National Cancer Institute-Common Terminology Criteria Research Articles

Effect of a medicinal and edible decoction YH0618 on chemotherapy-induced dermatologic toxicity: a randomized controlled trial

BackgroundDermatologic toxicities are the common adverse events (AE) with several chemotherapy agents, but they are usually neglected in the research literature and clinical practice, and there are no clinically safe and effective methods to solve the problem. This study was to determine whether a medicinal and edible decoction YH0618 is effective in accelerating reducing chemotherapy-induced dermatologic toxicity in cancer patients who have completed chemotherapy.MethodsThis was a prospective randomized controlled trial conducted between 2015 and 2017. Cancer patients who have completed chemotherapy (received taxanes or anthracyclines or fluoropyrimidine) within two weeks were enrolled and then they were randomly divided into YH0618 decoction group (n=104) and wait-list control (n=110). The primary end points were the incidence of protocol-specified grade ≥2 dermatologic toxicities after 6-week intervention assessed using the National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE) Chinese version 4.0, and changes of fingernails color and skin color evaluated by L*a*b after 6 weeks of intervention. Secondary end points included assessment of quality of life (QOL) and fatigue, and some clinical objective indicators associated with myelosuppression, hepatotoxicity and nephrotoxicity.ResultsThe study included 214 participants [mean (SD) age, 52.49 (9.08) years in YH0618 group and 50.44 (9.71) years in wait-list group]. At 6-week, YH0618 significantly reduced the incidence of grade ≥2 in nail discoloration [odds ratio (OR), 0.653; 95% CI, 0.5–0.9; P=0.005] and alopecia (OR, 0.776; 95% CI, 0.6–1.0; P=0.048) compared with control group. Besides, YH0618 increased the L* value and reduced the a* and b* values compared with control group, indicating that YH0618 increased the brightness and reduced hyperpigmentation. YH0618 also significantly reduced chemotherapy-induced fatigue (95% CI, 0.2–4.8; P=0.033).ConclusionsYH0618 may be a safe method in ameliorating chemotherapy-induced dermatologic toxicity especially nail discoloration, alopecia and skin hyperpigmentation, and on improving fatigue.Trial registrationThe trial was registered in the Chinese Clinical Trials Registry, ChiCTR-IOR-15006486.

MP61-08 A PHASE I/II TRIAL OF TRANSURETHRAL SURGERY FOLLOWED BY A COMBINATION OF ATEZOLIZUMAB AN ANTI-PDL-1 (MPDL3280A) WITH TRIMODAL THERAPY IN PATIENTS WITH MUSCLE-INVASIVE BLADDER CANCER

INTRODUCTION AND OBJECTIVE: Bladder preserving strategies such as trimodality therapy (TMT) remain associated with suboptimal local control of muscle invasive bladder cancer (MIBC). Recently, immune checkpoint programmed death-ligand 1 therapy (PD-L1) has shown rapid and lasting responses in metastatic MIBC. Our aim was to evaluate safety and toxicity profile of concurrent Atezolizumab (anti-PDL-1) in combination with TMT in patients with MIBC. METHODS: Phase I/II non-randomized safety/efficacy study including T2-T4a N0M0 MIBC patients electing for bladder preservation therapy (NCT03620435). Patients were treated with a trans-urethral resection of bladder tumor (TURBT) followed by intensity modulated radiation therapy (IMRT) (50 Gy/20 fractions. 2.5 Gy per fraction – 5 times per week for 4 weeks), Gemcitabine (for 4 weeks at 100 mg/m2, IV once weekly) and Atezolizumab (1200 mg IV on day 1 of 3 week cycle). This trial recruited patients par block of 3 to assess dose related toxicity (DLT) in case of severe side effects the atezolizumab dose was reduced to 840mg. The primary endpoint was safety assessed using the national cancer institute-common terminology criteria for adverse events (NCI-CTCAE) version 4.03. RESULTS: Between December 2017 and January 2019, our study included 8 patients (6 males); median age was 68 (IQR 60; 70). Six patients were cT2 and 2 patients cT3. The first five patients received atezolizumab at 1200 mg and 3 of them developed grade 3 side effects (table 1). The atezolizumab dose was reduced to 840 mg for the 3 last. Study was terminated due to the presence of grade 3 side effects even with the reduced atezolizumab dose. No grade 4 side effects were observed. No deaths occurred. CONCLUSIONS: Concurrent administration of immune checkpoint inhibition with chemoradiation for MIBC was associated with unacceptable toxicity. These results do not support their concurrent use with trimodality therapySource of Funding: Sponsored by F. Hoffmann-La Roche Ltd

Taxane-induced peripheral neuropathy and quality of life in breast cancer patients.

Taxane-induced peripheral neuropathy (TIPN) is a common and bothersome toxicity. This study aimed to determine the incidence and severity of TIPN in patients with breast cancer and to investigate the relationship between TIPN and quality of life. A total of 82 breast cancer patients with TIPN symptoms were included in this study. The criteria of National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE v4.03) and the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ-C30, version 3.0) were used to evaluate grading of sensory neuropathy and quality of life, respectively. Analysis of the data was done by IBM SPSS statistics version 23. A total of 346 patients received taxane-based chemotherapy and 82 patients (23.7%) experience TIPN. The mean (SD) global health status/quality of life, physical functioning, role functioning, and pain subscales were 60.63 (5.26), 80.64 (9.05), 81.77 (10.41), and 43.88 (11.27), respectively. There were significant negative correlations between global health status/quality of life, physical functioning, and role functioning subscales with the grade of neuropathy (r = -0.33, -0.80, and -0.61, respectively) and positive correlation between pain subscale and the grade of neuropathy (r = 0.70). This study shows a clear association between TIPN and worsened quality of life. These findings emphasize on detecting and management of TIPN in an effort to improve the quality of life of breast cancer patients.

A simple method of quantifying chemotherapy-induced peripheral neuropathy using PainVision PS-2100®.

This study aimed to validate a simplified method of quantifying chemotherapy-induced peripheral neuropathy using the PainVision PS-2100® (PV) electrical perception system. We assessed patients diagnosed with epithelial ovarian cancer, fallopian tube cancer, or peritoneal cancer and were about to undergo first-time paclitaxel and carboplatin chemotherapy. Peripheral neuropathy was assessed before and after chemotherapy administration in all patients according to the National Cancer Institute-Common Terminology Criteria for Adverse Events Version 4.0 (NCI-CTCAE4.0), using a conventional assessment in combination with the PV system. The PV device comprises electrodes attached to the ulnar side of the forearm and the first joint of index fingers on both the left and right sides to measure the electrical perceptual threshold. The average of three threshold measurements was recorded for each patient. Thirty female patients (age 51.6 ± 12.2 [mean ± SD]) were included, and median number of chemotherapy drug treatments was 5 (first quartile: 4, second quartile: 5, and third quartile: 5). Twenty-seven patients (90%) reported posttreatment numbness; NCI-CTCAE4.0 perceptual anomaly grades were as follows: G1, 57 (40%); G2, 19 (13%); and G3, 7 (5%). A positive correlation was identified between right medial side PV threshold score and perceptual anomaly grade on measurements of the inner right-hand side only. Our preliminary results suggest that peripheral neuropathy may be quantified using PV. As CIPN often lowers QOL, it needs to be appropriately evaluated. Future studies with a larger patient cohort and methodological refinements to improve accuracy are warranted.

Therapeutic efficacy, prognostic variables and clinical outcome of 177Lu-PSMA-617 PRLT in progressive mCRPC following multiple lines of treatment: prognostic implications of high FDG uptake on dual tracer PET-CT vis-à-vis Gleason score in such cohort.

To evaluate the therapeutic response, progression free survival (PFS), overall survival (OS) and clinical toxicity of 177Lu-PSMA-617 PSMA targeted radioligand therapy (PRLT) in the setting of heavily pre-treated metastatic castrate-resistant prostate cancer (mCPRC) patients and also examine the association of prognostic variables with therapeutic outcome in such patient cohort. We examined the medical records of mCRPC patients who had undergone 177Lu-PSMA-617 PRLT from March 2017 to February 2019 in our institute. Patients receiving equal to or more than two cycles were included and analyzed in this retroprospective study.The 68Ga-PSMA-11 PET-CT and 18-fludeoxyglucose positron emission tomography (18FDG PET)-CT scan findings, serum prostate-specific antigen (PSA) change, health-related quality of life (HRQoL) scales (Eastern Cooperative Oncology Group/Karnofsky score) and Gleason score were assessed for their implications on the outcome of therapy. The treatment response was evaluated under three categories: (a) symptomatic (b) biochemical and (c) imaging response.The PFS and OS following first PRLT were determined and the association of various variables with PSA doubling time (DT) and FDG uptake in the lesions were analyzed. Toxicity assessment was undertaken objectively by National Cancer Institute-Common Terminology Criteria for Adverse Events scale v. 5.0 for haematological and nephrotoxicity, and salivary gland toxicity assessed by xerostomia inventory score. A total of 40 mCRPC patients (age range: 46-84 years; median 63 years), who had undergone 177Lu-PSMA-617 PRLT, of at least two cycles was identified and selected for the analysis. FDG uptake was noted in 87.5% of patients (n = 35). Out of 40 cases, 21 were responders (CR, PR and SD) and 19 were non-responders (PD) on symptomatic and biochemical scales while on molecular imaging response, 16 (43%) were responders and remaining 21 (57%) were non-responders. Lesion-wise, 68Ga-PSMA-11 avid metastatic nodal disease responded well with 177Lu PSMA-617 PRLT, as compared to hepatic and skeletal lesions. The median OS and PFS was 12 and 7 months respectively following first PRLT. Patients with negative serum PSA-DT demonstrated superior 1 year PFS as compared to those with positive serum PSA-DT (52.5 vs 47.5%) (p = 0.029). Patients receiving greater than two cycles PRLT demonstrated a higher negative PSA-DT as compared to those receiving two cycles (p-value = 0.03). Grade 1 xerostomia was observed in two patients (5%) (mean xerostomia score of 23), haematotoxicity in seven patients [Grade I (n = 2, 5%) and Grade II (n = 5, 14%)]. 177Lu-PSMA-617 PRLT was well-tolerated and able to produce disease control with good symptomatic and biochemical responses in the context of heavily pre-treated mCRPC with progressive disease, with low toxicity profile. Evident association of high FDG uptake was observed with aggressive disease biology coupled with increasing Gleason score and poorer 12 months PFS. Negative PSA-DT following therapy demonstrated longer PFS. The results demonstrate important future role of 177Lu-PSMA-617 PRLT in the treatment of mCRPC. The present work explored in a large teriary cancer care setting, the efficacy of 177Lu-PSMA-617 PRLT, in an aggressive and unselected subset of mCRPC. The response and outcome was correlated with a number of prognostic variables, including molecular imaging findings (FDG uptake in the metastatic lesions), PSA DT and Gleason score.

A Phase I, Randomized, Single-Dose Study Evaluating the Biosimilarity of TAB008 to Bevacizumab in Healthy Volunteers.

Objective: This study compared the pharmacokinetics (PK), safety, and immunogenicity of the biosimilar TAB008 monoclonal antibody to bevacizumab (Avastin®) in normal healthy Chinese male volunteers. Methods: In this randomized, double-blind, parallel controlled study, a total of 100 healthy Chinese male subjects were randomized (1:1) to receive a single 1 mg/kg intravenous dose of TAB008 or Avastin® over a 90-min infusion. The subjects were followed for 99 days after drug administration. Primary endpoints were bioequivalence of major pharmacokinetic parameters (AUC0-t and AUC0-∞) and maximum observed serum concentration (Cmax). Secondary endpoints included safety and immunogenicity parameters. Results: The two groups of test subjects (49 subjects in the TAB008 group and 50 subjects in the Avastin® group) were well matched in regards to all demographic and baseline characteristics. The treatment group ratios of LS geometric means for the three primary PK parameters were fully contained within the bioequivalence limits of 80.00–125.00% (90% CI was 103.66–118.33% for Cmax, 94.32–111.72% for AUC0-t, and 94.69–112.23% for AUC0-∞). Treatment-emergent adverse events (TEAEs) were reported for 24 (49.0%) subjects in the TAB008 group and 22 (44.0%) subjects in the Avastin® group. TEAEs related to the study drug were reported for 19 (38.8%) subjects in the TAB008 group and 19 (38.0%) subjects in the Avastin® group. National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE) Grade 3 TEAEs were reported for 1 (2.0%) subject in the TAB008 group and 3 (6.0%) subjects in the Avastin® group. There were no Grade 4 or 5 TEAEs or serious adverse events (SAEs) during the study. Anti-drug antibody generation was reported once only in each group, and neutralizing antibody (Nab) analysis was negative upon follow-up. Conclusion: TAB008 attained pharmacokinetic similarity to bevacizumab, and was safe and well tolerated.

Identifying the incidence of respiratory complications following diaphragmatic cytoreduction and hyperthermic intraoperative intraperitoneal chemotherapy.

In patients with peritoneal carcinomatosis (PC), the incidence of respiratory complications following cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) is not well established. We aimed to describe the center-specific incidence and patient characteristics associated with respiratory complications following CRS and HIPEC in patients receiving treatment for PC. We used the University Hospital of Arrixaca study database to identify patients who underwent CRS and HIPEC for PC. Patients who experienced a post-operative respiratory complication were categorized according to the National Cancer Institute-Common Terminology Criteria for Adverse Events. Multivariable regression methods were used to identify independent risk factors for developing a respiratory complication following CRS and HIPEC. Between 2008 and 2017, we identified 247 patients who underwent CRS and HIPEC for PC. A total of eight patients (3.2%) were categorized as having a post-operative respiratory complication. A diaphragmatic peritonectomy and a PC index of > 14 were identified as independent risk factors for developing a respiratory complication. Radiographic evidence of a pleural effusion was identified in 72 patients who had CRS of the diaphragmatic peritoneum; however, only 6 (8.3%) of these patients required pleural drainage. Only 3.2% of patients developed a symptomatic respiratory complication following CRS and HIPEC. A pleural effusion was identified in almost all patients requiring a diaphragmatic peritonectomy as part of their CRS; however, less than one in ten of these patients required pleural drainage. Prophylactic insertion of a pleural drainage tube is, therefore, not indicated following CRS and HIPEC.

Construction of a flow chart-like risk prediction model of ganciclovir-induced neutropaenia including severity grade: A data mining approach using decision tree.

Haematological toxicities such as neutropaenia are a common side effect of ganciclovir (GCV); however, risk factors for GCV-induced neutropaenia have not been well established. Decision tree (DT) analysis is a typical technique of data mining consisting of a flow chart-like framework that shows various outcomes from a series of decisions. By following the flow chart, users can estimate combinations of risk factors that may increase the probability of certain events. In our previous study, we demonstrated the usefulness of this approach in the evaluation of adverse drug reactions. Therefore, we aimed to construct a risk prediction model of GCV-induced neutropaenia including severity grade. We performed a retrospective study at the Hokkaido University Hospital and enrolled patients who received GCV between April 2008 and March 2018. Neutropaenia was defined as an absolute neutrophil count (ANC) <1500cells/mm3 and a decrease to <75% relative to baseline. We classified the patients who developed neutropaenia in three groups (Grades 2-4) based on the National Cancer Institute-Common Terminology Criteria for Adverse Events. Data collection was achieved through the retrieval of medical records. We employed a chi-squared automatic interaction detection algorithm to construct the DT model and compared the accuracies to the logistic regression model (a conventional statistical method) to evaluate the established model. In total, 396 adult patients were included in the study; 61 (15.4%) developed neutropaenia. Three predictive factors (hematopoietic stem cell transplantation, baseline ANC <3854cells/mm3 and duration of therapy ≥15days) were extracted using the DT analysis to produce five subgroups, the incidence of neutropaenia ranged between 1.7% and 52.8%. In each subgroup, patients who developed neutropaenia were categorized based on the severity. The accuracies of each model were the same (84.6%), which indicated precision. We successfully built a risk prediction model of GCV-induced neutropaenia including severity grade. This model is expected to assist decision-making in the clinical setting.

The Correlation of the Grading of Chemotherapy-Induced Peripheral Neurotoxicity (CIPN) Using the Total Neuropathy Score-Reduced and Various Electrophysiological Parameters in Breast Cancer Patients

Background The accurate grading of chemotherapy-induced peripheral neuropathy (CIPN) represents an unsolved issue. This study evaluated usefulness of the reduced version of Total Neuropathy Score TNS (TNSr) and the correlation of this scale with various electrophysiological parameters. Methods Neuropathic symptoms and quality of life were assessed using the neuropathy symptom scale and the Functional Assessment of Cancer Therapy/Gynecologic Oncology Group Neurotoxicity (FACT/GOG-NTX) scale. A detailed neurologic examination, nerve conduction study (NCS), and the current perception threshold (CPT) were also performed.The TNSr score was calculated by a single examiner. We divided the patients with small fiber neuropathy and large fiber neuropathy and compared each variable between groups. Also, we analyzed correlations of the TNSr score with various parameters (NCS data, CPT score, and neuropathy symptom scales). Results Of 30 recruited patients, 16 (53%) had large fiber neuropathy, and the other 14 (47%) had small fiber neuropathy. Patients with large fiber neuropathy had a lower sural sensory nerve action potential (SNAP) (p=0.000), lower peroneal compound muscle action potential (CMAP) (p=0.002), higher National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE, NTC) sensory grade (p=0.029) and higher TNSr score (p=0.000). There were no differences in any domain of the FACT/G, neuropathy symptom scale, or FACT/GOG-NTX between the two groups. The TNSr score was most significantly correlated with the sural SNAP (p=0.000), NTC-sensory grade (p=0.000), neuropathy symptom scale (p=0.001), FACT/GOG-NTX score (p=0.009), and pin score (p=0.002). Conclusions The TNSr score is correlated with sensory peripheral neurotoxicity and also present the symptom severity in CIPN. Key Words: Breast neoplasms, Polyneuropathies, Neurologic manifestations

The Effect of Docosahexaenoic Acid and α-Lipoic Acid as Prevention of Bortezomib-Related Neurotoxicity in Patients With Multiple Myeloma.

Background and Aims: In cancer patients, a common complication during chemotherapy is chemotherapy-induced peripheral neuropathy (CIPN). For this reason, we decided to conduct a phase II prospective study on 33 patients with multiple myeloma at first diagnosis, to evaluate whether a nutraceutical compound given for 6 months during bortezomib (BTZ) treatment succeeded in preventing the onset of neurotoxicity. Methods: Neurological evaluation, electroneurography, and functional and quality of life (QoL) scales were performed at baseline and after 6 months. We administered a tablet containing docosahexaenoic acid 400 mg, α-lipoic acid 600 mg, vitamin C 60 mg, and vitamin E 10 mg bid for 6 months. Results: Concerning the 25 patients who completed the study, at 6-month follow-up, 10 patients had no neurotoxicity (NCI-CTCAE [National Cancer Institute-Common Terminology Criteria for Adverse Events] = 0), while 13 progressed to NCI-CTCAE grade 1, 1 had NCI-CTCAE grade 1 with pain, and 1 experienced a NCI-CTCAE grade 2. Painful symptoms were reported only in 2 patients, and we observed stability on functional and QoL scales in all patients. None of the 25 patients stopped chemotherapy due to neurotoxicity. Conclusions: Our data seem to indicate that the co-administration of a neuroprotective agent during BTZ treatment can prevent the appearance/worsening of symptoms related to CIPN, avoiding the interruption of BTZ and maintaining valuable functional autonomy to allow normal daily activities. We believe that prevention remains the mainstay to preserve QoL in this particular patient population, and that future studies with a larger patient population are needed.

Characterization of the Long-Term Efficacy and Safety of Duvelisib Monotherapy in Patients with Relapsed/Refractory CLL/SLL on Treatment for > 2 Years across 4 Clinical Studies

Characterization of the Long-Term Efficacy and Safety of Duvelisib Monotherapy in Patients with Relapsed/Refractory CLL/SLL on Treatment for > 2 Years across 4 Clinical Studies

Enhancing a Specialized Nursing Care Guidelines Improves Acute Lymphoblastic Leukemia Patients' Outcome during Induction Phase; A Developing Country Experience

Introduction: Pediatric Cancer patients are treated with therapeutic research protocols that detail medical treatment in low- and middle-income countries (LMICs). Unfortunately, there is no precise definition of a structured nursing care plan that is mandatory to enhance the quality of care needed for these patients. Our study aimed to examine the impact of implementing a designed nursing care guidelines (NCG) on acute lymphoblastic leukemia (ALL) patient outcomes during the induction phase concerning; incidence, duration, and intensity of the patient's gastrointestinal tract GIT adverse events.Methods: A Quasi-experimental research design was utilized in this study with posttest only control group conducted at the Hematology Units of Children Cancer Hospital Egypt 57357. Seventy-four oncology nurses received adequate education for the designed nursing care plan. A total of (132) ALL children in induction phase were enrolled in the study and were divided into two groups: group 1 (intervention group) was implemented the nursing care guidelines and group II (control group) who was left to the routine hospital care.Tools: data collection instruments included; “patient outcomes audit chart” to assess the GIT adverse - events data: the incidence, duration, and intensity. The intensity grading of the adverse events Adopted from the NCI (National Cancer Institute) Common Terminology Criteria for Adverse Events v4.0 (CTCAE) Published on May 28, 2009.Results: A significant positive correlation between implementing the NCG and GIT adverse events incidence, duration and severity were observed (Figure 1). Incidence was reported higher in the control group than the study group with a mean score of ±SD (2.48± .949) versus (0.67± 0.751) respectively, and a p-value (P<0.0001). The duration of incidence was (15.32± 5.920) versus (3.70± 5.108) in the intervention group (t =12.074) df (130) and a p-value (P<0.0001). The intensity grading of the adverse events was less in the study group than the control. (figure 2)Mean scores for nurses' post-NCG knowledge in the study group were significantly higher than the nurse's knowledge scores in the control group. The intensity of incidence revealed that a significantly higher on the intervention group.Conclusion: Designing and implementing NCG for all treatment protocols is essential for the enhancement of patients' outcomes. Developing a pediatric oncology nurse residency program for education and teaching of the required practical skills in LMIC is mandatory.Figure 1 Figure 2 DisclosuresNo relevant conflicts of interest to declare.

Long-term neurotoxicity and Raynaud's phenomenon in patients treated with cisplatin-based chemotherapy for malignant ovarian germ cell tumor.

The aim was to evaluate "overall neuropathy", defined as peripheral paresthesia and Raynaud's phenomenon, in long-term survivors of malignant ovarian germ cell tumors (MOGCTs) treated with cisplatin-based chemotherapy (CBCT). Ninety-three MOGCT survivors recorded in Norway in 1980-2009 (median follow up: 15years) were included in this analysis. Forty-nine received CBCT (CBCT group) and 44 received other or no chemotherapy (non-CBCT group). Applying the scale for chemotherapy-induced neurotoxicity, the prevalence of overall neuropathy (ie score >1 on a 0-3 scale) was compared between the two groups. Forty women from the CBCT group also underwent neurophysiological and neurological examinations; results from the neurological examination were graded according to the National Cancer Institute-Common Terminology Criteria for Adverse Effects version 4 (NCI-CTCAE scale v4). These women were then categorized into subgroups of low (≤3 cycles of CBCT, n=23) and high CBCT (≥4 cycles of CBCT, n=17). Twenty-eight (57%) women from the CBCT group reported overall neuropathy, compared with 20 (45%) in the non-CBCT group (P=.06). Of the 40 MOGCT survivors in the CBCT group who underwent neurophysiological and neurological examinations, 14 (35%) showed NCI-CTCAE grade ≥1 signs or symptoms of peripheral neuropathy. Pathological findings of NCI-CTCAE grade 2 or 3 signs or symptoms were found in four survivors (10%) from the high CBCT subgroup, all of whom also showed objective signs of neuropathy. Though about half of our MOGCT survivors reported overall neuropathy after CBCT, more severe pathological neurological/neurophysiological findings that impacted daily living were recorded in only 10% of them. Our observations of a similar prevalence of self-reported overall neuropathy in the CBCT and non-CBCT group, combined with limited objective neurological findings, warrant further study to increase the understanding of the specific pathophysiological pathways of long-term CBCT-induced neuropathy.

Risk factors for radiation pneumonitis after stereotactic radiation therapy for lung tumours: clinical usefulness of the planning target volume to total lung volume ratio.

To identify risk factors for symptomatic radiation pneumonitis (RP) after stereotactic radiation therapy (SRT) for lung tumours. We retrospectively evaluated 68 lung tumours in 63 patients treated with SRT between 2011 and 2015. RP was graded according to the National Cancer Institute-Common Terminology Criteria for Adverse Events version 4.0. SRT was delivered at 7.0-12.0 Gy per each fraction, once daily, to a total of 48-64 Gy (median, 50 Gy). Univariate analysis was performed to assess patient- and treatment-related factors, including age, sex, smoking index(SI), pulmonary function, tumour location, serum Krebs von den Lungen-6 value(KL-6), dose-volume metrics (V5, V10, V20, V30, V40 and VS5), homogeneity index of the planning target volume (PTV), PTV dose, mean lung dose (MLD), contralateral MLD and V2, PTV volume, lung volume and the PTV/lung volume ratio (PTV/Lung). Performance of PTV/Lung in predicting symptomatic RP was also analysed using receiver operating characteristic (ROC) analysis. The median follow-up period was 21 months. 10 of 63 patients (15.9%) developed symptomatic RP after SRT. On univariate analysis, V10, V20, PTV volume and PTV/Lung were significantly associated with occurrence of RP≥Grade 2. ROC curves indicated that symptomatic RP could be predicted using PTV/Lung [area under curve(AUC): 0.88, confidence interval (CI:0.78-0.95), cut-off value: 1.09, sensitivity: 90.0% and specificity: 72.4%]. PTV/Lung is a good predictor of symptomatic RP after SRT. Advances in knowledge: The cases with high PTV/Lung should be carefully monitored with caution for the occurrence of RP after SRT.

TOXICAN: a guide for grading dermatological adverse events of cancer treatments.

The dermatological toxicity of cancer treatments is frequent and sometimes debilitating. Its reference classification, the NCI-CTCAE (National Cancer Institute-Common Terminology Criteria for Adverse Events), is sometimes difficult to use and does not include yet the newest toxicities. Our objective was to create a guide, TOXICAN, based on the CTCAE, which is easy to use in everyday practice and which facilitates the recognition and grading of these dermatological toxicities. This guide was developed by a working group ("GESTIM") comprising oncodermatologists, allergists, pathologists, and researchers from Nantes University Hospital. It was based on the dermatological toxicities found in the CTCAE and adapted to daily practice. These toxicities were grouped into categories and associated with photographs of typical cases to aid recognition. A simplified grading scale derived from the CTCAE was also created. This booklet was validated by means of user evaluation, and then the Delphi consensus method. We selected 32 dermatological toxicities, including 12 created by our group, sorted into 7 categories: skin rash, dry skin/pruritus, hyperkeratotic papules, palmoplantar changes, hair and nail changes, mucosal changes, and others. Our simplified grading scale only differed from the CTCAE for one item, urticaria. Three items were modified after evaluation by the user group and 11 after application of the Delphi method. The objective of our practical guide is to facilitate the use of the CTCAE for recognizing and grading dermatological toxicity of cancer treatments in order to provide optimal guidance for therapeutic adaptations. Its impact on clinical practice remains to be evaluated.

Single Nucleotide Polymorphisms of Paclitaxel-induced Peripheral Sensory Neuropathy in Chinese Han Population.

Objective To study the single nucleotide polymorphisms (SNPs)that predict a patient's risk of grade 2-3 paclitaxel-induced peripheral sensory neuropathy (PSN) in Chinese Han populations.Methods Totally 216 patients received paclitaxel in Peking Union Medical College Hospital from May 2014 to December 2016 were enrolled.DNA was isolated from peripheral blood.Genotyping for eight candidate SNPs was performed on Sequenom-MassARRARYiPLEX platform.Patients were followed up and PSN was assessed by trained physicians according to National Cancer Institute-Common Terminology Criteria for Adverse Events v4.03.Results A total of 209 patients entered the final analysis.Among the candidate SNPs,only rs4141404:A>C(LIMK2) was significantly associated with grade 2/3 PSN (OR:4.32,95%CI:2.37-7.89,P<0.0001).In multivariate logistic regression analysis,both rs4141404:A>C(LIMK2) and history of receiving platinum compound (OR:2.70,95%CI:1.32-5.51,P=0.007) were associated with grade 2/3 PSN.Conclusion rs4141404:A>C(LIMK2) may be the markers of risk of grade 2/3 PSN.

Patient-reported tolerability of adverse events in phase 1 trials

BackgroundPhase I experts recommend revisiting dose-limiting toxicity (DLT) definition to include chronic and cumulative toxicities induced by new molecularly targeted therapies. Patient’s assessment of late toxicities’ tolerability is, however, unknown.Materials and methodsA prospective survey on adverse events (AEs) tolerability on 23 National Cancer InstituteCommon Terminology Criteria for Adverse Event, Version 4 (NCI-CTCAE.v4) items was conducted at Gustave Roussy’s Phase I department. Patients’ maximum tolerability duration was recorded at baseline, during trial and at trial completion. Results were compared with the corresponding physicians’ survey.Results52 patients enrolled in 27 Phase I trials between May 2014 and November 2015 completed 102 forms. At baseline, the most feared G2/G3 AEs were haematuria (74%), vomiting (71%) and hyperglycemia (64%)/dry mouth (94%), hyperglycemia (92%) and vomiting (92%). At trial completion, the most feared G2/G3 AEs were personality change (83.3%), haematuria (82%) and fever (80%)/dry mouth, fever and dizziness (100% each). Tolerability score did not differ over time. More previous treatments and occurrence of severe AEs were associated with better tolerability at study completion (p=0.0234 and p=0.0153, respectively, in multivariate analysis). Patient’s tolerability differed from physician’s assessment.ConclusionAEs considered intolerable by patients are toxicities that directly impact their quality of life and differ from those feared by physicians or included in DLT definition. Patient-reported tolerability of AEs may help in optimising drug development.

European Post-Approval Safety Study (PASS) of Relapsed/Refractory Multiple Myeloma (RRMM): Safety, Including SPM, in a Large Cohort of Patients Treated with Lenalidomide, Thalidomide, and Bortezomib

Background: EU PASS is an observational, noninterventional study designed to investigate the safety of lenalidomide (LEN) and other agents in the treatment of RRMM in a real-world setting.Aims:To assess the incidence of adverse events (AEs) of special interest, including neutropenia, thrombocytopenia, venous thromboembolism (VTE), peripheral neuropathy (PN), and second primary malignancies (SPMs) in RRMM patients (pts) treated with LEN and other antimyeloma therapies according to current clinical practice.Methods: Pts with RRMM who were commencing LEN treatment were enrolled at the investigator’s discretion into a LEN cohort (LEN + dexamethasone, the approved combination for the treatment of RRMM); pts who received ≥ 1 prior therapy and were commencing a non-LEN-based therapy were enrolled into a background cohort (all other treatments, including novel agents). Thromboprophylaxis was per local standard practice. AEs were graded according to National Cancer Institute-Common Terminology Criteria for Adverse Events (version 3). SPMs were defined using Medical Dictionary for Regulatory Activities (MedDRA) terms under the category Neoplasms SOC. Following protocol amendment in 2011, assessments for SPMs were to be conducted up to 36 mos after treatment discontinuation.Results: As of June 2016, 3632 pts across 269 institutions in 17 European countries were included in the safety population. Of those, 59.2% received LEN (n = 2151), 32.7% received bortezomib (BORT; n = 1188), 3.8% received thalidomide (THAL; n = 137), and 4.3% received other therapies (n = 156). The majority of pts had discontinued from treatment (97.9%; n = 3556); of the 2.1% (n = 76) ongoing pts, 66 are treated with LEN, 6 with BORT, 0 with THAL, and 4 with other substances. Baseline characteristics were similar across the cohorts. Median age was 70 yrs (range, 25-95 yrs) and 54.0% were male. Of 2985 pts with available ECOG data, 2865 (96.0%) had good performance status (ECOG score 0-2), and the remaining 4.0% had an ECOG score of 3/4. The median number of prior therapies was 1 (range, 1-6) but was higher in the LEN cohort (2; range, 1-6) than in the BORT (1; range, 1-6) and THAL (1; range, 1-5) cohorts; the proportion of pts with only 1 prior treatment was also lower in the LEN cohort (44.3%), whereas BORT was 70.8% and THAL 56.2%. Overall, 50.7% of pts (n = 1842) had grade 3/4 AEs. Grade 3/4 neutropenia occurred in 17.1%, 3.5%, and 4.4% of pts in the LEN, BORT, and THAL cohorts, respectively, and grade 3/4 thrombocytopenia in 9.2%, 7.3%, and 3.6%. The incidence rate of SPM was 3.63 per 100 pt-yrs, with 3.18 per 100 pt-yrs in the LEN cohort, 5.23 per 100 pt-yrs in the BORT cohort, 2.73 per 100 pt-yrs in THAL, and 6.48 per 100 pt-yrs in others. AEs of interest of all grades are listed in Table 1. The median duration on study treatment was 6.6 mos (range, 0.1-81.6 mos) for LEN, 4.1 mos (range, 0-63.6 mos) for BORT, and 4.6 mos (range, 0.2-36.9 mos) for THAL. Treatment discontinuation rate due to AEs was similar in each cohort (22.1% in the LEN, 20.0% in the BORT, and 21.2% in the THAL cohorts). In the LEN cohort, dose reductions occurred in 38.1% of pts, with a median time to first dose reduction due to AEs of 12.4 weeks. Treatment-emergent adverse events leading to dose reductions were similar across cohorts, with 23.7% in the LEN cohort, 21.4% in the BORT cohort, and 17.5% in the THAL cohort.Conclusions: Results of this noninterventional study in RRMM show that AEs were similar across cohorts except for higher rates of neutropenia and lower rates of PN with LEN compared with THAL or BORT. Higher rates of neutropenia did not translate into increased febrile neutropenia. Infections, independent from neutrophil counts, occurred in all cohorts, but few pts developed serious infections such as pneumonia. VTEs as well as myocardial infarctions were low throughout all cohorts. The occurrence of SPMs was generally low and comparable between cohorts. LEN was generally well tolerated. [Display omitted] DisclosuresTholouli:Johnson and Johnson: Speakers Bureau; Amgen: Honoraria, Speakers Bureau; Celgene: Honoraria; MSD: Speakers Bureau; Giles: Speakers Bureau. Hájek:Janssen: Honoraria; Takeda: Consultancy; BMS: Honoraria; Amgen: Consultancy, Honoraria, Research Funding; Celgene: Consultancy, Research Funding. Minnema:Celgene: Consultancy; BMS: Consultancy; Amgen: Consultancy; Jansen Cilag: Consultancy. Dimopoulos:Celgene: Consultancy, Honoraria, Membership on an entity’s Board of Directors or advisory committees; Amgen: Consultancy, Honoraria, Membership on an entity’s Board of Directors or advisory committees; Janssen: Consultancy, Honoraria, Membership on an entity’s Board of Directors or advisory committees; Genesis: Consultancy, Honoraria; Novartis: Consultancy, Honoraria, Membership on an entity’s Board of Directors or advisory committees. Frost Andersen:Celgene: Research Funding. Waage:Amgen: Speakers Bureau; Celgene: Consultancy, Honoraria; Novartis, Amgen, Celgene: Membership on an entity’s Board of Directors or advisory committees. Crotty:BMS, Takeda, Novartis, Janssen, Roche: Honoraria. Kueenburg:Celgene International Sarl: Consultancy, Honoraria. Di Micco:Celgene: Employment. Bacon:Celgene: Employment, Equity Ownership.

European Post-Approval Safety Study (Registry) of Relapsed/Refractory Multiple Myeloma (RRMM): Safety of Patients Treated with Pomalidomide

Background: This EU PASS is an observational, non-interventional registry designed to characterize the safety profile of pomalidomide (POM) in the treatment of RRMM in a real-world setting.Objectives:To assess the incidence of adverse events (AEs) of special interest, including neutropenia, thrombocytopenia, venous thromboembolism, peripheral neuropathy, and second primary malignancies in patients (pts) with RRMM treated with POM according to current clinical practice.Methods: Pts with symptomatic RRMM were enrolled at the investigator's discretion and after the decision was made to treat with POM. Thromboprophylaxis was administered per local standard practice. AEs were graded according to National Cancer Institute-Common Terminology Criteria for Adverse Events (version 4). The study is ongoing and open for recruitment in centers across Europe.Results: As of June 2016, 218 pts across 100 institutions in 8 European countries were included in the safety population. At the time of this abstract, 153 pts (70.2%) were ongoing. Median age was 68 yrs (range, 37-88 yrs), with 39.9% of pts < 65 yrs, 32.6% between 65 and 75 yrs, and 27.5% ≥ 75 yrs; 56.9% were male. Median time from diagnosis was 4.7 yrs (range, 0.4-25.4 yrs). Median number of prior therapies was 3 (range, 0-10); 80.8% of pts had at least 3 prior lines. Most pts (95%) received prior lenalidomide (given in second line in 66.1% and in third line in 20.2%). Prior bortezomib was administered in 96.8% of pts (given in second line in 54.6% and in third line in 28.4%). Almost half of the pts (49.5%) had a good performance status (Eastern Cooperative Oncology Group performance status 0-1). In this analysis, median treatment duration was 12.9 wks (range, 0.7-87.9 wks).Overall, 50.9% of pts (n = 111) had grade 3-4 AEs. AEs of all grades occurred in 79.8% (n = 174). Neutropenia of all grades was only reported in 22% of pts (n = 48), and febrile neutropenia in 2.3% of pts (n = 5). Infections of all grades occurred in 44.5% of pts (n = 97); of those, 11.5% were pneumonia. Thrombocytopenia occurred in 7.8% (n = 17). Fatigue occurred frequently in 13.8% of pts (n = 30). There were some gastrointestinal disorders, such as diarrhea in 7.8% (n = 17), constipation in 6.4% (n = 14), and nausea in 6.0% (n = 13) of pts. Peripheral polyneuropathy was uncommon (3.2%; n = 8). Acute myocardial infarction and deep vein thrombosis were observed in 1 pt each, and 1 pt developed basal cell carcinoma.Conclusions: Results of this ongoing non-interventional study in RRMM on the use of POM in the real-world setting show a similar AE profile to that in the pivotal trial published by San Miguel in Lancet Oncology (2013). POM was generally well tolerated, and the overall safety profile is similar to that seen in pivotal trials. Updated data will be presented at the meeting. DisclosuresDi Raimondo:ARIAD; Bristol-Myers Squibb; Novartis; Roche: Consultancy; Bristol-Myers Squibb; Celgene; Novartis: Speakers Bureau; Gilead Sciences: Other: Travel Expenses. Bentsen:Celgene, Teva: Other: Travel expenses. Kueenburg:Celgene International Sarl: Consultancy, Honoraria. Lersch:Celgene: Employment. Bacon:Celgene: Employment, Equity Ownership. Plesner:Janssen: Membership on an entity's Board of Directors or advisory committees, Research Funding.

371P Effect of oral silymarin administration on prevention of radiotherapy induced mucositis: A randomized, double- blinded, placebo-controlled clinical trial

Background Mucositis is a frequent severe complication of radiation therapy in patients with head and neck cancer. Silymarin is a polyphenolic flavonoid extracted from the milk thistle that exhibits a strong antioxidant and anti-inflammatory activities. In this study, we evaluated silymarin efficacy in prevention of radiotherapy-induced mucositis in patients with head and neck cancer as the first in human study. Methods During this pilot, randomized, double-blinded, placebo-controlled clinical trial, the effect of oral silymarin 420 mg daily in three divided doses starting at the first day of radiotherapy session and continuing for six weeks on oral mucositis occurrence were assessed. Twenty-seven patients fulfilled the inclusion criteria assigned to the silymarin or placebo group. World Health Organization (WHO) and National Cancer Institute-Common Terminology Criteria (NCI-CTC) oral mucositis grading scale scores were recorded at baseline and weekly during the 6 weeks. Results The median WHO and NCI-CTC scores was significantly lower in the silymarin group at the end of the first to sixth week (P < 0.05). The scores increased significantly in both placebo and silymarin groups during radiotherapy but there was a delay for mucositis development and progression in the silymarin group. Conclusions: Prophylactic administration of conventional form of silymarin tablets could reduce radiotherapy-induced mucositis in patients with head and neck cancer. Legal entity responsible for the study: N/A Funding Research Council of Mashhad University of Medical Sciences and to Goldaroo Company Disclosure All authors have declared no conflicts of interest.