Addition Of Chemotherapy Research Articles

Influence of lymphovascular invasion on outcome of colon cancer

Background: Colon cancer is the third most common type of cancer. High lymphovascular levels are linked to a number of cancers, including colon cancer, while lymph vascular invasion levels as a predictor of outcome are not well understood. Objective: Determine the influence of lymphovascular invasion on the recurrence of colon cancer. Patients and Methods: it was collected 126 colon cancer patients who had surgery and additional chemotherapy. The patients attended in the Baquba teaching hospital oncology centre and the Al Jawad oncology centre of Alkadhemiya hospital. Results: it was shown in this study that the high percentage ages of colon cancer patients was between 55-60 years, and there were more in women (57 %) than in men (43 %). The most common stage of the tumours was stage 3 (42.9 %), and in grade 2 (76.2 %). In terms of return, in this study, 71.4 % of people who had lymphovascular invasion positive and had a return of cancer in a percentage 73.3% of colon cancer patients. Conclusion: LVI plays an essential role for increasing recurrence of colon cancer, and there were a strong link between them.

Efficacy of Doxorubicin in the Adjuvant Treatment of Canine Splenic Visceral Hemangiosarcoma

Introduction. Splenic hemangiosarcoma is a highly malignant neoplasm that affects geriatric patients. The incidence in dogs is 45–50% of all splenic tumours and about 2% of all oncological pathologies. The visceral form of splenic hemangiosarcoma is characterised by the most aggressive course of the disease and early metastasis to other organs. The average life expectancy of animals after splenectomy, according to various scientific data, is from 20 to 90 days. The article studies the efficacy of additional doxorubicin-based adjuvant chemotherapy to increase the life expectancy of dogs at different stages of the disease.Materials and Methods. To compare the life expectancy, the patients were divided into 4 groups receiving different treatments for splenic hemangiosarcoma. Examination of patients, visual diagnostics and pathomorphological diagnostics were used for making a diagnosis, determining the stage of the disease and prescribing treatment. Treatment efficacy was assessed based on the median relapse-free period, median life expectancy and survival rate of patients after 3, 6, and 12 month periods. Statistical analysis was performed using the Fisher's exact test.Results. The obtained data demonstrated a more favourable course of disease in dogs with the stage I tumour process. Splenectomy made it possible to increase the life expectancy of patients to 243 days with a 6–month survival rate in 62.5% of patients. Postoperative chemotherapy treatment combined with doxorubicin significantly improved the longterm prognosis and led to more than twofold increase in life expectancy of dogs (up to 475 days) with a one-year survival rate in 83.3% of patients. However, no substantial statistical significance was determined in the studied groups (p=0.7).Discussion and Conclusion. The results of the research have revealed the efficacy of adjuvant doxorubicin-based chemotherapy in dogs with the visceral forms of splenic hemangiosarcoma. In animals with early stages of the disease, a significant increase in life expectancy has been discovered. The development of hemagdomain and/or the presence of metastasis to abdominal organs indicate the unfavourable course of the disease and, as a consequence, early metastasis. Nevertheless, even at these stages, doxorubicin can increase the life expectancy of patients.

Assessment of endobronchial chemotherapy in patients with bronchogenic carcinoma

Background Malignant airway obstruction is commonly found in patients with lung cancer and is associated with significant morbidity and mortality. Relieving malignant obstruction may improve symptoms, quality of life, and life expectancy. The aim of the present work is to determine the efficacy of endobronchial intratumoral injection of 5-Fluorouracil as a chemotherapeutic agent in palliative care for patients with inoperable nonsmall-cell lung cancer (NSCLC). Patients and methods A total of 30 patients diagnosed as inoperable advanced-stage NSCLC were included into this randomized prospective controlled comparative study and divided into two groups (group A: 15 patients received the conventional sessions of systemic chemotherapy only and group B: 15 patients received the conventional sessions of systemic chemotherapy in addition to two to three sessions of local endobronchial intratumoral chemotherapy using 5-fluorouracil). Patient characteristics, histology, airways infiltrated with the tumor, performance status, treatment cycles, complications, and therapeutic outcomes were evaluated. Tumor response was analyzed based on bronchoscopic evaluation performed on completion of the final treatment session. Results There was no significant difference in the total objective response between patients who used systemic chemotherapy alone for treatment of advanced NSCLC and those who used systemic chemotherapy in addition to sessions of local chemotherapy using 5-fluorouracil that was injected intratumorally through bronchoscopy in multiple sessions. Conclusion We concluded that endobronchial intratumoral chemotherapy using 5-fluorouracil is not an effective promising treatment approach for palliative treatment of patients with advanced malignant endobronchial NSCLC.

Optimizing workflow for OncotypeDx result turnaround time from surgery to report at safety net hospital.

317 Background: OncotypeDx test has been widely used for breast cancers patients with early-stage (I-IIIa), hormone-receptor positive, HER2-negative disease. It predicts the benefit of adjuvant chemotherapy in addition to hormone therapy. Delivering OncotypeDx results in a timely manner is important to inform treatment decisions. As a quality improvement project, we implemented a strategy to reduce the Turn Around Time (TAT) from breast surgery to OncotypeDx report at Bellevue Cancer Center, the tertiary referral center of the NYC Health and Hospitals System. Methods: The primary measure was TAT from surgery to receiving OncotoypeDx result in electronic medical record (EMR). We compared TAT before and after implementation of the strategy. The historical control was from 5/2021 through 3/2022, while the group after strategy implementation was from 6/2023 to 1/2024. The strategy revolved around streamlining the identification of eligible patients by collaborating with the breast surgery team, creating and utilizing a smart phrase in the EMR. It also involved ordering OncotypeDx by closely communicating with the pathology department, obtaining insurance approval by working with the OncotypeDx vendor, and tracking OncotypeDx results. The above process was done by a breast surgery provider that offered real time updates in the EMR. Results: The patient groups were similar both before and after implementing the strategy, including patient number (26 and 27 respectively) and patient mean age (61 and 59). The majority of both groups were minority patients (77% and 81%). We found that a higher percentage of patients were from Medically Underserved Areas and Populations (MUA/P) in the group after strategy implementation (35% and 56%). Our strategy reduced the average TAT from 56 days to 30 days. Conclusions: We developed a strategy to optimize the OncotypeDx workflow in a large safety net health system despite an increase in patients from MUA/P. Initiating ordering of OncotypeDx by breast surgery along with communication with pathology and the vendor significantly reduced TAT. EMR integration with OncotypeDx vendor would be the next step to further improve the process. Before Strategy Implementation (n=26) After Strategy Implementation (n=27) Patient Mean Age 61 59 Race (%) White 27 18.5 Hispanic 39 44.4 Black 7 25.9 Asian 23 11.1 Other 4 0 Ethnicity (%) Hispanic 39 44.4 Non-Hispanic 61 55.6 Underserved Area and Population (%) 35 56 Health Professional Shortage Area (%) 50 59 Non-English Speaking (%) 50 40.7

Systemic chemotherapy in addition to CRS-HIPEC for colorectal peritoneal metastases: A critical systematic review on the impact on overall survival.

In patients with resectable colorectal peritoneal metastases, it is unclear whether systemic chemotherapy, in addition to cytoreductive surgery-hyperthermic intraperitoneal chemotherapy(CRS-HIPEC), improves overall survival (OS). This systematic review of 12 retrospective studies involving 3721 patients aimed to summarize the available evidence. Contradictory results were found regarding the effectiveness of neoadjuvant, adjuvant, and perioperative systemic therapies on OS, with a high risk of bias. Available evidence remains inconclusive, stressing the need for prospective, randomized trials, like the ongoing Dutch CAIRO6-trial.

Cervical gastric decompression tube: safety and efficacy outcomes for inoperable malignant bowel obstruction.

Inoperable malignant bowel obstruction, which results in chronic nausea, vomiting and abdominal pain, often requires nasogastric tube decompression. However, these tubes are often uncomfortable for patients and require hospitalization during the end-of-life care. Cervical esophago-gastric (CEG) decompression tubes are a potential palliative solution. The objective of this study is to present the outcomes of CEG tubes in 11 patients with malignant bowel obstruction. We performed a retrospective review of patients requiring nasogastric tube decompression who received CEG decompression tubes for inoperable malignant bowel obstructions between 2016-2022. CEG tube placement was performed percutaneously through the left neck using a guidewire and an endoscopic technique. The average age of patients was 58 years (31-72 years), with metastatic colorectal cancer (36.4%) and ovarian cancer (27.3%) being the most common causes of malignant bowel obstruction. All procedures were completed percutaneously, without requiring conversion to open procedures. The morbidity of the procedure was 27%, which included tube dislodgement, local cellulitis, or bleeding at the insertion site. None of the patients required reoperation, with most of the patients successfully treated conservatively. Most patients were discharged home after the procedure (82%); however, 45% were readmitted (mostly due to abdominal pain). Most patients (73%) were able to continue additional chemotherapy after tube placement. The average survival from cancer diagnosis was approximately six months, whereas the average survival after the procedure was about four months. No mortalities occurred due to CEG tube placement. A CEG decompression tube is safe for patients with malignant bowel obstruction. The procedure allows patients to undergo additional chemotherapy and be discharged home with a more comfortable tube.

Dr. Sidney Farber (1903-1973): Founder of Pediatric Pathology and the Father of Modern Chemotherapy.

Dr. Sidney Farber (Farber) was a distinguished pediatric pathologist and widely recognized pioneer of modern chemotherapy. In 1948, his influential study showed that various anti-folates, particularly 4-aminopteroylglutamic acid, also known as aminopterin, induced transient disease control in kids who had acute undifferentiated leukemia. The findings laid the basis for developing and using additional chemotherapies, individually or in combination, for treating pediatric and adult cancers. Farber also introduced actinomycin D to treat Wilms tumor in various stages. Underneath his oversight, the 'Jimmy Fund,' one of the earliest dedicated pediatric oncology centers, and the Children's Cancer Research Foundation, which subsequently evolved into the Dana-Farber Cancer Institute, was established. Farber is known as the "Founder of Pediatric Pathology" and the "Father of Modern Chemotherapy," citing his immense contributions. This article is a tribute to the great scientist Farber for his significant contributions to the scientific field and the countless individuals he has impacted.

Fertility preservation in men with hypogonadotropic hypogonadism secondary togerminoma: two cases of gonadotropin replacement therapy before induction of anticancer chemotherapy.

Hypogonadotropic hypogonadism can be caused by brain tumors. For a malignancy such as a germ cell tumor, chemotherapy combined with radiation is administered. In patients who wish for children, the inability to undergo sperm cryopreservation before treatment because of impaired spermatogenesis and/or ejaculation dysfunction can be problematic. We herein present two cases involving a 26-year-old man and a 30-year-old man with hypogonadotropic hypogonadism due to an intracranial germinoma and both wished to have children. Gonadotropin replacement therapy prior to anticancer chemotherapy resulted in subsequent spontaneous pregnancy or assisted reproductive therapy. Subsequent treatment of the tumor resulted in no recurrence for 9 and 2years, respectively. Close consultation with an oncologist is mandatory in such cases. Depending on the tumor prognosis, however, it may be possible to delay tumor treatment and prioritize fertility because there is a possibility of impaired spermatogenesis due to additional chemotherapy.

Prognostic significance of microsatellite instability in patients with resectable gastric cancer

BackgroundMicrosatellite instability (MSI) gastric cancer (GC) generally has a better prognosis than microsatellite-stable (MSS) GC and has been associated with nonsurvival benefit with the addition of chemotherapy (CMT) compared with surgery alone. However, patients with MSI have distinct clinicopathological characteristics. This study aimed to compare the survival outcomes between patients with MSI GC and those with MSS GC. In addition, this study analyzed the survival outcomes of patients with MSI GC who received CMT. MethodsThis study reviewed all patients with GC who underwent curative gastrectomy. Patients were divided into MSI group and the MSS group. Propensity score matching (PSM) was used to match clinicopathological factors. ResultsAmong the 378 patients enrolled, 78 (20.6%) had MSI. Older age (P < .001), subtotal gastrectomy (P = .008), pN0 (P = .020), and earlier pTNM stage (P = .012) were associated with MSI GC. Survival analysis showed better disease-free survival (DFS) and overall survival (OS) of patients in the MSI group (P = .012 and P = .019, respectively). After PSM, 78 patients were matched to each group. All variables assigned to the scores were well matched, and both groups became equivalent. After the matching, the differences in DFS and OS according to MSI/MSS status were estimated to be larger than before (DFS: 63.3% vs 41.4%; P = .002; OS: 65.8% vs 42.5%; P = .002). Regarding patients referred for CMT, there was no difference in DFS and OS between patients with MSI GC who underwent CMT and those who underwent surgery alone (P = .255 and P = .178, respectively). ConclusionEven after controlling for clinicopathological characteristics, MSI was identified as a prognostic factor for patient survival. MSI GC showed no significant survival benefit with the addition of CMT.

Detection of Contralateral Malignancies on Breast MRI.

Women with unilateral breast cancer are at increased risk for having simultaneous cancer of the contralateral breast. Overall, earlier detection of contralateral breast cancer prevents the burden of additional surgery or chemotherapy rounds and is associated with higher overall survival. However, MRI screening for the contralateral breast is seldom done following an initial unilateral breast cancer diagnosis. The purpose of this study is to retrospectively evaluate patients with known, biopsy-proven malignancy who went on to obtain a breast MRI and were later found to have cancer of the contralateral breast. Methods: This was a retrospective study that reviewed the charts of women aged over 18 years who were determined to have synchronous bilateral breast cancer from January 2017 to January 2022 at the University of Florida, Gainesville, FL. The study extracted data from this institution's cancer registry database, which provided information on patients with breast cancer diagnoses. The study conducted a review of mammography (MAM) and MRI imaging reports to ascertain the presence or absence of contralateral breast cancer identified by each respective imaging modality. Surgical pathology reports from the biopsy of the contralateral breast were reviewed to obtain information on the histological type of cancer and TNM (tumor, node, metastasis) staging. Of the 17 cases in which MAM missed contralateral cancer, follow-up MRI detected contralateral malignancy in 12 cases (70.59%) and subsequently changed management, resulting in additional imaging, biopsy, and eventual diagnosis and treatment of contralateral breast cancer. Examining the number of contralateral breast cancers detected by patients who had undergone MAM followed by MRI and those who had only undergone MAM, the study found that the detection rate of contralateral breast cancer from MAM was 45.45% (15/33). The tumor stages of the missed cancers were all T1 or Tis stage with one T1mi, and there was no nodal involvement. Conclusion: In addition to its utility in staging breast cancers, MRI also has the superior ability to detect otherwise undetected contralateral breast malignancy. This retrospective study found that MRI imaging led to a considerable increase in the detection of contralateral cancer. The study found that these undetected contralateral breast cancers by MAM were often of lower staging with no nodal involvement, highlighting the opportunity for MRI to assist in early cancer detection while the patient's prognosis is still good. Its high cost should be balanced with staging and occult malignancy detection utility in future practice.

Outcomes associated with total neoadjuvant therapy with non-operative intent for rectal adenocarcinoma.

To evaluate rates of clinical complete response (cCR), surgery-free survival, permanent ostomy-free survival, and factors associated with these outcomes in patients treated with total neoadjuvant therapy (TNT) with intent for non-operative management of rectal adenocarcinoma. A retrospective review was conducted of patients treated with TNT for stage II-IV rectal adenocarcinoma (n=45) at our institution between 2013 - 2022 with curative intent. All patients received radiation with concurrent capecitabine and additional chemotherapy, either prior to or following chemoradiation (CRT), with intent for non-operative management. Response rates were determined based on post-treatment MRI and endoscopy. Kaplan-Meier method was utilized to estimate the 1- and 2-year surgery- and permanent ostomy-free survivals. Cox regression was used to evaluate associations between surgery- and permanent ostomy-free survivals and various factors of interest, including patient and tumor characteristics and clinical response. Chi-squared analysis compared rates of cCR and surgery by sequence of TNT modality and cell count ratios. Of the 45 patients treated with TNT, most patients had low-lying rectal tumors with a median distance of 4.1cm from the anal verge (range, 0.0 - 12.0). Overall, 64.4% (n=29) achieved cCR after TNT. 13 patients (28.9%) underwent surgical resection following TNT, 12 of whom had incomplete response and one who elected to undergo surgery after reaching cCR. At median follow up of 32.0 months (range, 7.1 - 86.1), 22.2% (n=10) of patients had a permanent colostomy, with only 2 of these completed for tumor regrowth after cCR. At one and two years, respectively, surgery-free survival was 77.3% and 66.2%, and permanent ostomy-free survival was 90.9% and 78.2%. Rates of cCR were higher in patients who received CRT first compared to those who received chemotherapy first (72.2% vs. 33.3%, p=0.029) and rates of surgery were also lower in patients who received CRT first compared to those who received chemotherapy first (19.4% vs. 66.7%, p=0.005). On Cox regression model, cCR on 6 month post-CRT endoscopy was associated with surgery-free survival (p=0.006) and permanent ostomy-free survival (p=0.033). Clinical response at earlier follow up points did not predict surgery- nor permanent ostomy-free survival. These results support evidence that TNT may be a non-surgical option for select patients with rectal adenocarcinoma who desire organ preservation. In this investigation at a single institution, the treatment response on 6-month post-CRT endoscopy was the best predictor of surgery- and permanent ostomy-free survival, which are outcomes that are important to patient quality of life. CRT followed by consolidation chemotherapy was associated with higher rates of cCR and lower rates of surgery compared to those treated with induction chemotherapy.

Real Implication of Fertility-Sparing Surgery for Ovarian Cancer: Reproductive Outcomes.

to prove the effectivity of fertility-sparing procedures in early-stage ovarian cancer by assessing pregnancy rates and obstetrical outcomes. we performed a retrospective multicenter study among 55 Spanish hospitals, collecting patients from 18 to 40 years old with diagnosis of early-stage ovarian cancer, epithelial (EOC) or non-epithelial (non-EOC), from January 2010 to December 2019. Data on the use of assisted reproductive techniques, pregnancy attempts and obstetrical outcomes were collected. a total of 150 patients met inclusion criteria, 70 (46.6%) EOC and 80 (53.4%) non-EOC. Pregnancy attempts were reported in 51 (34%) patients, with 42 (28%) patients carrying the pregnancy to term. Among them, 30 (71.4%) underwent surgery alone and 12 (28.6%) had additional postoperative chemotherapy. A total of 32 (76.1% patients) had spontaneous pregnancies and 10 (23.9%) required in vitro fertilization. There was only one (2.4%) complication reported. Vaginal delivery was reported in twenty-nine (69%) patients and cesarean section in five (11.9%) patients. fertility-sparing management for ovarian cancer seems to be an option with proven good pregnancy rates and low complications. The selection of patients must consider strict criteria in order to maintain a good prognosis.

Intraperitoneal Irrigation Chemotherapy with Lobaplatin in Locally Advanced Gastric Cancer: A Special Type of Abdominal Chemotherapy.

This study evaluated the safety and efficiency of intraperitoneal irrigation chemotherapy with lobaplatin for the treatment of advanced gastric cancer (GC). A total of 56 locally advanced GC patients (experimental group) who received intraoperative intraperitoneal irrigation chemotherapy in addition to undergoing radical D2 surgery were matched 1:1 based on 8 covariates to 56 patients without drug treatment (control group). Clinical data were collected and analyzed. The two groups were well balanced in basic characteristics and had comparable clinical indices. All patients had similar time to first flatus (2.8 ± 0.3 vs. 2.9 ± 0.3 d, P = 0.076), time to first oral intake (3.5 ± 3.4 vs. 4.1 ± 4.6 d, P = 0.439), and duration of postoperative hospitalization (9.1 ± 3.2 vs. 9.6 ± 4.0 d, P = 0.446). There were no significant differences in postoperative complications including anastomotic and duodenal stump leakage, abdominal and anastomotic bleeding, seroperitoneum, and incision infection between the experimental and control groups (P > 0.05). The rates of chemotherapy-related side effects including allergic reaction, neurotoxicity, diarrhea, and nausea/vomiting were also similar between the two groups, and there were no abnormalities in leukocyte and platelet levels and liver and renal function during the first 5 days after surgery. Intraperitoneal irrigation chemotherapy with lobaplatin is safe for patients with advanced gastric cancer.

Neuroendocrine cervical cancer: Have we made any steps forward in its management?

IntroductionNeuroendocrine tumors (NEC) were first described by Albores-Saavedra in 1972 and these tumors account for only 0.9% to 1.5% of all invasive cervical cancers.1,2 The most common type is small cell neuroendocrine carcinoma (SCNEC) of the cervix, which accounts for 80% of cases.2 The poor prognosis despite advances in treatment remains still a huge problem, so the aim of our review is to cover all current therapeutic options. MethodWe searched for all available interventional studies, reviews, case reports and meta-analyses published from 1995 to 2023. ResultsIn 2017 Castle et al.9 published a systematic review and meta-analysis and concluded that SCNC and large cell neuroendocrine carcinoma (LCNC) are, in most cases, caused by HPV, primarily HPV18 and HPV16. Comparative genomics data suggest that cervical NEC may be genetically more similar to common cervical cancer subtypes than to extra-cervical SCNEC of the lung and bladder.13 Surgery is recommended as the primary treatment in early stages of disease, with radical hysterectomy and nodal assessment followed by adjuvant pelvic radiotherapy and/or chemotherapy. However, simple hysterectomy may be adequate when followed by adjuvant radiotherapy with concurrent cisplatin and etoposide as additional chemotherapy.15 Considering that pathologic and clinical behavior is similar to small cell lung cancer, patients usually receive platinum and etoposide as part of their primary therapy.16 The recurrent disease remains a major clinical problem, because there is no standard treatment modality for these patients, and individualized therapy is recommeded. ConclusionCurrent therapeutic modalities are mainly based on experience in the treatment of SCNEC of the lung. Certainly, a multidisciplinary approach is very important inorder to design a personalized management plan.

Current Applications and Future Directions of Circulating Tumor Cells in Colorectal Cancer Recurrence.

The ability to predict or detect colorectal cancer (CRC) recurrence early after surgery enables physicians to apply appropriate treatment plans and different follow-up strategies to improve patient survival. Overall, 30-50% of CRC patients experience cancer recurrence after radical surgery, but current surveillance tools have limitations in the precise and early detection of cancer recurrence. Circulating tumor cells (CTCs) are cancer cells that detach from the primary tumor and enter the bloodstream. These can provide real-time information on disease status. CTCs might become novel markers for predicting CRC recurrence and, more importantly, for making decisions about additional adjuvant chemotherapy. In this review, the clinical application of CTCs as a therapeutic marker for stage II CRC is described. It then discusses the utility of CTCs for monitoring cancer recurrence in advanced rectal cancer patients who undergo neoadjuvant chemoradiotherapy. Finally, it discusses the roles of CTC subtypes and CTCs combined with clinicopathological factors in establishing a multimarker model for predicting CRC recurrence.

RADT-05. MATURE OUTCOMES OF A PHASE II PROSPECTIVE STUDY OF PROTON RADIOTHERAPY FOR LOCALIZED BRAIN TUMORS

Abstract BACKGROUND Proton radiotherapy (PRT) is a highly targeted form of radiation that spares more normal brain tissue compared to modern photon radiotherapy. Therefore, we expect the late effect profile in children treated with PRT with curable brain tumors should be improved. METHODS Between 2010-2022, 100 patients were enrolled, treated with PRT, and then followed for disease control, hearing, neurocognitive and endocrine outcomes. Late effects of the tumor and treatment delivered were graded using CTCAE v4.0. RESULTS Median age at PRT was 8.0 years (1.1-20.8) and median follow up was 8.7 years (0.3-12.7). Tumor types included 40 (40%) ependymomas, 19 (19%) low grade gliomas (LGG), 21 (21%) craniopharyngiomas, and 20 (20%) other histologies. 26% of patients were treated with chemotherapy in addition to PRT. The location of PRT was 38 (38%) infratentorial, 56 (56%) supratentorial, and 6 (6%) both. The median radiation dose was 52.2 GyRBE (48.6-59.4). 8-year event-free survival (EFS) and overall survival (OS) was 71.7% and 86.2% for all patients. 8-year EFS and OS was 59.9% and 82.4% for ependymomas, 78.2% and 94.7% for LGG, 80.0% and 87.7% for craniopharyngiomas and 79.1% and 84.7% for all other tumor types. 19% of patients had new grade 3+ toxicities that were at least possibly related to radiotherapy. Baseline full-scale intelligence quotient (FSIQ) was 98.0 and follow-up FSIQ was 101.8 (p=0.14). 43% of patients had new endocrine deficiencies after radiation. 8 patients suffered new high-grade hearing loss after PRT. Dosimetry on critical brain structures was collected and correlated with late effects. More details will be presented at the conference. CONCLUSION PRT remains an effective treatment for children with curable brain tumors. While late effects of the tumor and treatment are still present, the overall burden of late effects is lower than other reports.

EPEN-23. TARGETING TRISOMY MDM4 INDUCES CELL DEATH IN 1Q+ PFA EPENDYMOMA THROUGH REACTIVATION OF THE P53 PATHWAY

Abstract BACKGROUND Gain of chromosome 1q (1q+), gives a grave prognosis in pediatric posterior fossa group A ependymoma (PFA). The prevalence of 1q+ in newly diagnosed PFA stands at 25%, escalating to 50% upon recurrence. Conventional therapeutic modalities, such as complete resection and radiation, exhibit minimal efficacy in cases of 1q+ PFA, and the incorporation of additional chemotherapy in clinical trials has failed to yield substantial improvements. In this investigation, we delineate the trisomy-induced overexpression of the MDM4 gene on chromosome 1q as a driver of malignant progression in 1q+ PFA and a viable therapeutic target via idasanutlin, an MDM4 pathway inhibitor. METHODS We are using genetic and pharmaceutical inhibition of the MDM4/MDM2 pathway high-risk PFA 1q+ in vitro and in vivo models to test the efficacy of idasanutlin in a preclinical setting. Treatment effects are measured utilizing growth assays as well as genomic and transcriptomic analysis. RESULTS Our investigation reveals that two 1q+ in vitro models demonstrate a dose dependent sensitivity to idasanutlin compared to normal brain tissue. Upon exposure to idasnutlin, they also have an increase in p21 expression, a critical marker demonstrating reactivation of the p53 pathway, evidenced at both the gene expression and protein levels. Moreover, we found radiation synergistically enhances the efficacy of idasanutlin. Currently, we are evaluating our in vitro results with combination radiation and idasanutlin treatment in our 1q+ PFA preclinical in vivo models. CONCLUSIONS In summary, our study advocates for the exploration of small molecule inhibitors, with a primary focus on the promising idasanutlin compound, as a therapeutic avenue for addressing the challenge posed by ultra-high-risk 1q+ PFA. The compelling preclinical evidence presented herein lays the groundwork for advancing our understanding of the molecular intricacies underlying this malignancy, paving the way for novel and targeted treatment strategies.

GCT-26. INTRACRANIAL NON-GERMINOMATOUS GERM CELL TUMOR WITH MALIGNANT TRANSFORMATION TO EMBRYONAL RHABDOMYSARCOMA

Abstract BACKGROUND Non-germinomatous germ cell tumors (NGGCT) constitute 35%- 45% of intracranial germ cell tumors. Growing teratoma syndrome has been observed in patients with NGGCTs after starting chemotherapy. While growing teratomas are typically benign, this process can rarely involve malignant transformation and result in poor prognosis. We present the case of a patient with pineal NGGCT and growing teratoma syndrome with malignant transformation to embryonal rhabdomyosarcoma. CASE REPORT A 13-year-old male presented with headaches and vision changes. An MRI brain demonstrated a 26 x 25 x 19 mm (AP X TR X CC) mixed solid and cystic pineal mass with no evidence of metastatic disease. Due to elevated alpha fetoprotein levels in the serum and cerebrospinal fluid, he was diagnosed with intracranial NGGCT. Treatment was initiated with alternating cycles of Carboplatin/Etoposide and Ifosfamide/Etoposide. After 2 cycles of chemotherapy, a complete biochemical response was noted but MRI showed increased tumor size (presumed growing teratoma syndrome). The patient underwent complete tumor resection. Histology showed embryonal rhabdomyosarcoma as a somatic malignancy arising in a mature teratoma. Further molecular characterization revealed somatic NF1 and KRAS pathogenic mutations that are consistent with the primary diagnosis. Methylation profiling, however, did not exhibit a match with any known malignancies. Continued complete response was noted following two additional chemotherapy cycles. The patient is planned for six total chemotherapy cycles followed by high-dose craniospinal radiation with boost to the primary tumor. CONCLUSIONS Malignant transformation is a rare phenomenon in NGGCT. There is no standard of care for these patients. Further studies are needed to define ideal therapy for this patient population.

Immune checkpoint inhibitor-related reproductive adverse effects: A pharmacovigilance analysis based on the FAERS database.

e14707 Background: There exists a critical need to systematically understand the extent and magnitude of immune checkpoint inhibitor (ICI)-related reproductive adverse effects, which may not only pose long-term implications for patients who may desire future fertility, but also impact the quality of life. We aim to better understand this underexplored area. Methods: Our focus was on ICIs approved by the FDA as of June 31, 2023, including anti-PD-1 agents (nivolumab, pembrolizumab, cemiplimab, dostarlimab, retifanlimab), anti-PD-L1 agents (atezolizumab, avelumab, durvalumab), anti-CTLA-4 agents (ipilimumab, tremelimumab), and an anti-LAG-3 agent (relatlimab). We analyzed 13,702,373 cases from January 1, 2015, to June 30, 2023. We included adverse reactions under the 'Reproductive system and breast disorders' category in the SOC (System Organ Classes). For signal detection, we used the reporting odds ratio (ROR) method. Results: We identified 133,512 patients administered with ICIs, among whom 568 reported irRAEs. Abnormal spermatogenesis (ROR025: 7.91), scrotal irritation (ROR025: 3.83), scrotal oedema (ROR025: 1.90), perineal rash (ROR025: 1.38), prostatitis (ROR025: 1.25), acquired phimosis (ROR025: 1.20), and scrotal erythema (ROR025: 1.08) in males and genital tract fistula in females (ROR025: 2.72) were detected as significant irRAEs. Among them, the most commonly reported irRAEs were prostatitis (n=29), scrotal oedema (n=12), and abnormal spermatogenesis (n=6) in males and genital tract fistula (n=34) in females. Male patients had a lower risk compared to females (OR=0.68 [0.57-0.81], p&lt;0.0001). There was no marked difference between the patients on polytherapy vs. monotherapy (OR=0.90 [0.71-1.13], p=0.36). PD-1 inhibitors pose the greatest risk when compared with CTLA-4 inhibitors (OR=1.65 [1.05-2.79], p=0.045). Gynecologic cancers in females (OR=3.77 [2.82-4.99], p&lt;0.0001) and urogenital cancers in males (OR=1.56 [1.17-2.06], p=0.0018) were strong risk factors. Additional targeted therapy, particularly lenvatinib (OR=3.79 [2.71-5.15], p&lt;0.0001) and cabozantinib (OR=2.69 [1.66-4.09], p&lt;0.0001) significantly increased the risk (OR=1.87 [1.52-2.29], p&lt;0.0001) and this risk appeared to be more pronounced in females (OR=2.32 [1.76-3.02], p&lt;0.0001). Additional chemotherapy was associated with a significantly reduced risk in males (OR=0.65 [0.42-0.96], p=0.042). However, doxorubicin (OR=2.58 [1.10-5.05], p=0.013) and cyclophosphamide (OR=2.36 [0.93-4.83], p=0.038) were linked to an elevated risk. Conclusions: Our findings demonstrated that ICIs could lead to a wide range of irRAEs in both males and females. Additional therapies could change the risk of irRAEs. Despite the current lack of high-quality clinical data on this topic, it is reasonable to inform patients about the plausible risk of irRAEs.

Assessing the feasibility and cost-effectiveness of all oral adjuvant chemotherapy (cyclophosphamide, methotrexate, capecitabine) in high-risk hormone receptor positive breast cancer.

TPS616 Background: Women with high-risk HR+/HER2- breast cancer (BCA) receive additional chemotherapy to reduce disease recurrence. Preferred Taxane and Anthracycline based chemotherapy regimens have debilitating side effects such as cardiotoxicity, leukemia, peripheral neuropathy, severe fatigue, alopecia, downtime which are more common in black women thereby necessitating dose reductions. Metronomic cyclophosphamide, methotrexate, 5-fluourouracil (CMF) is an option but less preferred due to frequent dosing and longer therapy duration. Head-to-head comparison of CMF to anthracycline-based chemotherapy conducted 3 decades ago in early-stage BCA showed anthracycline benefit was driven by HER2+ disease with no benefit for HR+/HER2- BCA. Head-to-head comparison trials of CMF and Taxane-based regimen have not been conducted but single institution data suggest similar disease-free and similar overall survival but different toxicity profiles favoring CMF. In our ongoing trial, we converted all three chemotherapy drugs in CMF regimen to an all-oral regimen namely oral Cyclophosphamide, oral Methotrexate, oral Capecitabine (CMC) with the potential benefit of increased patient convenience, decreased costs (oral agents are generic; no chair time; no growth factors), and improved toxicity profile (low rates of grade III neutropenia, no port complications, no alopecia). This trial in progress aims to evaluate the feasibility of oral CMC by measuring the relative dose intensity in addition to the safety and tolerability of oral CMC. We hypothesize that 80% of patients will receive &gt;85% of the intended dose of oral CMC. Methods: This is a Phase II, single arm, non-randomized study enrolling 25 patients with high-risk early-stage HR+ HER2- breast cancer to receive oral CMC regimen based on dose conversion equivalent bioavailability with conventional metronomic CMF chemotherapy. Enrolled patients will receive adjuvant therapy of oral cyclophosphamide 60 mg/m2 PO days 1-21 continuously, Methotrexate 15 mg/m2 PO Day 1, 8, and 15 and Capecitabine 650 mg/m2 PO BID Day 1- 14 to be given every 21 days for 8 cycles. The primary objective is to assess feasibility which is defined as 80% of patients (greater than 20 patients) maintaining a relative dose intensity (RDI) &gt; 85%. The RDI is calculated as the ratio of the actual dose intensity/standard dose intensity; the average RDI for oral CMC regimen is the sum of RDI for each drug divided by 3. This study will be stopped if &gt;25% of patients report Grade 4+ toxicity on oral CMC. The secondary objectives will assess quality of life as reported by the patients and report adverse effects. Clinical trial information: NCT06085742 . [Table: see text]