AND METHODS: CRC patients recalcitrant to previous treatments received amniotic bladder therapy (ABT) comprised of intra-detrusor injections of 100 mg micronized AM (Clarix Flo) diluted in 10 mL 0.9% preservative-free sodium chloride. Clinical evaluation and questionnaires (Interstitial Cystitis Symptom Index (ICSI), Interstitial Cystitis Problem Index (ICPI), Bladder Pain/ Interstitial Cystitis Symptom Score (BPIC-SS), Overactive Bladder (OAB) Assessment Tool, and SF-12 Health Survey) were repeated at preop and 2, 4, 8 and 12 weeks post-injection. RESULTS: Five consecutive female patients aged 64.4 ± 20.1 years with a median CRC disease duration of 10 years were included. After ABT, BPIC-SS scores improved from baseline to 12 weeks (36.6 ± 1.1 to 12.6 ± 3.1) and this was associated with an improvement in ICSI, ICPI, OAB, and SF-12 scores. One patient had an acute urinary tract infection at 2 weeks but was successfully treated with oral antibiotics. No other adverse events related to micronized AM injections were observed. Uroflow assessments showed increases in voided volume for all five patients. CONCLUSIONS: This data provides additional evidence for the potential benefit of ABT in patients with chronic inflammatory conditions of bladder such as CRC.

Lutetium-177-PSMA-617 for Metastatic Castration-Resistant Prostate Cancer.

BACKGROUND: Metastatic castration-resistant prostate cancer remains fatal despite recent advances. Prostate-specific membrane antigen (PSMA) is highly expressed in metastatic castration-resistant prostate cancer. Lutetium-177 (177Lu)-PSMA-617 is a radioligand therapy that delivers beta-particle radiation to PSMA-expressing cells and the surrounding microenvironment. METHODS: We conducted an international, open-label, phase 3 trial evaluating 177Lu-PSMA-617 in patients who had metastatic castration-resistant prostate cancer previously treated with at least one androgen-receptor-pathway inhibitor and one or two taxane regimens and who had PSMA-positive gallium-68 (68Ga)-labeled PSMA-11 positron-emission tomographic-computed tomographic scans. Patients were randomly assigned in a 2:1 ratio to receive either 177Lu-PSMA-617 (7.4 GBq every 6 weeks for four to six cycles) plus protocol-permitted standard care or standard care alone. Protocol-permitted standard care excluded chemotherapy, immunotherapy, radium-223 (223Ra), and investigational drugs. The alternate primary end points were imaging-based progression-free survival and overall survival, which were powered for hazard ratios of 0.67 and 0.73, respectively. Key secondary end points were objective response, disease control, and time to symptomatic skeletal events. Adverse events during treatment were those occurring no more than 30 days after the last dose and before subsequent anticancer treatment. RESULTS: From June 2018 to mid-October 2019, a total of 831 of 1179 screened patients underwent randomization. The baseline characteristics of the patients were balanced between the groups. The median follow-up was 20.9 months. 177Lu-PSMA-617 plus standard care significantly prolonged, as compared with standard care, both imaging-based progression-free survival (median, 8.7 vs. 3.4 months; hazard ratio for progression or death, 0.40; 99.2% confidence interval [CI], 0.29 to 0.57; P<0.001) and overall survival (median, 15.3 vs. 11.3 months; hazard ratio for death, 0.62; 95% CI, 0.52 to 0.74; P<0.001). All the key secondary end points significantly favored 177Lu-PSMA-617. The incidence of adverse events of grade 3 or above was higher with 177Lu-PSMA-617 than without (52.7% vs. 38.0%), but quality of life was not adversely affected. CONCLUSIONS: Radioligand therapy with 177Lu-PSMA-617 prolonged imaging-based progression-free survival and overall survival when added to standard care in patients with advanced PSMA-positive metastatic castration-resistant prostate cancer. (Funded by Endocyte, a Novartis company; VISION ClinicalTrials.gov number, NCT03511664.).

Prognostic value of changes in neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR) and lymphocyte-to-monocyte ratio (LMR) for patients with cervical cancer undergoing definitive chemoradiotherapy (dCRT).

BACKGROUND: Peripheral NLR, PLR, and LMR have prognostic value in various malignancies as they are surrogates for inflammation. Recent studies have identified NLR, PLR, and LMR correlate with patient outcomes in cervical cancer patients however there remains uncertainty regarding the optimal time point for assessing these markers. METHODS: We retrospectively reviewed cervical cancer patients underoing definitive chemoradiation therapy (dCRT). NLR, PLR, and LMR values were identified before, during, and after dCRT and both relative and absolute changes in these values were calculated and compared with patient outcmoes. RESULTS: Ninety-nine patients who met the includsion criteria were identified. NLR values before, during, and after dCRT correlated with progression free survival (PFS) and overall survival (OS). In addition, increasing NLR after treatment was associated with worse PFS and OS. LMR before and after treatment had a positive correlation with PFS however increasing LMR during dCRT was found to have a negative correlation with PFS and OS. CONCLUSIONS: NLR serves as a prognostic indicator irrespective of timing with response to dCRT. While higher LMR before treatment was a positive prognostic indicator, increasing LMR was found to negatively correlate with PFS and OS.