Adjuvant Therapy Regimens Research Articles

ThP2.4 - Unveiling the Odds: Identifying the Axillary Recurrence rates in Invasive Breast Cancer Surgery in a district general hospital - Seventeen years of Surgical Performance decoded

Abstract Introduction Axillary recurrence should be minimised by effective staging and treatment where appropriate Minimum standard <5% axillary recurrence at 5 years Target <3% axillary recurrence at 5 years according to UK ABS guidelines. Methods All patients with primary cancer diagnosed at our institution between January 2004 and December 2020 were identified from a prospectively maintained database of operations obtained from the medical coding department. Demographics of the patients, pre-operative investigations, MDT discussion outcomes, operative details (and complications), post-operative pathology, neo-adjuvant and adjuvant therapy regimens and follow-up data were recorded. All patients were followed up to the censoring date of December 2021 which gave a median follow-up of 18 months (range, 12- 204). Axillary recurrence and treatment regimens were recorded. Primary outcome measures were overall axillary recurrence and disease-free. IBM SPSS Statistics (Version 26.0 (IBM Corporation, Armonk, NY, USA) was used for statistical analysis to determine patient and pre-operative pathological characteristics that were predictive of isolated axillary recurrence after completion of the primary treatment course. Significance was defined as P<0.05. Results There were 4024 women diagnosed with breast cancer in Midyorks trust between this period who were referred and had surgical intervention. Of these, 107 patients were identified with recurrences. 12 were found to have an isolated axillary recurrence (8 ANC 4 SLNB) Conclusion The 17-year isolated axillary recurrence rate of women treated was 0.3%. Multimodality management at the time of recurrence, including axillary surgery, radiation, and systemic therapy, significantly improved the morbidity

LGG-15. DEEP LEARNING ENABLES LONGITUDINAL RISK PREDICTION FOR PEDIATRIC LOW-GRADE GLIOMAS AFTER SURGERY

Abstract BACKGROUND Disease progression is challenging to predict following surgery for pediatric low-grade glioma (pLGG), and early progression indicators on MRI surveillance imaging would help guide management. Longitudinal surveillance imaging data may capture subtle temporal tumor changes and patterns that could inform recurrence risk but are difficult to synthesize clinically. We applied deep, self-supervised learning to longitudinal surveillance MRI to predict short-interval event-free-survival (EFS) risk from time-of-scan. METHODS We retrospectively collected data from 278 patients (2,174 scans) who underwent surgical resection for pLGG at Dana-Farber Cancer Institute/Boston Children’s Hospital (DFCI/BCH) from 1990-2022. A deep-learning model was pretrained with T2-FLAIR sequences to determine the chronological scan order for each patient (temporal pretraining). The model was fine-tuned to predict 1-year EFS from point-of-scan using a subset of scans from DFCI/BCH and then validated on a hold-out dataset (511 scans, 67 patients). Separately, the model was fine-tuned on an external dataset from the Children’s Brain Tumor Network (CBTN) and validated on a hold-out set (204 scans, 61 patients). Results were compared to a model trained without temporal pretraining. RESULTS Median follow-up and interval between scans were 73 and 6.3 months for DFCI/BCH and 20 and 5.8 months for CBTN. Temporal pretraining improved performance for 1-year EFS, for DFCI/BCH (AUC: 0.83 [0.71-0.90] vs. 0.78 [0.62-0.91]; F1-score: 0.80 vs. 0.67), and CBTN hold-out sets (AUC: 0.75 [0.58-0.90] vs. 0.53 [0.35-0.70], p=0.01; F1-score: 0.65 vs. 0.55). Increasing the number of longitudinal scans available to the model incrementally improved performance up to 7 scans/patient for DFCI/BCH and 10 scans/patient for CBTN. CONCLUSIONS Deep-learning with temporal pretraining improves the predictive analysis of tumor growth patterns in postoperative pLGG surveillance MRI, enabling accurate short-interval EFS prediction. This model could help inform patients and clinicians regarding surveillance regimen and initiation of adjuvant therapy.

Non-Metastatic Uterine Carcinosarcoma: A Tailored Approach or One Size Fits All?

Purpose: Uterine carcinosarcomas are highly aggressive tumors of the endometrium and are associated with a poor prognosis. The optimal adjuvant treatment for both early and advanced-stage patients remains unclear. Methods: Cases of uterine carcinosarcoma were identified in our institution’s pathology database between 2000 and 2022. Kaplan–Meier estimates were calculated for the local and distant recurrence-free, disease-free and overall survival; hazard ratios were calculated using Cox proportional hazards modelling for independent prognostic factors including the stage and treatment. Results: A total of 48 patients were identified as having uterine carcinosarcoma, of whom 70.8% were surgically staged. In total, 43 patients had pelvic-confined disease, while five had positive omental or peritoneal biopsies at surgery. There were 10 pelvic (20.8%) and 19 (39.6%) distant recurrences. None of the patients with stage IA disease who received chemotherapy and brachytherapy experienced disease recurrence. The local recurrence-free survival was 54.95%, the distant recurrence-free survival was 44.7%, and the overall survival was 59.6% at 5 years. Local recurrence-free survival and overall survival were inversely associated with advanced-stage OR 1.23 (p = 0.005) and OR 1.28 (p = 0.017), respectively, and no chemotherapy was associated with OR 1.96 (p = 0.06) and OR 2.08 (p = 0.056), respectively. Conclusion: The local and distant recurrence rates were high for advanced=stage patients even when treated with aggressive adjuvant therapy regimens. Chemotherapy may improve recurrence and survival. Early-stage patients may perform well with vaginal vault brachytherapy and chemotherapy. Further prospective comparisons are required between sequential, sandwich, and concurrent approaches to chemotherapy and radiotherapy, to optimize outcomes in this high-risk population.

Prognostic significance of real-world (RW) recurrence patterns after resection or ablation of early-stage hepatocellular carcinoma (HCC): Insights from the US Medicare population.

e16241 Background: The prognosis after curative-intent resection or ablation of early-stage HCC remains poor, largely due to high rates of recurrence. We aimed to characterize real-world recurrence patterns and determine whether the timing of recurrence was associated with overall survival (OS). Methods: Patients (pts) with early-stage HCC who underwent resection and/or ablation were identified from the SEER-Medicare database (2010-2019). Pts who received liver transplant were excluded. A proxy for recurrence was defined as the receipt of new HCC treatments (surgery, locoregional therapy, systemic therapy) or a secondary malignant neoplasm claim (excluding liver). Pseudo-recurrence dates were assigned to pts without recurrence to match the distribution of time between initial resection/ablation and recurrence in the recurrence cohort, to avoid immortal time bias. Early vs late recurrence was defined as occurring within 1 year vs after 1 year of initial resection/ablation. Primary outcome was OS as measured both from the time of recurrence/pseudo-recurrence and initial resection/ablation. Results: 1,146 eligible pts with early-stage HCC were identified. 63% were male, mean age was 74 yrs, and initial therapy was resection (39%), ablation (50%), or both (11%). 736 (64%) experienced recurrence. Among them, 53% received ablation, 37% surgery, and 11% received both. Median OS from recurrence or pseudo-recurrence was 22 months (mo) vs 67 mo (p < 0.001) for pts with vs without recurrence, respectively. When measured from resection/ablation date, median OS was 39 mo vs 83 mo (p < 0.001). After adjusting for relevant demographic and clinico-pathologic factors, including type of index therapy, in a multivariable Cox regression model, recurrence remained significantly associated with an increased risk of death (hazard ratio [HR]: 2.24; 95% CI: 1.85-2.71; p < 0.001). Among pts who recurred, 380 (52%) had early recurrence and 356 (48%) had late recurrence. Median OS from recurrence was 17 mo vs 30 mo (p < 0.001) for early vs late recurrence, respectively, and 23 mo vs 63 mo when measured from resection/ablation The adjusted HR for the risk of death associated with early recurrence was 1.39 (95% CI: 1.14-1.68; p < 0.001) compared to late recurrence. Other significant prognostic factors associated with reduced OS included larger tumor size ( > = 5cm), greater extent of disease, and poor differentiation (grade III and above). Conclusions: In this study among US Medicare pts, early recurrence within one year after curative-intent treatment of early-stage HCC was significantly associated with decreased OS compared to pts who recur later or without recurrence. This highlights the need for developing and utilizing effective adjuvant therapy regimens to delay or avoid recurrence.

Abstract 1399: The role of CCN5 in regulation of tumor-infiltrating lymphocytes (TILS) in triple-negative breast cancer (TNBC) cells

Abstract TNBC accounts for about 15-20 percent of all breast cancer cases, with a high incidence in young and African-American women. TNBC lacks the expression of estrogen receptor, progesterone receptor, and normal human epidermal growth factor receptor type 2 (HER2) copy number with expression. Thus, TNBC is not sensitive to endocrine and targeted molecular therapies. Therefore, surgery and systemic chemotherapy are the primary treatment methods for TNBC. The adjuvant therapy regimen includes anthracycline, paclitaxel, or both in (Neo-) early TNBC. However, this treatment is often ineffective after recurrence or metastasis. Therefore, continuously searching for new targeted therapies and immunotherapies becomes a focus in TNBC treatment in patients with diverse communities. The studies showed that TNBC is more immunogenic than other subtypes of breast cancers with tumor-infiltrating lymphocytes (TILs) in its microenvironment. More importantly, Cytotoxic CD8+ TILs of the adaptive immune system are the most potent effectors in the anticancer immune response and constitute the backbone of cancer immunotherapy. Therefore, a high number of CD8+TILs in TNBC patients' tumors are considered a better prognosis following neoadjuvant chemotherapy. Hence, increasing and activating CD8+ TILs could be an exciting and appropriate approach to treating TNBC. Blocking immune checkpoints can inverse the microenvironment immunosuppressive state and enhance the function of tumor cell clearance. One of the major immune checkpoint therapies has involved a monoclonal antibody against programmed cell death-1 (PD-1)/programmed cell death-ligand 1 (PD-L1), expressed in various tumor cells, including TNBC and immune cells. The studies found that PD-1/PD-L1 negatively regulates CD8+ TILs in cancers, and blockade of PD-1 can induce CD8+ TILs responses in advanced melanoma. Interestingly, PD-1/PD-L1 immunotherapy has also progressed in suppressing TNBC growth and progression. However, the currently available immune checkpoint therapies have therapeutic limitations with the toxicity of the drugs. Thus, new therapeutic options are urgently needed. Our studies found that the expression of CCN5, an anti-invasive gene, correlates with the number of cytotoxic CD8+ TILs in ER+ and HER-2 positive breast cancer samples. Furthermore, we also observed that PD-L1 (programmed death-ligand 1), which was found to have high and low expression in MDA-MB-231 and 4T1, respectively, was suppressed in MDA-MB-231 and 4T1 TNBC cell lines by CCN5 recombinant protein treatment for 48 h. These findings might provide a novel immune checkpoint mechanistic explanation of CCN5 that mediates TNBC growth and progression suppression. Citation Format: Upasana Biswas, Anjali Kambhampati, Noor Haideri, Archana De, Sunil Upadhyay, Snigdha Banerjee, Sushanta Banerjee. The role of CCN5 in regulation of tumor-infiltrating lymphocytes (TILS) in triple-negative breast cancer (TNBC) cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 1399.

Abstract 2566: Molecular characteristic profile in early colorectal cancer with V600E and non-V600E BRAF mutations

Abstract Background: The BRAF V600E mutation in colorectal cancer (CRC) is a significant indicator of poor prognosis, especially in tumors exhibiting microsatellite instability (MSI). It is more common on the right side of the colon but can occur anywhere within the colon. Although other BRAF mutations existed, current research primarily focused on BRAF V600E. Most clinical data sets were centered on advanced colorectal cancer. There was limited understanding of the molecular characteristics of early-stage colorectal cancer patients with BRAF mutations, which impacted postoperative prognosis management, including refining adjuvant therapy regimens. Therefore, we analyzed the molecular characteristics of early-stage CRC surgical patients. Methods: Tumor tissue from 767 early-stage CRC patients diagnosed between 2021 to 2022 in China were analyzed using NGS (panel on 733 gene) to validate the mutation characteristics. Tumor specimens were tested for the BRAF mutation and MSI status. Result: Among 767 early CRC cases tested, BRAF mutations accounted for 6.52% (50/767), with 62% (31/50) being BRAF V600E, followed by 14% (7/50) for BRAF D594G. Notably, there were two cases of fusion variations, TRIM24-BRAF, and one case of BRAF copy gain. Among the BRAF mutation population, 11 cases were MSI-H, with 8 of them being BRAF V600E/MSI-H. Only one MSH-H patient had a germline mutation in the MLH1 gene, with a concurrent mutation in BRAF K601T.Interestingly, when comparing the mutation profiles of the BRAF V600E population with those of the non-V600E BRAF mutation population, we found distinct co-mutated genes despite both being BRAF mutations. In the BRAF V600E group, the top three frequently mutated genes were TP53 (52%), RNF43 (32%), and SMAD4 (32%). Additionally, the BRAF V600E/MSI-H subgroup presented a distinct mutation profile, with minimal occurrences of TP53 and SMAD4 mutations. In the non-V600E BRAF mutation group, the top three frequently mutated genes were TP53 (84%), APC (63%), and KRAS (32%). Conclusions: In examining the mutation profile characteristics of early colorectal cancer with BRAF mutations, the proportion of BRAF V600E/MSI-H appeared to have been lower than that reported in advanced cases. Furthermore, in terms of the frequency of co-mutated genes, it seemed that BRAF V600E had exhibited a higher malignant driving mutation effect as a single gene, while non-V600E mutations had required more cooperative tumor suppressor genes or oncogenes. Analyzing the molecular characteristics of early colorectal cancer patients with V600E and non-V600E BRAF mutations could help improve postoperative management and further our understanding of tumor progression. Citation Format: Zhang Quan An. Molecular characteristic profile in early colorectal cancer with V600E and non-V600E BRAF mutations [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 2566.

Targeting Oral Squamous Cell Carcinoma with Combined Polo-Like-Kinase-1 Inhibitors and γ-Radiation Therapy.

Polo-like-kinase-1 (PLK-1) is a serine/threonine kinase that regulates the cell cycle and acts as an oncogene in multiple cancers, including oral squamous cell carcinoma (OSCC). The loss of PLK-1 can inhibit growth and induce apoptosis, making it an attractive therapeutic target in OSCC. We evaluated the efficacy of PLK-1 inhibitors as novel, targeted therapeutics in OSCC. PLK-1 inhibition using BI6727 (volasertib) was found to affect cell death at low nanomolar concentrations in most tested OSCC cell lines, but not in normal oral keratinocytes. In cell lines resistant to volasertib alone, pre-treatment with radiotherapy followed by volasertib reduced cell viability and induced apoptosis. The combinatorial efficacy of volasertib and radiotherapy was replicated in xenograft mouse models. These findings highlight the potential of adding PLK-1 inhibitors to adjuvant therapy regimens in OSCC.

Assessing the effectiveness of targeted agents in adjuvant therapy for patients with metastatic colorectal cancer undergoing surgical resection: a retrospective cohort study.

Primary tumor resection and metastasectomy may be beneficial for many patients with metastatic colorectal cancer (mCRC). To assess the differences in postoperative survival outcomes between adjuvant therapy with chemotherapy alone and chemotherapy plus targeted agents (TAs). Retrospective cohort study. Patients with mCRC who underwent surgical resection for primary colorectal tumor and distant metastases and received adjuvant therapy from 1 January 2010 to 31 December 2017 were enrolled in the Taiwan Cancer Registry. We analyzed the overall survival of patients with resectable or initially unresectable mCRC who received adjuvant chemotherapy alone and chemotherapy plus TAs. We enrolled 1124 and 542 patients with resectable and initially unresectable mCRC, respectively. Adjuvant chemotherapy plus TAs and chemotherapy alone resulted in similar mortality rates among patients with resectable mCRC [adjusted hazard ratio (aHR) = 1.13; 95% confidence interval (CI), 0.93-1.36]; however, it marginally reduced the mortality rate among patients with initially unresectable mCRC who underwent conversion surgery after neoadjuvant therapy (aHR = 0.81; 95% CI, 0.62-1.06). The subgroup analysis of patients who received more than nine cycles of TAs preoperatively and anti-epidermal growth factor receptor agents revealed aHRs of 0.48 (95% CI, 0.27-0.87) and 0.33 (95% CI, 0.18-0.60), respectively. Adjuvant chemotherapy plus TAs may improve survival in patients with initially unresectable tumors who underwent conversion surgery following neoadjuvant therapy with TAs, especially in those who respond well to the targeted therapy. Our study underscores the importance of stratifying patients with mCRC based on tumor resectability when selecting the adjuvant therapy regimen.

Pharmacoeconomic analysis of using empegfilgrastim for the treatment of early and locally advanced HER2+ breast cancer in the Russian Federation

Objective: to assess budget impact of using empegfilgrastim for the prevention of febrile neutropenia in patients with early and locally advanced human epidermal growth factor receptor 2 positive (HER2+) breast cancer who receive neoadjuvant “docetaxel / carboplatin / trastuzumab + pertuzumab” regimen, considering possible subsequent adjuvant therapy with trastuzumab emtansine or trastuzumab within the Russian healthcare system.Material and methods. We searched and analyzed published clinical, epidemiological and pharmacoeconomic studies as well as regulatory and legal documents. A decision tree model was constructed to reflect the probabilities of switching to different adjuvant therapy regimens depending on the achievement of pathomorphological complete response in patients with early and locally advanced HER2+ breast cancer. The budget impact analysis was carried out comparing two primary prophylactic options, empegfilgrastim and filgrastim.Results. Despite the higher costs of prevention with empegfilgrastim compared to filgrastim (249 vs. 134 thousand rubles), due to the higher rate of achieving a pathomorphological complete response and, accordingly, fewer cases requiring adjuvant therapy with the more expensive trastuzumab emtanzine, savings of 916 thousand rubles per 1 patient per 1 year of therapy are possible. In general, prophylaxis in the target population diagnosed with early and locally advanced HER2+ breast cancer using empegfilgrastim will result in a cost reduction of 9.4 billion rubles per 1 year compared to filgrastim.Conclusion. Empegfilgrastim prophylaxis, despite its higher annual cost, is an efficient option within the Russian healthcare system. In addition to reducing the incidence of febrile neutropenia, the frequency and dose of chemotherapy are preserved, resulting in increased efficacy of the primary therapy.

Factors affecting the survival of patients with glioblastoma treated with standard and hypofractionated radiation regimens

Background. Glioblastoma has the worst prognosis and is the most common primary tumor of the central nervous system (CNS) among adults. Since it is multimodal treatment that increases survival chances of patients with glioblastoma, the analysis of factors that affect survival is a necessary precondition for developing more effective therapeutic approaches for this cohort. Such analysis makes it possible to determine the subgroups of patients which demonstrate the biggest therapeutic benefit from certain types of multimodal treatment, thus leading to implementation of personalized neuro-oncological treatment. Purpose. To analyze factors affecting cancer-specific survival (CSS) of patients with glioblastoma in stratification of the cohort according to the regimen of adjuvant radiation therapy into groups of standard and hypofractionated treatment regimens. Materials and methods. The single-center non-randomized study is based on the analysis of the results of the cohort of 159 patients with primarily diagnosed glioblastoma that were treated over the period from 2014 to 2020 at the State Institution «Romodanov Neurosurgery Institute of the National Academy of Medical Sciences of Ukraine». According to the regimen of radiation therapy, the patients of the cohort (n=159) were stratified into two groups: standard regimen group – 49 (30.8%) patients (30 fractions, total radiation dose of 60.0 Gy) and hypofractionated regimen group – 110 (69.2%) patients (15 fractions, total radiation dose of 52.5 Gy). The survival of the patients was analyzed by the Kaplan–Meier method. The log-rank test was used for comparing Kaplan–Meier survival curves for different studied groups. For the purpose of studying impact of independent variables on the survival, we used regression analysis according to semiparametric proportional hazards model. Hazard ratio was calculated with 95% confidence intervals (CI). Results and discussion. The median CSS in the total cohort was 16.6 (95% CI 14.1–17.8 months) months in median follow-up time of 23.8 (95% CI 21.9–27.3) months. In standard regimen group, the median CSS was 15.7 (95% CI 14.1–17.8) months in median follow-up time of 24.4 (95% CI 23.1–25.3) months. In hypofractionated regimen group, the median CSS was 17.5 (95% CI 14.6–19.7) months in median follow-up time of 22.3 (95% CI 21.3 – 27.2) months. According to the logrank test (taking into consideration cautions about its use), no statistically significant difference in CSS of patients of both groups was determined р=0.07>0.05. For analysis of the impact of clinical factors (age, sex, radicality of the surgical treatment, chemotherapeutic treatment, functional status according to the Karnofsky scale) on the CSS of both groups, they were considered as the ones that may have different base hazard. Statistically significant impact of all studied covariates on the CSS was registered (p70 points, ceteris paribus. For male patients, the hazard of death is 1.7 times higher (р=0.016267; HR 1.7; 95% CI 1.1–2.5) than for female patients, ceteris paribus. Absence of chemotherapy in adjuvant treatment increases hazard of death by 2.37 times (HR 2.37; 95% CI 1.6–3.2), ceteris paribus. The hazard of death decreases, ceteris paribus, by 82% in chemotherapy with temozolomide and by 47% when the patient is younger than 60 years old (HR 0.53; 95% CI 0.4–0.8). Conclusions. This analysis is a stage of the study of differentiated treatment effect in groups of standard and hypofractionated regimens of radiation therapy in patients with glioblastoma. These data can be used for an in-depth subgroup analysis and serve as the basis for development of personalized approaches in treatment of neuro-oncological patients.

The Current Role of Neoadjuvant Chemotherapy in the Management of HER2-Positive, Triple-Negative, and Micropapillary Breast Cancer: A Narrative Review.

Currently, the prevailing approach for managing breast carcinoma involves initiating neoadjuvant chemotherapy (NAC) as a part of the treatment regimenbefore surgery.NACis being applied progressivelyin the therapeutic management of locally advanced breast carcinoma because of its capability to aid insurgery and facilitate the surgical treatment of patients who were once thought to be inoperable. Patients must be managed by a team of professionals from the start to thecompletion of the therapy. Pathological complete response (pCR), reduces the degree of recurrence of the disease and denotes the elimination of the tumor completely from the breast, it also indicates elimination of the tumor from theaxillary lymph nodes. There is currently sufficient information to support the idea that patients would perform better if NAC resulted in a pCR. The administration of the same regimen of adjuvant therapy in neoadjuvant therapy provides women with similar improvements in overall survival. NAC offers potential benefits, such as enhancing the likelihood of breast conservation and broadening the scope of available surgical options. Based on how well they respond to neoadjuvant treatment, women receive a personalized prognosis evaluation.NAC has been proven to be very effective. However, patients can be resistant to medications easily which is not desirable for patients receiving this therapy going forward. In this review, we have discussed the purpose of managing patients with this therapy in locally advanced breast cancer. We have also discussed the various benefits of NAC as well as the application of different drugs,their advantages, and disadvantages that are given to the patient. The application of NAC in cases ofhuman epidermal growth factor 2 (HER2) positive breast cancer and micropapillary breast cancer has also been discussed briefly in this review.

THU357 A Case Of Recurrent Insulin-induced Edema In A Pediatric Adolescent Patient

Abstract Disclosure: G.J. Mora Calderon: None. R.L. Aguirre: None. D. Preston: None. Introduction: Insulin induced edema is a very rare complication seen after initiation of insulin therapy or after escalation of previous insulin regimen in patients with diabetes. The exact incidence of this condition is unknown. Insulin induced edema seems to have a female predominance and is associated primarily with patients who are underweight. The severity of insulin induced edema can range from mild localized peripheral edema to more severe and generalized complications, including cardiac failure and serosal effusions. There is a higher risk for severe complications in older patients with pre-existing cardiac, hepatic, or renal conditions. Usually, the course is benign and self-resolved without any intervention. Severe and prolonged cases have been reported to need adjuvant therapy (e.g diuretics or sympathomimetic agents) or sodium-restricted dietary regimens. Increasing blood glucose target with a decreased insulin regimen has been proposed as a possible option to prevent insulin induced edema. We present a 14 year-old-male patient with history of poor controlled type 1 diabetes mellitus and recurrent insulin-induced edema after strengthening of his insulin therapy. Case Presentation: A 14-year-old male with poorly controlled type 1 diabetes mellitus presented to the emergency with pitting edema of his face and hands that started a week after intensification of his insulin regimen. His weight increased from 73 kg to 84 kg in about 10 days. His vital signs at presentation were stable and besides the pitting edema, the rest of the physical examination was unremarkable. His mother reported a previous episode of edema that occurred approximately a year before this presentation and about a month after he was first diagnosed with diabetes mellitus. His most recent HbA1c was 14.4%. Patient was admitted for evaluation. Electrocardiogram, transthoracic echocardiogram, chest x-ray, and multiple laboratories (including a comprehensive metabolic panel, complete blood count, B-type natriuretic peptide, urine microalbumin, and thyroid function test ) came back all normal. The edema slowly improved and was eventually discharged. No adjuvant therapy was needed during his hospitalization. Conclusion: The diagnosis of insulin induced edema is primarily based on the exclusion of other etiologies. Most cases reported only one episode after initiation of insulin therapy or after escalation of previous insulin regimen, but it can happen multiple times as noted in our patient. Presentation: Thursday, June 15, 2023

Survival of elderly patients with glioblastoma after hypofractionated radiation therapy

Background. Glioblastoma (GB) is the most common primary brain tumor that is malignant, and its incidence increases with age. The prognosis for elderly patients with GB (GBe) is significantly worse than that of younger patients. Due to the global trend of aging population and age-related features of the GB cohort, the number of GBe patients is expected to increase. Although there is no full consensus regarding the clinical management of GBe, hypofractionated radiation therapy (RT) has become a common therapeutic option for elderly and/or poor prognosis GB patients.
 Purpose. To analyze the survival of patients with glioblastoma in the age group ≥60 years old after standard and hypofractionated regimens of adjuvant radiation therapy.
 Materials and methods. A retrospective single-center non-randomized study based on a total cohort of 53 patients (≥60 years old) with histogically verified diagnosis of GB was performed at the State Institution «Romodanov Neurosurgery Institute of the National Academy of Medical Sciences of Ukraine» over the period of 6 years, from 2014 to 2020. According to the RT regimen, patients were stratified into 2 groups: standard RT (SRT group) – 16 (30.2%) patients (30 fractions, 2.0 Gy per fraction, total radiation dose – 60.0 Gy) and hypofractionated RT (HRT group) – 37 (69.8%) patients (15 fractions, 3.5 Gy per fraction, total dose – 52.5 Gy). Cancer-specific survival (CSS) and progression-free survival (PFS) were analyzed in the total cohort and both groups separately.
 Results. With a median follow-up of 21.9 months (95% CI (confidence interval) 20.7 – 32.3), the median CSS in the total cohort was 15.0 (95% CI 13.3 – 17.3) months; the median PFS – 9.0 (95% CI 8.0 – 10.6) months. In the HRT group, the median CSS was 14.7 (95% CI 10.5 – 18.5) months; in the SRT group – 15.0 (95% CI 12.4 – 19.3) months. In the HRT group, the median PFS was 9.0 (95% CI 7.0 – 11.9) months; in the SRT group – 9.0 (95% CI 8.0 – 11.0) months. Before and after the stratification point of 15 months, the HRT and SRT groups did not differ significantly in CSS (Log-rank test p = 0.0588 and p = 0.2009, respectively). There was no significant difference in PFS between the HRT and SRT groups before and after the stratification point of 9 months (Log-rank test p = 0.0653 and p = 0.0722, respectively). Conclusions. Improving survival of GBe pts is an urgent issue, especially taking into account global trends in population aging and age-specific features of GB. The proposed hypofractionated RT regime can be considered as an optional approach in the complex treatment of GBe pts.

Unplanned 30-Day Readmission in Glioblastoma Patients: Implications for the Extent of Resection and Adjuvant Therapy.

Unplanned early readmission (UER) within 30 days after hospital release is a negative prognostic marker for patients diagnosed with glioblastoma (GBM). This work analyzes the impact of UER on the effects of standard therapy modalities for GBM patients, including the extent of resection (EOR) and adjuvant therapy regimen. Records were searched for patients with newly diagnosed GBM between 2014 and 2020 who were treated at our facility. Exclusion criteria were being aged below 18 years or missing data. An overall survival (OS) analysis (Kaplan-Meier estimate; Cox regression) was performed on various GBM patient sub-cohorts. A total of 276 patients were included in the study. UER occurred in 13.4% (n = 37) of all cases, significantly reduced median OS (5.7 vs. 14.5 months, p < 0.001 by logrank), and was associated with an increased hazard of mortality (hazard ratio 3.875, p < 0.001) in multivariate Cox regression when other clinical parameters were applied as confounders. The Kaplan-Meier analysis also showed that patients experiencing UER still benefitted from adjuvant radio-chemotherapy when compared to radiotherapy or no adjuvant therapy (p < 0.001 by logrank). A higher EOR did not improve OS in GBM patients with UER (p = 0.659). UER is negatively associated with survival in GBM patients. In contrast to EOR, adjuvant radio-chemotherapy was beneficial, even after UER.

Comparison of different adjuvant therapy regimen efficacies in patients with high risk of recurrence after radical resection of hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) has a high recurrence rate even after radical surgery. Postoperative adjuvant transhepatic arterial chemoembolization (PA-TACE), postoperative adjuvant hepatic arterial infusion chemotherapy (PA-HAIC), postoperative adjuvant radiotherapy (PA-RT), and postoperative adjuvant molecular targeted therapy have been demonstrated to be effective in reducing the postoperative recurrence rate. The present network meta-analysis was conducted to compare the effects of PA-TACE, PA-HAIC, PA-RT and postoperative adjuvant molecular targeted therapy on the overall survival (OS) and disease-free survival (DFS) in HCC patients after radical resection and to determine the optimal treatment strategy. Network meta-analysis was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. PubMed, Embase, Cochrane Library, and Web of Science were used to collect eligible studies up to December 25, 2022. Studies related to PA-TACE, PA-HAIC, and postoperative adjuvant molecular targeted therapy after radical HCC resection was included. The endpoints were OS and DFS, and the effect size was determined using hazard ratio with a 95% confidence interval. R software and "gemtc" package were employed to analyze the results. A total of 38 studies involving 7079 patients with HCC after radical resection were ultimately enrolled to be analyzed. Four postoperative adjuvant therapy measures and two oncology indicators were evaluated. In this study, OS-related investigations validated that PA-Sorafenib and PA-RT markedly enhanced the OS rates in patients after radical resection when compared to PA-TACE and PA-HAIC. However, statistical analysis revealed no significant difference between PA-Sorafenib and PA-RT, as well as PA-TACE and PA-HAIC. In the DFS-related investigations, PA-RT demonstrated superior efficacy over PA-Sorafenib, PA-TACE, and PA-HAIC. Additionally, PA-Sorafenib displayed better efficacy than PA-TACE. Nevertheless, there was no statistical significance between PA-Sorafenib and PA-HAIC, as well as PA-TACE and PA-HAIC. We also performed a subgroup analysis of studies focusing on HCC complicated by microvascular invasion after radical resection. In terms of OS, both PA-RT and PA-Sorafenib demonstrated a noteworthy improvement over PA-TACE, whereas no statistical significance was detected between PA-RT and PA-Sorafenib. Likewise, for DFS, both PA-Sorafenib and PA-RT exhibited superior efficacy compared to PA-TACE. In patients with HCC after radical resection and a high risk of recurrence, both PA-Sorafenib and PA-RT significantly improved OS and DFS when compared to PA-TACE and PA-HAIC. Notably, PA-RT exhibited superior efficacy over PA-Sorafenib, PA-TACE, and PA-HAIC in terms of DFS. Similarly, PA-Sorafenib appeared to be more effective than PA-TACE for DFS.

Clinical implications of receptor conversions in breast cancer patients who have undergone neoadjuvant chemotherapy.

In this study, we aimed to determine the incidence of receptor conversions after neoadjuvant chemotherapy (NAC) for breast cancer and assess the rate at which receptor conversion leads to changes in adjuvant therapy regimens. We performed a retrospective review of female breast cancer patients treated with NAC at an academic breast center between January 2017 and October 2021. Patients with residual disease on surgical pathology and complete receptor status information for both pre-NAC and post-NAC specimens were included. Incidence of receptor conversions, defined as a change in at least one hormone receptor (HR) or HER2 status compared to preoperative specimens, was tabulated, and adjuvant therapy modalities were reviewed. Factors associated with receptor conversion were analyzed using chi-square tests and a binary logistic regression. Of the 240 patients with residual disease after NAC, 126 (52.5%) had receptor testing repeated. After NAC, 37 specimens (29%) had a receptor conversion. Receptor conversion resulted in the addition or removal of an adjuvant therapy in 8 patients (6%), indicating a number needed to screen of 16. Prior history of cancer, receipt of initial biopsy at an outside site, HR-positive tumors, and a pathologic stage of II or lower were factors associated with receptor conversions. HR and HER2 expression profiles frequently change after NAC and drive adjustments in adjuvant therapy regimens. Repeat testing of HR and HER2 expression should be considered in patients who receive NAC, especially in patients with early stage, HR-positive tumors whose initial biopsies were performed externally.

Anthracycline-induced cardiomyopathy in the long-term period after chemotherapy: clinical case

Background. As is known, the treatment of the oncological process leads either to the occurrence of cardiovascular pathology, or to an increase in the risk of death from cardiovascular diseases. Currently, the concept of ˝cardiovascular toxicity˝ has been introduced, which is associated with the treatment of cancer (CTR-CVT). Systemic drug anthracycline-containing anticancer therapy can cause a number of cardiovascular complications, such as myocardial systolic dysfunction, coronary heart disease, cardiac arrhythmias, arterial hypertension. Particular attention is paid to anthracycline drugs, because they are still included in combinations of many adjuvant therapy regimens and first-line treatment of both the most common cancers and rarer ones.&#x0D; Clinical Case Description. The article presents a clinical case of a patient who received adjuvant polychemotherapy for breast cancer in 2017 with AC 4 D 4 regimen, in which chronic anthracycline-induced cardiomyopathy manifested years after completion of antitumor therapy. The development of anthracycline cardiomyopathy is possible even in patients with initially low cardiac risk.&#x0D; Conclusion. The clinical case highlights the importance of monitoring patients after the end of anthracycline antitumor therapy, in particular, they are shown to periodically perform an echocardiographic study in order to detect delayed asymptomatic myocardial dysfunction.

Clinical Determinants of Extraurinary Tract Recurrence and Survival after Radical Surgery for pT2 Upper Tract Urothelial Carcinoma

Oncologic outcomes for pT2N0M0 upper tract urothelial carcinoma (UTUC) after nephroureterectomy are not well defined, with most previous studies focused on a heterogeneous population. Therefore, we aimed to investigate the clinical determinants of extraurinary tract recurrence and survival after radical surgery in patients with localized UTUC. We retrospectively identified 476 patients with pT2N0M0 UTUC who underwent radical nephroureterectomy or ureterectomy between October 2002 and March 2022. To evaluate the prognostic impact, patients were divided into renal pelvic, ureteral, and both-region (renal pelvis plus synchronous ureter) groups based on tumor location. The outcomes included recurrence-free survival (RFS), cancer-specific survival (CSS), and overall survival (OS). Associations were evaluated using multivariable Cox regression analyses for prognostic factors and Kaplan-Meier analyses for survival curves. The renal pelvic, ureteral, and both-region groups consisted of 151 (31.7%), 314 (66.0%), and 11 (2.3%) patients, respectively. Kaplan-Meier analyses comparing the three tumor types showed significant differences in 5-year RFS (83.6% vs. 73.6% vs. 52.5%, p = 0.013), CSS (88.6% vs. 80.7% vs. 51.0%, p = 0.011), and OS (83.4% vs. 70.1% vs. 45.6%, p = 0.002). Multivariable analyses showed that age >60 years, previous bladder cancer history, ureteral involvement (ureteral and both-regional groups), and positive surgical margins were significant negative prognostic factors for the studied outcomes. Patients with pT2 UTUC and presence of ureteral involvement had more frequent disease relapse. Subsequent adjuvant therapy regimens and close follow-up in patients with negative prognostic factors are warranted despite complete pathological removal of the tumor.

Predictors of early and late hepatocellular carcinoma recurrence.

Hepatocellular carcinoma (HCC) is the most frequent liver neoplasm, and its incidence rates are constantly increasing. Despite the availability of potentially curative treatments (liver transplantation, surgical resection, thermal ablation), long-term outcomes are affected by a high recurrence rate (up to 70% of cases 5 years after treatment). HCC recurrence within 2 years of treatment is defined as "early" and is generally caused by the occult intrahepatic spread of the primary neoplasm and related to the tumor burden. A recurrence that occurs after 2 years of treatment is defined as "late" and is related to de novo HCC, independent of the primary neoplasm. Early HCC recurrence has a significantly poorer prognosis and outcome than late recurrence. Different pathogenesis corresponds to different predictors of the risk of early or late recurrence. An adequate knowledge of predictive factors and recurrence risk stratification guides the therapeutic strategy and post-treatment surveillance. Patients at high risk of HCC recurrence should be referred to treatments with the lowest recurrence rate and when standardized to combined or adjuvant therapy regimens. This review aimed to expose the recurrence predictors and examine the differences between predictors of early and late recurrence.

Heterogeneity of outcomes of endometrial cancer patients included in prospective clinical trials

ObjectiveTo assess heterogeneity in five-year overall survival of patients with endometrial cancer using a large retrospective database with cohorts defined by recent prospective clinical trials. MethodsThe National Cancer Database was used to identify patients with endometrial cancer who underwent hysterectomy from 2004 to 2016. The reported inclusion criteria for GOG-249, PORTEC-3, and GOG-258 were used to define the respective cohorts. Five-year overall survival for each cohort was stratified by tumor characteristics and adjuvant therapy regimens. ResultsA total of 89,133 patients were identified who would have fulfilled the entry criteria to GOG-249, PORTEC-3, or GOG-258. When stratified by tumor characteristics, irrespective of adjuvant therapy, five-year overall survival ranged from 59.9%–81.7% for patients meeting GOG-249 inclusion criteria, 40.2%–81.8% for patients meeting PORTEC-3 inclusion criteria, and 17.5%–75.0% for those meeting GOG-258 inclusion criteria. Analysis of subgroups by adjuvant therapy regimen revealed significant improvement in five-year overall survival for chemoradiotherapy compared to chemotherapy or radiotherapy alone for endometroid stage III and stage IVA disease and for some stages of serous and clear cell histology. ConclusionsRecent prospective trials of adjuvant therapy for endometrial cancer have included heterogeneous cohorts of patients based on five-year overall survival rates when the populations are stratified by tumor characteristics. The variation in expected five-year overall survival for subsets of patients may result in underpowered studies or misleading results.