NCMP-14. WHOLE BRAIN RADIOTHERAPY COMBINED WITH INTRATHECAL LIPOSOMAL CYTARABINE FOR LEPTOMENINGEAL METASTASIS – A SAFETY ANALYSIS AND VALIDATION OF THE EANO-ESMO CLASSIFICATION

BACKGROUND Although there is no proven standard therapy for leptomeningeal metastases (LM), treatment often includes intrathecal chemotherapy combined with whole brain radiation therapy (WBRT). Little is known on the toxicity of such combination therapies. We performed a retrospective safety analysis for the combination of intrathecal liposomal cytarabine with WBRT in patients with LM and validated the EANO-ESMO classification in this unique cohort. METHODS Treatment toxicities in patients diagnosed with LM between 2004 and 2014 were retrospectively analyzed according to the RTOG (Radiation Therapy Oncology Group) and NCI CTCAE V5.0 (Common Toxicity Criteria Adverse Events) toxicity criteria. Diagnostic criteria and treatment response as assessed by EANO-ESMO classification were correlated with survival by Kaplan Meier analysis and Breslow test. RESULTS 40 patients with LM who were treated with combined WBRT and intrathecal cytarabine, were identified. Ten patients (25%) experienced adverse events ≥ grade 3 according to the RTOG-toxicity criteria, in 22 patients (55%) CTCAE criteria ≥3 grade were detected. Median overall survival (mOS) was 124.0 days [72.9;175.1]. Median time to neurological progression was 52.0 days [41.1; 62.8]. When comparing the diagnostic criteria, patients with a positive CSF cytology (n=26) showed worse prognosis compared to patients with a negative CSF cytology (n=14) (mOS 84 days [44.0;124.0] versus 198.0 days [162.6;233.4] days, p=0.006, respectively). The EANO-ESMO response assessment correlated significantly with survival - “stable” (n=7) mOS 233.0 [76.5;389.5] days, “response” (n=10) mOS 206.0 [193.9;218.9] days, “progression” (n=17) mOS 45.0 [34.4;55.6] days, “suspicion of progression” (n=6) mOS 133.0 [65.8;200.2] days (overall, p< 0.001). CONCLUSIONS In this retrospective analysis, the treatment combination of WBRT and intrathecal liposomal cytarabine shows an acceptable safety profile. The EANO-ESMO classification for diagnosis and treatment response predicts survival

Correlation of Hematological Toxicity with the Bone Marrow Radiation Dose and Volume during Concurrent Chemo Radiation in Patients with Cervical Cancer

Aims & Objective: Hematological toxicity is common in patients with cervical cancer treated with concurrent chemo radiotherapy (CT-RT), so the purpose is to assess this hematological toxicity and correlate the toxicity with the dose and volume of bone marrow included in the field of radiation. Materials & Methods: Twenty five patients with histologically proven cervical cancer attending to our Cancer centre from July 2018-August 2019 were the subjects of this study. Patients were treated on 6 MV linear accelerator with a radical intent with concurrent chemotherapy using cisplatin 50 mg weekly. The planning CT was done for all the patients before the treatment and contouring of the pelvic bone marrow apart from other organs at risk was done. Hematological toxicity was assessed using RTOG common toxicity criteria weekly during and at 2 weeks after the completion of the treatment. Results: A total of 25 patients on CT-RT treatment were assessed. Sixteen patients were in locally advanced stage. The variation in HB, TLC, Platelets, and ANC counts from the baseline to 2 weeks after chemo radiotherapy were assessed. Grade II anemia was observed in 12 and Grade III in 2 patients. There were no toxicity as far as WBC and platelets were considered. There was also no correlation between the volume of bone marrow included in the field of irradiation and appearance of anemia. Conclusion: CT-RT for cervical cancer is safe and is associated with minimal hematological toxicity in the form of anemia. The toxicity is same for different volumes of bone marrow included in the field of irradiation with both 3DCRT as well as IMRT technique. The toxicity observed is probably contributed by Cisplatin.

Multi-institutional retrospective analysis of ultrahypofractionated radiotherapy for Japanese prostate cancer patients

To report outcomes and risk factors of ultrahypofractionated (UHF) radiotherapy for Japanese prostate cancer patients. This multi-institutional retrospective analysis comprised 259 patients with localized prostate cancer from 6 hospitals. A total dose of 35–36 Gy in 4–5 fractions was prescribed for sequential or alternate-day administration. Biochemical failure was defined according to the Phoenix ASTRO consensus. Toxicities were assessed using National Cancer Institute Common Toxicity Criteria version 4. Tumor control and toxicity rates were analyzed by competing risk frames. Median follow-up duration was 32 months (range 22–97 months). 2- and 3-year biochemical control rates were 97.7% and 96.4%, respectively. Initial prostate-specific antigen (p < 0.01) and neoadjuvant androgen deprivation therapy (p < 0.05) were identified as risk factors for biochemical recurrence. 2- and 3-year cumulative ≥ Grade 2 late genitourinary (GU) toxicities were 5.8% and 7.4%, respectively. Corresponding rates of gastrointestinal (GI) toxicities were 3.9% and 4.5%, respectively. Grade 3 rates were lower than 1% for both GU and GI toxicities. No grade 4 or higher toxicities were encountered. Biologically effective dose was identified as a risk factor for ≥ Grade 2 late GU and GI toxicities (p < 0.05). UHF radiotherapy offered effective, safe treatment for Japanese prostate cancer with short-term follow-up. Our result suggest higher prescribed doses are related to higher toxicity rates.

Bone Marrow-Sparing IMRT in Anal Cancer Patients Undergoing Concurrent Chemo-Radiation: Results of the First Phase of a Prospective Phase II Trial

Purpose: to investigate the role of selective avoidance of hematopoietically active BM within the pelvis, as defined with 18FDG-PET, employing a targeted IMRT approach, to reduce acute hematologic toxicity (HT) profile in anal cancer patients undergoing concurrent chemo-radiation. Methods: a one-armed two-stage Simon’s design was selected to test the hypothesis that BM-sparing approach would improve by 20% the rate of G0–G2 (vs. G3–G4) HT, from 42% of RTOG 0529 historical data to 62% (α = 0.05 and the β = 0.20). At the first stage, among 21 enrolled patients, at least 9 should report G0–G2 acute HT to further proceed with the trial. We employed 18FDG-PET to identify active BM within the pelvis. Acute HT was assessed via weekly blood counts and scored as per the Common Toxicity Criteria for Adverse Effects version 4.0. Results: from December 2017 to October 2019, 21 patients were enrolled. Maximum observed acute HT comprised 9% rate of ≥G3 leukopenia and 5% rate of ≥G3 neutropenia and anemia. Overall, only 4 out of 21 treated patients (19%) experienced ≥G3 acute HT. Conversely, 17 patients (81%) experienced G0–G2 events, way above the threshold set by the trial design. Conclusion: 18FDG-PET-guided BM-sparing IMRT was able to reduce acute HT in anal cancer patients treated with concomitant chemo-radiation. These results prompted us to conclude the second part of this prospective phase II trial.

Association between neutropenia and survival to nab-paclitaxel and gemcitabine in patients with metastatic pancreatic cancer

Neutropenia is a common side effect associated with nab-paclitaxel gemcitabine (Nab-Gem) therapy. We retrospectively investigated the association between neutropenia induced by first-line Nab-Gem and survival in metastatic pancreatic carcinoma patients. Metastatic pancreatic patients treated with first-line Nab-Gem were included in this retrospective analysis. Neutropenia was categorized using the National Cancer Institute Common Toxicity Criteria scale. Outcome measures were overall survival (OS), progression-free survival (PFS) and response rate. 115 patients were analyzed. Median PFS was 7 months (95% CI 5–8) for patients with grade ≥ 3 neutropenia and 6 months (95% CI 5–6) for patients with grade < 3 neutropenia [p = 0.08; hazard ratio (HR 0.68)]. Median OS was 13 months (95% CI 10–18) for patients with grade ≥ 3 neutropenia and 10 months (95% CI 8–13) for patients with grade < 3 neutropenia (p = 0.04; HR 0.44). In multivariate analysis, the occurrence of grade ≥ 3 neutropenia showed a statistically significant association with OS (HR 0.62; 95% CI 0.09–0.86; p = 0.05). Nab-Gem-induced neutropenia is associated with longer survival in metastatic pancreatic cancer patients.

Impact of single-heterozygous UGT1A1 on the clinical outcomes of irinotecan monotherapy after fluoropyrimidine and platinum-based combination therapy for gastric cancer: a multicenter retrospective study

Background It is unclear whether the UGT1A1 status, single heterozygous (SH) or wild type (WT), is associated with the efficacy and toxicity of irinotecan monotherapy in advanced gastric cancer (AGC). We investigated the association between clinical outcomes (efficacy and safety) and UGT1A1 status in patients who received irinotecan monotherapy. Methods We evaluated AGC patients who received irinotecan monotherapy between January 2011 and December 2017. Efficacy was assessed according to overall survival (OS) and progression-free survival (PFS). Toxicity was graded using the Common Toxicity Criteria for Adverse Events (version 4.0). Results A total of 100 patients were evaluated (62 and 38 patients with UGT1A1 WT and SH, respectively). In the WT and SH groups, the irinotecan dose was reduced in 19 (30.6%) and 18 (47.2%) patients (p = 0.135), respectively; treatment was delayed due to adverse events (AEs) in 19 (30.6%) and 13 (34.2%) patients (p = 0.826), respectively; the median PFS was 3.15 and 3.25 months (HR, 0.734; 95% CI 0.465–1.158; p = 0.184), respectively; and the median OS was 10.4 and 7.26 months (HR, 1.137; 95% CI 0.752–1.721; p = 0.543), respectively. Severe hematological AEs (Grade ≥ 3) were significantly more frequent in the SH group than in the WT group (63% vs. 36%; p = 0.008), while severe non-hematological AEs was not significantly different (16.0% vs. 6.5%; p = 0.173). Conclusion There was no significant difference in the efficacy of irinotecan monotherapy between UGT1A1 WT and UGT1A1 SH, but UGT1A1 SH was associated with a high frequency of severe hematological toxicity.

A perspective on the role of fugacity and activity for evaluating the PBT properties of organic chemicals and providing a multi-media synoptic indicator of environmental contamination

We present a perspective on how models based on the equilibrium criteria of fugacity and chemical activity can contribute to evaluation of persistence, bioaccumulation and toxicity criteria.

Life threatening pembrolizumabinduced myositis in a patient treated for advanced adenocarcinoma of the lung

The advent of immunotherapy in oncology has led to the emergence of a new spectrum of adverse effects. A number of these have the potential to contribute to life-threatening outcomes; and therefore require prompt identification and aggressive treatment to optimise management. In this report, we describe a case of pembrolizumab-induced CTCAE (common toxicity criteria for adverse events) grade 4 myositis in a non-small cell lung cancer patient.