Common Toxicity Criteria For Adverse Events Research Articles

Salvage Treatment of Nivolumab and Lenvatinib in Patients with Recurrent Hepatocellular Carcinoma

Background: The clinical efficacy of Lenvatinib (a multi‐kinase inhibitor) and Nivolumab (an immune checkpoint inhibitor) have been shown in the management of hepatocellular carcinoma (HCC). However, real-life experience data of HCC patients receiving the Nivolumab and Lenvatinib combination are scarce, especially those who experienced the first-line or even multi-line treatment. Methods: Recurrent HCC patients (n = 28) treated with Nivolumab plus Lenvatinib as salvage therapy in Hunan Provincial People's Hospital from December 2016 to March 31, 2020, were analyzed. All patients were treated with Nivolumab (3 mg/kg), and Lenvatinib (8 mg/day), and administered every three weeks. Demographics, clinical statistics, and start and end dates of combination therapy were collected and recorded. In addition, progression-free survival (PFS) and OS were calculated from the start of Nivolumab plus Lenvatinib. Treatment outcomes were scored based on the Common Toxicity Criteria for Adverse Events (CTCAE), version 4.0. SPSS17.0 software and GraphPad Prism were used for statistical analyses. Results: All the patients had portal vein tumor thrombus (PVTT) who were in Child-Pugh grade A and Barcelona Clinic Liver Cancer (BCLC) stage C. 11 patients (39.3%) were treated with sorafenib only, and 17 patients (60.7%) were treated with at least two lines of multi-target treatment. The disease control rate (CR+PR+SD) was 23/28 (82.1%), with the median overall survival (OS) and median progression-free survival (PFS) of 8.7 months and 5.7 months, respectively. Hyperbilirubinemia was the most common adverse event encountered with these combinations. However, no grade 3 or 4 toxicity was found in all HCC patients. Conclusions: The combination salvage therapy of Nivolumab and Lenvatinib was found effective in HCC patients, and most importantly, the side effects were controllable, and no grade 3 - 4 side effects were observed.

Dose-Volume Parameters to the Urinary Tract Sub-Volumes and Predictors of Genitourinary Acute Toxicity in a Phase 2 Clinical Trial Assessing MRI-Guided Prostate Boost for Localized Prostate Cancer - The Miami BlastM Trial.

The relationship between radiotherapy dose to the sub-volumes of the genitourinary (GU) tract and GU toxicity is poorly understood, particularly in prostate cancer patients treated with an intraprostatic dominant lesion (IDL) boost. While the use of IDL boost improves outcomes, it results in higher doses to GU structures and potentially increased toxicity. We investigated the association between dose-volume histogram (DVH) parameters for urinary tract sub-volumes and GU toxicity in the context of IDL boost in patients enrolled in the Miami BlastM Trial. DVH data were assessed for patients enrolled in the Miami BlastM, a randomized phase 2 trial (NCT20140627) evaluating upfront versus integrated IDL boost. IDL GTV boost consisted of either 12-14 Gy administered on day 1 or integrated boost of 2.4 Gy per fraction (91.2 Gy total, 98.5 Gy 2.0 Equiv), with the prostate receiving 76 Gy in 38 fractions. Bladder trigone (BTg) and urethra sub-volumes were contoured retrospectively on planning CT scans. GU toxicity was assessed using Common Toxicity Criteria for Adverse Events (CTCAE) version 4 and International Prostate Symptom Score (IPSS). DVHs of the bladder, BTg, bladder minus BTg, prostatic urethra, and bulbomembranous urethra were examined. The primary composite endpoint was CTCAE GU acute toxicity grade (G) ≥2 and/or IPSS increase of ≥10 from baseline. Secondary endpoints were GU acute toxicity G≥2, GU late toxicity G≥2, and IPSS increase of ≥10 from baseline. Univariable and multivariable logistic regression analyses were performed. A total of 129 patients treated between February 2015 and January 2022 were eligible for analysis. One hundred and one (78%) patients developed either GU acute toxicity G≥2 (68%) and/or an IPSS increase of ≥10 from baseline (30%). Less than 2% of patients developed GU toxicity G≥3. BTg V30 Gy was significantly associated with IPSS increase ≥10 (p = 0.046). The bulbomembranous urethral maximum dose was significantly associated with GU acute toxicity G≥2 and GU late toxicity G≥2 (p <0.05 for both). Average maximum and mean urethral doses were 88.9 and 81.5 Gy, respectively. The BTg maximum dose, V20 Gy, V30 Gy, and V40 Gy were not significantly associated with the primary composite endpoint (p = 0.56, 0.75, 0.89, 0.82, respectively). On multivariable analysis, a higher bulbomembranous urethral maximum dose was significantly associated with GU acute toxicity G≥2 and/or IPSS increase of ≥10 from baseline (p = 0.019). Our data suggest a dose-effect relationship between maximum doses to the bulbomembranous urethra and GU toxicity. A better understanding of RT-related changes to specific sub-volumes of the urethra and strategies to mitigate urethral dose could enhance the therapeutic ratio in prostate cancer patients treated with MRI-guided IDL boost.

Chemotherapy-Induced Nausea and Vomiting in Patients With Breast Cancer: Risk Factor and Predictive Model Using Classification and Regression Tree (CART).

Introduction Chemotherapy-induced nausea and vomiting (CINV) is a common and debilitating adverse effect of breast cancer chemotherapy. The incidence of CINV in the first cycle of chemotherapy is essential, as it sets the tone for anticipatory CINV and the overall patients' treatment experience. We aimed to investigate the risk factors of first cycle CINV in breast cancer patients and to develop a classification and regression tree (CART) model to predict its occurrence. Methods This is a cross-sectional study that nested in a prospective cohort. One hundred and thirty-seven female breast cancer patients receiving highly emetogenic chemotherapy were included. We used the Common Toxicity Criteria for Adverse Events (CTCAE) version 4.0 to assess patient-reported nausea and vomiting in the first chemotherapy cycle. The proportional difference of CINV between sociodemographic and clinicopathologic variables was analyzed using chi-square, and the strength and direction of the relationship with CINV were analyzed using bivariable logistic regression analysis. Multivariable logistic regression and CART analysis included variables with a p-value <0.250. Results The incidence of first-cycle CINV was 43.1%. The chi-square test revealed a significant association between insurance status and CINV (p<0.001) and between the stage at diagnosis and CINV (p<0.001). Underweight to normal body mass index (BMI) patients are significantly associated with an increased risk of first-cycle CINV (OR =2.17, 95% CI 1.03-4.56, p =0.041). In hierarchical order, three variables (stage at diagnosis, BMI, and age) were included in the CART model, which significantly influenced the probability of first cycle CINV. With an accuracy of 61.3%, the CART model had a sensitivity of 28.8%, a specificity of 85.9%, a positive predictive value of 60.7%, a negative predictive value of 61.5%, and an area under curve (AUC) of 0.602. Conclusion Breast cancer patients with an underweight to normal BMI have a higher risk of developing first-cycle CINV. Our CART model was better at identifying patients who would not develop CINV than those who would. The CART model may provide a simple and effective way to individualize patient care for first-cycle CINV.

Study Protocol STEREOLAB: Stereotactic Liver Ablation Assisted with Intra-Arterial CT Hepatic Arteriography and Ablation Confirmation Software Assessment.

This study aims to evaluate the technical efficacy and local tumor progression-free survival (LTPFS) of a standardized workflow for thermal ablation of colorectal liver metastases (CRLM) consisting of CT during hepatic arteriography (CTHA)-based imaging analysis, stereotactic thermal ablation, and computer-based software assessment of ablation margins. This investigator initiated, single-center, single-arm prospective trial will enroll up to 50 patients (≤ 5 CRLM, Measuring ≤ 5cm). Procedures will be performed in an angio-CT suite under general anesthesia. The primary objective is to estimate LTPFS with a follow-up of up to 2years and secondary objectives are analysis of the impact of minimal ablative margins on LTPFS, adverse events, contrast media utilization and radiation exposure, overall oncological outcomes, and anesthesia/procedural time. Adverse events (AE) will be recorded by CTCAE (Common Toxicity Criteria for Adverse Events), and Bayesian optimal phase-2 design will be applied for major intraprocedural AE stop boundaries. The institutional CRLM ablation registry will be used as benchmark for comparative analysis with the historical cohort. The STEREOLAB trial will introduce a high-precision and standardized thermal ablation workflow for CRLM consisting of CT during hepatic arteriography imaging, stereotactic guidance, and ablation confirmation. Trial Registration ClinicalTrials.gov identifier: (NCT05361551).

Evaluation of Pathological Response Rate and Complications of FOLFOX versus FLOT Regimen in Perioperative Chemotherapy for Resectable Gastric Cancer: A Prospective Study.

Previous studies have shown that the perioperative and postoperative chemotherapy can lead to an improvement in the prognosis of patients with resectable gastric cancer (GC). There is no preference for postoperative chemotherapy with the two common treatment regimens, FLOT and FOLFOX, in these patients. The aim of this study was to compare FOLFOX and FLOT regimens in perioperative chemotherapy in resectable GC based on pathological response and complications. This prospective cohort study was conducted on 112 patients with resectable GC who were admitted to Firozgar Hospital affiliated with Iran University of Medical Sciences, Tehran, Iran between 2021 to 2022. Given the inclusion criteria, 80 patients were enrolled in the present study. Patients were divided into 2 groups based on the type of treatment regimen, FOLFOX (40 patients) and FLOT (40 patients). Tumor response was classified using Mandard Tumor regression grading system criteria into five categories of TRG1 to 5. Also, the side effects were classified according to the National Cancer Institute Common Toxicity Criteria for Adverse Events (CTCAE) version 5.0. The rate of complete pathological response in FOLT group was significantly higher than FOLFOX group (35.0% vs 2.5%, p: 0.001). The frequency of neurological complications and hair loss in the FOLT group was significantly higher than the FOLFOX group (P<0.05). While no significant difference was observed in the frequency of hematological, Gastroenterological, hepatic, renal and stomatitis complications in the both groups (p>0.05). Our study showed that perioperative FLOT regimen has a better pathological response than FOLFOX regimen. The frequency of neurological complications and hair loss was significantly higher in patients treated with FLOT regimen. Thus, perioperative FLOT regimen may be recommended for treating GC patients.

Efficacy and safety of programmed cell death receptor 1 inhibition-based regimens in patients with pediatric malignancies: the real-world study in China.

Programmed death receptor 1 (PD-1) inhibition has shown durable response and mild adverse events (AEs) in adult malignancies. However, data on the clinical activity of PD-1 inhibition in pediatric patients are lacking. We comprehensively assessed the efficacy and safety of PD-1 inhibitor-based regimens for pediatric malignancies. We conducted a real-world, multi-institutional, retrospective analysis of pediatric malignancies treated with PD-1 inhibitor-based regimens. The primary endpoints were objective response rate (ORR) and progression-free survival (PFS). The secondary endpoints included disease control rate (DCR), duration of response (DOR), and AEs. The Kaplan-Meier method was used to calculate PFS and DOR. The National Cancer Institute Common Toxicity Criteria for AEs (version 5.0) were used to grade toxicity. A total of 93 and 109 patients were evaluated for efficacy and safety, respectively. For all efficacy-evaluable patients, PD-1 inhibitor monotherapy, combined chemotherapy, combined histone deacetylase inhibitor, and combined vascular endothelial growth factor receptor tyrosine kinase inhibitor cohorts, the ORR and DCR were 53.76%/81.72%, 56.67%/83.33%, 54.00%/80.00%, 100.00%/100.00%, and 12.50%/75.00%, respectively; the median PFS and DOR were 17.6/31.2 months, not achieved/not achieved, 14.9/31.2 months, 17.6/14.9 months, and 3.7/1.8 months, respectively; the incidence rate of AEs were 83.49%, 55.26%, 100.00%, 80.00%, and 100.00%, respectively. One patient in the PD-1 inhibitor-combined chemotherapy cohort discontinued treatment due to diabetic ketoacidosis. This largest retrospective analysis demonstrate that PD-1 inhibitor-based regimens are potentially effective and tolerable in pediatric malignancies. Our findings provide references for future clinical trials and practice of PD-1 inhibitors in pediatric cancer patients.

MP11-07 RADIOLIGAND THERAPY WITH 177 Lu-PSMA-I&amp;T IN PATIENTS WITH METASTATIC CASTRATION-RESISTANT PROSTATE CANCER: ONCOLOGICAL OUTCOMES AND TOXICITY PROFILE

You have accessJournal of UrologyCME1 Apr 2023MP11-07 RADIOLIGAND THERAPY WITH 177Lu-PSMA-I&T IN PATIENTS WITH METASTATIC CASTRATION-RESISTANT PROSTATE CANCER: ONCOLOGICAL OUTCOMES AND TOXICITY PROFILE Mehmet Onur Demirkol, Baris Esen, Melis Sen, Burcu Ucar, Sevgilay Kurtuldu, Nil Molinas Mandel, Sevil Bavbek, Okan Falay, Derya Tilki, and Tarik Esen Mehmet Onur DemirkolMehmet Onur Demirkol More articles by this author , Baris EsenBaris Esen More articles by this author , Melis SenMelis Sen More articles by this author , Burcu UcarBurcu Ucar More articles by this author , Sevgilay KurtulduSevgilay Kurtuldu More articles by this author , Nil Molinas MandelNil Molinas Mandel More articles by this author , Sevil BavbekSevil Bavbek More articles by this author , Okan FalayOkan Falay More articles by this author , Derya TilkiDerya Tilki More articles by this author , and Tarik EsenTarik Esen More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003226.07AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Prostate-specific membrane antigen (PSMA) targeted radioligand therapy (RLT) with 177Lu-PSMA-617 is associated with prolonged overall survival in patients with metastatic castration-resistant prostate cancer (mCRPC). Data regarding the oncological efficacy and toxicity profile of 177Lu-PSMA-I&T is limited. Herein, we aimed to investigate the oncological outcomes and toxicity profile of 177Lu-PSMA-I&T RLT in patients with mCRPC. METHODS: A total of 33 consecutive patients with mCRPC were treated with a total of 88 cycles (median 2 cycles, range 1-7) of 177Lu-PSMA-I&T RLT. The 177Lu-PSMA-I&T was given with a median activity of 7.5 GBq (IQR: 6.7 – 8.1) per cycle. Response to RLT were assessed according to prostate-specific antigen (PSA) changes and imaging response. Oncological outcomes were reported using clinical progression-free survival (cPFS), and overall survival (OS). Time interval from the first RLT cycle to any radiological or biochemical progression was considered clinical progression-free survival (cPFS). Common Toxicity Criteria for Adverse Events (CTCAE) criteria were utilized to assess toxicity. RESULTS: The mean patient age at the time of the first RLT cycle was 71.6 ± 10.7 years. Any PSA decline was detected in 22 (69%) cases after RLT. The number of patients achieving PSA declines of ≥30% and ≥50% were 18 (56%) and 11 (34%), respectively (Figure 1). The cPFS and OS after first cycle of RLT was 6.3 and 21.4 months, respectively. During RLT, nephrotoxicity occurred in 4 cases (12.1%); CTCAE grade according to estimated glomerular filtration rate worsening from I to II (n=2), II to III (n=1), III to IV (n=1). Six patients (18.2%) experienced a grade I/II myelotoxicity and 3 cases (9.1%) had grade III/IV myelotoxicity. CONCLUSIONS: 177Lu-PSMA-I&T RLT achieved a good PSA response (≥30%) in more than half of the patients with mCRPC with an acceptable toxicity profile. Further studies are required to assess the role of 177Lu-PSMA-I&T RLT in mCRPC. Source of Funding: European Urological Scholarship Programme through a 1-year research scholarship (to B.E.) © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e125 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Mehmet Onur Demirkol More articles by this author Baris Esen More articles by this author Melis Sen More articles by this author Burcu Ucar More articles by this author Sevgilay Kurtuldu More articles by this author Nil Molinas Mandel More articles by this author Sevil Bavbek More articles by this author Okan Falay More articles by this author Derya Tilki More articles by this author Tarik Esen More articles by this author Expand All Advertisement PDF downloadLoading ...

RISREAC Study: Assessment of Cutaneous Radiation Injury Through Clinical Documentation.

Radiation dermatitis (RD) occurs in 95% of patients receiving radiation therapy (RT) for cancer treatment, affecting 800 million patients annually. We aimed to demonstrate the feasibility of developing a historical RD cohort, Radiation Induced Skin Reactions (RISREAC) cohort. This retrospective study evaluated RD-related clinical documentation for 245 breast cancer patients who received RT at the University of Rochester Medical Center, to understand the RD progression, scoring, and management. All statistical analyses were performed at 0.05 level of significance. Clinician-documented RD severity was observed for 169 (69%) patients with a mean severity of 1.57 [1.46, 1.68]. The mean descriptor-based severity score of 2.31 [2.18, 2.45] moderately correlated (r = 0.532, P < 0.0001) with documented RD grade. Most patients (91.8%) received skin care treatment during RT, with 66.7% receiving more than 2 modalities. The RISREAC cohort is the first retrospective cohort established from clinical documentation of radiation-induced skin changes for the study of RD and cutaneous radiation injury (CRI). RD symptom descriptors were more reliably documented and suitable for all skin types compared to Radiation Therapy Oncology Group (RTOG) or Common Toxicity Criteria for Adverse Events (CTCAE) grades. A new descriptor-based scoring tool would be useful for RD and CRI.

CTNI-40. PHASE I TRIAL OF SULFASALAZINE COMBINED WITH STEREOTACTIC RADIOSURGERY FOR RECURRENT GLIOBLASTOMA: STUDY PROTOCOL FOR NCT04205357

Abstract Glioblastoma (GBM) is one of the most aggressive, radioresistant types of cancer with a dismal prognosis. Sulfasalazine (SAS) has shown tumor selective radiosensitizing properties in preclinical studies. The antioxidant glutathione (GSH) produced at high levels in glioma cells normally protects against radiation injury by scavenging reactive oxygen species produced during radiation therapy (RT). SAS blocks cysteine uptake through the xCT-channel, a rate-limiting step for GSH production. We have previously shown slowing of tumor growth and prolonged survival when SAS was combined with stereotactic radiosurgery (SRS) in vivo compared to either treatment alone. Our hypothesis is that SAS potentiates the efficacy of SRS for recurrent GBM with a low risk of adverse events (AE). The primary end-point is to establish the recommended dose for efficacy testing in phase II/III trials. This phase 1 dose-escalation trial utilizes a standard 3 + 3 design with 3-6 patients per cohort. Patients will be treated with oral SAS (1.5, 3.0, 4.5 or 6.0 g/day) 3 days prior to single session SRS. The SAS-dose will be escalated depending on the absence/presence of toxicity in the previous cohort of treated patients. If more than 1 of 3-6 patients ( ≥ 33 %) is experiencing grade 3 or higher toxicity levels, the study will be terminated. The dose below will be the recommended dose. Toxicity is graded using the Common Toxicity Criteria for Adverse Events (CTCAE) v5.0 recorded the first 30 days. Secondary end-points are assessments of 1) intratumoral GSH production (GSH-spectroscopy), 2) late AE utilizing 11C-MET-MRI-PET 3) changes in KPS/quality of life (FACT-Br), 4) need for steroidal treatment, 5) progression free and overall survival. Novel treatment modalities are urgently needed. This trial will establish the recommended dose for SAS repurposed as a radiosensitizer for a future phase 2/3 trial and may ultimately lead to improvement of current GBM treatment.

Hypofractionated radiotherapy after breast-conserving surgery: Clinical and dosimetric factors predictive of acute skin toxicity.

The purpose of this study was to evaluate acute skin toxicity in early breast cancer patients treated with hypofractionated radiotherapy (HFRT) after breast-conserving surgery and to identify factors predictive for grade ≥ 2 acute skin toxicity. Amonocentric retrospective study was carried out using cases treated between December 2017 and November 2020. We analyzed data from 202patients with early breast cancer treated with 3D hypofractionated RT (40.05 Gy in 15fractions) to the whole breast with or without regional lymph nodes, followed by 13.35 Gy in 5fractions to the tumor bed. Acute skin toxicity was monitored during RT according to CTCAE (common toxicity criteria for adverse events) scale. Univariate and multivariate analyses were performed to assess predictive factors of acute skin toxicity. Overall, there was no erythema in 9%, grade1 erythema in 64.5%, grade2 in 24%, and grade3 in 2.5%. No grade4 erythema was seen. Median delay between RT initiating and maximum skin reaction was 22days (range 4-44days). No patient interrupted treatment. In univariate analysis, the rate of acute skin toxicity grade 2---3 (G2-3) was significantly higher for patients with larger tumor size (p = 0.02), body mass index > 27 (p = 0.04), and time between chemotherapy (CT) and RT less than 20days (p = 0.01). Dosimetric risk factors for acute skin toxicity G2‑3 were breast volume > 800 cc (p = 0.000), boost volume > 18 cc (p = 0.002), V105% > 40 cc (p = 0.03), and Dmax > 56 Gy (p = 0.007). CT, trastuzumab, regional lymph node radiation, and age were not correlated with increased skin toxicity. In multivariate analysis, acute skin toxicity correlated with Tstage (p = 0.032), breast volume > 800 cc (p = 0.012), boost volume > 18 cc (p = 0.04), and Dmax > 56 Gy (p = 0.035). Our results confirm that whole breast with or without lymph nodes hypofractionated RT is safe and well tolerated. The factors strongly associated with adecreased risk of G2‑3 skin toxicity are T1, breast volume < 800 c, boost volume < 18 cc, and Dmax < 56 Gy. Long-term follow-up is needed to evaluate late toxicity.

Factores pronósticos de eficacia y seguridad que afectan a la supervivencia global de los pacientes con cáncer de próstata metastásico sometidos a tratamiento con [177Lu]Lu-PSMA-617: estudio en un único centro

BackgroundDetermining the efficacy, safety, and prognostic factors affecting overall survival (OS) among metastatic prostate cancer patients undergoing PSMA-targeted radioligand therapy (PRLT). MethodIn this retrospective study, from November 2016 and December 2019, 43 heavily pretreated (90.7% on 1st line androgen deprivation therapy (ADT), 53.5% on 2nd line ADT, 58.1% on docetaxel) metastatic prostate cancer patients with median age of 71 years (range: 51-88 years) were enrolled. Treatment cycles were repeated every 8 weeks (range: 6-12 weeks). To evaluate the biochemical response after each cycle, prostate specific antigen (PSA) levels were measured and analyzed according to the Prostate Cancer Working Group 3 (PCWG3) criteria cutoffs. Possible adverse events after therapy were retrospectively classified according to the Common Toxicity Criteria for Adverse Events (CTCAE) v.5.0. Kaplan-Meier and multivariable Cox proportional hazard regression analyses were used to identify factors associated with OS. ResultsA total of 112 cycles of PRLT with a median of 3 cycles (range: 1-6) and median administered activity per cycle of 6.29 GBq (range: 4.45-7.7 GBq) were used. PSA decline was observed in 65.1% of patients, and best PSA decline of ≥50% and ≥90% were achieved in 39.5% and 23.3% of patients, respectively. Major (grade III) anemia and thrombocytopenia occurred in 11.6% and 7% of patients, respectively. Median OS and median PSA progression-free survival were 52 and 20 weeks, respectively. In univariate analysis, baseline hemoglobin <11.2 g/dL, baseline platelets count ≥327,000/μL, PSA decline <20.94% after first cycle of therapy, Eastern Cooperative Oncology Group (ECOG) >2, baseline PSA ≥115 ng/ml, cumulative dose of 177Lu-PSMA <12.95 GBq, initial alkaline phosphatase ≥196.5 U/L, initial lactate dehydrogenase ≥380 U/L and superscan pattern in bone scintigraphy were associated with worse OS. In multivariable Cox regression analysis, higher baseline platelet count, lower baseline hemoglobin, superscan pattern, and lower cumulative dose of 177Lu-PSMA remained significant predictors of poor OS. ConclusionPRLT with 177Lu-PSMA is well-tolerated and effective in metastatic prostate cancer patients who have no other treatment options available. The novel prognostic markers found in this study (high platelet count, superscan pattern) were associated with poor overall survival.

HGG-16. Final analysis of the HIT-HGG-2007 trial (ISRCTN19852453): Significant survival benefit for pontine and non-pontine pediatric high-grade gliomas in comparison to previous HIT-GBM-C/-D trials.

The aim of the HIT-HGG-2007 trial (ISRCTN19852453) was to demonstrate therapeutic non-inferiority of temozolomide radiochemotherapy for pediatric patients (3-18 years) with high-grade gliomas (pedHGG) in comparison to the cisplatinum-based radiochemotherapy of the two previous clinical trials HIT-GBM-C/-D. Between 06/2009 and 12/2016, 456 patients were enrolled at 79 centers in Germany, Austria, and Switzerland (n=18 dropouts, remaining patients for confirmatory analysis: n=438). 438 patients from HIT-GBM-C/-D served as historical control. All pedHGG diagnoses had been confirmed by central neuroradiological and neuropathological review. Primary objective was achieved since non-inferiority of HIT-HGG-2007 in comparison to HIT-GBM-C/-D as indicated by 6 months event-free survival (EFS) was statistically confirmed (p=0.0125). Statistical survival analyses even revealed a better overall survival (OS) and EFS for HIT-HGG-2007 patients in comparison to their HIT-GBM-C/-D counterparts (EFS: p<0.0001; OS: p=0.0328). While EFS subgroup analyses for pontine and non-pontine pedHGG also showed a better survival of HIT-HGG-2007 patients (median EFS pontine pedHGG: 8.2 (n=152; confidence interval (CI): 7.6-9.4) versus 6.2 (n=170; CI: 5.5-6.9) months, p=0.0079; median EFS non-pontine pedHGG: 10.7 (n=276; CI: 9.6-12.4) versus 7.4 (n=267; CI: 6.4-9.2) months, p<0.0001), OS was only improved in HIT-HGG-2007 patients with non-pontine pedHGG (median OS non-pontine pedHGG: 19.3 (CI: 16.8-23.3) versus 16.2 (CI: 14.2-19.1) months; p=0.0181) but not with pontine pedHGG (median OS pontine pedHGG: 11.4 months versus 11.3 months, p=0.4021) Toxicity profile of HIT-HGG-2007 seemed very favorable with most CTCAE (common toxicity criteria adverse event) ≥ grade 3 as hematological toxicity, hepatotoxicity, and neurotoxicity. Less toxicity was observed during concomitant radiochemotherapy in comparison to HIT-GBM-C/-D. Further subgroup survival analyses as well as the assessment of the impact of MGMT promoter methylation are ongoing. In conclusion, our data show non-inferiority of the HIT-HGG-2007 trial with increased survival and less toxicity when compared with previous trials HIT-GBM-C/-D.

Metronomic chemotherapy using oral cyclophosphamide and bevacizumab for recurrent cervical cancer: A multi-institutional retrospective study

No standard chemotherapy is available after disease progression or anaphylaxis during platinum chemotherapy among patients with recurrent cervical cancer. Here we report the efficacy and toxicities of metronomic chemotherapy consisting of 50 mg of oral cyclophosphamide (CPA) daily and intravenous 15 mg/kg of bevacizumab (BEV) repeated every 3 weeks (CPA-BEV). Treated patients were retrospectively reviewed. Adverse events and response rates were recorded according to the Common Toxicity Criteria for Adverse Events (CTCAE) ver 5.0 and Response Evaluation Criteria In Solid Tumors ver 1.1, respectively. Eleven patients had been treated with CPA-BEV between 2016 and 2021.The pathologic types were squamous cell carcinoma in seven patients, adenocarcinoma in three, and large cell neuroendocrine carcinoma in one. Nine patients had primary concurrent chemoradiotherapy (CCRT). Five patients received more than one prior chemotherapy (excluding CCRT). Six patients had progressive disease during prior platinum-based chemotherapy, four patients recurred within 6 months of the last platinum administration, and one patient had platinum anaphylaxis. Grade 3 or more hematologic toxicities and grade 2 or more non-hematological toxicities were observed in one with grade 3 neutropenia and in one with grade 2 proteinuria, respectively. The median duration of chemotherapy was 2.8 months (range 0.2–30.6 months). One patient had CR but none had PR. Median progression-free survival was 2.8 months (95 %CI: 2.1–10.7 months), and median overall survival was 13.6 months (95 %CI: 8.4–33.7 months). In conclusion, the CPA-BEV regimen showed favorable antitumor activity with minimal toxicity and is promising candidate for second-line chemotherapy.

Identifying Patients Whose Symptoms Are Underrecognized During Treatment With Breast Radiotherapy

Understanding whether physicians accurately detect symptoms in patients with breast cancer is important because recognition of symptoms facilitates supportive care, and clinical trials often rely on physician assessments using Common Toxicity Criteria for Adverse Events (CTCAE). To compare the patient-reported outcomes (PROs) of patients with breast cancer who received radiotherapy from January 1, 2012, to March 31, 2020, with physicians' CTCAE assessments to assess underrecognition of symptoms. This cohort study included a total of 29 practices enrolled in the Michigan Radiation Oncology Quality Consortium quality initiative. Of 13 725 patients with breast cancer who received treatment with radiotherapy after undergoing lumpectomy, 9941 patients (72.4%) completed at least 1 PRO questionnaire during treatment with radiotherapy and were evaluated for the study. Of these, 9868 patients (99.3%) were matched to physician CTCAE assessments that were completed within 3 days of the PRO questionnaires. Patient and physician ratings of 4 symptoms (pain, pruritus, edema, and fatigue) were compared. We used multilevel multivariable logistic regression to evaluate factors associated with symptom underrecognition, hypothesizing that it would be more common in racial and ethnic minority groups. Of 9941 patients, all were female, 1655 (16.6%) were Black, 7925 (79.7%) were White, and 361 (3.6%) had Other race and ethnicity (including American Indian/Alaska Native, Arab/Middle Eastern, and Asian), either as self-reported or as indicated in the electronic medical record. A total of 1595 (16.0%) were younger than 50 years, 2874 (28.9%) were age 50 to 59 years, 3353 (33.7%) were age 60 to 69 years, and 2119 (21.3%) were 70 years or older. Underrecognition of symptoms existed in 2094 of 6781 (30.9%) observations of patient-reported moderate/severe pain, 748 of 2039 observations (36.7%) of patient-reported frequent pruritus, 2309 of 4492 observations (51.4%) of patient-reported frequent edema, and 390 of 2079 observations (18.8%) of patient-reported substantial fatigue. Underrecognition of at least 1 symptom occurred at least once for 2933 of 5510 (53.2%) of those who reported at least 1 substantial symptom. Factors independently associated with underrecognition were younger age (younger than 50 years compared with 60-69 years: odds ratio [OR], 1.35; 95% CI, 1.14-1.59; P < .001; age 50-59 years compared with 60-69 years: OR, 1.19; 95% CI, 1.03-1.37; P = .02), race (Black individuals compared with White individuals: OR, 1.56; 95% CI 1.30-1.88; P < .001; individuals with Other race or ethnicity compared with White individuals: OR, 1.52; 95% CI, 1.12-2.07; P = .01), conventional fractionation (OR, 1.26; 95% CI, 1.10-1.45; P = .002), male physician sex (OR, 1.54; 95% CI, 1.20-1.99; P = .002), and 2-field radiotherapy (without a supraclavicular field) (OR, 0.80; 95% CI, 0.67-0.97; P = .02). The results of this cohort study suggest that PRO collection may be essential for trials because relying on the CTCAE to detect adverse events may miss important symptoms. Moreover, since physicians in this study systematically missed substantial symptoms in certain patients, including younger patients and Black individuals or those of Other race and ethnicity, improving symptom detection may be a targetable mechanism to reduce disparities.

Abstract P1-13-08: Patterns of adjuvant endocrine therapy, discontinuations, toxicities and quality of life: Development of a model for early discontinuation using the CANTO cohort

Abstract Abstract. Long-term adherence to adjuvant endocrine therapy (ET, tamoxifen and aromatase inhibitors) is paramount for patients with early-stage breast cancer. Adherence to adjuvant endocrine therapy is hampered by numerous side effects associated with sustained estrogen deprivation. We aimed to describe recent real-world patterns of therapy, patients’ discontinuations of ET, toxicities, quality of life (QoL) and to develop a predictive model of early ET discontinuation. Methods. We used the first 9595 patients of the French CANTO cohort (NCT01993498), to evaluate among 6238 premenopausal and postmenopausal patients with HR+/HER2- stage I-III BC, who were prescribed adjuvant ET: a. treatment patterns of adjuvant ET including change of ET prescription during the follow-up course b. ET-associated toxicities and c. impact on QoL. Independent variables included medical history and toxicities as measured by : Common Toxicity Criteria Adverse Events (CTCAE) v4, Patient-Reported Outcomes (PROs) including European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaires (QLQ-C30) and Breast Cancer Module (BR23), and Hospital Anxiety and Depression Scale (HADS). Treatment discontinuation and treatment change were determined on the basis of patient’s declaration and medical decisions reported in the CANTO eCRF. We used patient data at 4 months from therapy initiation to train and evaluate on a held-out test set a machine-learning model (gradient-boosted trees) that is predictive of time to early discontinuation i.e. permanent discontinuation before four years of additional therapy. Results. 4052 post-menopausal patients and 2186 premenopausal patients were included in this analysis. Median follow-up after ET initiation is 3 years and 2 months. 86% of post-menopausal patients were prescribed a non-steroidal AI initially and 92% of premenopausal patients received tamoxifen first. Discontinuation rate of the first adjuvant endocrine therapy at 1 year was 14% and 10% in premenopausal and post-menopausal patients, respectively. Among 741 post-menopausal and 340 premenopausal patients who started a second ET, discontinuation of the second prescribed adjuvant ET at 1 additional year of therapy is 30% in both populations. Patients who switched from a first adjuvant ET to a second or further one continued to have more treatment-related toxicities and associated decrements in QoL. Exclusions due to data completeness and outcome definition led to 5331 patients being used for the model (4264 in the training set and 1067 in the validation set). In that population, the permanent discontinuation rate at 3 years is 6%. Our prediction model of time to early discontinuation obtains a C-index of 0.78 in the held-out validation set. Conclusion. Tolerability and continued adherence to ET remains a challenge for many patients. Early discontinuation models may assist in identifying patients who are likely to interrupt their adjuvant ET. Adapted clinical management, including robust support and management of toxicities, as well as new and more tolerable adjuvant endocrine therapies may improve the clinical outcomes of these patients. Citation Format: Felix Balazard, Aurélie Bertaut, Élise Bordet, Stéphane Mulard, Julie Blanc, Nathalie Briot, Gautier Paux, Asma Dhaini Merimeche, Olivier Rigal, Charles Coutant, Marion Fournier, Christelle Jouannaud, Patrick Soulie, Florence Lerebours, Paul-Henri Cottu, Olivier Tredan, Laurence Vanlemmens, Christelle Levy, Marie-Ange Mouret-Reynier, Mario Campone, Keri J. S. Brady, Medha Sasane, Megan Rice, Catherine Coulouvrat, Anne-Laure Martin, Alexandra Jacquet, Ines Vaz-Luis, Christina Herold, Barbara Pistilli. Patterns of adjuvant endocrine therapy, discontinuations, toxicities and quality of life: Development of a model for early discontinuation using the CANTO cohort [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P1-13-08.

Patterns of relapse following hippocampal avoidance prophylactic cranial irradiation for small cell lung carcinoma.

BackgroundHippocampal avoidance techniques are an evolving standard of care for patients undergoing cranial irradiation. Our aim was to assess the oncological outcomes and patterns of failure following hippocampal avoidance prophylactic cranial irradiation (HA-PCI) as a standard of care in unselected patients with both limited and extensive stage small cell lung carcinoma.Materials and methodsConsecutive patients with small cell lung carcinoma with a complete (limited stage) or good partial (extensive stage) response following chemotherapy were eligible to receive HA-PCI, with a total dose of 25 Gray in 10 fractions. All patients had a negative baseline MRI brain scan with gadolinium prior to HA-PCI. Patients had baseline and follow up Common Toxicity Criteria Adverse Event assessments. Following completion of HA-PCI, all patients had three-monthly MRI brain scans with gadolinium until confirmation of intracranial relapse, as well as three-monthly CT of the chest, abdomen and pelvis. Overall and progression-free survival were calculated using the Kaplan-Meier method.ResultsA total of 17 consecutive patients, 9 men and 8 women, with a mean age of 70 years received HA-PCI between May 2016 and June 2020 after completion of their initial chemotherapy. There were no Grade 4 or greater adverse events. No patient had an isolated hippocampal avoidance zone relapse alone; three of 17 patients had multifocal relapses that included the hippocampal avoidance zone.ConclusionIn our series, there were no hippocampal only relapses and we conclude that HA-PCI is a safe alternative to standard PCI in the setting of small cell lung cancer.

Hyperbaric oxygen treatment of mandibular osteoradionecrosis: Combined data from the two randomized clinical trials DAHANCA-21 and NWHHT2009-1

PurposeOsteoradionecrosis (ORN) of the mandible is a serious complication of head and neck radiotherapy. This study aims to investigate the effect of hyperbaric oxygen (HBO) treatment on ORN in two randomized, controlled multicentre trials. Methods and materialsPatients with ORN with indication for surgical treatment were randomised to either group 1: surgical removal of necrotic mandibular bone supplemented by 30 pre- and 10 postoperative HBO exposures at 243 kPa for 90 min each, or group 2: surgical removal of necrotic bone only. Primary outcome was healing of ORN one year after surgery evaluated by a clinically adjusted version of the Common Toxicity Criteria of Adverse Events (CTCAE) v 3.0. Secondary outcomes included xerostomia, unstimulated and stimulated whole salivation rates, trismus, dysphagia, pain, Activities of Daily Living (ADL) and quality of life according to EORTC. Data were combined from two separate trials. Ninety-seven were enrolled and 65 were eligible for the intent-to-treat analysis. The 33% drop-out was equally distributed between groups. ResultsIn group 1, 70% (21/30) healed compared to 51% (18/35) in group 2. HBO was associated with an increased chance of healing independent of baseline ORN grade or smoking status as well as improved xerostomia, unstimulated whole salivary flow rate, and dysphagia. Due to insufficient recruitment, none of the endpoints reached a statistically significant difference between groups. ADL data could only be obtained from 50 patients. ConclusionHyperbaric oxygen did not significantly improve the healing outcome of osteoradionecrosis after surgical removal of necrotic bone as compared to standard care (70% vs. 51%). This effect is not statistically significant due to the fact that the study was underpowered and is therefore prone to type II error.

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

Abstract 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&amp;lt; 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

Efficacy, safety and prognostic factors affecting overall survival among metastatic prostate cancer patients undergoing treatment with 177Lu-PSMA-617: A single center study

BackgroundDetermining the efficacy, safety, and prognostic factors affecting overall survival (OS) among metastatic prostate cancer patients undergoing PSMA-targeted radioligand therapy (PRLT). MethodIn this retrospective study, from November 2016 and December 2019, 43 heavily pretreated (90.7% on 1st line androgen deprivation therapy (ADT), 53.5% on 2nd line ADT, 58.1% on docetaxel) metastatic prostate cancer patients with median age of 71 years (range: 51−88 years) were enrolled. Treatment cycles were repeated every 8 weeks (range: 6–12 weeks). To evaluate the biochemical response after each cycle, prostate specific antigen (PSA) levels were measured and analyzed according to the Prostate Cancer Working Group 3 (PCWG3) criteria cutoffs. Possible adverse events after therapy were retrospectively classified according to the Common Toxicity Criteria for Adverse Events (CTCAE) v.5.0. Kaplan-Meier and multivariable Cox proportional hazard regression analyses were used to identify factors associated with OS. ResultsA total of 112 cycles of PRLT with a median of 3 cycles (range: 1–6) and median administered activity per cycle of 6.29 GBq (range: 4.45–7.7 GBq) were used. PSA decline was observed in 65.1% of patients, and best PSA decline of ≥50% and ≥90% were achieved in 39.5% and 23.3% of patients, respectively. Major (grade III) anemia and thrombocytopenia occurred in 11.6% and 7% of patients, respectively. Median OS and median PSA progression-free survival were 52 and 20 weeks, respectively. In univariate analysis, baseline hemoglobin <11.2 g/dL, baseline platelets count ≥327,000/μL, PSA decline <20.94% after first cycle of therapy, Eastern Cooperative Oncology Group (ECOG) >2, baseline PSA ≥ 115 ng/mL, cumulative dose of 177Lu-PSMA <12.95 GBq, initial alkaline phosphatase ≥196.5 U/L, initial lactate dehydrogenase ≥380 U/L and superscan pattern in bone scintigraphy were associated with worse OS. In multivariable Cox regression analysis, higher baseline platelet count, lower baseline hemoglobin, superscan pattern, and lower cumulative dose of 177Lu-PSMA remained significant predictors of poor OS. ConclusionPRLT with 177Lu-PSMA is well-tolerated and effective in metastatic prostate cancer patients who have no other treatment options available. The novel prognostic markers found in this study (high platelet count, superscan pattern) were associated with poor overall survival.

English

BACKGROUND Chemotherapy-induced nausea and vomiting (CINV) is a frequent and feared adverse effect of cancer chemotherapy. International guidelines recommend combinations of 5-hydroxytryptamine type 3 (5-HT3) receptor antagonists, dexamethasone, and/or neurokinin-1 (NK1) receptor antagonists for the control of CINV in patients receiving highly emetogenic chemotherapy (HEC) as a part of their treatment. Even though, nausea in delayed period is less controlled and poses a major concern for these patients. METHODS This open label, prospective study was conducted in a rural medical college in Etawah District in Uttar Pradesh, India from November 2017 to November 2018 over a period of 1 year to observe the efficacy of low dose (5 mg OD) olanzapine in combination with standard anti-emetic regimen for the prevention of CINV. Olanzapine is a food and drug administration (FDA) approved antipsychotic drug that has anti-emetic activity and has shown to improve CINV. Low dose olanzapine along with a standard combination of ondansetron, dexamethasone and aprepitant was given to patients receiving highly emetogenic chemotherapy (Cisplatin &gt;70 mg/m2 or doxorubicin-cyclophosphamide combination). CINV was assessed using common toxicity criteria of adverse events (CTCAE) version 5.0. RESULTS Complete response to nausea was observed in 90.90 %, 60.60 % and 54.54 % in acute, delayed and overall period respectively. Complete response to vomiting was observed in 96.96 %, 69.69 % and 66.66 % in acute, delayed and overall period respectively. Complete response to Grade-2 (or above) nausea was observed in 96.96 %, 93.93 % and 90.90 % in acute, delayed and overall period, respectively. Daytime Grade -3 somnolence which was seen in 2/33 patients (6.06 %) was attributable to olanzapine. Patients receiving olanzapine were more likely to have complete response of nausea and emesis in the early, late, and overall assessment periods especially of higher grade (G2 and G3). CONCLUSIONS The authors concluded that low dose olanzapine 5 mg OD combined with an NK1- receptor antagonist, a 5-HT3–receptor antagonist, and dexamethasone is safe and efficacious in the prevention of CINV in patients receiving HEC. KEYWORDS Olanzapine, Low Dose, CINV, HEC