Last Dose Of Chemotherapy Research Articles

Analysis of Pulmonary Complications in Pediatric Acute Lymphocytic Leukemia Patients following Three Years of Chemotherapy Treatment: A Cross-Sectional Study

Background: This study aimed to investigate the pulmonary side effects of chemotherapy drugs in children with Acute Lymphocytic Leukemia (ALL) three years after treatment. The results could be of great help in managing lung complications in pediatric oncology patients. Materials and Methods: This cross-sectional descriptive study included 50 patients (22 males and 28 females) with ALL. Data were collected from patients' files, including age, sex, duration of illness, last dose of chemotherapy, and medications such as PEG.Asparginas, Cyclophosphamid, thioguanine, Dexamethason, cytarabin, cytosin.arabinosid, vincristine, mercaptopurine, and methotrexate. Pulmonary function tests (Forced Vital Capacity (FVC), FEV1 (Forced Expiratory Volume in the first second)) were assessed by spirometry. Results: Out of 50 patients, 47 (94%) did not have pulmonary disorders, while 3 (6%) had pulmonary dysfunction. Forty-seven patients (94%) did not have respiratory symptoms. FVC results showed that 45 patients were normal, and 5 were abnormal. Similarly, 45 patients had normal FEV1, and 5 had abnormal results. Spirometry results were normal in 45 patients and abnormal in 5. A significant relationship was found between the use of these drugs in different doses and spirometry results, recurrence rate, and pulmonary complications (P <0.05). No significant relationship was observed between pulmonary dysfunction and other drugs (P> 0.05). No correlation was found between pulmonary complications due to chemotherapy with duration of chemotherapy, patient age, and patient gender (P> 0.05). Conclusion: Pulmonary dysfunction and respiratory syndrome were observed in 6% of patients receiving chemotherapy. A significant relationship was found between the frequency of pulmonary and respiratory complications with some chemotherapy drugs in children with ALL. Further research is needed to optimize treatment strategies and minimize lung complications in pediatric oncology patients.

Tracking the Levels of Adiponectin and Interleukin-18 for Assessing the Efficiency of Chemotherapy in Suppressing Breast Cancer Progression

Breast cancer is a genetically and clinically heterogeneous disease. Cancerous cells multiplying abnormally in the breast, eventually spreading to the rest of the body if untreated. Breast cancer almost exclusively occurs in women. Cancer is a major public health problem worldwide with millions of new cancer patients diagnosed each year and many deaths resulting from this disease. Worldwide, female breast cancer has now surpassed lung cancer as the most commonly diagnosed cancer. SUBJECTS: Ninety two females were included in the current study, they were classified into three groups, depending on their health status (patients and healthy women) and the type of tumor suffered by the study patients: 32 female patients with cancerous breast tumors before receiving chemotherapy, 30 female patients with benign breast tumors (the pathological control group) and 30 females, who were included as a healthy control group. METHODS: Sandwich-ELISA method was applied to evaluate adiponectin and interleukin-18 concentrations in the sera of the study participants. RESULTS: Assessment of the adiponectin revealed a significant increase in the samples of malignant breast tumors group when compared with those of benign breast tumors (p=0.000) and healthy individuals (p=0.002). Interleukin-18 levels in the malignancy tumor group were significantly lower than their levels in the pathological (p=0.007) as well as healthy (p=0.000) controls groups. This study shows apparent slight decrease of adiponectin concentrations in cancerous patients group after getting approximately three consecutive doses of chemotherapy in comparison with its levels pretreatment, while non-significant difference was noted when comparing interleukin-18 levels after receiving the last dose of chemotherapy with its level before starting treatment. Although the levels of interleukin-18 increased after the end of the recommended course of chemotherapy, it did not rise to the levels of this protein in the healthy control group. The individual efficiency (sensitivity) of the evaluated criteria in the current study for distinguishing between cancerous and benign breast tumors was convergent. While the study recorded the highest specificity (93%) for adiponectin while the lowest specificity (40%) was recorded in interleukin-18. Adiponectin and interleukin-18 were able to distinguish 28 out of 32 breast cancer samples (88%).

Sebaceous carcinoma in a 54-year-old Black African man after cancer chemotherapy: a case report

BackgroundSebaceous carcinoma is a very rare malignant skin adnexal tumor that is occasionally aggressive. We have not seen a case of sebaceous carcinoma in our center in the last 10 years. It is extremely rare in Black Africans.Case presentationWe described the case of a 55-year-old man African man who presented to our ophthalmologist with complaints of growth on the right upper eyelid for 8 months. He had surgery and chemotherapy for rectal carcinoma 6 years prior to presentation and received his last dose of chemotherapy 5 years before seeing our ophthalmologist. There was a history of spontaneous unprovoked bleeding from the lesion. He subsequently underwent surgical excision under general anesthesia. Histology of the mass showed an effaced architecture due to proliferating malignant epithelial cells disposed as trabecules, solid nests, and tongues. The microscopic features of widespread multivacuolated cytoplasm of the neoplastic cells led us to conclude that the tumor was a sebaceous carcinoma. The patient is alive and well.ConclusionSebaceous carcinoma is a rare malignant skin adnexal tumor in Black Africans. It can present as an eyelid mass with spontaneous bleeding. It can follow cancer chemotherapy either because of its association with other tumors in Muir–Torre syndrome or because of mutagenic effects of chemotherapeutic agents.

MAIN-CAV: Phase III randomized trial of maintenance cabozantinib (CABO) and avelumab (Av) vs Av after first-line platinum-based chemotherapy in patients (pts) with metastatic urothelial cancer (mUC; Alliance A032001).

TPS714 Background: 1st-line induction platinum-based chemotherapy followed by switch maintenance Av is the current preferred standard of care in patients (pts) with aUC who do not progress after platinum-based chemotherapy. There is an significant need to further improve outcomes by combining Av with an effective, non-cross resistant therapy with non-overlapping toxicity. CABO is an oral inhibitor of MET, VEGFR and TAM family receptors involved in tumor growth, angiogenesis and immune cell regulation and has shown efficacy in UC in combination with PD-1/PD-1L1 inhibitor. We hypothesized that CABO-Av combination would improve survival vs Av alone and have an acceptable safety profile as switch maintenance therapy in mUC. Methods: MAIN-CAV is a phase III randomized, multicenter, international trial for pts with locally advanced/metastatic UC (including cN3M0 only)) who do not progress after 4-6 cycles of any platinum-based chemotherapy (gem-cis, gem-carbo, MVAC or ddMVAC). 654 adults are randomized 1:1 within 3-10 weeks (wk) after last dose of chemotherapy to receive Av 800 mg IV every 2 wk or Av and CABO 40 mg daily for up to 2 yrs. Key eligibility criteria include ECOG PS 0-1, no prior use of anti-PD(L)1, no CNS metastases, no major surgery within 4 wks, no uncontrolled hypertension or cardiovascular disorders. Pts are stratified based on 1) best response to 1L chemotherapy: complete vs partial response vs stable disease and 2) presence vs absence of visceral metastases. The primary endpoint is overall survival (OS) with assumptions of 1-sided alpha 0.025, power 80%, median OS 21 months (mo) with Av and hazard ratio 0.75, thus hypothesizing median OS 28 mo on CABO-Av. Key secondary endpoints include progression-free survival, safety, tolerability, and efficacy of CABO-Av vs Av alone based on RECIST 1.1 and iRECIST criteria (and PD-L1 status).Quality of life (QOL) are assessed using EQ-5D-5L, PROMIS-Fatigue 4a, EORTC QLQ-C30, EORTC QLQ-BLM30 between pts on CABO-Av vs Av alone. Biomarkers of response and resistance to Av will be assessed using baseline archival tissues, baseline and serial blood, ctDNA, stool and urine. Imaging studies will test the correlation of established and new radiomic signatures with survival, adverse events and QOL and incorporate both radiologic and biologic features to assess their potential association with outcomes. This trial would be the first to systematically address whether adding the multitargeted TKI, CABO, to Av improves survival vs Av alone as 1L maintenance therapy. https://acknowledgments.alliancefound.org . Support: U10CA180821, U10CA180882; U24CA196171, U10CA180863 (CCTG); Clinical trial information: NCT05092958 .

End-of-Life Outcomes in Patients with Acute Myeloid Leukemia Receiving Non-Curative Chemotherapy

Background: Patients with acute myeloid leukemia (AML) frequently have poor-quality end of life (EOL) care including intensive care unit admissions and prolonged hospitalizations. Prognostic uncertainty and restrictions on transfusions during hospice are barriers that prevent patients with AML from having access to palliative care services. There is a paucity of data on EOL care on patients with AML that are unable to continue a venetoclax and hypomethylating agent (HMA-ven) treatment. Methods: A query was conducted using Northwell Cancer Institute's electronic health records to identify all transplant-ineligible patients with AML who received HMA-ven between January 2019 and December 2022 that had died. We retrospectively analyzed the charts of 84 patients who fit the criteria. EOL outcomes including rate of advanced care planning, location of death, and resource utilization were recorded. Overall survival (OS) was defined as the time from start of the last line of chemotherapy to death for patients that had disease-modifying treatment at EOL. For those that continued to best supportive care (BSC), OS was defined as the time from stopping the last dose of chemotherapy to death. Hospice length of stay (HLOS) was the time from a hospice referral to death for patients that chose to stop transfusions and pursue hospice. Kaplan-Meier method and log rank testing were used to compare time to event data. Results: In our cohort of 84 patients, 43% of patients died on hospice, 53% of patients died in the hospital, with 23% requiring an ICU admission at the end of life. 18% had either cardiopulmonary resuscitation (CPR) or an activation of the emergency response system within 24 hours of death. While more than half of patients opted to not have CPR, 15% of these decisions were made within the last 24 hours of life. Furthermore, of the patients only 65% saw a palliative care physician while admitted for treatment. Of note, 42 patients tolerated HMA-ven and were continued to take this medication until their death. However, 42 patients stopped HMA-Ven due to progression of disease (69%) or intolerance (31%). Of this cohort, 15 patients continued to subsequent line therapy following HMA-ven with a median OS of 56 days. 24 patients continued on to hospice without transfusion support, with a median HLOS of 7 days. Seven patients continued BSC with median OS of 41 days, requiring an average of 1.6 transfusions weekly. Of note, the patients that continued BSC did not transition to hospice as these patients were unable or unwilling to stop transfusions. There was no statistical difference in OS between receiving subsequent chemotherapy and BSC at EOL (p = 0.40). Patients receiving BSC had a lower percentage of patients dying in the ICU (55% vs 40%) and documented advanced directives with a health care proxy (29% vs 7%) compared to those that had received chemotherapy at EOL. Discussion: Our study identified opportunities to improve EOL care and goal-concordant care in patients with AML receiving non-curative therapy. A subset of this population significantly benefitted from transfusion-only support and stopping disease modifying treatment. Opting for BSC may drastically improve the EOL quality by decreasing ICU deaths and improving access to goal-concordant care. Further research on the timing of best supportive care to patients with AML undergoing non-curative intent therapy as opposed to continuing subsequent line chemotherapy regimens is needed.

Neoadjuvant chemotherapy with modified FOLFOXIRI for locally advanced rectal cancer to transform effectively EMVI and MRF from positive to negative: results of a long-term single center phase 2 clinical trial

PurposeChemoradiotherapy (CRT) remains the standard treatment for locally advanced rectal cancer (LARC). This phase 2 clinical trial was designed to evaluate the efficacy and safety of neoadjuvant triplet chemotherapy with mFOLFOXIRI (folinic acid, 5-fluorouracil, oxaliplatin, and irinotecan) in LARC.Patients and methodsThe patients with LARC (the lower edge more than 5 cm from the anal verge) received up to 5 cycles of mFOLFOXIRI. MRI was performed to assess the baseline and postchemotherapy TN stage. Radical resection was performed within 4–6 weeks from the last dose of chemotherapy if the tumor shrank or remained stable. Adjuvant chemotherapy with mFOLFOX6 or XELOX was recommended. Postoperative radiation was planned for R1 resection, ypT4b, ypN2 and a positive CRM. The primary endpoint was the pathological complete response (pCR) rate.ResultsFrom February 2016 to March 2019, 50 patients were enrolled. Forty-eight (96%) were clinically node-positive, 28 (56.5%) with MRF invasion and 39 (78.4%) were EMVI positive. The median cycle of neoadjuvant mFOLFOXIRI chemotherapy was 5 (range,1–5). A total of 46/50 (92%) patients underwent total mesorectal excision (TME) surgery, all with R0 resection. The pCR rate was 4.3% (2/46). Twenty-three of 46 (50%) patients with cN + achieved a pathological node-negative status. The proportions of pathologically positive CRM and EMVI were 2.2% and 34.7%, respectively. Adjuvant radiotherapy was given to 14/46 (30.4%) patients. The most common Grade 3 or > toxicities included neutrocytopenia (50%), leukopenia (14%) and diarrhea (12%) during the neoadjuvant chemotherapy period. Clinically meaningful postoperative complications included pneumonia (n = 1), pelvic infection (n = 1) and anastomotic fistula (n = 1). With a median follow-up time of 51.2 months, local recurrences and distant metastases were confirmed in 3 (6.5%) and 9 (19.6%) of cases, respectively. The 3-year disease free survival (DFS) and overall survival (OS)rates were 75.8% and 86.8%.ConclusionNeoadjuvant chemotherapy with mFOLFOXIRI yielded a significant down-staging effect and seemed to be effective in eliminating EMVI and transforming the positive MRF to negative in LARC. The survival results are promising. The long-term follow-up showed promising DFS and OS rates accompanied by a favorable safety profile.Trial registrationClinicalTrials.gov identifier: NCT03443661, 23/02/2018.

MAIN-CAV: Phase III randomized trial of maintenance cabozantinib and avelumab versus avelumab after first-line platinum-based chemotherapy in patients (pts) with metastatic urothelial cancer (mUC; Alliance A032001).

TPS4609 Background: First-line platinum-based chemotherapy followed by maintenance avelumab (Av) is the current preferred standard of care in patients (pts) with mUC who do not progress after platinum-based chemotherapy. There is an unmet need to further improve outcomes by combining Av with an effective, non-cross resistant therapy with non-overlapping toxicity. CABO is an oral inhibitor of MET, VEGFR and TAM family receptors involved in tumor growth, angiogenesis and immune cell regulation and has shown efficacy in UC in combination with PD-1/PD-1L1 inhibitors. We hypothesize that CABO-Av combination will be synergistic in pts with mUC with an acceptable safety profile and will improve upon the benefit seen with Av maintenance in mUC. Methods: MAIN-CAV is a phase III randomized, multicenter, international trial for locally advanced/mUC pts (including N3 only disease) who do not progress after 4-6 cycles of any platinum-based chemotherapy (gem-cis, gem-carbo, MVAC or ddMVAC). 654 adult pts will be randomized 1:1 within 3-10 weeks (wk) after last dose of chemotherapy to receive Av 800 mg IV every 2 wk or combination of Av and CABO 40 mg orally daily for up to 2 yrs. Key eligibility criteria include ECOG PS 0-1, no prior use of immunotherapy (exception of BCG), no central nervous system metastases, no major surgery within 4 wk, no uncontrolled hypertension or cardiovascular disorders. Pts will be stratified based on 1) best response to 1L therapy: complete response vs partial response vs stable disease and 2) presence or absence of visceral metastases. The primary endpoint is overall survival (OS) with assumptions of one-sided alpha of 0.025, power of 80%, median OS of 21 months (mo) on Av arm and hazard ratio (HR) of 0.75, thus hypothesizing a median OS of 28 mo on CABO-Av combination arm. Key secondary endpoints include progression-free survival, safety, tolerability, and activity of CABO-Av compared to Av alone based on RECIST 1.1 and iRECIST criteria and PD-L1 status of pts’ tumors. Quality of life (QOL) will be assessed using EQ-5D-5L, PROMIS-Fatigue 4a, EORTC QLQ-C30, EORTC QLQ-BLM30 between pts on CABO-avelumab vs avelumab alone. Biomarkers of response and resistance to Av will be assessed using baseline archival tissues, baseline and serial blood, ctDNA, stool and urine. Imaging studies will test correlation of established and new radiomic signatures with OS, adverse events and QOL and incorporate both radiologic and biologic features to predict outcomes. This trial would be the first to systematically address whether adding a multitargeted TKI, CABO to Av leads to improved clinical outcomes compared to Av alone. Clinical trial information: NCT05092958 .

Continuity of care and treatment intensity at the end of life in Swiss cancer patients.

Continuity of care (COC) was shown to be associated with fewer hospitalizations. We aimed to evaluate whether COC was associated with intensive intervention(s) at the end of life (IEOL), a preference-sensitive outcome, in cancer patients. The study is based on claims data of patients with incident use of anti-neoplastics in Switzerland. COC Index, Usual Provider Continuity score, Sequential Continuity index and Modified Modified Continuity Index were calculated based on consultations with the usual ambulatory care physician. Treatment intensity was evaluated in the last 6 months of life, and COC was evaluated in months 18-6 before death in those who died between 24 and 54 months after incident cancer. IEOL comprised life-sustaining interventions (cardiac catheterization, cardiac assistance device implantation, pulmonary artery wedge monitoring, cardiopulmonary resuscitation/cardiac conversion, gastrostomy, blood transfusion, dialysis, mechanical ventilator utilization and intravenous antibiotics) and measures specifically used in cancer patients (last dose of chemotherapy ≤14 days of death, a new chemotherapy regimen starting <30 days before death, ≥1 emergency visit in the last month of life, ≥1 hospital admission or spending >14 days in hospital in the last month of life and death in an acute-care hospital). All COC scores were inversely associated with the occurrence of an IEOL, as were older age, homecare nursing utilization and density of ambulatory care physicians. For COC Index, odds ratio was 0.55 (95% confidence interval 0.37-0.83). COC scores were consistently and inversely related to IEOL. The study supports efforts to improve COC for cancer patients at their end of life.

Randomized double-blind, placebo-controlled study of oral gabapentin for prevention of neuropathy in patients receiving paclitaxel

BackgroundPeripheral neuropathy is a common dose-limiting side effect of paclitaxel. To date, there is no effective strategy to prevent paclitaxel-induced peripheral neuropathy. A recent small phase II study demonstrated the potential role of oral gabapentin in this setting. This phase III study is aimed to assess the efficacy of oral gabapentin in preventing paclitaxel-induced neuropathy.ObjectiveTo compare the efficacy of oral gabapentin with placebo in preventing clinically significant peripheral neuropathy (NCI CTCAEv5.0 grade 2 or higher) in patients receiving paclitaxel.MethodsThis is a randomized, placebo-controlled, double-blind, parallel-group superiority trial. The primary outcome is the development of grade 2 or higher chemotherapy-induced peripheral neuropathy. Secondary outcomes include any grade neuropathy, the percentage change in sensory nerve conduction velocities in peripheral nerves, time to development of any grade neuropathy, paclitaxel dose reductions and delays due to peripheral neuropathy, patient-reported outcomes, adverse events, and adherence to oral therapy. A total of 136 patients receiving paclitaxel will be randomly allocated (stratified by weekly vs. non-weekly administration) to receive either oral gabapentin or placebo till three weeks after the last dose of chemotherapy or occurrence of the primary outcome.ConclusionThis study aims to find if oral gabapentin reduces the incidence of grade 2 or higher chemotherapy-induced peripheral neuropathy in patients receiving paclitaxel.Trial registrationThe trial is registered prospectively with the Clinical Trials Registry of India (CTRI/2022/02/040030) on April 4, 2022.

Olaparib First-Line Maintenance Monotherapy in BRCA-Mutated Epithelial Ovarian Cancer: Descriptive Analysis of the First French Real-World Data Study.

Olaparib, a poly(ADP-ribose) polymerase inhibitor, was approved by the European Commission in June 2019, following the results of the SOLO-1/GOG 3004 trial as maintenance monotherapy in adult patients with BRCA-mutated epithelial ovarian cancer. This study aimed to provide a descriptive analysis of the first real-world data from patients with BRCA-mutated ovarian cancer who received olaparib as first-line maintenance monotherapy in the French cohort Temporary Authorisation for Use (Autorisation Temporaire d'Utilisation de cohorte, ATUc) programme from 11 March, 2019 to 16 January, 2020. Eligible patients were aged 18 years and over with confirmed epithelial ovarian, primary peritoneal or Fallopian tube cancer and a deleterious or suspected deleterious germline or somatic BRCA 1/2 mutation. Patients were in complete or partial clinical response at the end of first-line platinum-based chemotherapy. Olaparib maintenance therapy was initiated within 8 weeks of the patients' last dose of chemotherapy. Real-world data were collected through treatment access request forms completed by physicians. Clinical and safety data were collected monthly until the end of the ATUc programme. A total of 107 centres in metropolitan France and the French Overseas Departments and Territories requested the inclusion for 238 patients, of whom 194 received maintenance olaparib. In total, 87.6% of the primary tumour locations were ovary, the most common histology was high-grade serous (93.0%) and the most common International Federation of Gynaecology and Obstetrics (Fédération Internationale de Gynécologie et d'Obstétrique) stage was IIIC (56.8%). BRCA testing was performed in routine practice, prior to inclusion into the ATUc programme. All patients had a BRCA mutation: 52.5% had a somatic mutation, 38.4% had a germinal mutation and 9.1% had germinal and somatic mutations. Twenty-four (12%) patients experienced serious adverse drug reactions at the last safety follow-up (17 February, 2020). The most common were anaemia (12 [6%] patients), neutropenia (3 [2%] patients) and thrombocytopenia (3 [2%] patients). The rapid enrolment into the ATUc programme highlighted the strong unmet need for patients with ovarian cancer and a BRCA mutation in first-line maintenance treatment. Olaparib was well tolerated and no new safety signals were observed in this real-world patient population.

Chemotherapy Induced Eosinophilia and its Significance among the Cancer Patients Treated at a Tertiary Care Teaching Hospital, West Bengal

AbstractBackground: Cancer is a major burden and threat to global society. It is one of the leading causes of death inboth developed and developing countries. The main modalities used for its treatment include surgery, radiation,chemotherapy, immunotherapy, and hormones.Materials &amp; Methods: The current study was performed to find incidence of chemotherapy induced eosinopilliain patients with different cancers who were receiving standard chemotherapy regimens (minimum two cycles andmaximum six to eight cycles). Total leucocyte count, absolute eosinophil count and differential leucocyte countwas done just before starting of chemotherapy. Differential leucocyte count (DLC) was reported after 1st cycle ofchemotherapy agents, before last dose of chemotherapy, after 6 weeks of completion of chemotherapy, and aftersix month of completion of chemotherapy to see the changes on eosinophil counts.Results: Most commonly used anticancer agents were 5 FU 61 (61%), doxorubicin 43 (43%), cyclophosphomide 53(53%), cisplatin 10 (10%), paclitaxel 20 (20%), carboplatin 25 (25%), gemcitabine 11 (11%), oxaliplatin 14 (14%) andcapecitabine 11 (11%). The pre-CT eosinophil count had a mean of 3.41 (range, 2 to 4) and post-CT after 1st dosehad a mean of 5.06 (range, 3 to 8) (p &lt;0.0001). The pre-CT eosinophil count had a mean of 3.41 (range, 2 to 4) andpost-CT after 6 months of chemotherapy had a mean of 6.85 (range, 5 to 8) (p &lt;0.0001). Increased eosinophil countafter 1st dose and 6 months completion of chemotherapy was highly significant from baseline values (P &lt; 0.0001).Conclusion: Study has generated a hypothesis that administration of many anticancer agents may increaseeosinophil count or peripheral eosinophilia. Additional large scale prospective studies must be performed toconfirm our results.

Associations between disrupted functional brain network topology and cognitive impairment in patients with rectal cancer during chemotherapy.

Cognitive impairment has been identified in patients with non-central nervous system cancer received chemotherapy. Chemotherapy-induced changes in the brain are considered as the possible causes of the cognitive deficits of patients. This study aimed to explore chemotherapy-related functional brain changes and cognitive impairment in rectal cancer (RC) patients who had just finished chemotherapy treatment. In this study, RC patients after chemotherapy (on the day patients received the last dose of chemotherapy) (n=30) and matched healthy controls (HCs) (n=30) underwent cognitive assessments, structural magnetic resonance imaging (MRI) and resting-state functional MRI. The functional brain networks were constructed by thresholding the partial correlation matrices of 90 brain regions in the Anatomical Automatic Labeling template and the topologic properties were evaluated by graph theory analysis. Moreover, correlations between altered topological measures and scores of cognitive scales were explored in the patient group. Compared with HCs, RC patients had lower scores of cognitive scales. The functional brain network had preserved small-world topological features but with a tendency towards higher path length in the whole network. In addition, patients had decreased nodal global efficiency (Eglo(i)) in the left superior frontal gyrus (dorsolateral), superior frontal gyrus (orbital part), inferior frontal gyrus (opercular part), inferior frontal gyrus (triangular part) and right inferior frontal gyrus (triangular part). Moreover, values of Eglo(i) in the superior and inferior frontal gyrus were positively associated with cognitive function in the patient group. These results suggested that cognitive impairment was associated with disruptions of the topological organization in functional brain networks of RC patients who had just finished chemotherapy, which provided new insights into the pathophysiology underlying acute effects of chemotherapy on cognitive function.

Quality of life among elderly women with breast cancer who received chemotherapy at Sohag Cancer Institute, Sohag Governorate

Background Breast cancer is the most frequent cancer among women all over the world. Breast cancer risk increases with age and about a third of female breast cancers are diagnosed in patients aged older than 70 years. Elderly breast cancer patients are affected by poorer quality of life (QoL) compared with younger patients. Aim The current study aimed to assess QoL of elderly women with breast cancer who received chemotherapy at Cancer Institute, Sohag Governorate. Research questions What is the QoL of breast cancer elderly women who received chemotherapy at Sohag Cancer Institute? Design Cross-sectional descriptive design was utilized. Sample Purposive sample of 100 elderly women with breast cancer, who completed all cycles of chemotherapy 1–3 months at least from the last dose of chemotherapy. Setting This study was conducted at the oncology building at outpatient clinics for cancer patients follow-up at Sohag Cancer Institute. Tools (1) Structured interviewing questionnaire for demographic and medical data. (2) QoL scale to assess QoL issues relevant to breast cancer patients (Algamdi and Hanneman, 2016). Results The results revealed that selected breast cancer elderly women aged from 60 to 80 years with mean 63.47±4.87 years. Seventy-two percent of them could not read and write, and 62% of them lived in rural areas. Seventy-eight percent suffered from chronic diseases. The mean of social well-being domain was 2.98±0.56, the mean of emotional well-being domain was 2.32±1.34, the mean of physical well-being domain was 1.79±1.15, and the mean of total Functional Assessment of Cancer Therapy – Breast was 2.24±0.31. More than half of the women had poor QoL, more than one-third of them had fair QoL, and a minority had good QoL. Conclusion The current study concluded that 60% of the selected breast cancer elderly women had poor QoL, whereas 38% had fair QoL and only 2% had good QoL. Also, it revealed that more than half of women had poor physical, functional well-being, and additional concerns and about half of them had good social well-being. Recommendations The current study recommends use of QoL scale in elderly women with breast cancer in oncology outpatient clinics in different cancer institutes and conduction of health education programs and further research works for improving QoL in elderly women with breast cancer.

PB2125: LYMPHOMATOID PAPULOSIS-LIKE (LYP-LIKE) AFTER BRENTUXIMAB VEDOTIN-CHP (BV-CHP) TREATMENT FOR ALK-NEGATIVE ANAPLASTIC LARGE CELL LYMPHOMA (ALCL)

Background: Lymphomatoid papulosis is an indolent form of CD30 primary cutaneous lymphoproliferative disorder characterized for recurrent crops of self-healing papular nodular lesions. Histological findings may overlap with those in primary cutaneous ALCL so clinical features and evolution determine the appropriate therapeutic approach. Most cases of LyP don’t require any treatment, but PUVA or low-dose oral methotrexate can reduce skin lesions. LyP-like is uncommon after a systemic ALCL. BV-CHP has become the new standard front-line treatment for ALCL in the last years; some aspects of the biological and clinical behavior of the disease with this new therapy are still under research. Aims: NA Methods: NA Results:Patient 1: 45 years female, diagnosed in January/20 with ALK-negative ALCL stage IV-A, IPI 3, involving multiple supra- and infradiaphragmatic lymphadenopathies, spleen, skin, bone and bone marrow. The diagnosis was performed by skin biopsy of an extensive ulcerated mass in the right chest area. FISH showed no rearrangements of DUSP22 and TP63. BV-CHP was started in January/20, achieving PR by PET-CT after 3 cycles. She completed 6 cycles. Four weeks after the last dose of chemotherapy she developed several papular skin lesions in the trunk and extremities. The skin biopsy was reported as ALCL. PET-CT showed metabolic CR at that time. After 3 weeks, the skin lesions spontaneously disappeared and she underwent ASCT conditioned with BEAM in July/20. Two months later, she developed new skin lesions and a new biopsy showed nonspecific findings: perivascular lymphocytic dermatitis with epidermal spongiotic changes. PET-CT showed two enlarged axillary lymphadenopathies with increased activity. A watch and wait strategy was adopted, until September/21 when she relapsed involving multiple lymphadenopathies, bone, spleen and new papulo-necrotic skin lesions. Skin biopsy showed a CD30+ lymphoprolipherative disorder. She received 3 cycles of ESHAP achieving PR, and an haploidentical stem cell transplantation was performed in January/22. Two months after transplant, the patient has no signs of disease and no skin lesions. Patient 2: 62 years male, diagnosed in August/21with systemic ALK-negative ALCL stage IV-B, IPI 3, with supra- and infradiaphragmatic lymphadenopathies and extensive colonic involvement. DUSP22-IRF4 and TP63 rearrangements were assessed, showing no abnormalities. Bone marrow and skin were not affected. He started front-line treatment with BV-CHP in September/21, with metabolic CR in the interim PET-CT after 4 cycles. He completed 6 cycles with good tolerance until late December/21. One month later, he developed papular and papulo-necrotic skin lesions in different evolutionary stages, affecting trunk, extremities and scalp. Skin biopsy was performed, showing a CD30+ lymphoprolipherative disorder. Another PET-CT demonstrated systemic CR. Clinicopathological findings were consistent with lymphomatoid papulosis. The patient underwent an ASCT as consolidation treatment. Currently, the skin lesions have involuted spontaneously. Image:Summary/Conclusion: These two similar cases illustrate an unusual scenario after systemic ALK-negative ALCL, both developed within weeks after frontline chemotherapy with BV-CHP. Diagnosis and therapeutic decisions are challenging. Further experience with this new regimen will reveal whether the addition of BV may play a role in the development of this condition, and whether the clinical course is the same as primary cases of LyP or precedes a relapse of systemic lymphoma.

MAIN-CAV: Phase III randomized trial of maintenance cabozantinib and avelumab versus avelumab after first-line platinum-based chemotherapy in patients with metastatic urothelial cancer (mUC) (Alliance A032001).

TPS4607 Background: First-line platinum-based chemotherapy followed by maintenance avelumab (Av) is the current preferred standard of care in patients (pts) with mUC who do not progress after platinum-based chemotherapy. There is an unmet need to further improve outcomes by combining Av with an effective, non-cross resistant therapy with non-overlapping toxicity. Cabozantinib (CABO) is an oral inhibitor of MET, VEGFR and TAM family receptors involved in tumor growth, angiogenesis and immune cell regulation and has shown efficacy in UC in combination with PD-1/PD-1L1 inhibitors. We hypothesize that CABO-Av combination will be synergistic in pts with mUC with an acceptable safety profile and will improve upon the benefit seen with Av maintenance in mUC. Methods: MAIN-CAV is a phase III randomized, multicenter, international trial for locally advanced/mUC pts (including N3 only disease) who do not progress after 4-6 cycles of any platinum-based chemotherapy (gem-cis, gem-carbo, MVAC or ddMVAC). 654 adult pts will be randomized 1:1 within 3-10 weeks (wk) after last dose of chemotherapy to receive Av 800 mg IV every 2 wk or combination of Av and CABO 40 mg orally daily for up to 2 yrs. Key eligibility criteria include ECOG PS 0-1, no prior use of immunotherapy (exception of BCG), no central nervous system metastases, no major surgery within 4 wk, no uncontrolled hypertension or cardiovascular disorders. Pts will be stratified based on 1) best response to 1L therapy: complete response vs partial response vs stable disease and 2) presence or absence of visceral metastases. The primary endpoint is overall survival (OS) with assumptions of one-sided alpha of 0.025, power of 80%, median OS of 21 months (mo) on Av arm and hazard ratio (HR) of 0.75, thus hypothesizing a median OS of 28 mo on CABO-Av combination arm. Key secondary endpoints include progression-free survival, safety, tolerability, and activity of CABO-Av compared to Av alone based on RECIST 1.1 and iRECIST criteria and PD-L1 status of pts’ tumors. Quality of life (QOL) will be assessed using EQ-5D-5L, PROMIS-Fatigue 4a, EORTC QLQ-C30, EORTC QLQ-BLM30 between pts on CABO-avelumab vs avelumab alone. Biomarkers of response and resistance to Av will be assessed using baseline archival tissues, baseline and serial blood, ctDNA, stool and urine. Imaging studies will test correlation of established and new radiomic signatures with OS, adverse events and QOL and incorporate both radiologic and biologic features to predict outcomes. This trial would be the first to systematically address whether adding a multitargeted TKI, CABO to Av leads to improved clinical outcomes compared to Av alone. Support: U10CA180821, U10CA180882, U24CA196171,U10CA180863 (CCTG); Clinical trial information: NCT05092958.

Clinical Outcomes of RTOG 9310 Protocol for Primary Central Nervous System Lymphoma: Single-Center Experience with 87 Patients.

The Radiation Therapy Oncology Group (RTOG) 9310 protocol clinical trial established high-dose methotrexate (HDMTX) as the standard for primary central nervous system lymphoma (PCNSL). We aimed to investigate the RTOG 9310 protocol’s PCNSL outcomes by examining progression-free survival (PFS) and overall survival (OS) rates and determining the influential factors. Between 2007 and 2020, 87 patients were histopathologically diagnosed with PCNSL and treated with the RTOG 9310 protocol. All received HDMTX 2.5 g/m2 and vincristine 1.4 mg/m2/day for 1 day during weeks 1, 3, 5, 7, and 9, and procarbazine 100 mg/m2/day for 1 day during weeks 1, 5, and 9. Dexamethasone was administered on a standard tapering schedule from the first week to the sixth week. Whole brain radiotherapy (WBRT), consisting of 45 Gy for patients with less than a complete response to the chemotherapy or 36 Gy for complete responders, was started 1 week after the last dose of chemotherapy was administered. Within three weeks of the completion of WBRT, patients received two courses of cytarabine, which were separated by 3–4 weeks. Clinical, radiological, and histopathological characteristics were retrospectively reviewed. All patients completed five HDMTX cycles and a mean follow-up of 60.2 (range, 6–150) months. Twenty-eight (32.2%) patients experienced recurrence during follow-up. The mean time to recurrence was 21.8 months, while the mean PFS was 104.3 (95% confidence interval (CI), 90.6–118.0) months. Eleven (12.6%) patients died; the mean OS was 132.1 (95% CI, 122.2–141.9) months. The 3- and 5-year survival rates were 92.0% and 87.4%, respectively. One patient experienced acute renal failure, while the remainder tolerated any cytotoxic side effects. On multivariate analysis, the Eastern Cooperative Oncology Group performance score ≤ 2; the International Extranodal Lymphoma Study Group low-risk status; XBP-1, p53, and c-Myc negativity; homogenous enhancement; gross total resection, independently correlated with long PFS and OS. The RTOG 9310 protocol is effective for PCNSL and features good outcomes.

PD55-01 AVELUMAB FIRST-LINE MAINTENANCE FOR ADVANCED UROTHELIAL CARCINOMA IN THE JAVELIN BLADDER 100 TRIAL: SUBGROUP ANALYSIS BY DURATION OF TREATMENT-FREE INTERVAL FROM END OF CHEMOTHERAPY TO START OF MAINTENANCE

PD55-01 AVELUMAB FIRST-LINE MAINTENANCE FOR ADVANCED UROTHELIAL CARCINOMA IN THE JAVELIN BLADDER 100 TRIAL: SUBGROUP ANALYSIS BY DURATION OF TREATMENT-FREE INTERVAL FROM END OF CHEMOTHERAPY TO START OF MAINTENANCE

Neoadjuvant atezolizumab (A) with gemcitabine and cisplatin (GC) in patients (pts) with muscle-invasive bladder cancer (MIBC): A multicenter, single-arm, phase 2 trial.

4517 Background: Neoadjuvant GC is standard for pts with MIBC and can result in pathologic downstaging to non-MIBC ( &lt; pT2N0) at radical cystectomy (RC), which correlates with improved survival. Based on the known activity of A in metastatic BC (mBC), we tested the combination of GC+A as neoadjuvant therapy for MIBC in a phase II trial (NCT02989584). Methods: Eligible pts with MIBC (cT2-T4aN0M0) received a single dose of A (1200 mg IV) and, two weeks later, began C (as either 70mg/m2 IV on D1 or 35 mg/m2 on D1,D8), G (1000 mg/m2 on D1,D8), and A (1200 mg IV on D8) every 21 days for 4 cycles followed by RC. Pts were also able to receive one additional dose of A 3 weeks after the last dose of A and prior to RC. The primary endpoint was proportion of pts with &lt; pT2N0. Pts were considered not evaluable for the primary endpoint if they received less than 2 cycles due to withdrawal of consent or unrelated adverse events (AEs). Secondary endpoints included the proportion of pts with pT0N0, recurrence-free survival (RFS), and safety. We prespecified null and alternate &lt; pT2N0 rates of 35% and 55%, respectively, with the null being rejected if at least 19 of 39 pts achieved &lt; pT2N0. Pretreatment tumors underwent centralized PD-L1 staining (SP142; positive if ≥5% of immune cells). Results: Between Feb 2018 and May 2020, 44 pts were enrolled from five institutions. Five pts were not evaluable (withdrawal of consent before C3, n = 4; unrelated AEs during C1, n = 1). Of the 39 evaluable pts (cT2N0 79%, cT3N0 18%, cT4N0 3%), 1 pt refused surgery and was considered a non-responder. The primary endpoint was met, with 27 of 39 pts (69%) &lt; pT2N0 at RC, including 15 (38%) pT0N0. All pts achieving &lt; pT2N0 are alive and disease free. The median RFS was not reached with a median follow-up of 16.7 months (range: 7.7-33.2). The median time from last dose of chemotherapy to RC was 7.8 weeks (range 5.1 – 17). The most common grade 3-4 treatment related AEs were due to chemotherapy and were neutropenia (36%), lymphopenia (16%), and anemia (11%). Possible grade 3-4 immune related AEs included 2 pts with asymptomatic grade 3 pancreatic enzyme elevation, 1 pt with grade 3 pancreatitis, and 1 pt with hepatitis requiring steroids. Only 4 of 39 (10%) pts had PD-L1 positive tumors, which is low compared to mBC (25% positive; Powles et al. Lancet 2017) and MIBC (40% positive; Powles et al. Nature Med 2019) cohorts also tested with the SP142 clone. All 4 pts with PD-L1 positive tumors achieved &lt; pT2N0. Twelve of 12 (100%) non-responding pts were PD-L1 negative and 23 of 27 (85%) responding pts were PD-L1 negative (p = 0.3). Conclusions: Neoadjuvant GC+A is an effective and safe regimen for the treatment of pts with MIBC. The PD-L1 positivity rate was low compared with other studies and was not predictive of pathologic downstaging. Additional interrogation of the genomic and host immune factors mediating response and resistance to GC+A is ongoing. Clinical trial information: NCT02989584.

Avelumab first-line (1L) maintenance for advanced urothelial carcinoma (UC) in the JAVELIN Bladder 100 trial: Subgroup analysis by duration of treatment-free interval (TFI) from end of chemotherapy to start of maintenance.

4527 Background: The phase 3 JAVELIN Bladder 100 trial, which enrolled patients (pts) with advanced UC that had not progressed with 1L platinum-containing chemotherapy, showed that maintenance therapy with avelumab + best supportive care (BSC) significantly prolonged overall survival (OS) compared with BSC alone (hazard ratio [HR], 0.69 [95% CI: 0.56, 0.86; 1-sided P= 0.0005]). However, the optimal timing for starting avelumab after completing 1L chemotherapy is unknown. In this post hoc analysis, we report efficacy by duration of the TFI from completion of 1L chemotherapy. Methods: In the JAVELIN Bladder 100 trial (NCT02603432), eligible pts had unresectable locally advanced or metastatic UC without disease progression following 4 to 6 cycles of 1L platinum-containing chemotherapy. Pts were randomized to receive avelumab + BSC (n = 350) or BSC alone (n = 350) after a TFI of 4 to 10 weeks from the last dose of chemotherapy. In this exploratory analysis, subgroups with a TFI of 4 to &lt; 6 weeks ( &lt; 42 days), 6 to &lt; 8 weeks (42 to &lt; 56 days), or 8 to 10 weeks (≥56 days) were evaluated. Results: In the avelumab + BSC and BSC alone arms, the TFI was 4 to &lt; 6 weeks in 143 and 158 pts, 6 to &lt; 8 weeks in 109 and 80 pts, and 8 to 10 weeks in 98 and 110 pts, respectively. Baseline characteristics in these subgroups were generally well balanced between arms. For both arms combined, however, the TFI 4 to &lt; 6 weeks subgroup vs the other 2 subgroups included more pts with visceral metastases (57.8% vs 54.0% and 50.0%), an objective response with 1L chemotherapy (76.4% vs 69.3% and 68.3%), and an ECOG performance status of 1 (44.5% vs 33.3% and 35.6%). OS was prolonged with avelumab + BSC vs BSC alone in all subgroups; the HR was 0.76 (95% CI: 0.546, 1.059) in the TFI 4 to &lt; 6 weeks subgroup (median OS, 19.9 months [95% CI: 16.3, 25.3] vs 13.5 months [95% CI: 11.7, 17.4]), 0.64 (95% CI: 0.404, 1.021) in the TFI 6 to &lt; 8 weeks subgroup (median OS, 26.1 months [95% CI: 19.9, not estimable] vs 21.0 months [95% CI: 10.7, not estimable]), and 0.70 (95% CI: 0.468, 1.035) in the TFI 8 to 10 weeks subgroup (median OS, 20.1 months [95% CI: 13.8, not estimable] vs 14.1 months [95% CI: 11.7, 19.6]). Conclusions: In patients with advanced UC that had not progressed with 1L platinum-containing chemotherapy, avelumab 1L maintenance prolonged OS irrespective of the TFI assessed in this study (4-10 weeks), supporting this new treatment strategy as a standard of care. Differences in duration of TFI were likely related to individual patient- and disease-specific characteristics or logistics and did not impact the OS benefit observed with avelumab 1L maintenance. Clinical trial information: NCT02603432.

Baseline neutrophil-to-lymphocyte ratio and absolute lymphocyte count in patients with HER2-negative breast cancer treated with eribulin may predict overall survival.

e13005 Background: In Japan, eribulin has been approved for inoperative or recurrent breast cancer, following treatment with an anthracyclines and a taxanes. We reported the efficacy and safety of eribulin as a first-line to third-line treatment in patients with advanced/metastatic breast cancer (MBC) previously treated with anthracylinsanthracyclines and taxanes (Breast 2017). Briefly, the main inclusion criteria were as follows: no history of eribulin administration; an Eastern Cooperative Oncology Group performance status (ECOG PS) of 0 to 2,; human epidermal growth factor receptor 2 (HER2)-negative,; 20–75 years; ≥4 weeks from the last dose of chemotherapy, or ≥2 weeks from the last dosing of endocrine or radiation therapy; measurable lesion based on Response Evaluation Criteria in Solid Tumors (RECIST) ver. 1.1; sufficient organ function; life expectancy of ≥3 months; and no significant abnormalities on electrocardiogram. Patients in this clinical trial were enrolled between December 1, 2011, and November 30, 2013. Eribulin was administered intravenously at a dose of 1.4 mg/m2 during a 2-5 min infusion on days 1 and 8 every 3 weeks. In contrast, baseline neutrophil-to-lymphocyte ratio (NLR) and absolute lymphocyte count (ALC) were reported to predict progression-free survival (PFS) or overall survival (OS). However, these reports were mainly retrospective analysis. Therefore, retrospective evaluation of NLR/ALC in a prospective clinical trial is important to understand the association between NLR/ALC and OS/PFS. Methods: Of 47 prospectively enrolled patients in a previous trial, 45 patients were retrospectively evaluated for baseline NLR/ACL and at the time of 3 cycles of eribulin. The association between NLR/ALC and OS/PFS was also were analyzed for association with OS/PFS. The Kaplan-Meier method was used to estimate the OS/PFS distribution. The cut-off values for baseline NLR and ALC were set at 3 and 1500 /ul, respectively. Results: The median OS of patients with a baseline NLR &lt; 3 was significantly longer than that of patients with a baseline NLR ≥ ≧3 (769 days vs. 409 days; log-rank test p = 0.0333). The median OS of patients with a baseline ALC ≥ ≧1500 was also significantly longer than that of patients with a baseline ALC &lt; 1500 (964 days vs.vs 427 days; log-rank test p = 0.0425). Association between baseline NLR/ALC and PFS were not seen, and also association between at the time of 3 cycles of NLR/ALC and OS/PFS were not seen neither. Conclusions: Baseline NLR and ALC in the patients with HER2- negative breast cancer who plan to treat eribulin may predict overall survival. Clinical trial information: UMIN000007121.