Common Toxicity Criteria For Adverse Events Research Articles

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< 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

Determinants for Oral Mucositis in Allogeneic Hematopoietic Stem Cell Transplantation: Prospective Evaluation and Risk Analysis

Background: Oral mucositis (OM), secondary to mucosal barrier injury of pre-hematopoietic stem cell transplantation (HSCT) conditioning, is a common and painful toxicity of transplantation. Mucositis has been associated with increased risk for infections, hospitalization, analgesia and total parenteral nutrition use, and higher costs. However, prevalence and incidence data for mucositis are inconsistent and underreported. We set to prospectively identify risk factors for oral mucositis in patients undergoing allogeneic HSCT.Methods: OM was prospectively evaluated on a weekly basis in patients undergoing allogeneic HSCT. The grade of OM was determined based on the National Cancer Institute Common Toxicity Criteria for Adverse Events (CTCAE) scale (v. 4.0). Severe OM was defined as grade 2 or higher. Conditioning regimens were evaluated individually and according to intensity; myeloablative (MAC), reduced intensity (RIC) or reduced toxicity (RTC). The latter category included only patients receiving Fludarabine and Treosulfan (Flu/Treo). Variables associated with severe OM (p<0.05) were initially identified by univariate analysis (Chi-square and Mann Whitney U tests) and then analyzed in a multivariate logistic regression model. Cox and Fine and Gray regression models were used to study the association between severe OM and overall survival or nonrelapse mortality, respectively.Results: A total of 95 patients who underwent an allogeneic HSCT from 2016 to 2017 were included. Median age was 61 (range 19-75). Leading indications for HSCT were acute myeloid leukemia (51%), followed by myelodysplastic syndrome (15%), and non-Hodgkin lymphoma (12%). The majority of patients had a comorbidity score ≥3 (51%), were exposed to systemic antibiotics preceding transplantation (53%), and had no history of recent smoking (86.%). Donors were primarily HLA matched unrelated (51.1%) or HLA matched siblings (40%). RIC, MAC, and RTC regimens were used in 41%, 34%, and 25% of the patients, respectively. Methotrexate (MTX) (72.6%) or Mycophenolate mofetil (MMF) (27.4%), in conjunction with Cyclosporine, were given for graft versus host disease (GVHD) prophylaxis. Median follow-up was 165 days (95% CI 130-200).Median OM grade was 2 (range 0-4), with 65% of the patients experiencing severe mucositis. Median time from HSCT to OM and duration of OM were 8 days (1-14) and 10 days (2-40), respectively. Patients receiving Flu/Busulfan (Bu)-4 days (Flu/Bu4) were more likely to develop severe OM (91% vs. 9%, p<0.01), while among those conditioned with Flu/Treo, 29% had severe OM vs. 71% who did not (p<0.01) (Figure). In a univariate analysis, considering a broad range of patient, disease, and transplant characteristics (Table), only a history of recent smoking (19% vs. 3%, p=0.028), exposure to antibiotics in the preceding month pre-HSCT (61% vs. 39%, p=0.049), and use of MTX for GVHD prophylaxis (85% vs. 49., p<0.001) were associated with severe mucositis. Patients receiving RTC (i.e. Flu/Treo conditioning) had lower rates of severe OM compared to both RIC and MAC (p<0.001). Pre-HSCT albumin levels, obesity, and a low estimated glomerular filtration rate (eGFR) were not associated with OM. In a multivariate logistic regression model use of MTX vs. MMF had an increased risk for severe OM (odds ratio [OR] 11.6 [95% CI 3.2-42.4], p<0.001); compared to MAC, the risk for severe OM was reduced with RTC (OR 0.1 [0.0-0.4], p=0.001. OR for recent smoking was 6.8 (0.7-64.5), with a trend toward statistical significance (p=0.09). Severe OM was not associated with a decrease in short term overall survival (HR 0.59 [95% CI 0.2-1.5] or increase in non-relapse morality (HR 0.51 [0.1-2]).Conclusion: Our findings suggest that administration of Fludarabine and Treosulfan is an appealing option for conditioning since the risk for oral toxicity is low while intensity is high. Though having a borderline statistical significance, peri-transplantation smoking emerges as an important risk factor for oral mucositis. Therefore, patient counseling about smoking could potentially lower rates of mucositis. In contrast to previous reports, obesity and pre-HSCT albumin and reduced eGFR were not associated with mucositis in our cohort. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Combined treatment with iodine-125 (125I) seed strand and transarterial chemoembolization (TACE) plus lenvatinib with anti-PD-1 antibodies in patients with unresectable hepatocellular carcinoma (uHCC) and portal vein tumor thrombus (PVTT): Real-world experience in China.

e16152 Background: We reviewed real-world outcomes for patients with uHCC and PVTT receiving TACE with 125I seed and stent implantation combined with lenvatinib plus anti-PD-1 antibodies. Methods: We retrospectively reviewed medical records from 62 consecutive adult (≥18 to ≤75 years) patients with HBV-related HCC and type III and IV PVTT with Child-Pugh class A or B liver function and ECOG performance status of 0-2 who received 125I seed strand and stent implantation combined with TACE at our center between November 2018 and May 2020. Patients were divided into two groups; those who had received adjuvant lenvatinib plus anti-PD-1 inhibitors, initiated 3 days after the first interventional procedure (Group A; n=18), and those who only received locoregional therapy (Group B; n=44). Propensity score matching (PSM) with a 1:1 ratio was used to reduce selection bias. Tumor response, progression-free survival (PFS, time from the first interventional procedure to progression or death for both Group A and Group B) and time-to-progression (TTP) were assessed using the modified Response Evaluation Criteria in Solid Tumors (mRECIST). Time to untreatable progression (TTUP) and overall survival (OS) were also assessed. Adverse events (AEs) were graded according to the Common Toxicity Criteria for Adverse Events (CTCAE) v4.0. Results: PSM resulted in 15 matched pairs of patients, and baseline demographic parameters were comparable between the two groups. The median follow-up time was 12.4 ± 4.6 and 9.4 ± 4.8 months for patients in Groups A (n=15) and B (n=15) after PSM, respectively. Compared with patients in Group B, those in Group A had a higher overall response rate (66.7 vs. 18.2%; p=0.001) and disease control rate (72.2 vs. 43.2%; p=.038) and a longer median PFS, TTP, TTUP and OS (Table). No serious complications related to locoregional procedures were reported in either group. In Group A, 13% (n=2) of patients experienced ≥1 AE but the majority were Grade &lt;3; one patient had Grade 2 hyperthyroidism and one had Grade 2 enteritis, which were both considered related to immunotherapy. Conclusions: These real-world data show that 125I seed strand and stent implantation combined with TACE plus adjuvant lenvatinib and anti-PD-1 antibodies led to better treatment responses and survival outcomes compared with locoregional treatment alone in patients with uHCC and PVTT, with an acceptable safety profile. Summary of survival outcomes in propensity score matched groups.[Table: see text]

Abstract GS3-07: Identifying patients whose symptoms are under-recognized during breast radiotherapy: Comparison of patient and physician reports of toxicity in a multicenter cohort

Abstract BACKGROUND: Evaluating whether physicians (MDs) accurately detect symptoms in patients (pts) is important because recognition of symptoms facilitates supportive care and because clinical trials often rely on MD assessments using the Common Toxicity Criteria for Adverse Events (CTCAE). METHODS: Breast cancer pts who received radiotherapy (RT) after lumpectomy at 29 practices were enrolled in a quality initiative, MROQC. Of 13,725 pts who completed RT between 1/1/2012 and 3/31/2020, 9,941 completed at least one pt-reported outcomes (PRO) questionnaire during RT. Where MD CTCAE assessments were available within 3 days of PRO evaluation, pt and MD ratings of 4 symptoms were compared. Pts reported breast pain via an approved modification of the Brief Pain Inventory, asking for ratings in the last 24 hours of pain at its worst, least, average, and “right now.” MDs were deemed to under-recognize pain when pts reported moderate pain (score 4-6) but MDs graded pain as 0 (absent) on the CTCAE, or when pts reported severe pain (score 7-10) but MDs’ CTCAE grade was ≤1. Bother from pruritis and edema were measured by modified scaled measures adapted from the Skindex. MDs were deemed to under-recognize pruritus and edema if they graded these as absent (grade 0) when pts reported bother often or all of the time from itching or swelling, respectively. MDs were deemed to under-recognize fatigue if they graded fatigue as absent (grade 0) when pts reported having significant fatigue most of the time or always.We describe the proportion of pts for whom under-recognition of at least 1 of these 4 symptoms occurred at least once during the treatment course and use multivariable logistic regression to evaluate predictors of this under-recognition, hypothesizing that it would be more common in racial minorities. RESULTS: 3,434/9,940 pts (34.5%) reported substantial breast pain, 3,039/9,923 (30.6%) frequent bother from pruritus, 2,363/9,906 (23.9%) frequent bother from edema, and 2,209/8,860 (24.9%) severe fatigue. We could evaluate under-recognition in 9,868 pts, with 37,593 independent paired observations of pt and MD reports (35,797 on the same date and 1,796 within 3 days). Under-recognition existed in 2,094/6,781 (30.9%) observations of pt-reported moderate/severe pain, 748/2,039 (36.7%) of pt-reported frequent pruritis, 2,309/4,492 (51.4%) of pt-reported frequent edema, and 390/2,079 (18.8%) of pt-reported severe fatigue. Under-recognition of at least 1 of these 4 symptoms occurred at least once during the pt’s treatment course for 2,933/5,510 (53.2%) of the pts who reported at least 1 substantial symptom during RT.Factors independently associated with under-recognition were (Table): younger age (OR=1.4 and 1.2 for &amp;lt;50 and 50-59 vs. 60-69, respectively), black or other race (OR=1.9 and 1.8 vs white, respectively), conventional fractionation (OR=1.2), not having a supraclavicular field (OR=1.3) and being treated at an academic center (OR=1.1). CONCLUSIONS: PRO collection appears essential for trials because relying on the CTCAE to detect adverse events may miss important symptoms. Moreover, since MDs systematically miss substantial symptoms in certain patients, including pts who are younger or of black or other race, improving symptom detection may be a targetable mechanism to reduce disparities in RT experiences and outcomes. Multivariable model of symptom under-recognitionOR95% CIpAge--0.001&amp;lt;501.351.15-1.58&amp;lt;0.00150-591.211.06-1.390.00660-691 (ref)--70+1.050.89-1.240.55Body Mass Index--0.67Underweight (&amp;lt;18.5).790.52-1.200.27Normal(18.5-&amp;lt;25).990.84-1.150.86Overweight (25-&amp;lt;30)1 (ref)--Obesity I (30-&amp;lt;35)1.010.87-1.180.87Obesity II (35-&amp;lt;40)1.050.88-1.250.61Obesity III (40+)1.110.92-1.340.27Race--&amp;lt;0.001White1 (ref)--Black1.921.65-2.23&amp;lt;0.001Asian1.320.84-2.080.23Other1.821.24-2.660.002Supraclavicular field used (yes vs no)0.800.68-0.950.01Fractionation (conventionalvs hypo fractionation)1.151.02-1.300.02Boost to tumor bed (yes vs no)0.950.80-1.120.53Facility(Academic vs Community)1.131.01-1.270.04 Citation Format: Reshma Jagsi, Kent A. Griffith, Frank Vicini, Thomas Boike, Michael Dominello, Gregory Gustafson, James A. Hayman, Jean M. Moran, Jeffrey Radawski, Eleanor Walker, Lori J. Pierce, on behalf of MROQC, the Michigan Radiation Oncology Quality Consortium. Identifying patients whose symptoms are under-recognized during breast radiotherapy: Comparison of patient and physician reports of toxicity in a multicenter cohort [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr GS3-07.

Safety and efficacy of Hypofractionated stereotactic radiosurgery for high-grade Gliomas at first recurrence: a single-center experience

BackgroundThe optimal treatment for recurrent high-grade gliomas (rHGGs) remains uncertain. This study aimed to investigate the efficacy and safety of hypofractionated stereotactic radiosurgery (HSRS) as a first-line salvage treatment for in-field recurrence of high-grade gliomas.MethodsBetween January 2016 and October 2019, 70 patients with rHGG who underwent HSRS were retrospectively analysed. The primary endpoint was overall survival (OS), and secondary endpoints included both progression-free survival (PFS) and adverse events, which were assessed according to Common Toxicity Criteria Adverse Events (CTCAE) version 5. The prognostic value of key clinical features (age, performance status, planning target volume, dose, use of bevacizumab) was evaluated.ResultsA total of 70 patients were included in the study. Forty patients were male and 30 were female. Forty-nine had an initial diagnosis of glioblastoma (GBM), and the rest (21) were confirmed to be WHO grade 3 gliomas. The median planning target volume (PTV) was 16.68 cm3 (0.81–121.96 cm3). The median prescribed dose was 24 Gy (12–30 Gy) in 4 fractions (2–6 fractions). The median baseline of Karnofsky Performance Status (KPS) was 70 (40–90). With a median follow-up of 12.1 months, the median overall survival after salvage treatment was 17.6 months (19.5 and 14.6 months for grade 3 and 4 gliomas, respectively; p = .039). No grade 3 or higher toxicities was recorded. Multivariate analysis showed that concurrent bevacizumab with radiosurgery and KPS > 70 were favourable prognostic factors for grade 4 patients with HGG.ConclusionsSalvage HSRS showed a favourable outcome and acceptable toxicity for rHGG. A prospective phase II study (NCT04197492) is ongoing to further investigate the value of hypofractionated stereotactic radiosurgery (HSRS) in rHGG.

Consequences to patients, clinicians, and manufacturers when very serious adverse drug reactions are identified (1997-2019): A qualitative analysis from the Southern Network on Adverse Reactions (SONAR).

BackgroundAdverse drug/device reactions (ADRs) can result in severe patient harm. We define very serious ADRs as being associated with severe toxicity, as measured on the Common Toxicity Criteria Adverse Events (CTCAE)) scale, following use of drugs or devices with large sales, large financial settlements, and large numbers of injured persons. We report on impacts on patients, clinicians, and manufacturers following very serious ADR reporting.MethodsWe reviewed clinician identified very serious ADRs published between 1997 and 2019. Drugs and devices associated with reports of very serious ADRs were identified. Included drugs or devices had market removal discussed at Food and Drug Advisory (FDA) Advisory Committee meetings, were published by clinicians, had sales > $1 billion, were associated with CTCAE Grade 4 or 5 toxicity effects, and had either >$1 billion in settlements or >1,000 injured patients. Data sources included journals, Congressional transcripts, and news reports. We reviewed data on: 1) timing of ADR reports, Boxed warnings, and product withdrawals, and 2) patient, clinician, and manufacturer impacts. Binomial analysis was used to compare sales pre- and post-FDA Advisory Committee meetings.FindingsTwenty very serious ADRs involved fifteen drugs and one device. Legal settlements totaled $38.4 billion for 753,900 injured persons. Eleven of 18 clinicians (61%) reported harms, including verbal threats from manufacturer (five) and loss of a faculty position (one). Annual sales decreased 94% from $29.1 billion pre-FDA meeting to $4.9 billion afterwards (p<0.0018). Manufacturers of four drugs paid $1.7 billion total in criminal fines for failing to inform the FDA and physicians about very serious ADRs. Following FDA approval, the median time to ADR reporting was 7.5 years (Interquartile range 3,13 years). Twelve drugs received Box warnings and one drug received a warning (median, 7.5 years following ADR reporting (IQR 5,11 years). Six drugs and 1 device were withdrawn from marketing (median, 5 years after ADR reporting (IQR 4,6 years)).InterpretationBecause very serious ADRs impacts are so large, policy makers should consider developing independently funded pharmacovigilance centers of excellence to assist with clinician investigations.FundingThis work received support from the National Cancer Institute (1R01 CA102713 (CLB), https://www.nih.gov/about-nih/what-we-do/nih-almanac/national-cancer-institute-nci; and two Pilot Project grants from the American Cancer Society's Institutional Grant Award to the University of South Carolina (IRG-13–043–01) https://www.cancer.org/ (SH; BS).

Multidisciplinary personalized approach in the management of vulvar cancer – the Vul.Can Team experience

IntroductionMultidisciplinary treatment strategy involving adjuvant radiotherapy for advanced vulvar cancer could be useful in offering the best personalized clinical approach. In 2013, the VULvar CANcer Multi-Disciplinary Team (Vul.Can MDT) was...

Non-Hodgkin lymphoma after liver and kidney transplantation in children. Experience from one center.

Post-transplantation lymphoproliferative disorder (PTLD) is a complication of organ transplantation and a life-threatening condition. Children who underwent organ transplantation are at risk of developing lymphoproliferative disorders and, among them, non-Hodgkin lymphoma (NHL) is the most serious. The objective of this study was to describe the clinical course of NHL after liver and kidney transplantation. Retrospective analysis of medical records of children who underwent liver/kidney transplantation and developed NHL. Nine children were identified, all girls, 6 after liver and 3 after kidney transplantations. Age at transplantation ranged from 1 year to 13 years (median: 4 years), while age at lymphoma diagnosis from 4 to 17 years (median: 12 years). Time from transplantation to lymphoma diagnosis ranged from 7 months to 12 years (median: 9 years). All but 1 patient developed mature B-cell lymphoma, 4 children - diffuse large B-cell lymphoma (DLBCL), 2 children - Burkitt's lymphoma, 1 child - mature B-cell leukemia, 1 child - Burkitt-like lymphoma, while 1 patient was diagnosed with T-cell lymphoblastic lymphoma. High levels of Epstein-Barr virus (EBV) DNA were found in blood of 3 patients, and EBV in tissue samples was detected in 4 patients. Six patients presented with stage III and 2 with stage IV disease. Two patients had graft involvement. Three children received chemotherapy according to R-CHOP, 3 LMB protocol (2 with addition of rituximab), while 1 received CHOP and 5 courses of COP. T-cell lymphoma patient was treated with Euro-LB protocol. Six out of 8 treated patients are alive with a median follow-up of 6 years. Two children died from disease progression during treatment and 1 from cerebral herniation before starting therapy. All patients experienced at least 1 toxic episode of grade 3 and 4 according to Common Toxicity Criteria Adverse Event (CTCAE). Complications of chemotherapy were manageable and there were no transplanted organ failures. Our study provides further data on the treatment and outcome of monomorphic PTLD and indicates that it is feasible to treat solid organ recipients with multiagent chemotherapy.

Safety and outcome of stereotactic body radiation therapy (SBRT) with rectal hydrogel spacer for prostate cancer.

76 Background: Ultra-hypofractionated radiotherapy delivered using stereotactic body radiotherapy (SBRT) is a cost-effective treatment for localized prostate cancer. Optimal dosing remains unclear, as commonly used 30-40Gy/5fx regimens appear to overestimate hypofractionation’s control benefits. Here, we report the largest experience of 45Gy/5Fx of SBRT for prostate cancer patients treated with hydrogel peri-rectal spacer (‘hydrogel’). Methods: An IRB-approved retrospective protocol was used to conduct a registry search identifying all patients with prostate cancer who received 45Gy/5Fx between 2015-2019 with hydrogel. Genitourinary (GU) and gastrointestinal (GI) toxicities were defined using the NCI Common Toxicity Criteria for Adverse Events (CTCAE) v.5.0. The ASTRO-Phoenix failure definition of Nadir+2 ng/mL was used for biochemical failure. Results: We analyzed 250 low (9.2%), intermediate (85.2%), and high-risk (5.6%) prostate cancer patients with a median follow-up of 9.9 months (range: 0-45.7 months). Acute GU and GI grade ≥ II toxicities were noted in 15.2% and 7.2% of patients, respectively. Late GU grade II and III toxicities occurred in 24.0% and 1.2% of patients, respectively, while late GI grade II and III toxicities occurred in 4.0% and 0.4% of patients, respectively. In patients (N=44) with follow-up &gt;2 years, late GU and GI grade III toxicities occurred in 4.55% and 2.27% of patients, respectively. A significant correlation was noted for acute GI and GU toxicity predicting the respective late GI and GU toxicity (p-value &lt; 0.001 for both). Physician-reported Grade ≥ II new onset erectile dysfunction was 17.2%. A gradual decline in prostate-specific antigen with a mean nadir of 0.04 (95% CI: [0.018, 0.067]) at 36 months was noted. The actuarial freedom from biochemical failure was 96.33% at 3 years. Overall survival was 94.09% at 3 years with no deaths attributed to prostate cancer. Conclusions: SBRT treatment of 45Gy/5Fx with hydrogel is well tolerated with GU/GI toxicities comparable to those reported for conventional fractionation. Although short, the 3-year biochemical control rate is encouraging. Longer follow-up and prospective evaluation are warranted.

Intensity-modulated radiotherapy (IMRT) in the treatment of squamous cell anal canal cancer: acute and early-late toxicity, outcome, and efficacy.

To retrospectively review our experience on 84 patients with squamous cell anal canal cancer (SCAC) within 12months after combined treatment with intensity-modulated RT (IMRT), in terms of acute and early-late toxicity, overall treatment time and interruptions, colostomy-free survival (CFS), and tumor response. Acute gastrointestinal (GI), genitourinary (GU), and cutaneous (CU) toxicities were assessed according to Common Toxicity Criteria for Adverse Events (CTCAE) version 4.03. Early-late toxicity was scored using the Radiation Therapy Oncology Group (RTOG) late radiation morbidity scoring system. Tumor response was evaluated with response evaluation criteria in solid tumors (RECIST) v1.1. Acute toxicity for 84 subjects (100%): severe (≥ G3) GI and skin toxicity was observed in 4 (5%) and 19 patients (23%), respectively. Early-late toxicity for 73 subjects (87%): severe (≥ G3) GI and vulvo-vaginal toxicity was observed in 2 (3%) and 2 (3%) patients, respectively. No acute or early-late severe GU toxicity was reported. A treatment interruption occurred in 65 patients (77%). CFS was 96% (95% CI 89-99) at 6months and 92% (95% CI 83-96) at 12months. At 6months complete response (CR), partial response (PR) and progressive disease (PD) was observed in 70 (83%), 3 (4%), and 7 patients (8%), respectively. At 12months, CR was observed in 60 patients (81%); eleven patients (15%) experienced PD. Our study showed an excellent clinical result and very low acute toxicity rates, confirming the IMRT as standard of care for curative treatment of anal cancer patients. The current trial was registered with the number IEO N87/11.

Tumour Treating Fields (TTFields) in combination with lomustine and temozolomide in patients with newly diagnosed glioblastoma.

In the EF-14 trial for newly diagnosed glioblastoma (ndGBM) patients addition of Tumour Treating Fields (TTFields) to temozolomide treatment resulted in a significantly improved overall survival (OS). In the NOA-09/CeTeG trial, combination of lomustine and temozolomide was superior to temozolomide monotherapy in patients with O6-methylguanine DNA methyltransferase (MGMT) promoter methylated (MGMTm) ndGBM. We evaluated combination of these two treatment modalities in patients with MGMTm ndGBM. There have been so far no data on the combination of these two efficient regimens. This bicentric retrospective analysis investigated 16 patients. Parameters evaluated included safety outcome as measured by Common Toxicity Criteria for Adverse Events (CTCAE), clinical outcomes, and compliance to treatment. Hematologic adverse events CTCAE ≥ 3 were observed in seven, hepatotoxic adverse events of CTCAE ≥ 3 in four patients. Mild to moderate skin toxicity was detected in six patients. At data cutoff, patients demonstrated a median progression-free survival (PFS) of 20months. The usage rate of TTFields showed a high median adherence (83%) to the therapy. This analysis provides first indication that the combination of TTFields/lomustine/temozolomide is safe and feasible. The observed survival outcomes might suggest potential beneficial effects.

Evaluation of two nutritional scores' association with systemic treatment toxicity and survival in metastatic colorectal cancer: an AGEO prospective multicentre study

IntroductionThe Patient-Generated Subjective Global Assessment (PG-SGA) is currently the standard nutritional assessment tool for patients with cancer. In a retrospective assessment of a prospective cohort, we showed that the Nutritional Risk Index (NRI) seemed to be associated with treatment toxicity and survival in patients with metastatic colorectal cancer (mCRC). ObjectiveThe objective of this study was to compare these two nutritional tools (PG-SGA and NRI) on their correlation with chemotherapy-related toxicity and survival in non–pre-treated patients with mCRC. MethodsThis prospective multicentre observational study enrolled non–pre-treated patients with mCRC. PG-SGA and NRI were performed at the onset of first-line chemotherapy. Treatment-related toxicities were registered according to National Cancer Institute Common Toxicity Criteria Adverse Event version 4.0. Progression-free survival (PFS) and overall survival (OS) were calculated from the start of treatment. ResultsA total of 168 patients were included from eight French centres. Patients were considered malnourished in 41% of cases according to PG-SGA and 56% of cases according to the NRI. In multivariate analysis, malnutrition according to PG-SGA was significantly associated with chemotherapy-related grade ≥2 clinical toxicities (odds ratio: 3.7; 95% confidence interval [CI]: 1.7–8.4; p = 0.001) and OS (hazard ratio [HR]: 2.6; 95% CI: 1.3–5.3; p = 0.006), but not with PFS (HR: 1.5; 95% CI: 0.8–2.6; p = 0.2). Conversely, malnutrition according to the NRI was not significantly associated with these tolerance and efficacy parameters. ConclusionAlthough more complex to perform in daily oncology practice, the PG-SGA score appears to be the best nutritional assessment tool because of its strong association with clinically relevant oncological outcomes such as OS and treatment-related toxicities in patients with mCRC.

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.

First Experience With 177Lu-PSMA-617 Therapy for Advanced Prostate Cancer in the Netherlands.

The present study summarizes the first experience with Lu-PSMA-617 (Lu-PSMA) treatment in metastatic castration-resistant prostate cancer (PCa) in our institution. This was an analysis of the first 30 consecutive patients who underwent Lu-PSMA therapy. Biochemical response was defined as prostate-specific antigen decrease of 50% or greater. Clinical toxicity was based on standardized physician's report, and biochemical and hematological toxicity was graded according to the Common Toxicity Criteria for Adverse Events (CTCAE) criteria. Clinical response was objectified in terms of severity of pain and usage of analgesics after separate treatment cycles. Thirty patients with advanced PCa received therapy cycles with 6 GBq Lu-PSMA (median, 4; range, 1-6). After the first cycle, usage of analgesics decreased in 45% of the patients. During treatment, maximum prostate-specific antigen decrease was 50% or greater and 90% or greater in 57% and 24% of the patients, respectively. Despite CTCAE grades III and IV anemia occurring in 2 patients (7%), all other newly originated biochemical toxicity was limited to maximum CTCAE grades I and II. Grade II xerostomia occurred in 17% of the patients. During a median follow-up length of 13.7 months (range, 9.8-32.3 months), median overall survival from start of the first therapy cycle was 11.3 months (range, 1.4-32.3 months). These results confirm the favorable safety and efficacy profile of Lu-PSMA, even up to 6 treatment cycles. Therefore, Lu-PSMA seems a promising therapeutic strategy for metastatic castration-resistant PCa patients. However, randomized controlled trials are warranted to obtain robust data.

Return to work after breast cancer: Comprehensive longitudinal analyses of its determinants.

11564 Background: The interplay between breast cancer (BC) late effects, psychosocial and work-related factors in return to work (RTW) is not well understood. Previous reports were retrospective and did not combine all these features. Methods: We used data of a French prospective cohort study (CANTO, NCT01993498) of stage I-III BC patients (pts) including detailed clinical data of 1,874 pts working at diagnosis (dx) and ≥5 years younger than legal retirement age. The outcome was non-RTW 2 years after dx. Multivariable regressions were conducted to identify correlates of non-RTW. First, we examined the independent effect of treatments, toxicities (Common Toxicity Criteria Adverse Events), and patient reported outcomes (EORTC BR23 and FA12; Hospital Anxiety and Depression Scale) collected shortly after end of primary treatment. Then, in a restricted sample of 1,003 pts with working conditions (WC) information available, we fitted models to account for detailed pre-dx WC including type of contract, working hours, strenuous postures, supportive environment, degree of autonomy and perception of work. All models were adjusted for age, stage, marital status, socioeconomic status and comorbidities. Results: Two years after dx, 21% of pts did not work. Adjusted odds of non-RTW were increased among pts treated with combinations of chemotherapy (CT) and trastuzumab (TR) (e.g. OR of CT-TR = 2.20 [95% CI 1.24-3.88] and OR of CT-TR-hormonotherapy (HT) = 1.72 [1.13-2.63] vs. treated only with CT-HT), who had severe arm morbidity (OR = 1.73 [1.27-2.36] vs. no), severe emotional fatigue (OR = 1.55 [1.03-2.32] vs. no), anxiety (OR = 1.51 [1.02-2.23] vs. no), or depression (OR = 2.23 [1.27-3.94] vs no). In addition, we also found that the odds of non-RTW were increased among pts who had shift working hours (OR = 2.23 [1.32-3.76] vs. no), who did not work in a supportive environment before dx (OR = 2.24 [1.44-3.50] vs. supportive) and who perceived their job as boring (OR = 3.57 [1.71-7.46] vs. not boring). Conclusions: More than 1/5 of pts did not RTW 2 years after dx, with treatment (trastuzumab), clinical, psychological and work-related factors being associated with job reintegration. Multidisciplinary strategies are needed to support BC survivors.

Radiotherapy related skin toxicity (RAREST-01): Mepitel\xae film versus standard care in patients with locally advanced head-and-neck cancer

BackgroundThe aim of the present trial is to investigate a new option of skin protection in order to reduce the rate of grade ≥ 2 skin toxicity in patients receiving radiotherapy alone or radiochemotherapy for locally advanced squamous cell carcinoma of the head-and-neck (SCCHN).Methods / DesignThis is a randomized, active-controlled, parallel-group multi-center trial that compares the following treatments of radiation dermatitis in patients with head-and-neck cancer: Mepitel® Film (Arm A) vs. standard care (Arm B). The primary aim of this trial is to investigate the rate of patients experiencing grade ≥ 2 radiation dermatitis (according to Common Toxicity Criteria for Adverse Events (CTCAE) Version 4.03) until 50 Gy of radiotherapy. Evaluation until 50 Gy of radiotherapy has been selected as the primary endpoint, since up to 50 Gy, the irradiated volume includes the primary tumor and the bilateral cervical and supraclavicular lymph nodes, and, therefore, is similar in all patients. After 50 Gy, irradiated volumes are very individual, depending on location and size of the primary tumor, involvement of lymph nodes, and the treatment approach (definitive vs. adjuvant). In addition, the following endpoints will be evaluated: Time to grade 2 radiation dermatitis until 50 Gy of radiotherapy, rate of patients experiencing grade ≥ 2 radiation dermatitis during radio(chemo)therapy, rate of patients experiencing grade ≥ 3 skin toxicity during radio(chemo)therapy, adverse events, quality of life, and dermatitis-related pain. Administration of Mepitel® Film will be considered to be clinically relevant, if the rate of grade ≥ 2 radiation dermatitis can be reduced from 85% to 65%.DiscussionIf administration of Mepitel® Film instead of standard care will be able to significantly reduce the rate of grade ≥ 2 radiation dermatitis, it could become the new standard of skin care in patients irradiated for SCCHN.Trial registrationclinicaltrials.gov NCT03047174. Registered on 26th of January, 2017. First patient included on 9th of May, 2017.

The relationship between dose to skeletal muscle area ratio and gemcitabine nab-paclitaxel toxicity in pancreatic ductal adenocarcinoma.

492 Background: Combination gemcitabine and nab-paclitaxel (Gem-Nab-P) is a common regimen used to treat metastatic pancreatic ductal adenocarcinoma (PDAC). Toxicity is less than that associated with other combination metastatic regimens (FOLFIRINOX), but it is still associated with significant morbidity. Currently, Gem-Nab-P is dosed using estimated body surface area. This study investigates whether skeletal muscle assessment could be a useful tool in the dosing of Gem-Nab-P in metastatic PDAC. Methods: This study involved two sites and included patients who had received Gem-Nab-P between January 2013 and March 2017. A review of medical records was used to identify demographic, disease and first-cycle treatment information. Chemotherapy toxicity was defined as grade 3 or 4 adverse events using the National Cancer Institute Common Toxicity Criteria Adverse Events manual v4.0. Body composition analysis was performed on computed tomography scans at spinal level L3, using SliceOmatic software. SPSS software was used to for all statistical analysis, with a p value of &lt; 0.05 considered significant. Results: We identified 52 patients treated with first-line Gem-Nab-P for PDAC. Median age was 65 years (57-73) and 24 (47%) were male. Median BMI at commencement of Gem-Nab-P was 24.7 kg/m2 (21.3-27.4) and 38 (58%) of the patients were myopenic before starting chemotherapy. Fourteen (27%) patients experienced toxicity during the first cycle of chemotherapy. Patients who experienced first-cycle chemotherapy-associated toxicity did not have a different median SkMA to those who did not (128.6 cm2 vs. 111.4 cm2, p= 0.2). There was also no difference in the gemcitabine dose to SkMA ratio (14.1 mg/cm2 vs. 14.4 mg/cm2, p=0.8), nab-paclitaxel to SkMA ratio (1.8 mg/cm2 vs. 1.8 mg/cm2, p=0.6) or combined dose equivalent to SkMA ratio (2.8 mg/cm2 vs. 2.9 mg/cm2, p=0.9) between the patients that experienced first cycle toxicity versus those that did not. Conclusions: This study suggests that a pancreatic cancer patient’s skeletal muscle area is unlikely to be a useful addition to conventional body surface area in the dosing of first line Gem-Nab-P, to reduce first-cycle toxicity.

Subsite-dependent prognostic impact of age in patients with nasopharyngeal and oropharyngeal cancer

Backgroud: Outcome results in elderly head and neck cancer (HNC) patients (pts) treated with concurrent chemoradiation are controversial. Comparative effectiveness analyses showed a lack of benefit in multimodal treatment; however, retrospective highly selected series reported older patients to have similar outcome compared to younger ones albeit with high burden of toxicities. Material and methods: Locally advanced oropharyngeal (OPC) and nasopharyngeal cancer (NPC) pts treated at our institution with concurrent platinum based chemotherapy (CHT) and intensity modulated radiation therapy (IMRT) techniques from 2004 to 2015 were retrospectively evaluated. Overall survival (OS) and Relapse Free Survival (RFS) Kaplan-Meier curves were estimated and compared with the log-rank test; acute toxicity rate >G3 according to Common Toxicity Criteria Adverse Event v4.0 was also analyzed, distinguishing between patients >65 years old (elderly) and ≤65 old. HPV status was recorded in all OPC patients. Results: 375 pts received IMRT-CHT, 215 in OPC and 160 in NPC cohort. Elderly pts represented 26% and 11% of OPC and NPC pts, respectively. OPC HPV positive cases were similarly represented in older (73% of the cases) and younger pts (66%); HPV positivity maintained a significant prognostic role independently of age and also across different age group. On the contrary, age did not significantly impact on survival in OPC. Five-years RFS was 68% in older versus 76% in younger patients p = 0.391; the corresponding figures for OS were 93% versus 87% p = 0.541. There was no significant difference in cumulative acute toxicity rate = G3 (39% in elderly vs 36% in younger p = 0.778). When analyzed separately, no difference was shown for what concerns dysphagia and mucositis. NPC pts showed a different outcome according to age both in terms of RFS (5-years probabilities 41% in elderly vs 80% in younger pts, p < 0.001) and OS (48% vs 90%, p < 0.001), which turned out to be a negative prognostic factor in this disease. Also for NPC pts, the two age subgroups did not significantly differ in acute toxicity rate = G3 (56% vs 61%, p = 0.800). No different platinum total dose was adopted in OPC and NPC elderly pts. Conclusion: We observed a subsite-specific impact of age on treatment outcome: older NPC pts showed markedly worse survival than the younger counterparts, while in OPC pts such an effect was inconsistent. HPV status was confirmed to be a positive prognostic factor independently of age.