A prospective, real-world, multinational study of febrile neutropenia (FN) occurrence in oncology patients receiving chemotherapy with intermediate risk of FN: a MASCC Neutropenia, Infection, and Myelosuppression Study Group initiative.

PURPOSE: Limited knowledge is available on the incidence of febrile neutropenia (FN) in intermediate-risk patients and the rationale for use of granulocyte colony-stimulating factor (G-CSF) in these patients. We aimed to estimate the rate at which patients associated with intermediate risk (10-20%) of FN would develop ≥ 1 episode of FN with a commonly used chemotherapy regimen in clinical practice. METHODS: This prospective, real-world, observational, multinational, multicenter study (December 2016-October 2019) recruited patients with solid tumors or Hodgkin's/non-Hodgkin's lymphoma. Patients receiving chemotherapy with intermediate risk of FN, but not G-CSF as primary prophylaxis were included and observed for the duration of the chemotherapy (≤ 6 cycles and ≤ 30 days after the last chemotherapy administration). RESULTS: In total, 364 patients (median age, 56 years) with 1601 cycles of chemotherapy were included in the analysis. The incidence of FN was 5% in cycle 1, 3% in cycles 2-3, and 1% in cycles 4-6. The rate of patients with ≥ 1 episode of FN was 9%, and 59% of FN events were reported during cycle 1. The rate of grade 4 neutropenia in cycle 1 was 11%, and 15% of patients experienced ≥ 1 episode of grade 4 neutropenia. CONCLUSIONS: Overall, the incidence of FN was low, with a high incidence in cycle 1 and a decrease in the subsequent cycles. These results provide the real FN risk for common chemotherapy regimens in patients generally excluded from clinical trials. Prophylactic G-CSF in intermediate-risk patients could be considered as per clinician's judgement.

Circulating Tumour DNA (ctDNA) as a Predictor of Clinical Outcome in Non-Small Cell Lung Cancer Undergoing Targeted Therapies: A Systematic Review and Meta-Analysis.

BACKGROUND: Liquid biopsy (LB) analysis using (ctDNA)/cell-free DNA (cfDNA) is an emerging alternative to tissue profiling in (NSCLC). LB is used to guide treatment decisions, detect resistance mechanisms, and predicts responses, and, therefore, outcomes. This systematic review and meta-analysis evaluated the impact of LB quantification on clinical outcomes in molecularly altered advanced NSCLC undergoing targeted therapies. METHODS: We searched Embase, MEDLINE, PubMed, and Cochrane Database, between 1 January 2020 and 31 August 2022. The primary outcome was progression-free survival (PFS). Secondary outcomes included overall survival (OS), objective response rate (ORR), sensitivity, and specificity. Age stratification was performed based on the mean age of the individual study population. The quality of studies was assessed using the Newcastle-Ottawa Scale (NOS). RESULTS: A total of 27 studies (3419 patients) were included in the analysis. Association of baseline ctDNA with PFS was reported in 11 studies (1359 patients), while that of dynamic changes with PFS was reported in 16 studies (1659 patients). Baseline ctDNA-negative patients had a trend towards improved PFS (pooled hazard ratio [pHR] = 1.35; 95%CI: 0.83-1.87; p < 0.001; I2 = 96%) than ctDNA-positive patients. Early reduction/clearance of ctDNA levels after treatment was related to improved PFS (pHR = 2.71; 95%CI: 1.85-3.65; I2 = 89.4%) compared to those with no reduction/persistence in ctDNA levels. The sensitivity analysis based on study quality (NOS) demonstrated improved PFS only for good [pHR = 1.95; 95%CI: 1.52-2.38] and fair [pHR = 1.99; 95%CI: 1.09-2.89] quality studies, but not for poor quality studies. There was, however, a high level of heterogeneity (I2 = 89.4%) along with significant publication bias in our analysis. CONCLUSIONS: This large systematic review, despite heterogeneity, found that baseline negative ctDNA levels and early reduction in ctDNA following treatment could be strong prognostic markers for PFS and OS in patients undergoing targeted therapies for advanced NSCLC. Future randomised clinical trials should incorporate serial ctDNA monitoring to further establish the clinical utility in advanced NSCLC management.

Chemotherapy in resectable or potentially resectable colon cancer with liver metastases.

INTRODUCTION: The treatment of colorectal cancer liver metastases has seen significant improvement in recent years and, for certain patients, the long-term survival and even cure are possible. Despite this improvement, many more questions are yet to be answered: the optimal combination, duration, sequence of therapies, role of biologics and the timing of surgical resection are debated in the literature, with conflicting trial results. AREAS COVERED: In this review, the authors highlight the current trial evidence for systemic chemotherapy and biologic therapy for colorectal cancer liver metastases in both the pre and post-resection setting. EXPERT OPINION: The treatment of colorectal liver metastases requires a multidisciplinary approach. The role of adjuvant chemotherapy with 5 fluorouracil and oxaliplatin in stage 3 colon cancer is well established. However, the options for patients with resectable or borderline liver metastases, either in the neoadjuvant or adjuvant settings, require further study. For patients with borderline resectable metastases, the combination of triplet chemotherapy with 5 fluorouracil, oxaliplatin and irinotecan (FOLFOXIRI) offers the best conversion rate. The role of biologic agents such as bevacizumab and EGFR inhibitors in these settings is less clear based on current evidence.

Survival and treatment outcomes of metaplastic breast carcinoma: Single tertiary care center experience in Pakistan.

BACKGROUND: Metaplastic breast carcinoma (MBC) is a rare disease with incidence of less than 1%. MBC present with a larger tumor size, less number of nodes involved, mostly undifferentiated triple negative tumors. We aimed to determine progression-free and overall survival and reported hospital-based incidence of MBC. MATERIAL AND METHODS: A retrospective closed Cohort study elicited data of 42 patients with MBC from January 2008 to December 2013; followed till August 2016. Kaplan-Meier method was applied to compute overall and progression-free survival analysis. Cox Proportional hazard ratios were computed to assess associations between survival and independent variables. RESULTS: Hospital-based incidence of MBC was 1.92% (42/2187), 95% CI [1.41-2.56]. The median age at tumor diagnosis was 54 years (range, 25-81 years). Thirty-nine (92.9%) patients had Grade III tumor. The most common histopathology was squamous (69%). The median tumor size was 4.5 cm (range, 0.8-17 cm). Nineteen (45.2%) patients had nodal involvement at diagnosis. Four patients (9.5%) had metastatic disease at presentation. Hormone receptors were positive in 19 (45.2%) patients. Her-2 neu receptor was positive in 9 (19%) patients. Sixteen (38.1%) patients had triple negative disease. Neoadjuvant and adjuvant chemotherapy was received by 10 (31.25%) and 19 (45.2%) patients respectively. Both median progression-free and overall survival was 38 months. CONCLUSION: Five-year progression-free and overall survival was 79.5% and 76.3%, respectively. We report better survival outcomes when compared to series described earlier despite our patient population presenting mostly with high grade, large tumors, and half of them exhibiting nodal and hormonal involvement.

Clinical audit to assess delays in chemotherapy administration at daycare oncology center at a tertiary care hospital in Karachi, Pakistan.

AIM: There were delays reported by patients in chemotherapy administration in daycare oncology. Therefore, we decided to audit all processes which are involved in chemotherapy administration. The objective was to improve our service by decreasing the time between admission and initiation of chemotherapy and identify the reasons for delays. MATERIALS AND METHODS: The audit was conducted in three parts. In Review I, audit tool was developed and information documented of 109 patients receiving chemotherapy at daycare center from April 14 to May 13, 2015. Five processes were assessed out of which delay in initial assessment by the nurse was the only factor identified leading to delay in chemotherapy. Review II was done from March 1 to 31, 2016 of 208 patients after increasing the number of nurses and Review III from June 7 to August 25, 2016 of 287 patients by dividing the initial assessment process at two different areas to decrease delay in initial assessment. RESULTS: Seventy-two percent of patients had their initial assessment done within 15 min of arrival in daycare in the first audit. In the second part of audit this percentage decreased to 55%, and finally, in the third part of the audit, percentage was improved and increased to 75% after separating initial assessment process into two areas (P < 0.001, Kruskal-Wallis test). CONCLUSION: After separating initial assessment process into two different areas, delays in chemotherapy administration were reduced.

Plasmablastic lymphoma of the oral cavity with breast recurrence: a case report.

BACKGROUND: Plasmablastic lymphoma is an aggressive variant of diffuse large B cell lymphoma, mostly found in the oral cavity and associated with human immunodeficiency virus. There are no clear guidelines for its treatment. Therapies more intensive than cyclophosphamide, doxorubicin, vincristine, and prednisone are not associated with a prolonged survival. Lymphomas of the breast are rare, in one series representing 0.14% of all female breast malignancies, with diffuse large B cell lymphoma comprising up to 55% of all cases. Only one case of plasmablastic lymphoma involving the breast has been reported in the literature. CASE PRESENTATION: A 30 year old Pakistani woman, presented with a small nodule in the floor of the mouth. An excisional biopsy revealed CD20, CD3, and CD117 negative and CD138, CD79a, CD56, MUM1/IFR4 and CD30 positive lesion with Ki-67 of 60% with cells which were plasmablastic in appearance. The morphological and immunohistochemistry features were consistent with plasmablastic lymphoma. The staging scans did not reveal any lymphadenopathy and the bone marrow biopsy and human immunodeficiency virus test were both negative. After treatment with four courses of CHOP and later radiation to the floor of the mouth, her disease was in complete remission. Two months later, she presented with velvety red lesions in both breasts and its trucut biopsy was consistent with plasmablastic lymphoma. Her CT scans revealed multiple nodules involving both breasts with no lymphadenopathy. The bone marrow was now positive for disease. Her disease continued to progress despite second and third line chemotherapy with DHAP (dexamethasone, cisplatin and cytarabine) and ICE (ifosfamide, carboplatin and etoposide) respectively. Her last CT scans revealed progressive disease with new lung lesions. The patient decided to opt for best supportive care. CONCLUSION: To our knowledge this is the second report of plasmablastic lymphoma involving the breast. The patient who was human immunodeficiency virus negative and immune competent had progressive disease despite three lines of chemotherapies with an overall survival (to date) of 15 months.

Vincristine-induced vocal cord palsy and successful re-treatment in a patient with diffuse large B cell lymphoma: a case report.

BACKGROUND: Vincristine, a type of vinca alkaloid, is widely used in the treatment of various childhood and adult malignancies. A well-known side effect of vincristine is its neurotoxicity and it is rarely indicted in vagus nerve involvement. Vincristine induced vocal cord palsy is a potentially reversible condition, with the mainstay of therapy being withdrawal of the offending drug. However, there are no clear guidelines regarding the possibility of re-treatment with the causative agent. CASE PRESENTATION: A 58 year old Asian male presented with constipation and abdominal distension. Diagnostic investigations revealed stage IVB diffuse large B cell lymphoma (DLBCL). The patient was subsequently started on R-CHOP (Rituximab, Cyclophosphamide, Doxorubicin, Vincristine, and Prednisolone). On day twelve of receiving course four of R-CHOP, our patient presented to the hospital with a history of hoarseness of voice. Clinical and radiological examination revealed bilateral vocal cord palsy. Tracheostomy was done in view of a compromised airway. The patient subsequently went on to receive two more cycles of R-CHOP. Two weeks later Flexible laryngoscopy showed no lesion and the vocal cords were moving normally. The tracheostomy was removed. His voice has improved since and the patient is currently in remission. CONCLUSION: The occurrence of vincristine induced vocal cord palsy has been well reported in the literature. We strongly believe that our patient developed vocal cord palsy secondary to vincristine. The uniqueness of our patient's case lies in successful re-treatment of our patient with the offending drug. To the best of our knowledge this is the third instance where a patient was successfully re-treated with vincristine after having developed vocal cord palsy as a result of its use.