Real-world efficacy and safety outcomes of imatinib treatment in patients with chronic myeloid leukemia: an Australian experience

Background: Tyrosine kinase inhibitors (TKI) have revolutionised the treatment of chronic myeloid leukaemia (CML), but patients still experience treatment-limiting toxicities or therapeutic failure. Aims: To investigate real-world use and outcomes of imatinib in patients with CML in Australia. Methods: A retrospective cohort study of patients with CML commencing imatinib (2001-2018) was conducted across two sites. Prescribing patterns, tolerability outcomes, survival and molecular response were evaluated. Results: 86 patients received 89 imatinib treatments. Dose modifications were frequently observed (12-month rate of 58%). At last follow-up, 62 patients (5-year rate of 55%) had permanently discontinued imatinib treatment, of which 44 switched to another TKI (5-year rate of 46%). Within 3 months of starting imatinib, 43% (95% CI, 32–53%) of patients experienced imatinib-related grade ≥3 adverse drug reactions (ADRs). Higher comorbidity score, lower body weight, higher imatinib starting dose, and Middle Eastern or North African ancestry were associated with a higher risk of grade ≥ 3 ADR occurrence on multivariable analysis (MVA). Estimated overall survival and event-free survival rates at 3 years were 97% (95% CI, 92–100%) and 81% (95% CI, 72–92%), respectively. Cumulative incidence of major molecular response (MMR) at 3 years was 63% (95% CI, 50–73%). On MVA, imatinib starting dose, ELTS score, BCR-ABL1 transcript type, pre-existing pulmonary disease, and potential drug-drug interactions were predictive of MMR. Conclusion: Imatinib induced deep molecular responses that translated to good survival outcomes in a real-world setting, but was associated with a higher incidence of ADRs, dose modifications and treatment discontinuations than in clinical trials.

Surgical strategy for squamous cell carcinoma of the external auditory canal: management of locally advanced cases with skull base involvement

Objective Surgical indications for advanced-stage squamous cell carcinoma (SCC) of the external auditory canal (EAC) are highly dependent on the skull base surgery team. The aim of this study was to evaluate the surgical outcomes in patients with SCC of the EAC and to clarify the surgical indication of far advanced cases using the T4-subclassification. Methods Patients with SCC of the EAC who underwent curative treatment from 2002-2021 were retrospectively reviewed at our hospital. Clinical and surgical results, including operative data, overall survival (OS), and disease-specific survival (DSS) were analyzed. To clarify the surgical indication for advanced stage, we proposed the T4-subclassification. Results In 46 patients, the tumors were in T1 stage in 8 patients, T2 in 10, T3 in 5, and T4 in 23. The 5-year DSS with T1, T2, T3, and T4 tumors were 100%, 85.7%, 100%, and 61.7%, respectively. No prognostic impacts for margin status were found between the 5-year OS and DSS (p = 0.23 and p = 0.13). Patients with far advanced stage (T4b) tumors were significantly associated with shorter DSS than those with early stage (T1/T2) and advanced stage (T3/T4a) tumors (p = 0.007 and p = 0.03). Conclusion The present study focused on patients with SCC of the EAC at a University hospital over a period of 20-years, especially with skull base involvement, and a T4-subclassification was proposed. Complete tumor resection in an en bloc fashion could help to achieve a good survival rate even in patients with locally advanced tumors.

EFFECT OF ADDITIONAL GINGER (Zingiber officinale var. amarum) ON FEED ON THE GROWTH AND SURVIVAL LEVEL OF GOLDFISH (Cyprinus Carpio)

Goldfish is one of the most popular freshwater cultivated fish because it is one of the freshwater commodities that has economic value and is sold at a price that is affordable to all groups. Ginger is a natural ingredient that can stimulate fish growth. The purpose of this study was to determine the effect of adding ginger to feed and to determine a good dose of ginger for growth and survival rates of carp (Cyprinus carpio). This research was conducted by experimental method using completely randomized design (CRD) with 5 treatments and 3 replications. The treatments given were Treatment 1: 0 grams, without adding ginger / kg of feed (control), Treatment 2: 2.5 grams of ginger / kg of feed, Treatment 3: 5 grams of ginger rhizome / kg of feed, Treatment 4: 7.5 grams of ginger / kg of feed, Treatment 5: 10 grams of ginger / kg of feed. The results showed that the addition of ginger had no significant effect on absolute length growth, absolute weight growth, feed conversion ratio, and feed efficiency, but had a significant effect on the survival rate of goldfish (cyprinus corpio). And a good dose of ginger is in P2 treatment with a dose of 2.5 grams of ginger, because it has been able to show a good survival rate of 100%.

Dental implants survival after nasal floor elevation: a systematic review

Purpose The aim of this work is to assess the clinical outcomes of implants placed after a nasal floor elevation procedure. Methods A systematic review was conducted using four electronic databases; Medline (Pubmed), Cochrane library, DOAJ and SCOPUS, following the PRISMA statement recommendations to answer the PICO question: “In patients undergoing dental implant placement in the maxillary anterior region (P), Do implants placed after nasal floor elevation (I) have a different survival (O) from those implants placed without grafting procedures (C)?. The study was pre-registered in PROSPERO (CRD42021229479). Included articles quality was assessed using the “NIH quality assessment tool”, “The Newcastle-Ottawa scale” and “JBI critical appraisal tools for case reports''. Results Twelve articles were finally selected, including 151 patients and 460 implants. The weighted mean follow-up was 32.2 months, and the weighted survival rate after this period was 97.64% (range 89.2-100%). No statistical differences could be inferred between the treatments performed in one-stage or two-stage, following a lateral approach or a transcrestal approach or using different grafting materials. A great heterogeneity was found in terms of study design and methodological aspects. For this reason, a quantitative analysis followed by meta-analysis was not possible. Conclusion Within the limitations of this study, implants placed after a nasal floor elevation present a good survival and a low range of complications. In absence of randomized studies, the level of evidence was low, attending the GRADE system and based on the study quality level, the strength of evidence attending the SORT taxonomy was B.

Cryopreservation of Arachis Hypogaea L. Varieties, from the INIAP-Ecuador Germplasm Bank

The peanut (Arachis hypogaea L.) is recognized as one of the most important legume crops globally for its use in human food; it is widely distributed and cultivated in tropical and subtropical regions. The purpose of this study was to evaluate the cryopreservation of five peanut varieties conserved in the INIAP Germplasm Bank, testing cryopreservation methods, evaluating the germination percentage of whole seeds and embryonic shoots. Subsequently, two quantitative variables, shoot length and root, were evaluated. The average germination percentage of varieties and treatments was higher when embryonic axes were isolated with 99.31% than 86.06% seeds. The best germination percentage of the five varieties for seeds and embryonic shoots was obtained by the Peruvian variety with 88.13% and 92.50%. The best treatments by variety for the germination of whole seeds and embryonic axes were obtained by the treatment (desiccation and NL) for whole seeds (GS2) with 95.42% and embryonic axes with 92.83%. Ageing and cryopreservation treatments positively affected germination and seedling vigor in whole seeds and embryonic axes. The two quantitative variables, shoot and root length showed variability between the five varieties; significant differences were observed between the four treatments evaluated for whole seeds and embryonic axes. The three treatments for whole seeds (GS1, GS2 GS3) and the non-cryopreserved control treatment (GSC), as well as the treatments for embryonic axes (GEA1, GEA2 GEA3) and the non-cryopreserved control treatment (GEAC), obtained good survival. They germinate whole seeds and embryonic axes with sprout development (aerial part) and root formation. With the most effective treatments for whole seeds (GS2) and embryonic axes (GEA2), the cryopreservation of the national peanut collection of the INIAP Germplasm Bank could be started.

Recovery patterns in patients undergoing revision surgery of the primary knee prosthesis

Purpose Despite good survival rates of revised knee prostheses, little is known about recovery trajectories within the first 12 months after surgery. This retrospective observational study explored recovery trajectories in terms of pain, function and quality of life in patients after revision knee arthroplasty over 12 months. Methods Eighty-eight revision knee arthroplasty patients rated changes in daily physical functioning using the anchor question (0: very much worsened; 7: very much improved). Patient reported outcome measures (PROMs) of pain (range 0–10), function (Oxford Knee Score) and quality of life (EQ-5D-3L) were assessed preoperatively, at 3 and 12 months postoperatively. Four recovery trajectories were identified using the anchor question at 3 and 12 months postoperatively: no improvement, late improvement, early improvement, and prolonged improvement. Repeated measures ANOVA was conducted with recovery trajectories as dependent variable and PROM assessments as independent variables. Results Sixty percent reported improvement in daily physical functioning at 12 months postoperatively. Age and reason for revision differed between groups. Pain, function and EQ-5D-3L differed between groups over time. Late and prolonged improvement groups improved on all PROMs at 12 months. The early improvement group did not report improvement in daily physical functioning at 12 months, while improvements in function and pain during activity were observed. Conclusions Different recovery trajectories seem to exist and mostly match PROMs scores over time. Not all patients may experience beneficial outcome of revision knee arthroplasty. These findings are of importance to provide appropriate information on possible recovery trajectories after revision knee arthroplasty to patients. Level of evidence III

The Outcome of Fatherhood in Patients with Philadelphia Negative Myeloproliferative Neoplasms, a Single Institution Experience"

Introduction Fertility is a complicated subject, it involves more than one individual, and it has profound psychological and economic implications. Moreover, it is affected by several factors, including age, presence of systemic disease, exposure to environmental toxins, medications, or radiation. Compared to the general population, fertility in patients with malignancy is a more complex topic. Cancer survivors, both male and female, may have reduced fertility due to cancer itself or the treatment received. This includes patients with Myeloproliferative neoplasms (MPN), especially that more patients are diagnosed at younger age and patients had good survival and quality of life. As a result, questions regarding fertility and fatherhood are rising, and the effect of the disease and treatment on male fertility is a big concern. There are limited studies that assessed fatherhood in Philadelphia-negative myeloproliferative neoplasms. Methods This is a single-center, mixed-design study (retrospective + phone interviews) conducted within the National Center for Cancer Care and Research. The aim is to evaluate fertility in the Philadelphia-negative MPN male patients and the effect of treatment received on male fertility and the outcome. Inclusion Criteria: Male patients, adult male patients aged >=18 years old, diagnosed with Philadelphia negative MPN (ET PV MF PMF) According to 2008 2016 WHO criteria and actively receiving treatment including tyrosine kinase inhibitors including (hydroxyurea, interferon, and ruxolitinib ) with the following: -patients with no previous fertility problems will be included in the study. -Patients with no known issues with regards to fertility (fertility is intact) will be included in the study. -Patients who developed fertility issues after diagnosis of Philadelphia negative MPN (ET PV MF PMF), who has been evaluated by an andrologist, and evaluation concluded it is related to treatment. Exclusion criteria: - Patient with Philadelphia positive MPN - Patients not fulfilling inclusion criteria are as follow: -Patient was known to have infertility before the diagnosis of Philadelphia-negative MPN. -Patient with infertility after Diagnosis of Philadelphia negative MPN (ET PV MF PMF): If a Clear underlying cause of infertility is not related to treatment, participants will be excluded from the study.if no evaluation was done for infertility or no clear cause for infertility, the patient will be excluded.The mother has documentation by gynecologist for infertility, or after examining the abortion, stillbirth or IUFD and checking the chromosomal analysis (any mother-related cause, whether endogenous or exogenous)will be excluded. Results: Of 120 patients interviewed, only 19 patients (15.7%) had met the inclusion criteria (Figure 1). The majority of patients had lost follow-up or cannot be contacted, and 29.1% of patients had their families completed by the time of diagnosis. The treatment received includes hydroxyurea, interferon, and ruxolitinib. The mode of delivery was normal vaginal delivery in 68% of the pregnancies. The total number of conceptions was 27; three stillbirths were reported; one intrauterine fetal death and one baby of a twin died in utero (table 1). Discussion and Conclusion: A significant percentage of patients diagnosed with Ph-negative MPN are young; the mean age of patients meeting the inclusion criteria at the time of diagnosis was 35 years. This means that a large number of patients are in the reproductive age group or are sexually active. Having a diagnosis of MPN will put these patients in huge psychological distress due to the unknown outcome about their fertility and sexual life and the fear of possible consequences on their children. The data showed that most MPN male patients on treatment had their offspring born normally with no delivery complications, no reported congenital anomaly or growth retardation, and no report of MPN-related cancers. Though, further studies with a larger sample size are required to fully understand the effect of medications on the outcome of fatherhood Philadelphia negative MPN patients. Nonetheless, a call for attention for better education to patients starting on medications addressing the possible psychological fear or concerns of having an unsatisfactory effect on their fertility/offspring, targeting better acceptance and adherence to treatment. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.

RADT-24. SYNTHETIC TREATMENT OF CENTRAL NERVOUS SYSTEM EWING/PRIMITIVE NEUROECTODERMAL TUMOR (EWING/PNET): A CASE REPORT

Ewing/PNET is a rare tumor of the central nervous system. After the standard treatment, there’re still 86.7% of patients had recurrence and no standard treatment after recurrence. Here we report a case of Ewing/PNET with a good survival after synthetic treatment to provide evidence for future clinical strategies. A 23-year-old male underwent resection of the left frontal tumor on April 28, 2017, the pathological diagnosis was Ewing/PNET. He received whole brain radiotherapy 36Gy in 18 fractions, and tumor bed boost to 56Gy in 28 fractions, with 3 courses of Nedaplatin adjuvant chemotherapy. The tumor recured 23 months after the surgery. The patient underwent the second resection, followed by 4 courses of ADM+VCR+CTX/IE chemotherapy. However, 27 months after the first surgery, the tumor evaluation progressive resection of recurrent tumors in the anterior cranial base-ethmoid sinus. During the chemotherapy, MRI showed that tumor still increased. There was a mass in the root of the forehead and nose. After the third recurrence, the patient received re-radiotherapy (50Gy in 25 fractions) 29 months later after the first RT. The tumor was significantly reduced after radiotherapy. Physical examination showed that the sense of smell continued to weaken, the visual acuity was the same as before. 8 courses of VIT (Irinotecan, vincristine, temozolomide) were followed by second RT, tumor was assessed every 2 courses. 44 months after the first surgery, he suffered a third recurrence in spina cord. And then he received rescue RT (20Gy in 10 fractions) in the recurrent tumor. The tumor was reduced after local radiotherapy. He was undergoing follow-up till May 2021, And the OS is 49 months. In conclusion, the incidence of this disease is low, especially in adults. However, the prognosis is poor. Early detection, early operation, combined with radiotherapy and chemotherapy are promising to improve the efficacy of Ewing/PNET.

SURG-02. NEUROSURGICAL RESECTION FOR LOCALLY RECURRENT BRAIN METASTASIS

BACKGROUND In patients with locally recurrent brain metastases (LRBMs), the role of (repeat) craniotomy is controversial. This study aimed to analyze long-term oncological outcomes in this heterogeneous population. METHODS Craniotomies for LRBM were identified from a tertiary neuro-oncological institution. First, we assessed overall survival (OS) and intracranial control (ICC) stratified by molecular profile, prognostic indices, and multimodality treatment. Second, we compared LRBMs to propensity score-matched patients who underwent craniotomy for newly diagnosed brain metastases (NDBM). RESULTS Across 180 patients, median survival after LRBM resection was 13.8 months and varied by molecular profile, with >24 months survival in ALK/EGFR+ lung adenocarcinoma and HER2+ breast cancer. Furthermore, 102 patients (56.7%) experienced intracranial recurrence; median time to recurrence was 5.6 months. Compared to NDBMs (n = 898), LRBM patients were younger, more likely to harbor a targetable mutation and less likely to receive adjuvant radiation (p < 0.05). After 1:3 propensity matching stratified by molecular profile, LRBM patients generally experienced shorter OS (hazard ratio 1.67 and 1.36 for patients with or without a mutation, p < 0.05) but similar ICC (hazard ratio 1.11 in both groups, p > 0.20) compared to NDBM patients with similar baseline. Results across specific molecular subgroups suggested comparable effect directions of varying sizes. CONCLUSIONS In our data, patients with LRBMs undergoing craniotomy comprised a subgroup of brain metastasis patients with relatively favorable clinical characteristics and good survival outcomes. Recurrent status predicted shorter OS but did not impact ICC. Craniotomy could be considered in selected, prognostically favorable patients.