Optimizing Patient Selection for Irreversible Electroporation of Locally Advanced Pancreatic Cancer: Analyses of Survival

BackgroundIrreversible electroporation (IRE) has emerged as a viable consolidative therapy after induction chemotherapy, in which this combination has improved overall survival of locally advanced pancreatic cancer (LAPC). Optimal timing and patient selection for irreversible electroporation remains a clinically unmet need. The aim of this study was to investigate preoperative factors that may assist in predicting progression-free and overall survival following IRE.MethodsA multi-institutional, prospectively maintained database was reviewed for patients with LAPC treated with induction chemotherapy followed by open-technique irreversible electroporation from 7/2015-5/2019. RECIST 1.1 criteria were used to assess tumor response and radiological progression. Overall survival (OS) and progression-free survival (PFS) were recorded. Survival analyses were performed using Kaplan Meier and Cox multivariable regression analyses.Results187 LAPC patients (median age 62 years range, 21 – 91, 65% men, 35% women) were treated with IRE. Median PFS was 21.7 months and median OS from diagnosis was 25.5 months. On multivariable analysis, age ≤ 61 (HR 0.41, 95%CI 0.21-0.78, p<0.008) and no prior radiation (HR 0.49, 95%CI 0.26-0.94, p=0.03) were positive predictors of OS after IRE. Age ≤ 61(HR 0.53, 95%CI, 0.28-.99, p=0.046) and FOLFIRINOX followed by gemcitabine/abraxane induction chemotherapy (HR 0.37,95%CI 0.15-0.89, p=0.027) predicted prolonged PFS after IRE. Abnormal CA19-9 values at the time of surgery negatively impacted both OS (HR 2.46, 95%CI 1.28-4.72, p<0.007) and PFS (HR 2.192, 95%CI 1.143-4.201, p=0.018) following IRE.ConclusionsAge, CA 19-9 response, avoidance of pre-IRE radiation, and FOLFIRINOX plus gemcitabine/abraxane induction chemotherapy are prominent factors to consider when referring or selecting LAPC patients to undergo IRE.

Rituximab With High-Dose Methotrexate In Newly Diagnosed Primary Central Nervous System Lymphoma: a Single-Center Experience From China

Induction chemotherapy based on high-dose methotrexate is considered as the standard approach for newly diagnosed primary central nervous system lymphomas (PCNSLs). However, the best combination chemotherapeutic regimen remains unclear. This study aimed to determine the efficacy and toxicities of rituximab with methotrexate (R-M regimen). Consecutive 37 Chinese patients receiving R-M regimen as induction chemotherapy were retrospectively identified from January 2015 to June 2020 from our center in eastern China. Fourteen patients receiving rituximab plus methotrexate with cytarabine (R-MA regimen) at the same period were identified as the positive control group. The response rates, survival, toxicities, length of hospital stay (LOS), and cost were compared. Compared with the R-MA regimen, the R-M regimen showed comparable response rate and survival outcomes, but had fewer grade 3-4 hematological toxicities, shorter LOS, lower mean total hospitalization cost and lower mean total antibiotic cost. Overall response after two cycles of chemotherapy, complete remission at the end of induction chemotherapy and ECOG>3 were independent prognostic factors for overall survival. In conclusion, R-M regimen is an effective and well-tolerated combination treatment for PCNSLs, which warrants further evaluation in randomized trials.

Nutritional Status And Its Impact On The Occurance Of Complications In Children With Acute Lymbhoblastic Leukemia During 1Stinduction Chemotherapy: The Experience At Bp Koirala Memorial Cancer Hospital

Malnutrition is a common problem in cancer patients. It has been recognized as an important component to influence on tolerance to treatment, increased morbidity, poor prognosis, decreased quality of life and increased health care costs. Acute leukemia is the most common malignancy in children of which acute lymphoblastic leukemia accounts for majority of the cases (75%). Chemotherapy is the main treatment modality for acute lymphoblastic leukemia(ALL). Under nutrition can contribute to the incidence and severity of treatment side effects and increases the risk of infection, thereby reducing the chances of survival. Objectives: To evaluate pretreatment nutritional status (BMI) in children with ALL and its effects during first induction chemotherapy. Methodology: This observational study included sixty-two consecutive children with acute lymphoblastic leukemia, admitted in Haemato-Oncology Ward of BPKMCH over a period of 27 months (15thy May, 2015 to 15th July, 2017) were measured for height and weight to calculate BMI for assessing nutritional status at presentation. Children were grouped into 2 group: normal weight and underweight usingCDC BMI percentile chart by World Health Organization(WHO). Day to day observation and documentation were maintained to identify any side effects and complications over a period of first induction chemotherapy. Findings of the study: Among 62 cases, majority were male (66%). Three forth of the cases were B-cell ALL. More than 34 percent of the cases (27) had under- weight (BMI< 5thpercentile). Effects like very severe neutropenia, febrile neutropenia, infections, musculoskeletal problems, severe pancytopenia, G/I problems were noted mostly in children with underweight. Conclusion: Baseline nutritional status negatively influences in the occurrence of complications during induction chemotherapy in children with ALL. The nutritional support has to be personalized according to the nutritional status of the single patient.

Prospective study evaluating dynamic changes of cell-free HPV DNA in locoregional viral-associated oropharyngeal cancer treated with induction chemotherapy and response-adaptive treatment

Background Human papillomavirus (HPV)-associated oropharyngeal cancer (OPC) has a favorable prognosis which has led to efforts to de-intensify treatment. Response-adaptive de-escalated treatment is promising, however improved biomarkers are needed. Quantitative cell-free HPV-DNA (cfHPV-DNA) in plasma represents an attractive non-invasive biomarker for grading treatment response and post-treatment surveillance. This prospective study evaluates dynamic changes in cfHPV-DNA during induction therapy, definitive (chemo)radiotherapy, and post-treatment surveillance in the context of risk and response-adaptive treatment for HPV + OPC. Methods Patients with locoregional HPV + OPC are stratified into two cohorts: High risk (HR) (T4, N3, $$\ge$$ ≥ 20 pack-year smoking history (PYH), or non-HPV16 subtype); Low risk (LR) (all other patients). All patients receive induction chemotherapy with three cycles of carboplatin and paclitaxel. LR with ≥ 50% response receive treatment on the single-modality arm (minimally-invasive surgery or radiation alone to 50 Gy). HR with ≥ 50% response or LR with ≥ 30% and < 50% response receive treatment on the intermediate de-escalation arm (chemoradiation to 50 Gy with cisplatin). All other patients receive treatment on the regular dose arm with chemoradiation to 70 Gy with concurrent cisplatin. Plasma cfHPV-DNA is assessed during induction, (chemo)radiation, and post-treatment surveillance. The primary endpoint is correlation of quantitative cfHPV-DNA with radiographic response. Discussion A de-escalation treatment paradigm that reduces toxicity without compromising survival outcomes is urgently needed for HPV + OPC. Response to induction chemotherapy is predictive and prognostic and can select candidates for de-escalated definitive therapy. Assessment of quantitative cfHPV-DNA in the context of response-adaptive treatment of represents a promising reliable and convenient biomarker-driven strategy to guide personalized treatment in HPV + OPC. Trial registration This trial is registered with ClinicalTrials.gov on October 1st, 2020 with Identifier: NCT04572100.