Administration Of Chemotherapy Research Articles

The impact of loco-regional treatment modality on the outcomes in breast cancer patients younger than forty years of age

PurposeTo determine the impact of the loco-regional treatment modality, on the loco-regional recurrence (LRR) rates and overall survival (OS) in breast cancer patients younger than 40 years.MethodsData of 623 breast cancer patients younger than 40 years of age were retrospectively reviewed. Patients were stratified according to the locoregional treatment approach into three groups: the mastectomy group (M), the mastectomy followed by radiation therapy group (MRX) and the breast conservative therapy group (BCT).ResultsMedian follow-up was 72 months (range, 6-180). Two hundred and nine patients were treated with BCT, 86 with MRM and 328 with MRX. The 10-year rate LRR rates according to treatment modality were: 13.4% for BCT, 15.1% for MRM and 8.5% for MRX (p 0.106). On univariate analysis, T stage (p 0.009), AJCC stage (p 0.047) and Her 2 status (p 0.001) were associated with LRR. Ten-year overall survival (OS) was 72.7% (78.5% in the BCT group, 69.8% in the MRM group and 69.8% in the MRX group, p 0.072).On Univariate analysis, age < 35 (p 0.032), grade III (p 0.001), N3 stage (p 0.001), AJCC stage III (p 0.005), ER negative status (0.04), Her 2-status positive (0.006) and lack of chemotherapy administration (p 0.02) were all predictors of increased mortality.ConclusionFor patients younger than 40 years of age, similar LRR and overall survival outcomes were achieved using BCT, M or MRX. Young age at diagnosis should not be used alone in recommending one loco-regional treatment approach over the others.

Patterns of chemotherapy use with primary radiotherapy for localized bladder cancer in patients 65 or older

IntroductionBladder preservation with concurrent chemoradiotherapy after maximum transurethral resection of bladder tumor is an alternative to radical cystectomy in select patients with muscle invasive bladder cancer (MIBC). Concurrent administration of radio-sensitizing chemotherapy and radiation therapy (RT) has been shown to have superior disease control compared with RT alone and can often be administered with modest added toxicity. We sought to describe national patterns of chemotherapy use.MethodsThe linked surveillance, epidemiology, and end results (SEER)-Medicare database was used to identify patients with cT2-4, N0/X, M0/X BC who received radiation between 2004 and 2018. Data on demographics, clinicopathologic factors, therapy and outcomes were extracted. Concurrent utilization of chemotherapy with RT was also identified (CRT). Multivariate logistic regression (MVA) models were used to explore factors associated with receipt of chemotherapy and overall survival (OS).Results2190 patients met inclusion criteria. Of these, 850 (38.8%) received no chemotherapy. Among those receiving chemotherapy, the most frequent regimens were single agent carboplatin, cisplatin, or gemcitabine. Factors that were independently associated with decreased likelihood of chemotherapy use were increasing age (OR 0.93, CI 0.92 – 0.95), Hispanic race (compared with White, OR 0.62, CI 0.39 – 0.99), cT3 or T4 (compared with cT2, OR 0.70, CI 0.55 – 0.90), and lower National Cancer Institute comorbidity index (OR 0.60, CI 0.51 – 0.70) (p &amp;lt; 0.05). Variables independently associated with increased likelihood of receipt of chemotherapy were married status (OR 1.28, CI 1.06 – 1.54), higher socioeconomic status (OR 1.31, CI 1.06 – 1.64), and later year of diagnosis (OR 1.09, CI 1.06 – 1.12). Receipt of concurrent chemotherapy with RT was associated with superior OS compared with RT alone.ConclusionOver a third of patients &amp;gt;/65 years old receiving curative-intent RT for MIBC do not receive concurrent chemotherapy. Considering the improvement in oncologic outcomes with CRT over RT alone and more options, such as low dose gemcitabine which can be administered with modest toxicity, efforts are needed to identify barriers to utilization and increase the use of radio-sensitizing chemotherapy.

Management of hematological patients requiring emergency chemotherapy in the intensive care unit.

Hematological malignancies may require rapid-onset treatment because of their short doubling time, notably observed in acute leukemias and specific high-grade lymphomas. Furthermore, in targeted onco-hematological scenarios, chemotherapy is deemed necessary as an emergency measure when facing short-term, life-threatening complications associated with highly chemosensitive hematological malignancies. The risks inherent in the disease itself, or in the initiation of treatment, may then require admission to the intensive care unit (ICU) to optimize monitoring and initial management protocols. Hyperleukocytosis and leukostasis in acute leukemias, tumor lysis syndrome, and disseminated intravascular coagulation are the most frequent onco-hematological complications requiring the implementation of emergency chemotherapy in the ICU. Chemotherapy must also be started urgently in secondary hemophagocytic lymphohistiocytosis. Tumor-induced microangiopathic hemolytic anemia and plasma hyperviscosity due to malignant monoclonal gammopathy represent infrequent yet substantial indications for emergency chemotherapy. In all cases, the administration of emergency chemotherapy in the ICU requires close collaboration between intensivists and hematology specialists. In this review, we provide valuable insights that aid in the identification and treatment of patients requiring emergency chemotherapy in the ICU, offering diagnostic tools and guidance for their overall initial management.

The Mortality Rate in Neutopenic Children Population in Oncology an Algerian Study

Febrile neutropenia consecutive to the administration of chemotherapy constitutes the most serious and the most frequent complication of cytotoxic chemotherapies. It is often a sign of infection, being able to quickly turn in septicemia if no treatment is begun; it thus constitutes an emergency for diagnosis and therapeutics. The objective of this work is to study the epidemiological, clinical, biological, etiologic and evolutionary characteristics of the episodes of febrile neutropenia, to evaluate the importance of the infectious risk and the main involved germs, to identify the difficulties of the management and the follow-up of the children having developed a febrile neutropenia and finally. During our retrospective study concerning the episodes of febrile neutropenias diagnosed in the pediatric oncology unit of the pediatric department of the university hospital of Alger over a period of 04 years (from 1 January 2017 to 31 December 2020). 205 patients having solid tumor were collected. Among them 45 cases presented febrile episodes, the average age was 5.75 years with a maximum frequency of them were male, and the main motive for consultation was the fever. The average deadline of occurrence of neutropenia was of 14.6 days. A documentation of the fever is obtained clinically at 20 % of the cases, while in 80 % of the cases, the fever remains unknown origin. The infectious sites found are: a) Skin (6.6%), digestive (4.4%), respiratory (8.8%). b) The average duration of the neutropenia was of 18.8 days. Upon completing this work, we emphasize the need of prompt and appropriate management of the hematological emergency that is febrile neutropenia by an adapted empirical antibiotic therapy after a good bacteriological investigation, without forgetting the importance of prophylaxis based mainly on hygienic mucocutaneous measures and the information/education of parents about the risk of infection and means of prevention.

B vitamins and homocysteine in cancer patients with solid malignancies before chemotherapy administration

Recently, the role of vitamin imbalance in carcinogenesis has been actively discussed. Studies aimed at assessing their role in the processes of cancer development are various, and the evaluation of the initial level of vitamins is relevant when planning antitumor therapy.Objective. To determine the state of the initial level of B vitamins and homocysteine before chemotherapy in patients of different oncologic profile.Material sand Methods. The level of vitamins B1, B6, B9, active form of B12* and homocysteine in fresh frozen plasma was determined by enzyme[1]linked immunosorbent assay (ELISA) using test systems in 66 patients with verified malignant neoplasms before chemotherapy. The study included 66 patients: women n=40 and men n=26, with cancer: gastric n=12, colorectal cancer n=21, cancer lung n=11, cancer pelvic organs n=22.Results. According to the results of the study the increase in the level of holotranscobalamin (Holo-TC) and decrease in homocysteine in comparison with reference values was observed in 100% of cases. Significant difference was found only for B1: reliable differences between patients with colorectal cancer and with pelvic cancer (in the latter the mean value of B1 levels was 2.4 times higher at p = 0.0425). According to the results of correlation analysis, a weak correlation between B12 and B9 was determined. When comparing the levels of vitamin B12 and homocysteine in patients after surgical treatment and without it, no significant differences were found.Conclusion. Increased Holo-TC levels and decreased homocysteine levels by ELISA are characteristic of all varieties of solid cancer, independent of sex, age, stage and previous surgical intervention. A relative decrease in vitamin B1 is characteristic of colorectal cancer

The Outcome of Outpatient Intermediate and High Dose Cytarabine Consolidation Chemotherapy in Patients with Acute Myeloid Leukemia. The Experience of King Fahad Specialist Hospital in Dammam, Saudi Arabia

Background: Adult patients with Acute Myeloid Leukemia (AML) have traditionally been hospitalized for the duration of intensive consolidation chemotherapy until blood count recovery to avoid complications. Recently, there has been a trend to shift the care of AML patients treated with intensive chemotherapy from inpatient to outpatient settings to reduce treatment costs and save beds. Methods and materials: A retrospective study of AML patients who received cytarabine consolidation chemotherapy between the 1st of August 2016 and the 31st of December 2023 at King Fahad Specialist Hospital in Dammam, Saudi Arabia was performed. Results: Over a period of 7 years and 4 months, 62 patients received a total of 127 cycles of intensive consolidation chemotherapy at outpatient setting. At diagnosis: 12 patients had extramedullary disease, and 17 patients had adverse cytogenetic abnormalities. Following the 127 cycles of chemotherapy, 38 episodes of febrile neutropenia were encountered, and 46 hospital admissions were required. No complications were encountered following 62.2% of the cycles of consolidation therapy and no early mortality due to intensive consolidation therapy was reported. Out of 62 patients studied, 36 patients underwent various forms of hematopoietic stem cell transplantation. Disease relapses were encountered in 24 patients and the 5-year incidence of relapse for the entire group of patients was 42%. The 5-year leukemia-free survival for the: entire study patients, transplanted patients, and non-transplanted patients were: 43%, 38%, and 50% respectively. The 5-year overall survival for the: entire study patients, transplanted patients, and non-transplanted patients were: 44%, 34%, and 65% respectively. At the end of follow-up: 37 patients (59.68%) were alive, 24 patients (38.71%) were dead, and the fate of 1 patient (1.61%) was unknown as the patient moved to another hospital. Conclusion: Administration of intensive consolidation chemotherapy for patients with AML at outpatient setting is safe, feasible, and cost-effective. The incidence of infectious complications was relatively low. No early treatment-related mortality due to intensive consolidation therapy was encountered. Outpatient administration of intensive consolidation therapy can save beds, reduce hospital costs, and is associated with short-term and long-term outcomes that are comparable to inpatient administration of consolidation therapy.

Establishment and evaluation of a prognostic model for patients with unresectable gastric cancer liver metastases

BACKGROUND Liver metastases (LM) is the primary factor contributing to unfavorable outcomes in patients diagnosed with gastric cancer (GC). The objective of this study is to analyze significant prognostic risk factors for patients with GCLM and develop a reliable nomogram model that can accurately predict individualized prognosis, thereby enhancing the ability to evaluate patient outcomes. AIM To analyze prognostic risk factors for GCLM and develop a reliable nomogram model to accurately predict individualized prognosis, thereby enhancing patient outcome assessment. METHODS Retrospective analysis was conducted on clinical data pertaining to GCLM (type III), admitted to the Department of General Surgery across multiple centers of the Chinese PLA General Hospital from January 2010 to January 2018. The dataset was divided into a development cohort and validation cohort in a ratio of 2:1. In the development cohort, we utilized univariate and multivariate Cox regression analyses to identify independent risk factors associated with overall survival in GCLM patients. Subsequently, we established a prediction model based on these findings and evaluated its performance using receiver operator characteristic curve analysis, calibration curves, and clinical decision curves. A nomogram was created to visually represent the prediction model, which was then externally validated using the validation cohort. RESULTS A total of 372 patients were included in this study, comprising 248 individuals in the development cohort and 124 individuals in the validation cohort. Based on Cox analysis results, our final prediction model incorporated five independent risk factors including albumin levels, primary tumor size, presence of extrahepatic metastases, surgical treatment status, and chemotherapy administration. The 1-, 3-, and 5-years Area Under the Curve values in the development cohort are 0.753, 0.859, and 0.909, respectively; whereas in the validation cohort, they are observed to be 0.772, 0.848, and 0.923. Furthermore, the calibration curves demonstrated excellent consistency between observed values and actual values. Finally, the decision curve analysis curve indicated substantial net clinical benefit. CONCLUSION Our study identified significant prognostic risk factors for GCLM and developed a reliable nomogram model, demonstrating promising predictive accuracy and potential clinical benefit in evaluating patient outcomes.

Intraperitoneal chemotherapy for peritoneal metastases of gastric origin: a systematic review and meta-analysis.

Gastric cancer with peritoneal metastases is associated with a dismal prognosis. Normothermic catheter-based intraperitoneal chemotherapy and normothermic pressurized intraperitoneal aerosol chemotherapy (PIPAC) are methods to deliver chemotherapy intraperitoneally leading to higher intraperitoneal concentrations of cytotoxic drugs compared to intravenous administration. We reviewed the effectiveness and safety of different methods of palliative intraperitoneal chemotherapy. Embase, MEDLINE, Web of Science and Cochrane were searched for articles studying the use of repeated administration of palliative intraperitoneal chemotherapy in patients with gastric cancer and peritoneal metastases, published up to January 2024. The primary outcome was overall survival. Twenty-three studies were included, representing a total of 999 patients. The pooled median overall survival was 14.5 months. The pooled hazard ratio of the two RCTs using intraperitoneal paclitaxel and docetaxel favoured the intraperitoneal chemotherapy arm. The median overall survival of intraperitoneal paclitaxel, intraperitoneal docetaxel and PIPAC with cisplatin and doxorubicin were respectively 18.4 months, 13.2 months and 9.0 months. All treatment methods had a relatively safe toxicity profile. Conversion surgery after completion of intraperitoneal therapy was performed in 16% of the patients. Repeated intraperitoneal chemotherapy, regardless of method of administration, is safe for patients with gastric cancer and peritoneal metastases. Conversion surgery after completion of the intraperitoneal chemotherapy is possible in a subset of patients.

Abstract PO5-02-04: Irish National Analysis of the Clinical and Economic impact of 21-gene Oncotype DX® testing in Early-Stage, 1-3 lymph node positive, Hormone Receptor positive (HR+), HER2-Negative (HER2-), Breast Cancer (BC)

Abstract PO5-02-04: Irish National Analysis of the Clinical and Economic impact of 21-gene Oncotype DX® testing in Early-Stage, 1-3 lymph node positive, Hormone Receptor positive (HR+), HER2-Negative (HER2-), Breast Cancer (BC)

Abstract PO5-01-08: The impact of Human Epidermal growth factor Receptor 2 (HER2) expression by RT-PCR on tumor characteristics and outcome in estrogen receptor (ER) positive, HER2 negative early-stage breast cancer

Abstract Background: The role of HER2 expression in HER2 negative breast cancer is evolving. Whether HER2 expression has an impact on ER positive, HER2 negative early-stage breast cancer in unclear. Oncotype DX assay Recurrence Score comprises of standardized quantitative HER2 mRNA expression levels by RT-PCR. The objective of this study was to investigate the impact of Oncotype HER2 score on tumor characteristics and outcome. Methods: All women assigned to the Clalit Health Services registry between 2006 to 2011 with ER positive, HER2 negative early-stage breast cancer whose tumor were sent for oncotype were identified. Patients in which HER2 score was reported in the oncotype results were included. Differences in age, tumor characteristics and chemotherapy administration between lower HER2 score (H1), i.e. HER2 score ≤ 9.1, to higher HER2 score (H2), i.e. 9.2-10.7, were analyzed. 5-year Kaplan–Meier for distant recurrence free survival (DRFS) and overall survival (OS) were estimated and differences between H1 and H2 were evaluated. Analyses were repeated separately for node negative and for node positive (N mic and 1-3 lymph nodes) disease. Results: A total of 1535 patients were included, 948 patients with node negative disease and 587 with node positive disease. Of these, 814 and 721 patients were categorized to the H1 and H2 groups, respectively. Median follow-up was 5.4 years. The distribution of oncotype RS was different, with significantly lower proportion of patients with RS between 0-10 and higher proportion of RS above 25 in the H1 group compared to the H2 groups. This difference was identified both for patients with node negative and node positive disease (Table). The distributions of age, tumor size and histological subtype were comparable between the H1 and the H2 groups, both for node negative and node positive disease. Within each RS group, administration of chemotherapy was comparable between H1 and H2 groups, regardless of nodal involvement. DRFS and OS were not associated with HER2 score. For RS 0-25, node negative disease, 5-year DRFS was 96.2% in H1 and 96.4% in H2 groups (p=0.92) and 5-year OS was 97.2% in H1 and 98.1% in H2 groups (p=0.39). For RS &amp;gt;25, node negative disease, 5-years DRFS was 89% in H1 and 90.8% in H2 groups (p=0.33) and 5-year OS was 90.6% in H1 and 90.8% in H2 groups (p=0.7). Similarly, for node positive disease, DRFS and OS were comparable between H1 and H2 group in all subgroups. Conclusions: Low HER2 mRNA expression by Oncotype RT-PCR assay was associated with significantly high Oncotype RS. Patients' outcome was not directly affected by HER2 score and was determined by RS. Further study is desired to clarify the role of HER2 expression in early stage, luminal breast cancer. Table. Comparison of age and tumor characteristics between low (H1) and high (H2) HER2 score Citation Format: Hadar Goldvaser, Raz Mutai, Salomon Stemmer, Iryna Kuchuk, Margarita Tokar, Shani Paluch-Shimon, Rinat Yerushalmi, Karen Drumea, Ella Evron, Amir Sonnenblick, Einav Gal-Yam, Gil Bar Sela, Ayelet Shai, Rotem Merose, Avital Bareket-Samish, Lior Soussan-Gutman. The impact of Human Epidermal growth factor Receptor 2 (HER2) expression by RT-PCR on tumor characteristics and outcome in estrogen receptor (ER) positive, HER2 negative early-stage breast cancer [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO5-01-08.

Nomograms for predicting the overall and cancer-specific survival in patients with non-urothelial carcinoma of the bladder: A population-based study.

Non-urothelial carcinoma of the bladder (NUCB) is a relatively rare condition, with limited comprehensive studies conducted to date. This research aims to establish nomograms for forecasting overall survival (OS) and cancer-specific survival (CSS) in NUCB patients. It utilizes data of 2,522 patients from the Surveillance, Epidemiology, and End Results (SEER) database spanning from 2004 to 2015. The effectiveness of these nomograms was assessed using receiver operating characteristic (ROC) curves, calibration curves and decision curve analysis (DCA). Key independent predictors for OS included age, race, marital status, histological variants, grade, T stage, N stage, M stage, radical cystectomy and chemotherapy administration. For CSS, the predictors were similar, encompassing age, sex, marital status, histological variants, grade, T stage, N stage, M stage, radical cystectomy and chemotherapy. The nomograms showed strong predictive accuracy. In the training cohort, the area under the curve (AUC) values were 0.796 (OS) and 0.799 (CSS) at 1-year, 0.807 (OS) and 0.824 (CSS) at 3-year, and 0.807 (OS) and 0.827 (CSS) at 5-year intervals. In the validation cohort, AUC values were 0.798 (OS) and 0.798 (CSS) at 1-year, 0.810 (OS) and 0.826 (CSS) at 3-year, and 0.811 (OS) and 0.825 (CSS) at 5-year intervals, consistently around 0.8. Calibration curves indicated high congruence between predicted and actual probabilities of OS and CSS, while DCA demonstrated the models' substantial clinical utility. Overall, this study successfully developed and validated prognostic nomograms for NUCB, capable of accurately predicting OS and CSS at 1-, 3-, and 5-years, thereby offering valuable support in clinical decision-making and the design of clinical trials.

Abstract PO3-03-08: Use of adjuvant Capecitabine after neoadjuvant chemotherapy: A Cohort Study among Elderly Patients with Early-Stage Triple-Negative Breast Cancer

Abstract Background: The use of capecitabine in the adjuvant setting in patients with residual disease after neoadjuvant chemotherapy has been incorporated into practice based on the results of the CREATE-X trial. We evaluate utilization patterns of adjuvant capecitabine use, its association with outcomes, and subsequent hospitalizations and emergency room (ER) visits among elderly patients with early-stage triple-negative breast cancer (TNBC). Methods: We identified patients aged ≥66, diagnosed with early-stage TNBC between 2010 and 2017 in the SEER and Texas Cancer Registry (TCR)-linked Medicare databases. All patients were treated with neoadjuvant chemotherapy for localized or regional-stage disease. All patients had continuous enrollment in Medicare Parts A &amp; B without a Health Maintenance Organization enrollment 12 months before cancer diagnosis and 12 months after cancer diagnosis. Chemotherapy administration was identified using HCPCS codes from outpatient and physician’s carrier claims. We analyzed the patterns of capecitabine use, its association with survival outcomes, and the frequency of ER visits and hospitalizations during treatment (between the first capecitabine claim and 30 days after the last claim for capecitabine). Descriptive statistics were used. Primary analyses included logistic regression, Kaplan-Meier estimates, and Cox regression models with propensity score adjustments. This study adhered to the STROBE guidelines for cohort studies. Results: 1,239 patients with localized or regional TNBC treated with neoadjuvant chemotherapy were included (median 72 years). Of them, 96 (7.7%) were prescribed adjuvant capecitabine. Treatment with capecitabine was associated with recent year of diagnosis, regional disease, and residing in non-metropolitan areas. Specifically, the use of capecitabine increased from 1% in 2010 to 10% in 2016 and 21% in 2017. The median duration of capecitabine treatment was 4 cycles. In multivariable logistic regression analyses, older age was associated with decreased odds of receiving ≥4 cycles of capecitabine (OR=0.25; 95% CI: 0.11–0.60; p =0.002). Among capecitabine users, 3-year OS was 46% and 78% for patients who received 1-3 and ≥4cycles of capecitabine, respectively (p&amp;lt; 0.001). The 3-year estimate of BCSS was 43% and 85% respectively (p&amp;lt; 0.001). After multivariable adjustment for comorbidity score, stage, and propensity score, receiving ≥4 cycles of capecitabine was associated with decreased risk of death (HR=0.29; 95%CI 0.13–0.63, p=0.002) and breast cancer-specific death (HR=0.15; 95%CI: 0.05–0.51, p=0.002) compared to receiving 1-3 cycles. Twenty-seven (28%) patients had ER/hospitalization during capecitabine treatment; median time from initial capecitabine claim to ER/hospitalization was 24 days (IQ 13-39). The median number of capecitabine cycles was 3 (IQR 2-5) and 5 (IQR 3-8) for those with and without ER/hospitalization (p=0.02). The most common diagnosis codes associated with ER/hospitalization included pleural effusion, GI symptoms, pneumonia, and acute kidney failure. A higher comorbidity score at diagnosis was associated with an increased risk of ER/hospitalization (HR=2.76; 95%CI 1.05-7.28, p=0.04). Conclusion: We demonstrate an increasing trend in capecitabine utilization among elderly patients with early-stage TNBC. Although the limited sample size hindered a conclusive analysis, more cycles of capecitabine were associated with improved survival outcomes. Notably, a significant proportion of patients undergoing capecitabine treatment experienced ER/hospitalizations. These findings contribute valuable information on the risks and benefits of capecitabine treatment, aiding evidence-based decision-making to prevent serious complications. Citation Format: Marija Sullivan, Xiudong Lei, Catalina Malinowski, Sharon Giordano, Marianna Chavez. Use of adjuvant Capecitabine after neoadjuvant chemotherapy: A Cohort Study among Elderly Patients with Early-Stage Triple-Negative Breast Cancer [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO3-03-08.

Abstract PO4-03-07: The impact of chemotherapy relative dose intensity on pathological complete response in patients with triple negative breast cancer treated with neoadjuvant chemotherapy

Abstract Background: Neoadjuvant chemotherapy (NACT) is the preferred treatment approach for early-stage triple negative breast cancer (TNBC). Achieving pathologic complete response (pCR) after NACT is associated with improved event-free survival and overall survival in patients with TNBC. Major research efforts have been deployed to identify predictive biomarkers for pCR in TNBC. However, the values of chemotherapy (CT) relative dose intensity (RDI) in predicting pCR remain unclear. Methods: A retrospective analysis was conducted among 96 consecutive patients with early stage TNBC who received NACT between February 2018 and January 2023 at the University of Naples Federico II (Naples, Italy). Patients’ demographics, clinical-pathological features, and type of CT schedules were retrieved from electronic medical records. pCR was defined as the absence of residual invasive or in situ carcinoma in primary tumor and/or lymph nodes, upon chemotherapy administration. RDI was calculated as the ratio of delivered to planned CT dose intensity. RDI was defined as low if &amp;lt; 85% or high if ≥85%, respectively. Univariate and multivariate logistic regression were used to evaluate the association between age, tumor stage, RDI, CT regimen dose type, and pCR. Results: All patients were included in the analysis. Median age at diagnosis was 51 years (range 28-75). Sixty-five (68%) and 31 (32%) patients were diagnosed with stage II and stage III TNBC, respectively. Nineteen (19%) patients received a sequential schedule of anthracycline plus cyclophosphamide (AC) and a taxane (T). Sixty-one (64%) patients received AC followed by concurrent carboplatin-paclitaxel (CaP). Sixteen (17%) patients received the anti-PD1 pembrolizumab in addition to ACCaP chemotherapy backbone (ACCaP-Pem). Fifty-four (56%) patients received a dose-dense AC-based CT. A pCR was achieved in 59 (61%) patients. Interestingly, patients who received a dose-dense AC based neoadjuvant CT had higher chance to achieve a pCR compared with those treated with a non dose-dense AC based CT (70% vs 46%, p = 0.03). Overall, 79 (82%) and 17 (18%) patients received a RDI high and RDI low CT, respectively. No difference in terms of age, body mass index, performance status, tumor stage, type of chemotherapy was observed between the two groups (Table 1). At univariate analysis RDI high (OR 5.18, 95%CI: 1.65-16.31, p=0.005) and dose dense AC-based CT (OR 2.42, 95%CI: 0.18-0.97, p=0.04) were significantly associated with pCR. In a multivariate model including RDI, age, tumor stage, and AC regimen dose type, RDI was the only variable independently associated with pCR (OR 4.60, 95% CI: 1.40-15.06, p = 0.01). Conclusion: A chemotherapy RDI≥ 85% independently predicts pCR in early stage TNBC patients treated with standard NACT. In our cohort, one in five patients received a suboptimal chemotherapy dose intensity affecting at least in part tumor response. Studies with larger TNBC patient populations are warranted to confirm the impact of RDI on pCR and long-term outcomes. Table 1 Citation Format: Roberto Buonaiuto, Giuseppe Neola, Aldo Caltavituro, Paola Trasacco, Federica Pia Mangiacotti, Giovanna Pecoraro, Matteo Lambertini, Erica Pietroluongo, Pietro De Placido, Sabino De Placido, Valeria Forestieri, Mario Giuliano, Grazia Arpino, Carmine De Angelis. The impact of chemotherapy relative dose intensity on pathological complete response in patients with triple negative breast cancer treated with neoadjuvant chemotherapy [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO4-03-07.

Abstract PS04-01: Clinical impact of timing of systemic therapy in patients with early triple negative breast cancer

Abstract Introduction TNBC is known for its aggressive nature, with early recurrence and limited treatment options beyond chemotherapy and recently immunotherapy. We aim to clarify, whether timing of systemic therapy has an impact on survival in patients with early TNBC. Methods Data from a large population-based regional cancer registry covering over 2.2 million people was used for evaluation, including women with diagnoses of TNBC between 2010 and 2018. Patients were categorized into subgroups according to the interval from TNBC pathologic diagnosis to the date of first administration of NACT (TTNC) or according to the interval from primary surgery to the date of first administration of adjuvant chemotherapy (TTAC). Univariable analyses of survival rates were conducted using the Kaplan-Meier method, the log-rank test was used for group comparisons. IBM SPSS Statistic 25 was used to perform statistical analysis, with hazard ratios, p-values, and 95% confidence intervals calculated for each model. All tests were two-sided, and significance was set at p &amp;lt; .05. Results We identified 37 382 patients with malignant neoplasms of the mammary gland. The final study cohort included 732 patients with early TNBC, of whom 43.6% were treated with NACT and 40.3% with adjuvant chemotherapy. Timing of NACT 270 patients with TNBC treated with NACT had a valid TTNC. Median follow up was 3.5 years. Patients with TTNC ≤14, ≤42, &amp;gt;42, and &amp;gt;56 days had estimated mean OS of 8.4, 6.9, 4.6, and 3.3 years, respectively. Patients with a TTNC ≤14 days were more likely to survive than patients with a TTNC ≥ 56 days (p= 0.054). Significance was barely not reached in the group of NACT. Timing of adjuvant chemotherapy 245 patients with TNBC treated with adjuvant chemotherapy had a valid TTAC. Treatment given within 22-28 days led to the best outcome with a mean OS of 10.2 years, while later treatment (29-35, 36-42 days, or &amp;gt;6 weeks) had significant reduced mean OS of 8.3, 7.8, and 6.9 years. Patients who received therapy within 22-28 days had significantly better survival than those who received therapy between 29-35 days (p=0.043) or after more than 43 days (p=0.033). Conclusion Although significance was barely not reached in the subgroup of patients treated with NACT, the results in this large population-based study indicate that there are critical time intervals for initiation of systemic therapy in patients with early TNBC, with reduced OS if NACT is applied later than 42 days after diagnosis or if adjuvant chemotherapy is applied later than 42 days after surgery. We recommend not to exceed the 6-week interval until the initiation of systemic therapy in patients with early TNBC. Citation Format: Maria Eleni Hatzipanagiotou, Miriam Pigerl, Michael Gerken, Sophie Räpple, Verena Zeltner, Madeleine Hetterich, Elisabeth C. Inwald, Monika Klinkhammer-Schalke, Olaf Ortmann, Stephan Seitz. Clinical impact of timing of systemic therapy in patients with early triple negative breast cancer [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PS04-01.

Next-generation skin cancer treatment: A quality by design perspective on artificial neural network-optimized cationic ethosomes with bleomycin sulphate

Skin cancer, exacerbated by environmental factors like ozone layer depletion, poses a global health concern. Topical administration of chemotherapy, a promising approach, minimizes systemic toxicity. Bleomycin Sulphate (BLM), effective intravenously, faces challenges due to limited skin penetration. Cationic ethosomes, known for superior skin penetration, address this by enhancing electrostatic interactions with cancer cells. This ensures localized drug delivery, preventing systemic circulation. Employing thin film hydration, we prepared cationic ethosomes with BLM, optimizing through Artificial Neural Network (ANN) and Response Surface Methodology (RSM). Characterization included entrapment efficiency, vesicle size, morphology, and zeta potential. In-vitro drug release and various kinetic models were analyzed. Ex-vivo evaluations, like dermatokinetic studies and fluorescence microscopy, and in-vivo skin sensitivity testing were conducted. Results showed the optimized formulation with 27.1 % entrapment efficiency, 144.3 nm vesicle size, smooth surface morphology, and positive zeta potential. Ex-vivo assessments indicated favorable skin retention and in-vivo tests suggested suitability for topical administration, highlighting its potential in skin cancer treatment. This research offers a promising strategy for localized and effective skin cancer therapy, addressing challenges associated with systemic toxicity and limited drug penetration.

Precise timing of audiovisual stimulation conquers chemobrain

In a recent study, Kim et al. utilized gamma entrainment using sensory stimuli (GENUS) to rescue cognitive impairment and glial dysregulation associated with cisplatin and methotrexate chemotherapy, specifically when applied both throughout and after chemotherapy administration. GENUS provides a time-dependent, non-invasive method for treating chemobrain, with broader implications for resolving neurodegenerative neuroinflammation.

Predicting survival in locally advanced rectal cancer with effective chemoradiotherapy response

BackgroundLocally advanced rectal cancer patients often display favorable responses and favorable oncologic outcomes. Due to the low recurrence rate, there is scarcity of studies investigating the prognostic factors influencing their survival. Therefore, our study sought to assess the prognostic factors associated with survival in rectal cancer patients who achieved either a pathologic complete response or a pathologic stage I after neoadjuvant chemoradiotherapy combined with radical resection. MethodsIn this retrospective study, we analyzed data from cohort of 1394 patients diagnosed with locally advanced rectal cancer who underwent neoadjuvant chemoradiotherapy combined with total mesorectal excision from January 2008 to April 2017. Finally, we selected 474 (34.2 %) who exhibited either a pathologic complete response or attained pathologic stage I following the treatment. Subsequently, we analyzed the prognostic factors influencing disease-free and overall survival. ResultsA total of 161 (34 %) achieved a pathologic complete response. Our analysis revealed that circumferential resection margin and the administration of adjuvant chemotherapy were prognostic factors for disease-free survival (p = 0.011, p = 0.022). Furthermore, factors influencing overall survival included the clinical N stage and administration of adjuvant chemotherapy (p = 0.035, p = 0.015). ConclusionIn conclusion, the circumferential resection margin, clinical N stage, and administration of adjuvant chemotherapy were prognostic factors for survival in patients showing good response to neoadjuvant chemoradiotherapy in locally advanced rectal cancer. For patients with a positive circumferential resection margin and clinical N (+) stage, intensive follow-up might be needed to achieve favorable oncologic outcomes. Also, we recommend considering adjuvant chemotherapy as a beneficial treatment approach for these patients.

Specific mortality in patients with diffuse large B-cell lymphoma: a retrospective analysis based on the surveillance, epidemiology, and end results database.

The full potential of competing risk modeling approaches in the context of diffuse large B-cell lymphoma (DLBCL) patients has yet to be fully harnessed. This study aims to address this gap by developing a sophisticated competing risk model specifically designed to predict specific mortality in DLBCL patients. We extracted DLBCL patients' data from the SEER (Surveillance, Epidemiology, and End Results) database. To identify relevant variables, we conducted a two-step screening process using univariate and multivariate Fine and Gray regression analyses. Subsequently, a nomogram was constructed based on the results. The model's consistency index (C-index) was calculated to assess its performance. Additionally, calibration curves and receiver operator characteristic (ROC) curves were generated to validate the model's effectiveness. This study enrolled a total of 24,402 patients. The feature selection analysis identified 13 variables that were statistically significant and therefore included in the model. The model validation results demonstrated that the area under the receiver operating characteristic (ROC) curve (AUC) for predicting 6-month, 1-year, and 3-year DLBCL-specific mortality was 0.748, 0.718, and 0.698, respectively, in the training cohort. In the validation cohort, the AUC values were 0.747, 0.721, and 0.697. The calibration curves indicated good consistency between the training and validation cohorts. The most significant predictor of DLBCL-specific mortality is the age of the patient, followed by the Ann Arbor stage and the administration of chemotherapy. This predictive model has the potential to facilitate the identification of high-risk DLBCL patients by clinicians, ultimately leading to improved prognosis.

Pressurised Intraperitoneal Aerosolised Chemotherapy-Results from the First Hundred Consecutive Procedures.

PIPAC is a new and promising technique for the intraperitoneal administration of chemotherapy. It can be used in patients with various peritoneal cancer metastases. It is mainly a palliative treatment, but there is some neoadjuvant treatment potential. We have operated on 41 patients with various intra-abdominal cancers. PIPAC was performed every 6 weeks. The indication was extension of peritoneal carcinomatosis beyond the criteria for cytoreductive surgery and HIPEC. The effect was evaluated according to the peritoneal cancer index, the peritoneal regression grading score and the amount of ascites. Complications were classified according to the Clavien-Dindo system. We have performed 100 PIPAC procedures. There were two major complications, classified as Clavien Dindo III (2%). The number of procedures varied from 1 to 6. Five patients switched to cytoreductive surgery and HIPEC, and one was indicated for the watch and wait strategy due to total regression according to PRGS. Three patients are still continuing treatment. The others stopped treatment mainly because of progression of the disease and loss of metastases. We observed a reduction in ascites production soon after PIPAC application. PIPAC is a safe and well-tolerated treatment modality. It is mainly a palliative treatment that can improve the quality of life by reducing the production of ascites, but in about 10% of cases, it can reduce the extent of the disease and allow for further radical treatment.

Therapy-related myeloid neoplasms after treatment for ovarian cancer: A retrospective single-center case series.

Therapy-related myeloid neoplasms (t-MNs) are often fatal and arise as late complications of previous anticancer drug treatment. No single-center case series has examined t-MNs in epithelial ovarian cancer (EOC). All patients with EOC treated at Chiba University Hospital between 2000 and 2021 were included. We retrospectively analyzed the characteristics, clinical course, and outcomes of patients who developed t-MNs. Among 895 cases with EOC, 814 cases were treated with anticancer drugs. The median follow-up period was 45 months (interquartile range, 27-81) months. Ten patients (1.2%) developed t-MNs (FIGO IIIA in one case, IIIC in three, IVA in one, and IVB in five). Nine patients were diagnosed with myelodysplastic syndrome and one with acute leukemia. One patient with myelodysplastic syndrome developed acute leukemia. The median time from the first chemotherapy administration to t-MN onset was 42 months (range, 21-94 months), with t-MN diagnoses resulting from pancytopenia in four cases, thrombocytopenia in three, and blast or abnormal cell morphology in four. The median number of previous treatment regimens was four (range, 1-7). Paclitaxel + carboplatin therapy was administered to all patients, gemcitabine and irinotecan combination therapy to nine, bevacizumab to eight, and olaparib to four. Six patients received chemotherapy for t-MN. All patients died (eight cancer-related deaths and two t-MN-related deaths). None of the patients was able to restart cancer treatment. The median survival time from t-MN onset was 4 months. Patients with EOC who developed t-MN were unable to restart cancer treatment and had a significantly worse prognosis.